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Study findings support uncapping MELD score
Uncapping the current Model for End-Stage Liver Disease score may provide a better path toward making sure that patients most in need of a liver transplant get one, results from a large, long-term analysis showed.
Established in 2002, the Model for End-Stage Liver Disease (MELD) scoring system “was arbitrarily capped at 40 based on the presumption that transplanting patients with MELD greater than 40 would be futile,” researchers led by Mitra K. Nadim, MD, reported in the September 2017 issue of the Journal of Hepatology (67[3]:517-25. doi: 10.1016/j.jhep.2017.04.022). “As a result, patients with MELD greater than 40 receive the same priority as patients with MELD of 40, differentiated only by their time on the wait list.”
The mean age of patients was 53 years, and most were white men. The researchers reported that 3.3% of wait-listed patients had a MELD score of 40 or greater at registration, while 7.3% had MELD scores increase to 40 or greater after wait-list registration. In all, 30,369 patients (40.6%) underwent liver transplantation during the study period. Of these, 2,615 (8.6%) had a MELD score of 40 or greater at the time of their procedure. Compared with patients who had a MELD score of 40, those who had a MELD score of greater than 40 had an increased risk of death within 30 days, and the risk increased with rising scores. Specifically, the hazard ratio was 1.4 for those with a MELD score of 40-44, an HR of 2.6 for those with a MELD score of 45-49, and an HR of 5.0 for those with a MELD score of 50 or greater. There were no survival differences between the two groups at 1 and 3 years, but there was a survival benefit associated with liver transplantation as the MELD score increased above 40, the investigators reported.
“The arbitrary capping of the MELD at 40 has resulted in an unforeseen lack of objectivity for patients with MELD [score of greater than] 40 who are unjustifiably disadvantaged in a system designed to prioritize patients most in need,” they concluded. “Uncapping the MELD score is another necessary step in the evolution of liver allocation and patient prioritization.” They added that a significant number of patients with a MELD score of 40 or greater “likely suffer from acute-on-chronic liver failure (ACLF), a recently recognized syndrome characterized by acute liver decompensation, other organ system failures, and high short-term mortality in patients with end-stage liver disease. A capped MELD score fails to capture acute liver decompensation adequately, and data suggest that a model incorporating sudden increases in MELD predicts wait-list mortality better.”
Dr. Nadim and her associates acknowledged certain limitations of the study, including its retrospective design “and that factors relating to a patient’s suitability for transplantation or to a center’s decision to accept or reject a liver allograft, both of which affect graft and patient survival, were not accounted for in the analysis. Despite these limitations, the study results have important implications for improving the current liver allocation policy.”
The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
PRIMARY SOURCE: J Hepatol. 2017;67[3]:517-25. doi: 1016/j.jhep.2017.04.022
Uncapping the current Model for End-Stage Liver Disease score may provide a better path toward making sure that patients most in need of a liver transplant get one, results from a large, long-term analysis showed.
Established in 2002, the Model for End-Stage Liver Disease (MELD) scoring system “was arbitrarily capped at 40 based on the presumption that transplanting patients with MELD greater than 40 would be futile,” researchers led by Mitra K. Nadim, MD, reported in the September 2017 issue of the Journal of Hepatology (67[3]:517-25. doi: 10.1016/j.jhep.2017.04.022). “As a result, patients with MELD greater than 40 receive the same priority as patients with MELD of 40, differentiated only by their time on the wait list.”
The mean age of patients was 53 years, and most were white men. The researchers reported that 3.3% of wait-listed patients had a MELD score of 40 or greater at registration, while 7.3% had MELD scores increase to 40 or greater after wait-list registration. In all, 30,369 patients (40.6%) underwent liver transplantation during the study period. Of these, 2,615 (8.6%) had a MELD score of 40 or greater at the time of their procedure. Compared with patients who had a MELD score of 40, those who had a MELD score of greater than 40 had an increased risk of death within 30 days, and the risk increased with rising scores. Specifically, the hazard ratio was 1.4 for those with a MELD score of 40-44, an HR of 2.6 for those with a MELD score of 45-49, and an HR of 5.0 for those with a MELD score of 50 or greater. There were no survival differences between the two groups at 1 and 3 years, but there was a survival benefit associated with liver transplantation as the MELD score increased above 40, the investigators reported.
“The arbitrary capping of the MELD at 40 has resulted in an unforeseen lack of objectivity for patients with MELD [score of greater than] 40 who are unjustifiably disadvantaged in a system designed to prioritize patients most in need,” they concluded. “Uncapping the MELD score is another necessary step in the evolution of liver allocation and patient prioritization.” They added that a significant number of patients with a MELD score of 40 or greater “likely suffer from acute-on-chronic liver failure (ACLF), a recently recognized syndrome characterized by acute liver decompensation, other organ system failures, and high short-term mortality in patients with end-stage liver disease. A capped MELD score fails to capture acute liver decompensation adequately, and data suggest that a model incorporating sudden increases in MELD predicts wait-list mortality better.”
Dr. Nadim and her associates acknowledged certain limitations of the study, including its retrospective design “and that factors relating to a patient’s suitability for transplantation or to a center’s decision to accept or reject a liver allograft, both of which affect graft and patient survival, were not accounted for in the analysis. Despite these limitations, the study results have important implications for improving the current liver allocation policy.”
The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
PRIMARY SOURCE: J Hepatol. 2017;67[3]:517-25. doi: 1016/j.jhep.2017.04.022
Uncapping the current Model for End-Stage Liver Disease score may provide a better path toward making sure that patients most in need of a liver transplant get one, results from a large, long-term analysis showed.
Established in 2002, the Model for End-Stage Liver Disease (MELD) scoring system “was arbitrarily capped at 40 based on the presumption that transplanting patients with MELD greater than 40 would be futile,” researchers led by Mitra K. Nadim, MD, reported in the September 2017 issue of the Journal of Hepatology (67[3]:517-25. doi: 10.1016/j.jhep.2017.04.022). “As a result, patients with MELD greater than 40 receive the same priority as patients with MELD of 40, differentiated only by their time on the wait list.”
The mean age of patients was 53 years, and most were white men. The researchers reported that 3.3% of wait-listed patients had a MELD score of 40 or greater at registration, while 7.3% had MELD scores increase to 40 or greater after wait-list registration. In all, 30,369 patients (40.6%) underwent liver transplantation during the study period. Of these, 2,615 (8.6%) had a MELD score of 40 or greater at the time of their procedure. Compared with patients who had a MELD score of 40, those who had a MELD score of greater than 40 had an increased risk of death within 30 days, and the risk increased with rising scores. Specifically, the hazard ratio was 1.4 for those with a MELD score of 40-44, an HR of 2.6 for those with a MELD score of 45-49, and an HR of 5.0 for those with a MELD score of 50 or greater. There were no survival differences between the two groups at 1 and 3 years, but there was a survival benefit associated with liver transplantation as the MELD score increased above 40, the investigators reported.
“The arbitrary capping of the MELD at 40 has resulted in an unforeseen lack of objectivity for patients with MELD [score of greater than] 40 who are unjustifiably disadvantaged in a system designed to prioritize patients most in need,” they concluded. “Uncapping the MELD score is another necessary step in the evolution of liver allocation and patient prioritization.” They added that a significant number of patients with a MELD score of 40 or greater “likely suffer from acute-on-chronic liver failure (ACLF), a recently recognized syndrome characterized by acute liver decompensation, other organ system failures, and high short-term mortality in patients with end-stage liver disease. A capped MELD score fails to capture acute liver decompensation adequately, and data suggest that a model incorporating sudden increases in MELD predicts wait-list mortality better.”
Dr. Nadim and her associates acknowledged certain limitations of the study, including its retrospective design “and that factors relating to a patient’s suitability for transplantation or to a center’s decision to accept or reject a liver allograft, both of which affect graft and patient survival, were not accounted for in the analysis. Despite these limitations, the study results have important implications for improving the current liver allocation policy.”
The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
PRIMARY SOURCE: J Hepatol. 2017;67[3]:517-25. doi: 1016/j.jhep.2017.04.022
FROM THE JOURNAL OF HEPATOLOGY
Key clinical point: .
Major finding: Compared with patients who had a MELD score of 40, the increased risk of death within 30 days was 1.4 for those with a MELD score of 40-44.
Study details: A retrospective analysis of 65,776 patients listed for a liver transplant from February 2002 to December 2012.
Disclosures: The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
Source: Mitra K. Nadim, MD, et al. Inequity in organ allocation for patients awaiting liver transplantation: Rationale for uncapping the model for end-stage liver disease. J Hepatol. 2017;67(3):517-25. doi: 10.1016/j.jhep.2017.04.022.
NASH did not increase risk of poor liver transplantation outcomes
Adults with nonalcoholic steatohepatitis (NASH) fared as well on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities, according to the results of a single-center retrospective cohort study.
Major morbidity, mortality, and rates of graft survival after 90 days were similar between patients who underwent transplantation for NASH and those who underwent it for another cirrhotic liver condition, wrote Eline H. van den Berg, MD, of University Medical Center Groningen (the Netherlands) with her associates. “These results are comforting, considering the expected increase of patients with NASH cirrhosis in the near future,” the researchers concluded. “Future analysis regarding the recurrence of nonalcoholic fatty liver disease, development of long-term complications, long-term graft patency, and occurrence of comorbid diseases after LT [liver transplantation] is mandatory to better understand the natural history and risk profile of NASH patients and to prevent and treat its complications.” The findings were published online in Digestive and Liver Disease (Dig Liver Dis. 2017 Aug 11. doi: 10.1016/j.dld.2017.08.022).
Nonalcoholic fatty liver disease begins as steatosis and can progress to NASH, fibrosis, and cirrhosis. The global obesity epidemic is amplifying its incidence, and about 26% of patients who develop NASH ultimately develop cirrhosis. Cirrhosis itself increases the risk of in-hospital death or prolonged length of postoperative stay, but patients with NASH also have obesity and cardiovascular disease, which might “tremendously increase” the risk of poor postoperative outcomes, the researchers said. Because prior research had focused mainly on mortality and had reported conflicting results, they used the Clavien-Dindo classification system to retrospectively study rates of complications among 169 adults who underwent liver transplantation at their center from 2009 through 2015, including 34 (20%) patients with NASH cirrhosis.
Patients with NASH were significantly older than other transplant recipients (59 versus 55 years, P = .01) and had markedly higher rates of obesity (62% versus 8%; P less than .01), diabetes mellitus (74% versus 20%; P less than .01), metabolic syndrome (83% versus 38%; P less than .01), hypertension (61% versus 30%; P less than .01), and cardiovascular disease (29% versus 11%; P less than .01). Despite these differences, the groups had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival posttransplantation (94% and 90%, respectively), and major postoperative complications, including biopsy-proven acute cellular rejection (3% and 7%), hepatic artery thrombosis (0% and 7%), relaparotomy (15% and 24%), primary nonfunction (0% and 1.6%), retransplantation (6% and 7%), sepsis (12% and 13%), gastrointestinal infection (24% and 36%), fever of unknown origin (18% and 14%), and renal replacement therapy (15% and 24%).
After accounting for age, sex, transplant year, and donor characteristics, NASH patients were at significantly increased risk of grade 2 urogenital infections, compared with other patients (odds ratio, 3.4; 95% confidence interval, 1.1 to 10.6; P = .03). Grade 1 complications also were more common with NASH than otherwise (77% versus 59%), and the difference remained statistically significant in the multivariable analysis (OR, 1.6; 95% CI, 1.03 to 2.63; P = .04).
The study used a strict, internationally accepted definition of NASH – all patients either had cases confirmed by biopsy, had metabolic syndrome, or had obesity and type 2 diabetes mellitus, and, further, none had hepatitis or alcoholic liver disease. None of the patients in the study received transplants for acute liver failure or noncirrhotic liver disease, and none were 70 years or older, which is the cutoff age for liver transplantation in the Netherlands.
The investigators received no funding for the study and reported having no conflicts of interest.
Adults with nonalcoholic steatohepatitis (NASH) fared as well on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities, according to the results of a single-center retrospective cohort study.
Major morbidity, mortality, and rates of graft survival after 90 days were similar between patients who underwent transplantation for NASH and those who underwent it for another cirrhotic liver condition, wrote Eline H. van den Berg, MD, of University Medical Center Groningen (the Netherlands) with her associates. “These results are comforting, considering the expected increase of patients with NASH cirrhosis in the near future,” the researchers concluded. “Future analysis regarding the recurrence of nonalcoholic fatty liver disease, development of long-term complications, long-term graft patency, and occurrence of comorbid diseases after LT [liver transplantation] is mandatory to better understand the natural history and risk profile of NASH patients and to prevent and treat its complications.” The findings were published online in Digestive and Liver Disease (Dig Liver Dis. 2017 Aug 11. doi: 10.1016/j.dld.2017.08.022).
Nonalcoholic fatty liver disease begins as steatosis and can progress to NASH, fibrosis, and cirrhosis. The global obesity epidemic is amplifying its incidence, and about 26% of patients who develop NASH ultimately develop cirrhosis. Cirrhosis itself increases the risk of in-hospital death or prolonged length of postoperative stay, but patients with NASH also have obesity and cardiovascular disease, which might “tremendously increase” the risk of poor postoperative outcomes, the researchers said. Because prior research had focused mainly on mortality and had reported conflicting results, they used the Clavien-Dindo classification system to retrospectively study rates of complications among 169 adults who underwent liver transplantation at their center from 2009 through 2015, including 34 (20%) patients with NASH cirrhosis.
Patients with NASH were significantly older than other transplant recipients (59 versus 55 years, P = .01) and had markedly higher rates of obesity (62% versus 8%; P less than .01), diabetes mellitus (74% versus 20%; P less than .01), metabolic syndrome (83% versus 38%; P less than .01), hypertension (61% versus 30%; P less than .01), and cardiovascular disease (29% versus 11%; P less than .01). Despite these differences, the groups had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival posttransplantation (94% and 90%, respectively), and major postoperative complications, including biopsy-proven acute cellular rejection (3% and 7%), hepatic artery thrombosis (0% and 7%), relaparotomy (15% and 24%), primary nonfunction (0% and 1.6%), retransplantation (6% and 7%), sepsis (12% and 13%), gastrointestinal infection (24% and 36%), fever of unknown origin (18% and 14%), and renal replacement therapy (15% and 24%).
After accounting for age, sex, transplant year, and donor characteristics, NASH patients were at significantly increased risk of grade 2 urogenital infections, compared with other patients (odds ratio, 3.4; 95% confidence interval, 1.1 to 10.6; P = .03). Grade 1 complications also were more common with NASH than otherwise (77% versus 59%), and the difference remained statistically significant in the multivariable analysis (OR, 1.6; 95% CI, 1.03 to 2.63; P = .04).
The study used a strict, internationally accepted definition of NASH – all patients either had cases confirmed by biopsy, had metabolic syndrome, or had obesity and type 2 diabetes mellitus, and, further, none had hepatitis or alcoholic liver disease. None of the patients in the study received transplants for acute liver failure or noncirrhotic liver disease, and none were 70 years or older, which is the cutoff age for liver transplantation in the Netherlands.
The investigators received no funding for the study and reported having no conflicts of interest.
Adults with nonalcoholic steatohepatitis (NASH) fared as well on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities, according to the results of a single-center retrospective cohort study.
Major morbidity, mortality, and rates of graft survival after 90 days were similar between patients who underwent transplantation for NASH and those who underwent it for another cirrhotic liver condition, wrote Eline H. van den Berg, MD, of University Medical Center Groningen (the Netherlands) with her associates. “These results are comforting, considering the expected increase of patients with NASH cirrhosis in the near future,” the researchers concluded. “Future analysis regarding the recurrence of nonalcoholic fatty liver disease, development of long-term complications, long-term graft patency, and occurrence of comorbid diseases after LT [liver transplantation] is mandatory to better understand the natural history and risk profile of NASH patients and to prevent and treat its complications.” The findings were published online in Digestive and Liver Disease (Dig Liver Dis. 2017 Aug 11. doi: 10.1016/j.dld.2017.08.022).
Nonalcoholic fatty liver disease begins as steatosis and can progress to NASH, fibrosis, and cirrhosis. The global obesity epidemic is amplifying its incidence, and about 26% of patients who develop NASH ultimately develop cirrhosis. Cirrhosis itself increases the risk of in-hospital death or prolonged length of postoperative stay, but patients with NASH also have obesity and cardiovascular disease, which might “tremendously increase” the risk of poor postoperative outcomes, the researchers said. Because prior research had focused mainly on mortality and had reported conflicting results, they used the Clavien-Dindo classification system to retrospectively study rates of complications among 169 adults who underwent liver transplantation at their center from 2009 through 2015, including 34 (20%) patients with NASH cirrhosis.
Patients with NASH were significantly older than other transplant recipients (59 versus 55 years, P = .01) and had markedly higher rates of obesity (62% versus 8%; P less than .01), diabetes mellitus (74% versus 20%; P less than .01), metabolic syndrome (83% versus 38%; P less than .01), hypertension (61% versus 30%; P less than .01), and cardiovascular disease (29% versus 11%; P less than .01). Despite these differences, the groups had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival posttransplantation (94% and 90%, respectively), and major postoperative complications, including biopsy-proven acute cellular rejection (3% and 7%), hepatic artery thrombosis (0% and 7%), relaparotomy (15% and 24%), primary nonfunction (0% and 1.6%), retransplantation (6% and 7%), sepsis (12% and 13%), gastrointestinal infection (24% and 36%), fever of unknown origin (18% and 14%), and renal replacement therapy (15% and 24%).
After accounting for age, sex, transplant year, and donor characteristics, NASH patients were at significantly increased risk of grade 2 urogenital infections, compared with other patients (odds ratio, 3.4; 95% confidence interval, 1.1 to 10.6; P = .03). Grade 1 complications also were more common with NASH than otherwise (77% versus 59%), and the difference remained statistically significant in the multivariable analysis (OR, 1.6; 95% CI, 1.03 to 2.63; P = .04).
The study used a strict, internationally accepted definition of NASH – all patients either had cases confirmed by biopsy, had metabolic syndrome, or had obesity and type 2 diabetes mellitus, and, further, none had hepatitis or alcoholic liver disease. None of the patients in the study received transplants for acute liver failure or noncirrhotic liver disease, and none were 70 years or older, which is the cutoff age for liver transplantation in the Netherlands.
The investigators received no funding for the study and reported having no conflicts of interest.
FROM DIGESTIVE AND LIVER DISEASES
Key clinical point: Adults with nonalcoholic steatohepatitis (NASH) fared as well as on key outcome measures as other liver transplant recipients, despite having significantly more comorbidities.
Major finding: Patients with and without NASH had statistically similar rates of postoperative mortality (3% in both groups), 90-day graft survival (94% and 90%, respectively), and major postoperative complications.
Data source: A single-center retrospective cohort study of 169 adult liver transplant recipients, of whom 20% were transplanted for NASH cirrhosis.
Disclosures: The investigators received no funding for the study and reported having no conflicts of interest.
Solid organ transplantation contributes significantly to incidence of NHL among children and adolescents
Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.
Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).
In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).
The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.
“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”
Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.
The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.
“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”
This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
ezimmerman@fronlinemedcom.com
On Twitter @eaztweets
Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.
Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).
In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).
The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.
“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”
Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.
The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.
“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”
This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
ezimmerman@fronlinemedcom.com
On Twitter @eaztweets
Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.
Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).
In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).
The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.
“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”
Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.
The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.
“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”
This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
ezimmerman@fronlinemedcom.com
On Twitter @eaztweets
FROM CANCER
Key clinical point: Solid organ transplant recipients contribute a disproportionate fraction of pediatric NHL cases, especially DLBCL cases.
Major finding: Incidence of NHL among the pediatric transplant population was 257 times higher at 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general pediatric population.
Data source: Retrospective cohort study of children and adolescents in the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012.
Disclosures: This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
Distance from transplant center predicted mortality in chronic liver disease
Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).
The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.
A total of 879 (5.2%) patients lived more than 150 miles from the nearest liver transplant center, the analysis showed. Even after controlling for etiology of liver disease, this subgroup was at significantly greater risk of mortality (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated. Distance from a transplant center also predicted overall and transplant-free mortality when modeled as a continuous variable, with hazard ratios of 1.02 (P = .02) and 1.03 (P = .04), respectively. “Although patients living more than 150 miles from a liver transplant center had fewer outpatient gastroenterologist visits, this covariate did not affect the final models,” the investigators reported. Rural locality did not predict mortality after controlling for distance from a transplant center, and neither did living in a low-income zip code, they added.
Data from the Centers for Disease Control and Prevention indicate that age-adjusted rates of death from liver disease are lowest in New York, where the entire population lives within 150 miles of a liver transplant center, the researchers noted. “By contrast, New Mexico and Wyoming have the highest age-adjusted death rates, and more than 95% of those states’ populations live more than 150 miles from a [transplant] center,” they emphasized. “The management of most patients with CLF is not centered on transplantation, but rather the spectrum of care for decompensated cirrhosis and hepatocellular carcinoma. Thus, maintaining access to specialized liver care is important for patients with CLF.”
Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).
The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.
A total of 879 (5.2%) patients lived more than 150 miles from the nearest liver transplant center, the analysis showed. Even after controlling for etiology of liver disease, this subgroup was at significantly greater risk of mortality (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated. Distance from a transplant center also predicted overall and transplant-free mortality when modeled as a continuous variable, with hazard ratios of 1.02 (P = .02) and 1.03 (P = .04), respectively. “Although patients living more than 150 miles from a liver transplant center had fewer outpatient gastroenterologist visits, this covariate did not affect the final models,” the investigators reported. Rural locality did not predict mortality after controlling for distance from a transplant center, and neither did living in a low-income zip code, they added.
Data from the Centers for Disease Control and Prevention indicate that age-adjusted rates of death from liver disease are lowest in New York, where the entire population lives within 150 miles of a liver transplant center, the researchers noted. “By contrast, New Mexico and Wyoming have the highest age-adjusted death rates, and more than 95% of those states’ populations live more than 150 miles from a [transplant] center,” they emphasized. “The management of most patients with CLF is not centered on transplantation, but rather the spectrum of care for decompensated cirrhosis and hepatocellular carcinoma. Thus, maintaining access to specialized liver care is important for patients with CLF.”
Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).
The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.
A total of 879 (5.2%) patients lived more than 150 miles from the nearest liver transplant center, the analysis showed. Even after controlling for etiology of liver disease, this subgroup was at significantly greater risk of mortality (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated. Distance from a transplant center also predicted overall and transplant-free mortality when modeled as a continuous variable, with hazard ratios of 1.02 (P = .02) and 1.03 (P = .04), respectively. “Although patients living more than 150 miles from a liver transplant center had fewer outpatient gastroenterologist visits, this covariate did not affect the final models,” the investigators reported. Rural locality did not predict mortality after controlling for distance from a transplant center, and neither did living in a low-income zip code, they added.
Data from the Centers for Disease Control and Prevention indicate that age-adjusted rates of death from liver disease are lowest in New York, where the entire population lives within 150 miles of a liver transplant center, the researchers noted. “By contrast, New Mexico and Wyoming have the highest age-adjusted death rates, and more than 95% of those states’ populations live more than 150 miles from a [transplant] center,” they emphasized. “The management of most patients with CLF is not centered on transplantation, but rather the spectrum of care for decompensated cirrhosis and hepatocellular carcinoma. Thus, maintaining access to specialized liver care is important for patients with CLF.”
Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Geographic isolation from a liver transplant center independently predicted mortality among patients with chronic liver failure.
Major finding: In adjusted analyses, patients who lived more than 150 miles from a liver transplant center were at significantly greater risk of mortality (HR, 1.2; 95% CI, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated.
Data source: A retrospective cohort study of 16,824 patients with chronic liver failure who were included in the Healthcare Integrated Research Database between 2006 and 2014.
Disclosures: Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
Skin cancer risk similar for liver and kidney transplant recipients
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
AT ACDASM 2017
Key clinical point: Liver transplant recipients should be screened and followed for the development of nonmelanoma skin cancers as closely as are kidney transplant recipients.
Major finding: Over 5 years, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, a difference that was not statistically significant after a multivariate analysis was done.
Data source: A longitudinal cohort study of 230 kidney or liver transplant recipients attending a dermatology clinic affiliated with an organ transplant unit.
Disclosures: No conflicts of interest were disclosed.
Hospital infections top WHO’s list of priority pathogens
The World Health Organization is urging governments to focus antibiotic research efforts on a list of urgent bacterial threats, topped by several increasingly powerful superbugs that cause hospital-based infections and other potentially deadly conditions.
The WHO listed the top 20 bacteria that it believes are most harmful to human health, other than mycobacteria such as Mycobacterium tuberculosis, which causes tuberculosis. The germ was not included in the list because it’s generally accepted to be the most urgent priority for new antibiotic research and development, Marie-Paule Kieny, PhD, a WHO assistant director, said at a press conference.
The priority list is needed because the antibiotic pipeline is “practically dry,” thanks to scientific research challenges and a lack of financial incentives, according to Dr. Kieny. “Antibiotics are generally used for the short term, unlike therapies for chronic diseases, which bring in much higher returns on investment,” she said. The list “is intended to signal to the scientific community and the pharmaceutical industry the areas they should focus on to address urgent public health threats.”
The WHO list begins with Priority 1/“Critical” pathogens that it believes most urgently need to be targeted through antibiotic research and development: Acinetobacter baumannii, carbapenem-resistant; Pseudomonas aeruginosa, carbapenem-resistant; and Enterobacteriaceae (including Klebsiella pneumonia, Escherichia coli, Enterobacter spp., Serratia spp., Proteus spp., Providencia spp., and Morganella spp.), carbapenem-resistant, extended-spectrum beta-lactamase–producing.
“These bacteria are responsible for severe infections and high mortality rates, mostly in hospitalized patients, transplant recipients, those receiving chemotherapy, or patients in intensive care units,” Dr. Kieny said. “While these bacteria are not widespread and do not generally affect healthy individuals, the burden for patients and society is now alarming – and new, effective therapies are imperative.”
Priority 2/”High” pathogens are Enterococcus faecium, vancomycin-resistant; Staphylococcus aureus, methicillin-resistant, vancomycin intermediate and resistant; Helicobacter pylori, clarithromycin-resistant; Campylobacter, fluoroquinolone-resistant; Salmonella spp., fluoroquinolone-resistant; Neisseria gonorrhoeae, third-generation cephalosporin-resistant and fluoroquinolone-resistant.
Pathogens in this category can infect healthy individuals, Dr. Kieny noted. “These infections, although not associated with significant mortality, have a dramatic health and economic impact on communities and, in particular, in low-income countries.”
Priority 3/”Medium” pathogens are Streptococcus pneumoniae, penicillin–non-susceptible; Haemophilus influenzae, ampicillin-resistant; and Shigella spp., fluoroquinolone-resistant.
These pathogens “represent a threat because of increasing resistance but still have some effective antibiotic options available,” Dr. Kieny said.
According to a statement provided by the WHO, the priority list doesn’t include streptococcus A and B or chlamydia, because resistance hasn’t reached the level of a public health threat.
One goal of the list is to focus attention on the development of small-market, gram-negative drugs that combat hospital-based infections, explained Nicola Magrini, MD, a WHO scientist who also spoke at the press conference.
Over the last decade, he said, the pipeline has instead focused more on gram-positive agents – mostly linked to beta-lactamase – that have wider market potential and generate less resistance.
“From a clinical point of view, these multidrug-resistant gram-negative clinical trials are very difficult and expensive to do, more than for gram-positive,” noted Evelina Tacconelli, MD, PhD, a contributor to the WHO report. “Because when we talk about gram-negative, we need to cover multiple pathogens and not just one or two, as in the case of gram-positive.”
Dr. Magrini said he couldn’t provide estimates about how many people worldwide are affected by the listed pathogens. However, he said a full report with numbers will be released by June.
It does appear that patients with severe infection from antibiotic-resistant germs face a mortality rate of up to 60%, while extended-spectrum beta-lactamase–positive E. coli accounts for up to 70% of urinary tract infections in many countries, explained Dr. Tacconelli, head of the division of infectious diseases at the University of Tübingen, Germany.
“Even if we don’t know exactly how many,” she said, “we are talking about millions of people affected.”
The World Health Organization is urging governments to focus antibiotic research efforts on a list of urgent bacterial threats, topped by several increasingly powerful superbugs that cause hospital-based infections and other potentially deadly conditions.
The WHO listed the top 20 bacteria that it believes are most harmful to human health, other than mycobacteria such as Mycobacterium tuberculosis, which causes tuberculosis. The germ was not included in the list because it’s generally accepted to be the most urgent priority for new antibiotic research and development, Marie-Paule Kieny, PhD, a WHO assistant director, said at a press conference.
The priority list is needed because the antibiotic pipeline is “practically dry,” thanks to scientific research challenges and a lack of financial incentives, according to Dr. Kieny. “Antibiotics are generally used for the short term, unlike therapies for chronic diseases, which bring in much higher returns on investment,” she said. The list “is intended to signal to the scientific community and the pharmaceutical industry the areas they should focus on to address urgent public health threats.”
The WHO list begins with Priority 1/“Critical” pathogens that it believes most urgently need to be targeted through antibiotic research and development: Acinetobacter baumannii, carbapenem-resistant; Pseudomonas aeruginosa, carbapenem-resistant; and Enterobacteriaceae (including Klebsiella pneumonia, Escherichia coli, Enterobacter spp., Serratia spp., Proteus spp., Providencia spp., and Morganella spp.), carbapenem-resistant, extended-spectrum beta-lactamase–producing.
“These bacteria are responsible for severe infections and high mortality rates, mostly in hospitalized patients, transplant recipients, those receiving chemotherapy, or patients in intensive care units,” Dr. Kieny said. “While these bacteria are not widespread and do not generally affect healthy individuals, the burden for patients and society is now alarming – and new, effective therapies are imperative.”
Priority 2/”High” pathogens are Enterococcus faecium, vancomycin-resistant; Staphylococcus aureus, methicillin-resistant, vancomycin intermediate and resistant; Helicobacter pylori, clarithromycin-resistant; Campylobacter, fluoroquinolone-resistant; Salmonella spp., fluoroquinolone-resistant; Neisseria gonorrhoeae, third-generation cephalosporin-resistant and fluoroquinolone-resistant.
Pathogens in this category can infect healthy individuals, Dr. Kieny noted. “These infections, although not associated with significant mortality, have a dramatic health and economic impact on communities and, in particular, in low-income countries.”
Priority 3/”Medium” pathogens are Streptococcus pneumoniae, penicillin–non-susceptible; Haemophilus influenzae, ampicillin-resistant; and Shigella spp., fluoroquinolone-resistant.
These pathogens “represent a threat because of increasing resistance but still have some effective antibiotic options available,” Dr. Kieny said.
According to a statement provided by the WHO, the priority list doesn’t include streptococcus A and B or chlamydia, because resistance hasn’t reached the level of a public health threat.
One goal of the list is to focus attention on the development of small-market, gram-negative drugs that combat hospital-based infections, explained Nicola Magrini, MD, a WHO scientist who also spoke at the press conference.
Over the last decade, he said, the pipeline has instead focused more on gram-positive agents – mostly linked to beta-lactamase – that have wider market potential and generate less resistance.
“From a clinical point of view, these multidrug-resistant gram-negative clinical trials are very difficult and expensive to do, more than for gram-positive,” noted Evelina Tacconelli, MD, PhD, a contributor to the WHO report. “Because when we talk about gram-negative, we need to cover multiple pathogens and not just one or two, as in the case of gram-positive.”
Dr. Magrini said he couldn’t provide estimates about how many people worldwide are affected by the listed pathogens. However, he said a full report with numbers will be released by June.
It does appear that patients with severe infection from antibiotic-resistant germs face a mortality rate of up to 60%, while extended-spectrum beta-lactamase–positive E. coli accounts for up to 70% of urinary tract infections in many countries, explained Dr. Tacconelli, head of the division of infectious diseases at the University of Tübingen, Germany.
“Even if we don’t know exactly how many,” she said, “we are talking about millions of people affected.”
The World Health Organization is urging governments to focus antibiotic research efforts on a list of urgent bacterial threats, topped by several increasingly powerful superbugs that cause hospital-based infections and other potentially deadly conditions.
The WHO listed the top 20 bacteria that it believes are most harmful to human health, other than mycobacteria such as Mycobacterium tuberculosis, which causes tuberculosis. The germ was not included in the list because it’s generally accepted to be the most urgent priority for new antibiotic research and development, Marie-Paule Kieny, PhD, a WHO assistant director, said at a press conference.
The priority list is needed because the antibiotic pipeline is “practically dry,” thanks to scientific research challenges and a lack of financial incentives, according to Dr. Kieny. “Antibiotics are generally used for the short term, unlike therapies for chronic diseases, which bring in much higher returns on investment,” she said. The list “is intended to signal to the scientific community and the pharmaceutical industry the areas they should focus on to address urgent public health threats.”
The WHO list begins with Priority 1/“Critical” pathogens that it believes most urgently need to be targeted through antibiotic research and development: Acinetobacter baumannii, carbapenem-resistant; Pseudomonas aeruginosa, carbapenem-resistant; and Enterobacteriaceae (including Klebsiella pneumonia, Escherichia coli, Enterobacter spp., Serratia spp., Proteus spp., Providencia spp., and Morganella spp.), carbapenem-resistant, extended-spectrum beta-lactamase–producing.
“These bacteria are responsible for severe infections and high mortality rates, mostly in hospitalized patients, transplant recipients, those receiving chemotherapy, or patients in intensive care units,” Dr. Kieny said. “While these bacteria are not widespread and do not generally affect healthy individuals, the burden for patients and society is now alarming – and new, effective therapies are imperative.”
Priority 2/”High” pathogens are Enterococcus faecium, vancomycin-resistant; Staphylococcus aureus, methicillin-resistant, vancomycin intermediate and resistant; Helicobacter pylori, clarithromycin-resistant; Campylobacter, fluoroquinolone-resistant; Salmonella spp., fluoroquinolone-resistant; Neisseria gonorrhoeae, third-generation cephalosporin-resistant and fluoroquinolone-resistant.
Pathogens in this category can infect healthy individuals, Dr. Kieny noted. “These infections, although not associated with significant mortality, have a dramatic health and economic impact on communities and, in particular, in low-income countries.”
Priority 3/”Medium” pathogens are Streptococcus pneumoniae, penicillin–non-susceptible; Haemophilus influenzae, ampicillin-resistant; and Shigella spp., fluoroquinolone-resistant.
These pathogens “represent a threat because of increasing resistance but still have some effective antibiotic options available,” Dr. Kieny said.
According to a statement provided by the WHO, the priority list doesn’t include streptococcus A and B or chlamydia, because resistance hasn’t reached the level of a public health threat.
One goal of the list is to focus attention on the development of small-market, gram-negative drugs that combat hospital-based infections, explained Nicola Magrini, MD, a WHO scientist who also spoke at the press conference.
Over the last decade, he said, the pipeline has instead focused more on gram-positive agents – mostly linked to beta-lactamase – that have wider market potential and generate less resistance.
“From a clinical point of view, these multidrug-resistant gram-negative clinical trials are very difficult and expensive to do, more than for gram-positive,” noted Evelina Tacconelli, MD, PhD, a contributor to the WHO report. “Because when we talk about gram-negative, we need to cover multiple pathogens and not just one or two, as in the case of gram-positive.”
Dr. Magrini said he couldn’t provide estimates about how many people worldwide are affected by the listed pathogens. However, he said a full report with numbers will be released by June.
It does appear that patients with severe infection from antibiotic-resistant germs face a mortality rate of up to 60%, while extended-spectrum beta-lactamase–positive E. coli accounts for up to 70% of urinary tract infections in many countries, explained Dr. Tacconelli, head of the division of infectious diseases at the University of Tübingen, Germany.
“Even if we don’t know exactly how many,” she said, “we are talking about millions of people affected.”
Neoadjuvant chemoradiation may give transplant the edge over resection in biliary cancer
MIAMI BEACH – Survival for patients with hilar cholangiocarcinoma was similar between those who underwent transplantation and those who underwent resection, but neoadjuvant therapy may give transplant strategy the edge, findings of a study and meta-analysis suggest.
“Neoadjuvant chemoradiation therapy is clearly a factor that affects patient survival, and may be the only reason the patients who received transplantation had better overall survival than [did those who had] resection,” Michele Gage, MD, a general surgeon at Johns Hopkins Medicine in Baltimore, said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“We found survival in the group that received neoadjuvant chemoradiation therapy and transplant had a statistically significantly better outcome compared to a control group of resection,” Dr. Gage said. More importantly, patients who received a transplant without neoadjuvant therapy had a statistically significant worse outcome than patients who got resection alone.”
The investigators noted that patient selection for neoadjuvant therapy might also be a factor contributing to superior overall survival. In a multicenter study of 147 patients undergoing liver transplantation for hilar cholangiocarcinoma, a subgroup of patients who met the selection criteria of the Mayo Clinic protocol but had not undergone neoadjuvant therapy had a 59% 5-year survival rate (PLoS One. 2016:11:e0156127).
Study discussant Maria B. Majella Doyle, MD, a general surgeon at Washington University in St. Louis, agreed that patient selection for transplantation is a likely factor.
Dr. Doyle then asked Dr. Gage how she accounts for the heterogeneity among studies performed over a 20-year period.
“That is why we did subgroup analysis of neoadjuvant versus no neoadjuvant therapy,” Dr. Gage replied.
In the future, an intent-to-treat analysis might be more accurate, Dr. Majella Doyle said, because more patients are placed on a liver transplant list than typically have the procedure.
Dr. Gage noted that 28%-48% of patients started on neoadjuvant therapy in the two studies that offered both neoadjuvant therapy and a transplant in the meta-analysis never made it to transplantation. When they were included, overall survival dropped to approximately 35% in one study and 44% in the other.
In the primary meta-analysis (before the subanalysis looking at neoadjuvant therapy), 398 patients underwent resection and another 200 underwent liver transplantation between 1996 and 2106. Patient demographics were similar between groups, including more men than women, except the average age in the resection group was older, Dr. Gage said.
Overall survival favored the transplant group at each time point: 78% versus 70% with resection at 1 year; 56% versus 42% at 3 years; and 46% versus 29% at 5 years. The odds ratios, respectively, were 1.27, 1.49 and 1.83, but the findings were not statistically significant at a 95% confidence interval.
Margin involvement was 9% in the transplant patients versus 32% in the resection patients, Dr. Gage said. The best chance of cure is R0 resection, but half of patients with hilar cholangiocarcinoma, the most common cancer of the biliary tract, are unresectable, she added.
Six of the nine studies in the meta-analysis reported margin status. Of the 344 patients in these studies, 79% achieved R0 status overall.
“The goal of treatment is R0 resection,” Dr. Gage said in response to a question about when neoadjuvant therapy is warranted. “In the patients who are resectable, I think the correct answer would be to proceed with resection. However, for those patients who are borderline resectable, it would be reasonable to consider neoadjuvant therapy.”
“One of the major things that is undervalued is neoadjuvant therapy allows better patient selection,” said session moderator Eric Jensen, MD, FACS, of University of Minnesota Health in Minneapolis. “When you say an obviously resectable tumor, when you look at the data – we’re wrong 30% of the time. So I’m in favor of neoadjuvant therapy for everybody, but that is just my bias.”
The small number of studies is a limitation of the study, Dr. Gage said. Also, all the studies were nonrandomized and retrospective, and some research spanned many years, which could introduce bias because of changes in practice over time, she added.
Based on their findings, the investigators proposed that future studies explore routine administration of neoadjuvant therapy prior to resection.
Dr. Gage and Dr. Majella Doyle had no relevant financial disclosures.
MIAMI BEACH – Survival for patients with hilar cholangiocarcinoma was similar between those who underwent transplantation and those who underwent resection, but neoadjuvant therapy may give transplant strategy the edge, findings of a study and meta-analysis suggest.
“Neoadjuvant chemoradiation therapy is clearly a factor that affects patient survival, and may be the only reason the patients who received transplantation had better overall survival than [did those who had] resection,” Michele Gage, MD, a general surgeon at Johns Hopkins Medicine in Baltimore, said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“We found survival in the group that received neoadjuvant chemoradiation therapy and transplant had a statistically significantly better outcome compared to a control group of resection,” Dr. Gage said. More importantly, patients who received a transplant without neoadjuvant therapy had a statistically significant worse outcome than patients who got resection alone.”
The investigators noted that patient selection for neoadjuvant therapy might also be a factor contributing to superior overall survival. In a multicenter study of 147 patients undergoing liver transplantation for hilar cholangiocarcinoma, a subgroup of patients who met the selection criteria of the Mayo Clinic protocol but had not undergone neoadjuvant therapy had a 59% 5-year survival rate (PLoS One. 2016:11:e0156127).
Study discussant Maria B. Majella Doyle, MD, a general surgeon at Washington University in St. Louis, agreed that patient selection for transplantation is a likely factor.
Dr. Doyle then asked Dr. Gage how she accounts for the heterogeneity among studies performed over a 20-year period.
“That is why we did subgroup analysis of neoadjuvant versus no neoadjuvant therapy,” Dr. Gage replied.
In the future, an intent-to-treat analysis might be more accurate, Dr. Majella Doyle said, because more patients are placed on a liver transplant list than typically have the procedure.
Dr. Gage noted that 28%-48% of patients started on neoadjuvant therapy in the two studies that offered both neoadjuvant therapy and a transplant in the meta-analysis never made it to transplantation. When they were included, overall survival dropped to approximately 35% in one study and 44% in the other.
In the primary meta-analysis (before the subanalysis looking at neoadjuvant therapy), 398 patients underwent resection and another 200 underwent liver transplantation between 1996 and 2106. Patient demographics were similar between groups, including more men than women, except the average age in the resection group was older, Dr. Gage said.
Overall survival favored the transplant group at each time point: 78% versus 70% with resection at 1 year; 56% versus 42% at 3 years; and 46% versus 29% at 5 years. The odds ratios, respectively, were 1.27, 1.49 and 1.83, but the findings were not statistically significant at a 95% confidence interval.
Margin involvement was 9% in the transplant patients versus 32% in the resection patients, Dr. Gage said. The best chance of cure is R0 resection, but half of patients with hilar cholangiocarcinoma, the most common cancer of the biliary tract, are unresectable, she added.
Six of the nine studies in the meta-analysis reported margin status. Of the 344 patients in these studies, 79% achieved R0 status overall.
“The goal of treatment is R0 resection,” Dr. Gage said in response to a question about when neoadjuvant therapy is warranted. “In the patients who are resectable, I think the correct answer would be to proceed with resection. However, for those patients who are borderline resectable, it would be reasonable to consider neoadjuvant therapy.”
“One of the major things that is undervalued is neoadjuvant therapy allows better patient selection,” said session moderator Eric Jensen, MD, FACS, of University of Minnesota Health in Minneapolis. “When you say an obviously resectable tumor, when you look at the data – we’re wrong 30% of the time. So I’m in favor of neoadjuvant therapy for everybody, but that is just my bias.”
The small number of studies is a limitation of the study, Dr. Gage said. Also, all the studies were nonrandomized and retrospective, and some research spanned many years, which could introduce bias because of changes in practice over time, she added.
Based on their findings, the investigators proposed that future studies explore routine administration of neoadjuvant therapy prior to resection.
Dr. Gage and Dr. Majella Doyle had no relevant financial disclosures.
MIAMI BEACH – Survival for patients with hilar cholangiocarcinoma was similar between those who underwent transplantation and those who underwent resection, but neoadjuvant therapy may give transplant strategy the edge, findings of a study and meta-analysis suggest.
“Neoadjuvant chemoradiation therapy is clearly a factor that affects patient survival, and may be the only reason the patients who received transplantation had better overall survival than [did those who had] resection,” Michele Gage, MD, a general surgeon at Johns Hopkins Medicine in Baltimore, said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“We found survival in the group that received neoadjuvant chemoradiation therapy and transplant had a statistically significantly better outcome compared to a control group of resection,” Dr. Gage said. More importantly, patients who received a transplant without neoadjuvant therapy had a statistically significant worse outcome than patients who got resection alone.”
The investigators noted that patient selection for neoadjuvant therapy might also be a factor contributing to superior overall survival. In a multicenter study of 147 patients undergoing liver transplantation for hilar cholangiocarcinoma, a subgroup of patients who met the selection criteria of the Mayo Clinic protocol but had not undergone neoadjuvant therapy had a 59% 5-year survival rate (PLoS One. 2016:11:e0156127).
Study discussant Maria B. Majella Doyle, MD, a general surgeon at Washington University in St. Louis, agreed that patient selection for transplantation is a likely factor.
Dr. Doyle then asked Dr. Gage how she accounts for the heterogeneity among studies performed over a 20-year period.
“That is why we did subgroup analysis of neoadjuvant versus no neoadjuvant therapy,” Dr. Gage replied.
In the future, an intent-to-treat analysis might be more accurate, Dr. Majella Doyle said, because more patients are placed on a liver transplant list than typically have the procedure.
Dr. Gage noted that 28%-48% of patients started on neoadjuvant therapy in the two studies that offered both neoadjuvant therapy and a transplant in the meta-analysis never made it to transplantation. When they were included, overall survival dropped to approximately 35% in one study and 44% in the other.
In the primary meta-analysis (before the subanalysis looking at neoadjuvant therapy), 398 patients underwent resection and another 200 underwent liver transplantation between 1996 and 2106. Patient demographics were similar between groups, including more men than women, except the average age in the resection group was older, Dr. Gage said.
Overall survival favored the transplant group at each time point: 78% versus 70% with resection at 1 year; 56% versus 42% at 3 years; and 46% versus 29% at 5 years. The odds ratios, respectively, were 1.27, 1.49 and 1.83, but the findings were not statistically significant at a 95% confidence interval.
Margin involvement was 9% in the transplant patients versus 32% in the resection patients, Dr. Gage said. The best chance of cure is R0 resection, but half of patients with hilar cholangiocarcinoma, the most common cancer of the biliary tract, are unresectable, she added.
Six of the nine studies in the meta-analysis reported margin status. Of the 344 patients in these studies, 79% achieved R0 status overall.
“The goal of treatment is R0 resection,” Dr. Gage said in response to a question about when neoadjuvant therapy is warranted. “In the patients who are resectable, I think the correct answer would be to proceed with resection. However, for those patients who are borderline resectable, it would be reasonable to consider neoadjuvant therapy.”
“One of the major things that is undervalued is neoadjuvant therapy allows better patient selection,” said session moderator Eric Jensen, MD, FACS, of University of Minnesota Health in Minneapolis. “When you say an obviously resectable tumor, when you look at the data – we’re wrong 30% of the time. So I’m in favor of neoadjuvant therapy for everybody, but that is just my bias.”
The small number of studies is a limitation of the study, Dr. Gage said. Also, all the studies were nonrandomized and retrospective, and some research spanned many years, which could introduce bias because of changes in practice over time, she added.
Based on their findings, the investigators proposed that future studies explore routine administration of neoadjuvant therapy prior to resection.
Dr. Gage and Dr. Majella Doyle had no relevant financial disclosures.
AT AHPBA 2017
Racial differences in skin cancer risk after organ transplantation
Nonwhite organ transplant recipients (OTRs) are more likely to present with inflammatory or infectious conditions after transplantation, while white organ recipients more commonly present with malignant disease, new research suggests.
While the high incidence of skin cancers has been well described in patients who undergo solid organ transplants, little is known about the risk factors, incidence, locations, and types of skin disease that occur in nonwhite OTRs, wrote Christina Lee Chung, MD, from Drexel University, Philadelphia, and her coauthors in JAMA Dermatology.
In a retrospective review, the investigators examined the medical records of 412 organ transplant recipients treated at an academic referral center during 2011-2016, of whom 154 were white, 35 were Asian, 33 were Hispanic, and 190 were black (JAMA Dermatology. 2017 Mar 8. doi: 10.1001/jamadermatol.2017.0045).
Among the white patients, malignant or premalignant disease was the most common diagnostic category (67.8%), followed by inflammatory (20.7%) and infectious processes (11.6%). However, among nonwhite organ transplant recipients, inflammatory processes were present in 48.8% of patients, infectious processes in 37.5% and the remaining 13.7% presented with malignant or premalignant lesions.
Black and Hispanic patients were more likely to present with inflammatory or infectious disease; only 8.6% presented with malignant conditions and 16% presented with premalignant disease.
Among the Asian patient population, one-third presented with malignant or premalignant, one-third presented with infectious, and one-third presented with inflammatory conditions.
“Although early detection and treatment of cancer is vital, nonwhite OTRs would also benefit from addressing nonmalignant processes that are exacerbated by immunosuppression,” the authors wrote.
Overall, 389 skin cancers were diagnosed, with squamous cell carcinoma in situ (SCC) the most common type of skin cancer diagnosed in each racial or ethnic group. The mean time between transplant and first skin cancer lesion was 12.67 years in black patients, 6.5 years in Hispanic patients, 6.13 years among white patients, and 3.75 years in Asian patients.
The vast majority of skin cancers (95.1%) were found in white patients. While the majority of lesions in white and Asian patients were found in sun-exposed areas, the few skin cancers seen in black patients were more likely to be found in sun-protected areas, particularly the genitals.
Four of the six genital SCCs tested positive for high-risk human papillomavirus strains – in one Asian patient and three black patients – while the two SCCs found on lower extremities in Hispanic patients tested negative for HPV.
Researchers also looked at skin cancer awareness among the organ transplant recipients using data from initial visit questionnaires. They found that more than 17 of the 22 (77.3%) white organ transplant recipients surveyed were aware their skin cancer risk was increased, compared with 30 of the 44 (68.2%) nonwhite patients.
Similarly, 72.7% of white patients surveyed were aware that sunscreen decreased the risk of cancer, compared with 59.1% of nonwhite patients; 27.3% of white patients reported using a daily sunscreen, compared with 13.6% of nonwhite patients.
“Based on our findings, we suggest that optimal posttransplant dermatologic care be determined based on the race or ethnicity of the patients; however, regardless of skin type or race or ethnicity, a baseline full-skin assessment should be performed in all patients,” the authors wrote.
They proposed that skin cancer follow-up screenings should be given to Asian and Hispanic patients immediately after transplant, but that black organ transplant recipients could delay yearly screenings.
However, they said routine skin checks should begin earlier after transplantation for all nonwhite transplant recipients with a history of, or clinically evident HPV infection.
No conflicts of interest were declared.
Nonwhite organ transplant recipients (OTRs) are more likely to present with inflammatory or infectious conditions after transplantation, while white organ recipients more commonly present with malignant disease, new research suggests.
While the high incidence of skin cancers has been well described in patients who undergo solid organ transplants, little is known about the risk factors, incidence, locations, and types of skin disease that occur in nonwhite OTRs, wrote Christina Lee Chung, MD, from Drexel University, Philadelphia, and her coauthors in JAMA Dermatology.
In a retrospective review, the investigators examined the medical records of 412 organ transplant recipients treated at an academic referral center during 2011-2016, of whom 154 were white, 35 were Asian, 33 were Hispanic, and 190 were black (JAMA Dermatology. 2017 Mar 8. doi: 10.1001/jamadermatol.2017.0045).
Among the white patients, malignant or premalignant disease was the most common diagnostic category (67.8%), followed by inflammatory (20.7%) and infectious processes (11.6%). However, among nonwhite organ transplant recipients, inflammatory processes were present in 48.8% of patients, infectious processes in 37.5% and the remaining 13.7% presented with malignant or premalignant lesions.
Black and Hispanic patients were more likely to present with inflammatory or infectious disease; only 8.6% presented with malignant conditions and 16% presented with premalignant disease.
Among the Asian patient population, one-third presented with malignant or premalignant, one-third presented with infectious, and one-third presented with inflammatory conditions.
“Although early detection and treatment of cancer is vital, nonwhite OTRs would also benefit from addressing nonmalignant processes that are exacerbated by immunosuppression,” the authors wrote.
Overall, 389 skin cancers were diagnosed, with squamous cell carcinoma in situ (SCC) the most common type of skin cancer diagnosed in each racial or ethnic group. The mean time between transplant and first skin cancer lesion was 12.67 years in black patients, 6.5 years in Hispanic patients, 6.13 years among white patients, and 3.75 years in Asian patients.
The vast majority of skin cancers (95.1%) were found in white patients. While the majority of lesions in white and Asian patients were found in sun-exposed areas, the few skin cancers seen in black patients were more likely to be found in sun-protected areas, particularly the genitals.
Four of the six genital SCCs tested positive for high-risk human papillomavirus strains – in one Asian patient and three black patients – while the two SCCs found on lower extremities in Hispanic patients tested negative for HPV.
Researchers also looked at skin cancer awareness among the organ transplant recipients using data from initial visit questionnaires. They found that more than 17 of the 22 (77.3%) white organ transplant recipients surveyed were aware their skin cancer risk was increased, compared with 30 of the 44 (68.2%) nonwhite patients.
Similarly, 72.7% of white patients surveyed were aware that sunscreen decreased the risk of cancer, compared with 59.1% of nonwhite patients; 27.3% of white patients reported using a daily sunscreen, compared with 13.6% of nonwhite patients.
“Based on our findings, we suggest that optimal posttransplant dermatologic care be determined based on the race or ethnicity of the patients; however, regardless of skin type or race or ethnicity, a baseline full-skin assessment should be performed in all patients,” the authors wrote.
They proposed that skin cancer follow-up screenings should be given to Asian and Hispanic patients immediately after transplant, but that black organ transplant recipients could delay yearly screenings.
However, they said routine skin checks should begin earlier after transplantation for all nonwhite transplant recipients with a history of, or clinically evident HPV infection.
No conflicts of interest were declared.
Nonwhite organ transplant recipients (OTRs) are more likely to present with inflammatory or infectious conditions after transplantation, while white organ recipients more commonly present with malignant disease, new research suggests.
While the high incidence of skin cancers has been well described in patients who undergo solid organ transplants, little is known about the risk factors, incidence, locations, and types of skin disease that occur in nonwhite OTRs, wrote Christina Lee Chung, MD, from Drexel University, Philadelphia, and her coauthors in JAMA Dermatology.
In a retrospective review, the investigators examined the medical records of 412 organ transplant recipients treated at an academic referral center during 2011-2016, of whom 154 were white, 35 were Asian, 33 were Hispanic, and 190 were black (JAMA Dermatology. 2017 Mar 8. doi: 10.1001/jamadermatol.2017.0045).
Among the white patients, malignant or premalignant disease was the most common diagnostic category (67.8%), followed by inflammatory (20.7%) and infectious processes (11.6%). However, among nonwhite organ transplant recipients, inflammatory processes were present in 48.8% of patients, infectious processes in 37.5% and the remaining 13.7% presented with malignant or premalignant lesions.
Black and Hispanic patients were more likely to present with inflammatory or infectious disease; only 8.6% presented with malignant conditions and 16% presented with premalignant disease.
Among the Asian patient population, one-third presented with malignant or premalignant, one-third presented with infectious, and one-third presented with inflammatory conditions.
“Although early detection and treatment of cancer is vital, nonwhite OTRs would also benefit from addressing nonmalignant processes that are exacerbated by immunosuppression,” the authors wrote.
Overall, 389 skin cancers were diagnosed, with squamous cell carcinoma in situ (SCC) the most common type of skin cancer diagnosed in each racial or ethnic group. The mean time between transplant and first skin cancer lesion was 12.67 years in black patients, 6.5 years in Hispanic patients, 6.13 years among white patients, and 3.75 years in Asian patients.
The vast majority of skin cancers (95.1%) were found in white patients. While the majority of lesions in white and Asian patients were found in sun-exposed areas, the few skin cancers seen in black patients were more likely to be found in sun-protected areas, particularly the genitals.
Four of the six genital SCCs tested positive for high-risk human papillomavirus strains – in one Asian patient and three black patients – while the two SCCs found on lower extremities in Hispanic patients tested negative for HPV.
Researchers also looked at skin cancer awareness among the organ transplant recipients using data from initial visit questionnaires. They found that more than 17 of the 22 (77.3%) white organ transplant recipients surveyed were aware their skin cancer risk was increased, compared with 30 of the 44 (68.2%) nonwhite patients.
Similarly, 72.7% of white patients surveyed were aware that sunscreen decreased the risk of cancer, compared with 59.1% of nonwhite patients; 27.3% of white patients reported using a daily sunscreen, compared with 13.6% of nonwhite patients.
“Based on our findings, we suggest that optimal posttransplant dermatologic care be determined based on the race or ethnicity of the patients; however, regardless of skin type or race or ethnicity, a baseline full-skin assessment should be performed in all patients,” the authors wrote.
They proposed that skin cancer follow-up screenings should be given to Asian and Hispanic patients immediately after transplant, but that black organ transplant recipients could delay yearly screenings.
However, they said routine skin checks should begin earlier after transplantation for all nonwhite transplant recipients with a history of, or clinically evident HPV infection.
No conflicts of interest were declared.
FROM JAMA DERMATOLOGY
Key clinical point: Nonwhite organ transplant recipients are more likely than are white recipients to present with inflammatory or infectious conditions than with skin cancer after transplantation.
Major finding: Malignant or premalignant disease was seen in 67.8% of white organ transplant recipients but just 13.7% of nonwhite recipients.
Data source: A retrospective review of medical records from 412 organ transplant recipients.
Disclosures: No conflicts of interest were declared.
Antiviral medication successful for treating HCV in hepatocellular carcinoma
Direct-acting antiviral (DAA) medication was successful in treating hepatitis C in 74.5% of patients with hepatocellular carcinoma, and 93.4% of patients with HCC who underwent liver transplants, according to a study funded by Veterans Affairs.
In order to study the effectiveness of DAAs in this setting, Lauren A. Beste, MD, and her colleagues studied a cohort of 17,487 veterans; 624 patients reported having HCC, including 142 with HCC and liver transplantation (J Hepatol. 2017. doi. org/10.1016/j.jhep.2017.02.027).
Effects of the DAAs were also studied based on the genotype of patients’ HCV. According to analysis, patients with the genotype 1 HCV virus were most susceptible to the medication, with sustained virologic response (SVR) rates calculated at 79.1% for patients with HCC, 96.4% for HCC and transplant, and 93.1% for non-HCC.
For patients with genotype 2 virus, the SVR rate was 68.9% for those with HCC, and 86.5% for patients without HCC; for genotype 3, the rate of SVR was 68.9% and 86.5% for patients with and without HCC, respectively; and for genotype 4, the SVR rate was 50% and 90.2% for patients with and without HCC, respectively.
Unlike the genotype 1 population, which had 111 patients with HCC and liver transplantation, genotypes 2, 3, and 4 had only 4, 18, and 0 patients, respectively.
Dr. Beste and her colleagues attribute this to how common genotype 1 is, which made up 11,761 of 11,871 patients (99%) with known genotypes treated with either of the two medications.
An LDV/SOF-based regimen was given to more of those with genotype 1 who had HCC (88.1%) or HCC and liver transplantation (99.1%) than to those without HCC.
When comparing fibrosis and cirrhosis (FIB-4) scores among patients with an LDV/SOF-based and PrOD p/m ribavirin regimens, patients given PrOD regimens were less likely to have a higher FIB-4 score (47.7% vs. 73.1%), thrombocytopenia (23.1% vs. 40.2%), or elevated bilirubin (21.6% vs. 35.9%).
Patients with genotype 4 showed similar results in favor of PrOD treatment and genotype 2 patients only received LDV/SOF-based treatment; however genotype 3 showed the most positive results with LDV/SOF-based regimens, reporting a 100% success rate for the seven patients treated in the specific sample.
Overall, treatment was less successful for patients with HCC, compared with those without or who underwent transplantation. While Dr. Beste and her colleagues could not definitively explain this, the researchers suggested that it might be from the HCC itself. “The association between HCC and treatment failure persisted after adjustment for cirrhosis, markers of liver dysfunction, and genotype,” said Dr. Beste. “Therefore, these factors cannot explain the lower SVR in patients with HCC, and lead us to suspect that HCC itself could be causally linked to antiviral treatment failure.”
The researcher’s presented the hypothesis that “altered hepatic immune processes may predispose both to HCC and to poorer antiviral treatment outcomes.”
While the study was strengthened by the size and scope of the cohort, researchers were limited by a lack of data, including SVR data for 11.6% of HCC patients and 6.3% of HCC patients with transplantations. Researchers were also unable to attain HCC treatment data for nearly 24% of nontransplanted cases. Finally, the sample size was “overwhelmingly” male, which may give the study “limited generalizability to women.”
ezimmerman@frontlinemedcom.com
On Twitter @EAZweets
Direct-acting antiviral (DAA) medication was successful in treating hepatitis C in 74.5% of patients with hepatocellular carcinoma, and 93.4% of patients with HCC who underwent liver transplants, according to a study funded by Veterans Affairs.
In order to study the effectiveness of DAAs in this setting, Lauren A. Beste, MD, and her colleagues studied a cohort of 17,487 veterans; 624 patients reported having HCC, including 142 with HCC and liver transplantation (J Hepatol. 2017. doi. org/10.1016/j.jhep.2017.02.027).
Effects of the DAAs were also studied based on the genotype of patients’ HCV. According to analysis, patients with the genotype 1 HCV virus were most susceptible to the medication, with sustained virologic response (SVR) rates calculated at 79.1% for patients with HCC, 96.4% for HCC and transplant, and 93.1% for non-HCC.
For patients with genotype 2 virus, the SVR rate was 68.9% for those with HCC, and 86.5% for patients without HCC; for genotype 3, the rate of SVR was 68.9% and 86.5% for patients with and without HCC, respectively; and for genotype 4, the SVR rate was 50% and 90.2% for patients with and without HCC, respectively.
Unlike the genotype 1 population, which had 111 patients with HCC and liver transplantation, genotypes 2, 3, and 4 had only 4, 18, and 0 patients, respectively.
Dr. Beste and her colleagues attribute this to how common genotype 1 is, which made up 11,761 of 11,871 patients (99%) with known genotypes treated with either of the two medications.
An LDV/SOF-based regimen was given to more of those with genotype 1 who had HCC (88.1%) or HCC and liver transplantation (99.1%) than to those without HCC.
When comparing fibrosis and cirrhosis (FIB-4) scores among patients with an LDV/SOF-based and PrOD p/m ribavirin regimens, patients given PrOD regimens were less likely to have a higher FIB-4 score (47.7% vs. 73.1%), thrombocytopenia (23.1% vs. 40.2%), or elevated bilirubin (21.6% vs. 35.9%).
Patients with genotype 4 showed similar results in favor of PrOD treatment and genotype 2 patients only received LDV/SOF-based treatment; however genotype 3 showed the most positive results with LDV/SOF-based regimens, reporting a 100% success rate for the seven patients treated in the specific sample.
Overall, treatment was less successful for patients with HCC, compared with those without or who underwent transplantation. While Dr. Beste and her colleagues could not definitively explain this, the researchers suggested that it might be from the HCC itself. “The association between HCC and treatment failure persisted after adjustment for cirrhosis, markers of liver dysfunction, and genotype,” said Dr. Beste. “Therefore, these factors cannot explain the lower SVR in patients with HCC, and lead us to suspect that HCC itself could be causally linked to antiviral treatment failure.”
The researcher’s presented the hypothesis that “altered hepatic immune processes may predispose both to HCC and to poorer antiviral treatment outcomes.”
While the study was strengthened by the size and scope of the cohort, researchers were limited by a lack of data, including SVR data for 11.6% of HCC patients and 6.3% of HCC patients with transplantations. Researchers were also unable to attain HCC treatment data for nearly 24% of nontransplanted cases. Finally, the sample size was “overwhelmingly” male, which may give the study “limited generalizability to women.”
ezimmerman@frontlinemedcom.com
On Twitter @EAZweets
Direct-acting antiviral (DAA) medication was successful in treating hepatitis C in 74.5% of patients with hepatocellular carcinoma, and 93.4% of patients with HCC who underwent liver transplants, according to a study funded by Veterans Affairs.
In order to study the effectiveness of DAAs in this setting, Lauren A. Beste, MD, and her colleagues studied a cohort of 17,487 veterans; 624 patients reported having HCC, including 142 with HCC and liver transplantation (J Hepatol. 2017. doi. org/10.1016/j.jhep.2017.02.027).
Effects of the DAAs were also studied based on the genotype of patients’ HCV. According to analysis, patients with the genotype 1 HCV virus were most susceptible to the medication, with sustained virologic response (SVR) rates calculated at 79.1% for patients with HCC, 96.4% for HCC and transplant, and 93.1% for non-HCC.
For patients with genotype 2 virus, the SVR rate was 68.9% for those with HCC, and 86.5% for patients without HCC; for genotype 3, the rate of SVR was 68.9% and 86.5% for patients with and without HCC, respectively; and for genotype 4, the SVR rate was 50% and 90.2% for patients with and without HCC, respectively.
Unlike the genotype 1 population, which had 111 patients with HCC and liver transplantation, genotypes 2, 3, and 4 had only 4, 18, and 0 patients, respectively.
Dr. Beste and her colleagues attribute this to how common genotype 1 is, which made up 11,761 of 11,871 patients (99%) with known genotypes treated with either of the two medications.
An LDV/SOF-based regimen was given to more of those with genotype 1 who had HCC (88.1%) or HCC and liver transplantation (99.1%) than to those without HCC.
When comparing fibrosis and cirrhosis (FIB-4) scores among patients with an LDV/SOF-based and PrOD p/m ribavirin regimens, patients given PrOD regimens were less likely to have a higher FIB-4 score (47.7% vs. 73.1%), thrombocytopenia (23.1% vs. 40.2%), or elevated bilirubin (21.6% vs. 35.9%).
Patients with genotype 4 showed similar results in favor of PrOD treatment and genotype 2 patients only received LDV/SOF-based treatment; however genotype 3 showed the most positive results with LDV/SOF-based regimens, reporting a 100% success rate for the seven patients treated in the specific sample.
Overall, treatment was less successful for patients with HCC, compared with those without or who underwent transplantation. While Dr. Beste and her colleagues could not definitively explain this, the researchers suggested that it might be from the HCC itself. “The association between HCC and treatment failure persisted after adjustment for cirrhosis, markers of liver dysfunction, and genotype,” said Dr. Beste. “Therefore, these factors cannot explain the lower SVR in patients with HCC, and lead us to suspect that HCC itself could be causally linked to antiviral treatment failure.”
The researcher’s presented the hypothesis that “altered hepatic immune processes may predispose both to HCC and to poorer antiviral treatment outcomes.”
While the study was strengthened by the size and scope of the cohort, researchers were limited by a lack of data, including SVR data for 11.6% of HCC patients and 6.3% of HCC patients with transplantations. Researchers were also unable to attain HCC treatment data for nearly 24% of nontransplanted cases. Finally, the sample size was “overwhelmingly” male, which may give the study “limited generalizability to women.”
ezimmerman@frontlinemedcom.com
On Twitter @EAZweets
FROM JOURNAL OF HEPATOLOGY
Key clinical point:
Major finding: Of the 17,487 patients given HCV treatment, sustained virologic response was found in 91.9% of patients without HCC, 74.5% with HCC, and 93.4% of patients with HCC and liver transplantation.
Data source: 17,487 patient records from 2014-2015 obtained through the Veterans Affairs Corporate Data Warehouse. Tests were approved by the VA Puget Sound Institutional Review Board.
Disclosures: The study was funded in part by Clinical Science Research and Development, Office of Research and Development, Veterans Affairs. Researchers reported no conflicts of interest.
Herbal/dietary supplements linked to liver injury requiring transplant
Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States, according to a study of liver transplant registry data.
Researchers analyzed registry data for 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis between 2003 and 2015, 625 of whom were recorded as having drug-induced liver injury. Of these, 21 cases were reportedly due to herbal or dietary supplements, all of which occurred after 2007. Eight cases were attributed to Lipolyze, Hydroxycut, testosterone, and OxyElite Pro, a muscle-building and weight-loss dietary supplement containing a blend of plant-derived extracts. The remaining cases did not list a specific product (Transplantation Proc 2017;49[2]:322-5).
“The potential hepatotoxicity of these HDS [herbal/dietary supplement] agents can result in the need for liver transplantation for irreversible liver failure,” wrote Dr. Linda L. Wong of the University of Hawaii and coauthors, citing two cases in Hawaii where patients needed liver transplant after taking OxyElite Pro.
They also referred to other case reports and case series of liver transplantation occurring in individuals who had taken the supplements usnic acid, Herbalife, Hydroxycut, linoleic acid, black cohosh, Chinese herbs, kava kava, skullcap, ma huang, or bai fang herb. “The benefits of the current regulatory oversight of medications breaks down when patients misuse non-FDA [Food and Drug Administration] approved herbal/dietary supplements (HDS) or ‘natural remedies’ with their inherent unknown side effects, interactions, and complications,” they wrote.
The mean age of individuals for which an herbal/dietary supplement was thought to be the cause of the hepatotoxicity was 36.8 years, 14 of the 21 were female, and the mean waiting time for liver transplantation was 4.7 days. One of the 21 patients died.
Overall, the most common drug associated with drug-induced liver injury was acetaminophen (300 cases), followed by antituberculosis medications (30), and antibiotics (30).
The authors suggested the true figure for HDS-induced liver transplantation may be underestimated, pointing to the fact that in this study, a further 154 cases were recorded as drug-induced injury but no drug was listed.
“Transplant centers and physicians may have difficulty identifying the exact inciting agent because patients do not typically report HDS when queried about medication use,” the authors wrote.
Given this, they recommended that transplant professionals specifically ask potential transplant recipients about their use of HDS, and request a detailed list of these along with the time course of use. They noted that family members and friends may not be privy to this information, and the patients themselves may not be in a position to answer because of decompensation with encephalopathy.
“It is critical to obtain this information as early as possible in the evaluation of the potential liver transplant recipient with an unknown etiology of liver disease or who presents with acute hepatic decompensation,” they wrote.
They also called for transplant professionals to report any information about confirmed HDS use in their patients to the FDA.
“It is imperative that transplant professionals inform the FDA of these dangerous compounds, with the ultimate intent of enforcing regulatory oversight,” they wrote. “This adherence to strict reporting will in turn translate to a reduction in the need for liver transplantation from HDS use.”
No conflicts of interest were declared.
Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States, according to a study of liver transplant registry data.
Researchers analyzed registry data for 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis between 2003 and 2015, 625 of whom were recorded as having drug-induced liver injury. Of these, 21 cases were reportedly due to herbal or dietary supplements, all of which occurred after 2007. Eight cases were attributed to Lipolyze, Hydroxycut, testosterone, and OxyElite Pro, a muscle-building and weight-loss dietary supplement containing a blend of plant-derived extracts. The remaining cases did not list a specific product (Transplantation Proc 2017;49[2]:322-5).
“The potential hepatotoxicity of these HDS [herbal/dietary supplement] agents can result in the need for liver transplantation for irreversible liver failure,” wrote Dr. Linda L. Wong of the University of Hawaii and coauthors, citing two cases in Hawaii where patients needed liver transplant after taking OxyElite Pro.
They also referred to other case reports and case series of liver transplantation occurring in individuals who had taken the supplements usnic acid, Herbalife, Hydroxycut, linoleic acid, black cohosh, Chinese herbs, kava kava, skullcap, ma huang, or bai fang herb. “The benefits of the current regulatory oversight of medications breaks down when patients misuse non-FDA [Food and Drug Administration] approved herbal/dietary supplements (HDS) or ‘natural remedies’ with their inherent unknown side effects, interactions, and complications,” they wrote.
The mean age of individuals for which an herbal/dietary supplement was thought to be the cause of the hepatotoxicity was 36.8 years, 14 of the 21 were female, and the mean waiting time for liver transplantation was 4.7 days. One of the 21 patients died.
Overall, the most common drug associated with drug-induced liver injury was acetaminophen (300 cases), followed by antituberculosis medications (30), and antibiotics (30).
The authors suggested the true figure for HDS-induced liver transplantation may be underestimated, pointing to the fact that in this study, a further 154 cases were recorded as drug-induced injury but no drug was listed.
“Transplant centers and physicians may have difficulty identifying the exact inciting agent because patients do not typically report HDS when queried about medication use,” the authors wrote.
Given this, they recommended that transplant professionals specifically ask potential transplant recipients about their use of HDS, and request a detailed list of these along with the time course of use. They noted that family members and friends may not be privy to this information, and the patients themselves may not be in a position to answer because of decompensation with encephalopathy.
“It is critical to obtain this information as early as possible in the evaluation of the potential liver transplant recipient with an unknown etiology of liver disease or who presents with acute hepatic decompensation,” they wrote.
They also called for transplant professionals to report any information about confirmed HDS use in their patients to the FDA.
“It is imperative that transplant professionals inform the FDA of these dangerous compounds, with the ultimate intent of enforcing regulatory oversight,” they wrote. “This adherence to strict reporting will in turn translate to a reduction in the need for liver transplantation from HDS use.”
No conflicts of interest were declared.
Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States, according to a study of liver transplant registry data.
Researchers analyzed registry data for 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis between 2003 and 2015, 625 of whom were recorded as having drug-induced liver injury. Of these, 21 cases were reportedly due to herbal or dietary supplements, all of which occurred after 2007. Eight cases were attributed to Lipolyze, Hydroxycut, testosterone, and OxyElite Pro, a muscle-building and weight-loss dietary supplement containing a blend of plant-derived extracts. The remaining cases did not list a specific product (Transplantation Proc 2017;49[2]:322-5).
“The potential hepatotoxicity of these HDS [herbal/dietary supplement] agents can result in the need for liver transplantation for irreversible liver failure,” wrote Dr. Linda L. Wong of the University of Hawaii and coauthors, citing two cases in Hawaii where patients needed liver transplant after taking OxyElite Pro.
They also referred to other case reports and case series of liver transplantation occurring in individuals who had taken the supplements usnic acid, Herbalife, Hydroxycut, linoleic acid, black cohosh, Chinese herbs, kava kava, skullcap, ma huang, or bai fang herb. “The benefits of the current regulatory oversight of medications breaks down when patients misuse non-FDA [Food and Drug Administration] approved herbal/dietary supplements (HDS) or ‘natural remedies’ with their inherent unknown side effects, interactions, and complications,” they wrote.
The mean age of individuals for which an herbal/dietary supplement was thought to be the cause of the hepatotoxicity was 36.8 years, 14 of the 21 were female, and the mean waiting time for liver transplantation was 4.7 days. One of the 21 patients died.
Overall, the most common drug associated with drug-induced liver injury was acetaminophen (300 cases), followed by antituberculosis medications (30), and antibiotics (30).
The authors suggested the true figure for HDS-induced liver transplantation may be underestimated, pointing to the fact that in this study, a further 154 cases were recorded as drug-induced injury but no drug was listed.
“Transplant centers and physicians may have difficulty identifying the exact inciting agent because patients do not typically report HDS when queried about medication use,” the authors wrote.
Given this, they recommended that transplant professionals specifically ask potential transplant recipients about their use of HDS, and request a detailed list of these along with the time course of use. They noted that family members and friends may not be privy to this information, and the patients themselves may not be in a position to answer because of decompensation with encephalopathy.
“It is critical to obtain this information as early as possible in the evaluation of the potential liver transplant recipient with an unknown etiology of liver disease or who presents with acute hepatic decompensation,” they wrote.
They also called for transplant professionals to report any information about confirmed HDS use in their patients to the FDA.
“It is imperative that transplant professionals inform the FDA of these dangerous compounds, with the ultimate intent of enforcing regulatory oversight,” they wrote. “This adherence to strict reporting will in turn translate to a reduction in the need for liver transplantation from HDS use.”
No conflicts of interest were declared.
FROM TRANSPLANTATION PROCEEDINGS
Key clinical point: Herbal or dietary supplements are the fourth most common cause of drug-induced acute hepatic necrosis requiring liver transplantation in the United States.
Major finding: Twenty-one cases of liver transplantation linked to the use of herbal or dietary supplements were recorded between 2003 and 2015.
Data source: Analysis of registry data from 2,408 adults who underwent urgent liver transplantation for acute hepatic necrosis.
Disclosures: No conflicts of interest were declared.