Transplant

SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.

The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.

Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.

There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.

There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.

Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.

“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.

“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.

The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.

Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.

“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.

Mr. Mansh had no relevant disclosures.

aotto@frontlinemedcom.com

SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.

The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.

Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.

There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.

There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.

Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.

“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.

“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.

The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.

Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.

“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.

Mr. Mansh had no relevant disclosures.

aotto@frontlinemedcom.com

SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.

The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.

Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.

There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.

There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.

Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.

“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.

“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.

The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.

Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.

“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.

Mr. Mansh had no relevant disclosures.

aotto@frontlinemedcom.com

SAN DIEGO – Extracorporeal membrane oxygenation with spontaneous breathing is the optimal bridging strategy for patients who have rapidly advancing pulmonary disease and are awaiting lung transplantation, based on data from over 18,000 patients who received lung transplants.

In the study, patients on extracorporeal membrane oxygenation (ECMO) alone had outcomes that were comparable to those of patients requiring no invasive support prior to transplantation, Dr. Matthew Schechter of Duke University in Durham, N.C., reported at the annual meeting of the Society of Thoracic Surgeons.

Dr. Schechter and his colleagues analyzed the United Network for Organ Sharing database for all adult patients who underwent lung transplantations between January 2000 and September 2013.

The 18,392 patients selected for study inclusion were divided into cohorts based on the type of preoperative support they received: ECMO with mechanical ventilation; ECMO only; ventilation only; and no support of any kind. Nearly 95% of the patients received no invasive preoperative support. Over 4% received mechanical ventilation alone, less than 1% received ECMO with mechanical ventilation, and about 0.5%) received ECMO only.

By using Kaplan-Meier survival analyses with log-rank testing, Dr. Schechter and his associates were able to compare survival rates for each type of preoperative support. Cox regression models were used to ascertain whether any particular type of preoperative support could definitively be associated with mortality.

At 3 years post transplantation, the survival rates of patients on ECMO alone and of those who received no preoperative support of any kind were comparable at 66% and 65%, respectively. Survival rates at 3 years after transplant were 38% in patients who received ECMO and mechanical ventilation and 52% in patients who received mechanical ventilation alone. The survival advantage in the ECMO only and no support groups was significantly better when compared to the ECMO and mechanical ventilation and the mechanical ventilation alone cohorts (P < .0001).

The findings held up after a multivariate analysis; the hazard ratio was 1.96 (95% confidence interval, 1.36-2.84) for ECMO with mechanical ventilation and 1.52 (95% CI, 1.31-1.78) for mechanical ventilation only (P < .0001 for both).

ECMO alone was not associated with any significant change in survival rate (HR = 1.07; 95% CI, 0.57-2.01; P = .843).

Patients who received just ECMO had the shortest lengths of stay after lung transplant. They also had the lowest rate of acute rejection prior to discharge, although not to an extent that was statistically significant. The incidence of new-onset dialysis was highest in patients who received ECMO with mechanical ventilation.

“ECMO alone may provide a survival advantage over other bridging strategies,” Dr. Schechter concluded. “One advantage of using ECMO only is an avoidance of the risks that come with mechanical ventilation, [which] include generalized muscle atrophy, maladapted muscle fiber remodeling in the diaphragm – which leads to a decrease in the overall durability of this muscle – as well as the induction of the pulmonary and systemic inflammatory risk responses, [all of which] have been shown to affect outcomes following lung transplantation.”

Dr. Schechter explained that patients receiving ECMO without mechanical ventilation can actively rehabilitate themselves post transplantation since nonintubated ECMO patients can participate in physical therapy.

Further study is needed to find an optimal way of assessing patients and determining exactly which ones would be best suited for ECMO with spontaneous breathing support, he said.

Dr, Schechter had no relevant financial disclosures.

dchitnis@frontlinemedcom.com

SAN DIEGO – Extracorporeal membrane oxygenation with spontaneous breathing is the optimal bridging strategy for patients who have rapidly advancing pulmonary disease and are awaiting lung transplantation, based on data from over 18,000 patients who received lung transplants.

In the study, patients on extracorporeal membrane oxygenation (ECMO) alone had outcomes that were comparable to those of patients requiring no invasive support prior to transplantation, Dr. Matthew Schechter of Duke University in Durham, N.C., reported at the annual meeting of the Society of Thoracic Surgeons.

Dr. Schechter and his colleagues analyzed the United Network for Organ Sharing database for all adult patients who underwent lung transplantations between January 2000 and September 2013.

The 18,392 patients selected for study inclusion were divided into cohorts based on the type of preoperative support they received: ECMO with mechanical ventilation; ECMO only; ventilation only; and no support of any kind. Nearly 95% of the patients received no invasive preoperative support. Over 4% received mechanical ventilation alone, less than 1% received ECMO with mechanical ventilation, and about 0.5%) received ECMO only.

By using Kaplan-Meier survival analyses with log-rank testing, Dr. Schechter and his associates were able to compare survival rates for each type of preoperative support. Cox regression models were used to ascertain whether any particular type of preoperative support could definitively be associated with mortality.

At 3 years post transplantation, the survival rates of patients on ECMO alone and of those who received no preoperative support of any kind were comparable at 66% and 65%, respectively. Survival rates at 3 years after transplant were 38% in patients who received ECMO and mechanical ventilation and 52% in patients who received mechanical ventilation alone. The survival advantage in the ECMO only and no support groups was significantly better when compared to the ECMO and mechanical ventilation and the mechanical ventilation alone cohorts (P < .0001).

The findings held up after a multivariate analysis; the hazard ratio was 1.96 (95% confidence interval, 1.36-2.84) for ECMO with mechanical ventilation and 1.52 (95% CI, 1.31-1.78) for mechanical ventilation only (P < .0001 for both).

ECMO alone was not associated with any significant change in survival rate (HR = 1.07; 95% CI, 0.57-2.01; P = .843).

Patients who received just ECMO had the shortest lengths of stay after lung transplant. They also had the lowest rate of acute rejection prior to discharge, although not to an extent that was statistically significant. The incidence of new-onset dialysis was highest in patients who received ECMO with mechanical ventilation.

“ECMO alone may provide a survival advantage over other bridging strategies,” Dr. Schechter concluded. “One advantage of using ECMO only is an avoidance of the risks that come with mechanical ventilation, [which] include generalized muscle atrophy, maladapted muscle fiber remodeling in the diaphragm – which leads to a decrease in the overall durability of this muscle – as well as the induction of the pulmonary and systemic inflammatory risk responses, [all of which] have been shown to affect outcomes following lung transplantation.”

Dr. Schechter explained that patients receiving ECMO without mechanical ventilation can actively rehabilitate themselves post transplantation since nonintubated ECMO patients can participate in physical therapy.

Further study is needed to find an optimal way of assessing patients and determining exactly which ones would be best suited for ECMO with spontaneous breathing support, he said.

Dr, Schechter had no relevant financial disclosures.

dchitnis@frontlinemedcom.com

SAN DIEGO – Extracorporeal membrane oxygenation with spontaneous breathing is the optimal bridging strategy for patients who have rapidly advancing pulmonary disease and are awaiting lung transplantation, based on data from over 18,000 patients who received lung transplants.

In the study, patients on extracorporeal membrane oxygenation (ECMO) alone had outcomes that were comparable to those of patients requiring no invasive support prior to transplantation, Dr. Matthew Schechter of Duke University in Durham, N.C., reported at the annual meeting of the Society of Thoracic Surgeons.

Dr. Schechter and his colleagues analyzed the United Network for Organ Sharing database for all adult patients who underwent lung transplantations between January 2000 and September 2013.

The 18,392 patients selected for study inclusion were divided into cohorts based on the type of preoperative support they received: ECMO with mechanical ventilation; ECMO only; ventilation only; and no support of any kind. Nearly 95% of the patients received no invasive preoperative support. Over 4% received mechanical ventilation alone, less than 1% received ECMO with mechanical ventilation, and about 0.5%) received ECMO only.

By using Kaplan-Meier survival analyses with log-rank testing, Dr. Schechter and his associates were able to compare survival rates for each type of preoperative support. Cox regression models were used to ascertain whether any particular type of preoperative support could definitively be associated with mortality.

At 3 years post transplantation, the survival rates of patients on ECMO alone and of those who received no preoperative support of any kind were comparable at 66% and 65%, respectively. Survival rates at 3 years after transplant were 38% in patients who received ECMO and mechanical ventilation and 52% in patients who received mechanical ventilation alone. The survival advantage in the ECMO only and no support groups was significantly better when compared to the ECMO and mechanical ventilation and the mechanical ventilation alone cohorts (P < .0001).

The findings held up after a multivariate analysis; the hazard ratio was 1.96 (95% confidence interval, 1.36-2.84) for ECMO with mechanical ventilation and 1.52 (95% CI, 1.31-1.78) for mechanical ventilation only (P < .0001 for both).

ECMO alone was not associated with any significant change in survival rate (HR = 1.07; 95% CI, 0.57-2.01; P = .843).

Patients who received just ECMO had the shortest lengths of stay after lung transplant. They also had the lowest rate of acute rejection prior to discharge, although not to an extent that was statistically significant. The incidence of new-onset dialysis was highest in patients who received ECMO with mechanical ventilation.

“ECMO alone may provide a survival advantage over other bridging strategies,” Dr. Schechter concluded. “One advantage of using ECMO only is an avoidance of the risks that come with mechanical ventilation, [which] include generalized muscle atrophy, maladapted muscle fiber remodeling in the diaphragm – which leads to a decrease in the overall durability of this muscle – as well as the induction of the pulmonary and systemic inflammatory risk responses, [all of which] have been shown to affect outcomes following lung transplantation.”

Dr. Schechter explained that patients receiving ECMO without mechanical ventilation can actively rehabilitate themselves post transplantation since nonintubated ECMO patients can participate in physical therapy.

Further study is needed to find an optimal way of assessing patients and determining exactly which ones would be best suited for ECMO with spontaneous breathing support, he said.

Dr, Schechter had no relevant financial disclosures.

dchitnis@frontlinemedcom.com

Only about one in three available hearts was accepted for transplant in the United States in 2010, down from 44% 2 decades ago, researchers reported online Feb. 9 in the American Journal of Transplantation.

The decline stems in part from transplant centers rejecting “marginal” donor hearts, belying a growing need for heart transplants, longer waiting times, and multiple campaigns to expand the use of organs donated for transplantation, said Dr. Kiran Khush of Stanford (Calif.) University and her associates.

The researchers analyzed data on 82,053 potential donor hearts from the Organ Procurement and Transplantation Network. In 1995, 44% of available hearts were accepted for transplant, compared with only 29% in 2006 and 32% in 2010, they found. Meanwhile, rejection rates for donor hearts rose from 37% in 1995 to 52% in 2010, they reported (Am. J. Transplant. 2015 Feb. 10 [doi:10.1111/ajt.13055]).

Several factors might explain the trends, the investigators said. Potential heart donors tended to be older and more often had hypertension and diabetes by the final years of the study period, and transplant centers were less likely to accept hearts from such individuals. Also, mechanical circulatory devices were more commonly used, and centers might hesitate to transplant “marginal” hearts into “stable” recipients of such devices, Dr. Khush and her associates said. Furthermore, government scrutiny of post-transplant outcomes might make centers more conservative when evaluating potential donors, they added.

The study also uncovered regional variations in acceptance rates for donor hearts, with the lowest – about 25%-28% – found primarily in the southeastern United States. “Unfortunately, there are no standard guidelines for donor heart evaluation and acceptance, resulting in considerable inconsistencies in the types of donor hearts that are accepted by different transplant centers, and likely resulting in nonrecovery of potentially useful organs,” the investigators said. The findings “lend support to research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance,” they added.

The work was supported by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the Health Resources and Services Administration. The authors reported having no conflicts of interest.

Only about one in three available hearts was accepted for transplant in the United States in 2010, down from 44% 2 decades ago, researchers reported online Feb. 9 in the American Journal of Transplantation.

The decline stems in part from transplant centers rejecting “marginal” donor hearts, belying a growing need for heart transplants, longer waiting times, and multiple campaigns to expand the use of organs donated for transplantation, said Dr. Kiran Khush of Stanford (Calif.) University and her associates.

The researchers analyzed data on 82,053 potential donor hearts from the Organ Procurement and Transplantation Network. In 1995, 44% of available hearts were accepted for transplant, compared with only 29% in 2006 and 32% in 2010, they found. Meanwhile, rejection rates for donor hearts rose from 37% in 1995 to 52% in 2010, they reported (Am. J. Transplant. 2015 Feb. 10 [doi:10.1111/ajt.13055]).

Several factors might explain the trends, the investigators said. Potential heart donors tended to be older and more often had hypertension and diabetes by the final years of the study period, and transplant centers were less likely to accept hearts from such individuals. Also, mechanical circulatory devices were more commonly used, and centers might hesitate to transplant “marginal” hearts into “stable” recipients of such devices, Dr. Khush and her associates said. Furthermore, government scrutiny of post-transplant outcomes might make centers more conservative when evaluating potential donors, they added.

The study also uncovered regional variations in acceptance rates for donor hearts, with the lowest – about 25%-28% – found primarily in the southeastern United States. “Unfortunately, there are no standard guidelines for donor heart evaluation and acceptance, resulting in considerable inconsistencies in the types of donor hearts that are accepted by different transplant centers, and likely resulting in nonrecovery of potentially useful organs,” the investigators said. The findings “lend support to research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance,” they added.

The work was supported by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the Health Resources and Services Administration. The authors reported having no conflicts of interest.

Only about one in three available hearts was accepted for transplant in the United States in 2010, down from 44% 2 decades ago, researchers reported online Feb. 9 in the American Journal of Transplantation.

The decline stems in part from transplant centers rejecting “marginal” donor hearts, belying a growing need for heart transplants, longer waiting times, and multiple campaigns to expand the use of organs donated for transplantation, said Dr. Kiran Khush of Stanford (Calif.) University and her associates.

The researchers analyzed data on 82,053 potential donor hearts from the Organ Procurement and Transplantation Network. In 1995, 44% of available hearts were accepted for transplant, compared with only 29% in 2006 and 32% in 2010, they found. Meanwhile, rejection rates for donor hearts rose from 37% in 1995 to 52% in 2010, they reported (Am. J. Transplant. 2015 Feb. 10 [doi:10.1111/ajt.13055]).

Several factors might explain the trends, the investigators said. Potential heart donors tended to be older and more often had hypertension and diabetes by the final years of the study period, and transplant centers were less likely to accept hearts from such individuals. Also, mechanical circulatory devices were more commonly used, and centers might hesitate to transplant “marginal” hearts into “stable” recipients of such devices, Dr. Khush and her associates said. Furthermore, government scrutiny of post-transplant outcomes might make centers more conservative when evaluating potential donors, they added.

The study also uncovered regional variations in acceptance rates for donor hearts, with the lowest – about 25%-28% – found primarily in the southeastern United States. “Unfortunately, there are no standard guidelines for donor heart evaluation and acceptance, resulting in considerable inconsistencies in the types of donor hearts that are accepted by different transplant centers, and likely resulting in nonrecovery of potentially useful organs,” the investigators said. The findings “lend support to research and policy efforts aimed at establishing evidence-based criteria for donor heart evaluation and acceptance,” they added.

The work was supported by the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the Health Resources and Services Administration. The authors reported having no conflicts of interest.

Since 2004, there’s been almost a tripling of the number of nonalcoholic steatohepatitis patients waiting for liver transplants; the condition is now the second leading reason to be put on the waiting list in the United States, according to a study published in the March issue of Gastroenterology.*

Even so and for reasons that are not fully clear, adults with nonalcoholic steatohepatitis (NASH) are less likely to survive for 90 days on the wait list than are patients with alcoholic liver disease (ALD), and less likely to get a new liver within 90 days than are patients with ALD, hepatitis C virus (HCV), or a blend of both. For now, HCV remains the No. 1 reason for liver transplants in the United States (Gastroenterology 2014 Nov. 24 [doi: 10.1053/j.gastro.2014.11.039]).

“Our study provides valuable information about the changing epidemiology of chronic liver disease among wait-listed patients, and adds greatly to our understanding of the epidemiology of NASH in the United States,” the researchers wrote. The rapid rise in the prevalence of NASH is “a direct consequence of the worldwide obesity epidemic” as well as greater awareness of the condition. An expected decline in HCV-related cirrhosis due to effective antiviral therapy “will further contribute to the changing epidemiology of patients awaiting liver transplants in the United States,” said the authors, led by Dr. Robert Wong of the division of gastroenterology and hepatology at Highland Hospital, Oakland, Calif.

“Given the expected continued rise in the number of NASH patients awaiting liver transplant, additional research is needed to improve wait-list survival and ... outcomes among this cohort. In addition, the projection that overall donor availability will significantly diminish in the next 15-20 years emphasizes the need for additional research to improve liver transplant opportunities for NASH patients, including the option of living donor[s],” they said.

The researchers analyzed data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry.

From 2004 to 2013, new wait-list registrants with NASH increased by 170% from 804 to 2,174; those with ALD increased by 45% from 1,400 to 2,024; and those with HCV increased by 14% from 2,887 to 3,291. Registrants with both HCV and ALD decreased by 9% from 880 to 803. NASH became the second-leading disease among liver transplant wait-list registrants in 2013.

Patients with ALD had a significantly higher Model for End-Stage Liver Disease (MELD) score at the time of registration than did others. However, after adjustment for MELD and other variables, patients with ALD were less likely to die within 90 days than were NASH patients (OR 0.77; 95% CI 0.67–0.89; P < .001). No difference was seen in wait-list mortality between NASH and HCV and HCV/ALD patients.

Compared with NASH, patients with HCV (OR 1.45; 95% CI 1.35–1.55; P < .001), ALD (OR 1.15; 95% CI: 1.06–1.24; P < .001), and HCV/ALD (OR 1.29; 95% CI 1.18–1.42; P < .001) were all significantly more likely to receive a liver after 3 months on the wait list.

A “potential explanation for these observations might be etiology-specific differences in disease progression, such that more aggressive etiologies (e.g., HCV or HCV/ALD) can have a more rapid rise in MELD score, receive liver transplant, and have lower wait-list mortality, and etiologies with less rapid progression (e.g., NASH) can have slower rise in MELD score over time, lower rates of LT, but no significant increase in wait-list mortality,” the investigators said.

Overall 1-year wait-list survival among NASH patients decreased from 42.8% in 2004-2008 to 25.6% in 2009-2013, and overall 1-year probability of receiving liver transplant among NASH patients also decreased from 42.1% in 2004-2008 to 39.6% in 2009-2013. The trends were similar for other etiologies, perhaps in part because there are more people waiting for a liver.

The authors said they have no financial conflicts to disclose.

aotto@frontlinemedcom.com

*A change was made to the text on 3/12/2015.

Since 2004, there’s been almost a tripling of the number of nonalcoholic steatohepatitis patients waiting for liver transplants; the condition is now the second leading reason to be put on the waiting list in the United States, according to a study published in the March issue of Gastroenterology.*

Even so and for reasons that are not fully clear, adults with nonalcoholic steatohepatitis (NASH) are less likely to survive for 90 days on the wait list than are patients with alcoholic liver disease (ALD), and less likely to get a new liver within 90 days than are patients with ALD, hepatitis C virus (HCV), or a blend of both. For now, HCV remains the No. 1 reason for liver transplants in the United States (Gastroenterology 2014 Nov. 24 [doi: 10.1053/j.gastro.2014.11.039]).

“Our study provides valuable information about the changing epidemiology of chronic liver disease among wait-listed patients, and adds greatly to our understanding of the epidemiology of NASH in the United States,” the researchers wrote. The rapid rise in the prevalence of NASH is “a direct consequence of the worldwide obesity epidemic” as well as greater awareness of the condition. An expected decline in HCV-related cirrhosis due to effective antiviral therapy “will further contribute to the changing epidemiology of patients awaiting liver transplants in the United States,” said the authors, led by Dr. Robert Wong of the division of gastroenterology and hepatology at Highland Hospital, Oakland, Calif.

“Given the expected continued rise in the number of NASH patients awaiting liver transplant, additional research is needed to improve wait-list survival and ... outcomes among this cohort. In addition, the projection that overall donor availability will significantly diminish in the next 15-20 years emphasizes the need for additional research to improve liver transplant opportunities for NASH patients, including the option of living donor[s],” they said.

The researchers analyzed data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry.

From 2004 to 2013, new wait-list registrants with NASH increased by 170% from 804 to 2,174; those with ALD increased by 45% from 1,400 to 2,024; and those with HCV increased by 14% from 2,887 to 3,291. Registrants with both HCV and ALD decreased by 9% from 880 to 803. NASH became the second-leading disease among liver transplant wait-list registrants in 2013.

Patients with ALD had a significantly higher Model for End-Stage Liver Disease (MELD) score at the time of registration than did others. However, after adjustment for MELD and other variables, patients with ALD were less likely to die within 90 days than were NASH patients (OR 0.77; 95% CI 0.67–0.89; P < .001). No difference was seen in wait-list mortality between NASH and HCV and HCV/ALD patients.

Compared with NASH, patients with HCV (OR 1.45; 95% CI 1.35–1.55; P < .001), ALD (OR 1.15; 95% CI: 1.06–1.24; P < .001), and HCV/ALD (OR 1.29; 95% CI 1.18–1.42; P < .001) were all significantly more likely to receive a liver after 3 months on the wait list.

A “potential explanation for these observations might be etiology-specific differences in disease progression, such that more aggressive etiologies (e.g., HCV or HCV/ALD) can have a more rapid rise in MELD score, receive liver transplant, and have lower wait-list mortality, and etiologies with less rapid progression (e.g., NASH) can have slower rise in MELD score over time, lower rates of LT, but no significant increase in wait-list mortality,” the investigators said.

Overall 1-year wait-list survival among NASH patients decreased from 42.8% in 2004-2008 to 25.6% in 2009-2013, and overall 1-year probability of receiving liver transplant among NASH patients also decreased from 42.1% in 2004-2008 to 39.6% in 2009-2013. The trends were similar for other etiologies, perhaps in part because there are more people waiting for a liver.

The authors said they have no financial conflicts to disclose.

aotto@frontlinemedcom.com

*A change was made to the text on 3/12/2015.

Since 2004, there’s been almost a tripling of the number of nonalcoholic steatohepatitis patients waiting for liver transplants; the condition is now the second leading reason to be put on the waiting list in the United States, according to a study published in the March issue of Gastroenterology.*

Even so and for reasons that are not fully clear, adults with nonalcoholic steatohepatitis (NASH) are less likely to survive for 90 days on the wait list than are patients with alcoholic liver disease (ALD), and less likely to get a new liver within 90 days than are patients with ALD, hepatitis C virus (HCV), or a blend of both. For now, HCV remains the No. 1 reason for liver transplants in the United States (Gastroenterology 2014 Nov. 24 [doi: 10.1053/j.gastro.2014.11.039]).

“Our study provides valuable information about the changing epidemiology of chronic liver disease among wait-listed patients, and adds greatly to our understanding of the epidemiology of NASH in the United States,” the researchers wrote. The rapid rise in the prevalence of NASH is “a direct consequence of the worldwide obesity epidemic” as well as greater awareness of the condition. An expected decline in HCV-related cirrhosis due to effective antiviral therapy “will further contribute to the changing epidemiology of patients awaiting liver transplants in the United States,” said the authors, led by Dr. Robert Wong of the division of gastroenterology and hepatology at Highland Hospital, Oakland, Calif.

“Given the expected continued rise in the number of NASH patients awaiting liver transplant, additional research is needed to improve wait-list survival and ... outcomes among this cohort. In addition, the projection that overall donor availability will significantly diminish in the next 15-20 years emphasizes the need for additional research to improve liver transplant opportunities for NASH patients, including the option of living donor[s],” they said.

The researchers analyzed data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry.

From 2004 to 2013, new wait-list registrants with NASH increased by 170% from 804 to 2,174; those with ALD increased by 45% from 1,400 to 2,024; and those with HCV increased by 14% from 2,887 to 3,291. Registrants with both HCV and ALD decreased by 9% from 880 to 803. NASH became the second-leading disease among liver transplant wait-list registrants in 2013.

Patients with ALD had a significantly higher Model for End-Stage Liver Disease (MELD) score at the time of registration than did others. However, after adjustment for MELD and other variables, patients with ALD were less likely to die within 90 days than were NASH patients (OR 0.77; 95% CI 0.67–0.89; P < .001). No difference was seen in wait-list mortality between NASH and HCV and HCV/ALD patients.

Compared with NASH, patients with HCV (OR 1.45; 95% CI 1.35–1.55; P < .001), ALD (OR 1.15; 95% CI: 1.06–1.24; P < .001), and HCV/ALD (OR 1.29; 95% CI 1.18–1.42; P < .001) were all significantly more likely to receive a liver after 3 months on the wait list.

A “potential explanation for these observations might be etiology-specific differences in disease progression, such that more aggressive etiologies (e.g., HCV or HCV/ALD) can have a more rapid rise in MELD score, receive liver transplant, and have lower wait-list mortality, and etiologies with less rapid progression (e.g., NASH) can have slower rise in MELD score over time, lower rates of LT, but no significant increase in wait-list mortality,” the investigators said.

Overall 1-year wait-list survival among NASH patients decreased from 42.8% in 2004-2008 to 25.6% in 2009-2013, and overall 1-year probability of receiving liver transplant among NASH patients also decreased from 42.1% in 2004-2008 to 39.6% in 2009-2013. The trends were similar for other etiologies, perhaps in part because there are more people waiting for a liver.

The authors said they have no financial conflicts to disclose.

aotto@frontlinemedcom.com

*A change was made to the text on 3/12/2015.

Pregnancy outcomes were similar for women who underwent kidney transplants in childhood and those who received transplants as adults, according to findings published Feb. 2 in JAMA Pediatrics.

Live births occurred in 76% of pregnancies in women who received kidney transplants as children, compared with 77% of pregnancies among women who received transplants as adults, wrote Melanie L. Wyld and her colleagues from Sydney Medical School in Australia.

©London_England/Thinkstockphotos.com

The study examined a total of 101 pregnancies in 66 women who received transplants before age 18 years, and 626 pregnancies in 401 women who were adults at the time of transplant.

Mean gestational age and prematurity incidence were also similar in the two groups, with child-transplant recipients having a mean gestational age of 35 weeks, and adult-transplant recipients having a mean gestational age of 36 weeks.

Incidence of prematurity was 45% in child-transplant mothers and 53% in adult-transplant mothers, the researchers reported.

“To our knowledge, this study is the first to look at pregnancy outcomes for women who received a kidney transplant as a child,” the researchers wrote. These results should “provide comfort to such mothers and their physicians that their early onset of kidney failure and longer period of posttransplant exposure to immunosuppression do not adversely affect their pregnancy outcomes,” they added.

Read the full article at: JAMA Pediatr. 2015;169(2):e143626. (doi:10.1001/jamapediatrics.2014.3626).

Pregnancy outcomes were similar for women who underwent kidney transplants in childhood and those who received transplants as adults, according to findings published Feb. 2 in JAMA Pediatrics.

Live births occurred in 76% of pregnancies in women who received kidney transplants as children, compared with 77% of pregnancies among women who received transplants as adults, wrote Melanie L. Wyld and her colleagues from Sydney Medical School in Australia.

©London_England/Thinkstockphotos.com

The study examined a total of 101 pregnancies in 66 women who received transplants before age 18 years, and 626 pregnancies in 401 women who were adults at the time of transplant.

Mean gestational age and prematurity incidence were also similar in the two groups, with child-transplant recipients having a mean gestational age of 35 weeks, and adult-transplant recipients having a mean gestational age of 36 weeks.

Incidence of prematurity was 45% in child-transplant mothers and 53% in adult-transplant mothers, the researchers reported.

“To our knowledge, this study is the first to look at pregnancy outcomes for women who received a kidney transplant as a child,” the researchers wrote. These results should “provide comfort to such mothers and their physicians that their early onset of kidney failure and longer period of posttransplant exposure to immunosuppression do not adversely affect their pregnancy outcomes,” they added.

Read the full article at: JAMA Pediatr. 2015;169(2):e143626. (doi:10.1001/jamapediatrics.2014.3626).

Pregnancy outcomes were similar for women who underwent kidney transplants in childhood and those who received transplants as adults, according to findings published Feb. 2 in JAMA Pediatrics.

Live births occurred in 76% of pregnancies in women who received kidney transplants as children, compared with 77% of pregnancies among women who received transplants as adults, wrote Melanie L. Wyld and her colleagues from Sydney Medical School in Australia.

©London_England/Thinkstockphotos.com

The study examined a total of 101 pregnancies in 66 women who received transplants before age 18 years, and 626 pregnancies in 401 women who were adults at the time of transplant.

Mean gestational age and prematurity incidence were also similar in the two groups, with child-transplant recipients having a mean gestational age of 35 weeks, and adult-transplant recipients having a mean gestational age of 36 weeks.

Incidence of prematurity was 45% in child-transplant mothers and 53% in adult-transplant mothers, the researchers reported.

“To our knowledge, this study is the first to look at pregnancy outcomes for women who received a kidney transplant as a child,” the researchers wrote. These results should “provide comfort to such mothers and their physicians that their early onset of kidney failure and longer period of posttransplant exposure to immunosuppression do not adversely affect their pregnancy outcomes,” they added.

Read the full article at: JAMA Pediatr. 2015;169(2):e143626. (doi:10.1001/jamapediatrics.2014.3626).

CHICAGO – Portal vein recanalization using a transsplenic approach can be utilized to improve transplant candidacy in patients with cirrhosis and chronic portal vein thrombosis, according to Dr. Bartley Thornburg.

“It’s a safe and effective procedure that allows for end-to-end anastomoses at transplant in patients who otherwise would not be able to have them or would require thrombectomy without transplant, and we know that end-to-end anastomoses are associated with decreased morbidity and mortality,” said Dr. Thornburg of Northwestern University Medical Center in Chicago.

Historically, and at his institution, portal vein thrombosis (PVT) is a relative contraindication to liver transplant. The American Association for the Study of Liver Diseases also recommends that transjugular intrahepatic portosystemic shunt (TIPS) placement be avoided in patients with a Model for End-State Liver Disease (MELD) score >18.

Patrice Wendling/Frontline Medical News

In 2013, colleague Dr. Riad Salem demonstrated the efficacy of portal vein recanalization during TIPS using a transhepatic approach in 44 patients, with only one technical failure and three cases of rethrombosis. Among six patients with a baseline MELD score >18, four went on to successful liver transplant, one is awaiting transplant, and one died as a result of bleeding 45 days post procedure despite an improvement in MELD score.

The last three patients in the series underwent TIPS with a transsplenic approach, and not only were the results equally good, but the approach was technically easier, Dr. Thornburg said at a symposium on vascular surgery sponsored by Northwestern University.

Since then, this increasingly common alternative approach has been assessed in another 11 consecutive patients with cirrhosis, portal hypertension, and chronic PVT. All patients had been denied listing for transplant because of their PVT, and four had a baseline MELD score >18.

At the end of the procedure, thrombus persisted in 45% (5 of 11 patients). On a 1-month follow-up venogram, however, three of the five patients had complete resolution of the thrombus without any added anticoagulation, one had persistent partial thrombus that was smaller than at stent placement, and one went on to transplant, Dr. Thornburg said.

All six of the patients with portal vein (PV) patency post procedure have retained patency after a median follow-up of 6.4 months.

“What we’ve learned from doing these cases is that complete elimination of the portal vein thrombus at the time of TIPS placement isn’t necessary,” he said. “It would be easy to get carried away and do suction or AngioJet [mechanical thrombectomy], but what we’ve found is that because of how much flow there is in the portal vein once it’s recanalized and the TIPS is in place, basically establishing a flow allowed for clot clearance by 1 month in all patients, except one.”

The procedure starts like a typical TIPS, with access achieved by advancing a 21-guage needle into the peripheral splenic vein or hilum under ultrasound guidance. A 5-French sheath is then placed through the parenchyma to the origin of splenic vein or the clot and an intrahepatic venogram performed to confirm occlusion, Dr. Thornburg said.

A 5-French Kumpe catheter and glide wire are used to recanalize the thrombosed portal vein, with a 10-mm gooseneck snare placed through the Kumpe in the peripheral portal vein as a target for the TIPS needle.

“Then, we basically get through-and-through access from the IJ [internal jugular] through this splenic access, and that gives us the workability to get our sheath across the portal vein and place our TIPS,” he said.

The remainder of the procedure is similar to that of the transhepatic approach. Angioplasty of the thrombosed PV is performed with an 8-by-40-mm balloon, followed by deployment of a Viatorr stent graft. The stent and PV are dilated with a 10-by-40-mm balloon and the splenic tract embolized with a couple of 4-by-14-cm Nester coils.

Based on their experience, short TIPS are always placed to maximize the amount of portal vein that is available at transplant for the end-to-end anastomoses, Dr. Thornburg said.

All patients who went on to transplant have received end-to-end anastomoses on what transplant surgeons have described as “totally normal” walled portal veins, including one patient who underwent transplant just 1 week post TIPS, he added.

There have been no major bleeding events with the transsplenic approach and only two adverse events: one case of transient encephalopathy and one low-grade fever.

Dr. Thornburg and Dr. Salem reported having no relevant financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Portal vein recanalization using a transsplenic approach can be utilized to improve transplant candidacy in patients with cirrhosis and chronic portal vein thrombosis, according to Dr. Bartley Thornburg.

“It’s a safe and effective procedure that allows for end-to-end anastomoses at transplant in patients who otherwise would not be able to have them or would require thrombectomy without transplant, and we know that end-to-end anastomoses are associated with decreased morbidity and mortality,” said Dr. Thornburg of Northwestern University Medical Center in Chicago.

Historically, and at his institution, portal vein thrombosis (PVT) is a relative contraindication to liver transplant. The American Association for the Study of Liver Diseases also recommends that transjugular intrahepatic portosystemic shunt (TIPS) placement be avoided in patients with a Model for End-State Liver Disease (MELD) score >18.

Patrice Wendling/Frontline Medical News

In 2013, colleague Dr. Riad Salem demonstrated the efficacy of portal vein recanalization during TIPS using a transhepatic approach in 44 patients, with only one technical failure and three cases of rethrombosis. Among six patients with a baseline MELD score >18, four went on to successful liver transplant, one is awaiting transplant, and one died as a result of bleeding 45 days post procedure despite an improvement in MELD score.

The last three patients in the series underwent TIPS with a transsplenic approach, and not only were the results equally good, but the approach was technically easier, Dr. Thornburg said at a symposium on vascular surgery sponsored by Northwestern University.

Since then, this increasingly common alternative approach has been assessed in another 11 consecutive patients with cirrhosis, portal hypertension, and chronic PVT. All patients had been denied listing for transplant because of their PVT, and four had a baseline MELD score >18.

At the end of the procedure, thrombus persisted in 45% (5 of 11 patients). On a 1-month follow-up venogram, however, three of the five patients had complete resolution of the thrombus without any added anticoagulation, one had persistent partial thrombus that was smaller than at stent placement, and one went on to transplant, Dr. Thornburg said.

All six of the patients with portal vein (PV) patency post procedure have retained patency after a median follow-up of 6.4 months.

“What we’ve learned from doing these cases is that complete elimination of the portal vein thrombus at the time of TIPS placement isn’t necessary,” he said. “It would be easy to get carried away and do suction or AngioJet [mechanical thrombectomy], but what we’ve found is that because of how much flow there is in the portal vein once it’s recanalized and the TIPS is in place, basically establishing a flow allowed for clot clearance by 1 month in all patients, except one.”

The procedure starts like a typical TIPS, with access achieved by advancing a 21-guage needle into the peripheral splenic vein or hilum under ultrasound guidance. A 5-French sheath is then placed through the parenchyma to the origin of splenic vein or the clot and an intrahepatic venogram performed to confirm occlusion, Dr. Thornburg said.

A 5-French Kumpe catheter and glide wire are used to recanalize the thrombosed portal vein, with a 10-mm gooseneck snare placed through the Kumpe in the peripheral portal vein as a target for the TIPS needle.

“Then, we basically get through-and-through access from the IJ [internal jugular] through this splenic access, and that gives us the workability to get our sheath across the portal vein and place our TIPS,” he said.

The remainder of the procedure is similar to that of the transhepatic approach. Angioplasty of the thrombosed PV is performed with an 8-by-40-mm balloon, followed by deployment of a Viatorr stent graft. The stent and PV are dilated with a 10-by-40-mm balloon and the splenic tract embolized with a couple of 4-by-14-cm Nester coils.

Based on their experience, short TIPS are always placed to maximize the amount of portal vein that is available at transplant for the end-to-end anastomoses, Dr. Thornburg said.

All patients who went on to transplant have received end-to-end anastomoses on what transplant surgeons have described as “totally normal” walled portal veins, including one patient who underwent transplant just 1 week post TIPS, he added.

There have been no major bleeding events with the transsplenic approach and only two adverse events: one case of transient encephalopathy and one low-grade fever.

Dr. Thornburg and Dr. Salem reported having no relevant financial disclosures.

pwendling@frontlinemedcom.com

CHICAGO – Portal vein recanalization using a transsplenic approach can be utilized to improve transplant candidacy in patients with cirrhosis and chronic portal vein thrombosis, according to Dr. Bartley Thornburg.

“It’s a safe and effective procedure that allows for end-to-end anastomoses at transplant in patients who otherwise would not be able to have them or would require thrombectomy without transplant, and we know that end-to-end anastomoses are associated with decreased morbidity and mortality,” said Dr. Thornburg of Northwestern University Medical Center in Chicago.

Historically, and at his institution, portal vein thrombosis (PVT) is a relative contraindication to liver transplant. The American Association for the Study of Liver Diseases also recommends that transjugular intrahepatic portosystemic shunt (TIPS) placement be avoided in patients with a Model for End-State Liver Disease (MELD) score >18.

Patrice Wendling/Frontline Medical News

In 2013, colleague Dr. Riad Salem demonstrated the efficacy of portal vein recanalization during TIPS using a transhepatic approach in 44 patients, with only one technical failure and three cases of rethrombosis. Among six patients with a baseline MELD score >18, four went on to successful liver transplant, one is awaiting transplant, and one died as a result of bleeding 45 days post procedure despite an improvement in MELD score.

The last three patients in the series underwent TIPS with a transsplenic approach, and not only were the results equally good, but the approach was technically easier, Dr. Thornburg said at a symposium on vascular surgery sponsored by Northwestern University.

Since then, this increasingly common alternative approach has been assessed in another 11 consecutive patients with cirrhosis, portal hypertension, and chronic PVT. All patients had been denied listing for transplant because of their PVT, and four had a baseline MELD score >18.

At the end of the procedure, thrombus persisted in 45% (5 of 11 patients). On a 1-month follow-up venogram, however, three of the five patients had complete resolution of the thrombus without any added anticoagulation, one had persistent partial thrombus that was smaller than at stent placement, and one went on to transplant, Dr. Thornburg said.

All six of the patients with portal vein (PV) patency post procedure have retained patency after a median follow-up of 6.4 months.

“What we’ve learned from doing these cases is that complete elimination of the portal vein thrombus at the time of TIPS placement isn’t necessary,” he said. “It would be easy to get carried away and do suction or AngioJet [mechanical thrombectomy], but what we’ve found is that because of how much flow there is in the portal vein once it’s recanalized and the TIPS is in place, basically establishing a flow allowed for clot clearance by 1 month in all patients, except one.”

The procedure starts like a typical TIPS, with access achieved by advancing a 21-guage needle into the peripheral splenic vein or hilum under ultrasound guidance. A 5-French sheath is then placed through the parenchyma to the origin of splenic vein or the clot and an intrahepatic venogram performed to confirm occlusion, Dr. Thornburg said.

A 5-French Kumpe catheter and glide wire are used to recanalize the thrombosed portal vein, with a 10-mm gooseneck snare placed through the Kumpe in the peripheral portal vein as a target for the TIPS needle.

“Then, we basically get through-and-through access from the IJ [internal jugular] through this splenic access, and that gives us the workability to get our sheath across the portal vein and place our TIPS,” he said.

The remainder of the procedure is similar to that of the transhepatic approach. Angioplasty of the thrombosed PV is performed with an 8-by-40-mm balloon, followed by deployment of a Viatorr stent graft. The stent and PV are dilated with a 10-by-40-mm balloon and the splenic tract embolized with a couple of 4-by-14-cm Nester coils.

Based on their experience, short TIPS are always placed to maximize the amount of portal vein that is available at transplant for the end-to-end anastomoses, Dr. Thornburg said.

All patients who went on to transplant have received end-to-end anastomoses on what transplant surgeons have described as “totally normal” walled portal veins, including one patient who underwent transplant just 1 week post TIPS, he added.

There have been no major bleeding events with the transsplenic approach and only two adverse events: one case of transient encephalopathy and one low-grade fever.

Dr. Thornburg and Dr. Salem reported having no relevant financial disclosures.

pwendling@frontlinemedcom.com

SAN DIEGO – Cutaneous squamous cell carcinomas from organ transplant recipients had a more aggressive molecular profile than did tumor samples from immunocompetent patients, according to an RNA sequencing study presented at the annual meeting of the American Society for Dermatologic Surgery.

Specimens from organ transplant recipients showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, said Dr. Cameron Chesnut, a dermatologist in private practice in Spokane, Wash., who carried out the research while he was a dermatologic surgery resident at the University of California, Los Angeles.

Furthermore, the TP53 tumor suppressor gene was inhibited at least five times more in samples from organ transplant recipients, compared with those from immunocompetent patients, Dr. Chesnut said in an interview.

Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation, Dr. Chesnut and his associates noted. The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients, based on data published online in the journal F1000 Prime Reports, they said.

To characterize these high-risk SCCs and compare them with lower-risk SCCs, the researchers performed RNA sequencing of three normal skin samples and SCC specimens from 15 patients – 7 organ transplant recipients and 8 otherwise healthy individuals. The researchers used an Illumina GAIIx RNA Seq instrument to generate RNA sequencing libraries of the specimens. They also used the web-based Ingenuity Pathway Analysis technique to identify the major biological pathways regulated within the tumors.

In all, 690 highly expressed genes were induced at least fivefold in SCCs from organ transplant recipients compared with those from otherwise healthy patients. These genes encoded pathways related to fibrosis, extracellular remodeling, the cell cycle, and tumor signaling, the investigators said. The COX-2 pathway for prostaglandin synthesis also was induced fivefold or more in the high-risk SCCs compared with those from immunocompetent patients, Dr. Chesnut added.

The researchers also identified 1,290 highly expressed genes that were inhibited at least fivefold in SCCs from organ transplant recipients compared with specimens from immunocompetent patients. The most strongly inhibited pathways were related to sterol biosynthesis and epithelial differentiation, followed by nucleotide excision repair, interleukin-6 and IL-17, and apoptosis, they said.

Based on these findings, novel therapeutics might someday be able to target specific biologic pathways that are highly induced in SCCs from organ transplant recipients, Dr. Chesnut said. “It’s hard to say what the most likely candidates are,” but based on the study findings, “regulating inflammation may be a target,” he added. Dr. Chesnut and his associates reported no external funding sources or conflicts of interest.

SAN DIEGO – Cutaneous squamous cell carcinomas from organ transplant recipients had a more aggressive molecular profile than did tumor samples from immunocompetent patients, according to an RNA sequencing study presented at the annual meeting of the American Society for Dermatologic Surgery.

Specimens from organ transplant recipients showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, said Dr. Cameron Chesnut, a dermatologist in private practice in Spokane, Wash., who carried out the research while he was a dermatologic surgery resident at the University of California, Los Angeles.

Furthermore, the TP53 tumor suppressor gene was inhibited at least five times more in samples from organ transplant recipients, compared with those from immunocompetent patients, Dr. Chesnut said in an interview.

Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation, Dr. Chesnut and his associates noted. The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients, based on data published online in the journal F1000 Prime Reports, they said.

To characterize these high-risk SCCs and compare them with lower-risk SCCs, the researchers performed RNA sequencing of three normal skin samples and SCC specimens from 15 patients – 7 organ transplant recipients and 8 otherwise healthy individuals. The researchers used an Illumina GAIIx RNA Seq instrument to generate RNA sequencing libraries of the specimens. They also used the web-based Ingenuity Pathway Analysis technique to identify the major biological pathways regulated within the tumors.

In all, 690 highly expressed genes were induced at least fivefold in SCCs from organ transplant recipients compared with those from otherwise healthy patients. These genes encoded pathways related to fibrosis, extracellular remodeling, the cell cycle, and tumor signaling, the investigators said. The COX-2 pathway for prostaglandin synthesis also was induced fivefold or more in the high-risk SCCs compared with those from immunocompetent patients, Dr. Chesnut added.

The researchers also identified 1,290 highly expressed genes that were inhibited at least fivefold in SCCs from organ transplant recipients compared with specimens from immunocompetent patients. The most strongly inhibited pathways were related to sterol biosynthesis and epithelial differentiation, followed by nucleotide excision repair, interleukin-6 and IL-17, and apoptosis, they said.

Based on these findings, novel therapeutics might someday be able to target specific biologic pathways that are highly induced in SCCs from organ transplant recipients, Dr. Chesnut said. “It’s hard to say what the most likely candidates are,” but based on the study findings, “regulating inflammation may be a target,” he added. Dr. Chesnut and his associates reported no external funding sources or conflicts of interest.

SAN DIEGO – Cutaneous squamous cell carcinomas from organ transplant recipients had a more aggressive molecular profile than did tumor samples from immunocompetent patients, according to an RNA sequencing study presented at the annual meeting of the American Society for Dermatologic Surgery.

Specimens from organ transplant recipients showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, said Dr. Cameron Chesnut, a dermatologist in private practice in Spokane, Wash., who carried out the research while he was a dermatologic surgery resident at the University of California, Los Angeles.

Furthermore, the TP53 tumor suppressor gene was inhibited at least five times more in samples from organ transplant recipients, compared with those from immunocompetent patients, Dr. Chesnut said in an interview.

Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation, Dr. Chesnut and his associates noted. The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients, based on data published online in the journal F1000 Prime Reports, they said.

To characterize these high-risk SCCs and compare them with lower-risk SCCs, the researchers performed RNA sequencing of three normal skin samples and SCC specimens from 15 patients – 7 organ transplant recipients and 8 otherwise healthy individuals. The researchers used an Illumina GAIIx RNA Seq instrument to generate RNA sequencing libraries of the specimens. They also used the web-based Ingenuity Pathway Analysis technique to identify the major biological pathways regulated within the tumors.

In all, 690 highly expressed genes were induced at least fivefold in SCCs from organ transplant recipients compared with those from otherwise healthy patients. These genes encoded pathways related to fibrosis, extracellular remodeling, the cell cycle, and tumor signaling, the investigators said. The COX-2 pathway for prostaglandin synthesis also was induced fivefold or more in the high-risk SCCs compared with those from immunocompetent patients, Dr. Chesnut added.

The researchers also identified 1,290 highly expressed genes that were inhibited at least fivefold in SCCs from organ transplant recipients compared with specimens from immunocompetent patients. The most strongly inhibited pathways were related to sterol biosynthesis and epithelial differentiation, followed by nucleotide excision repair, interleukin-6 and IL-17, and apoptosis, they said.

Based on these findings, novel therapeutics might someday be able to target specific biologic pathways that are highly induced in SCCs from organ transplant recipients, Dr. Chesnut said. “It’s hard to say what the most likely candidates are,” but based on the study findings, “regulating inflammation may be a target,” he added. Dr. Chesnut and his associates reported no external funding sources or conflicts of interest.

Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).

“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”

In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.

The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.

“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”

In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.

“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.

Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”

Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.

“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”

The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.

dchitnis@frontlinemedcom.com

Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).

“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”

In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.

The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.

“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”

In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.

“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.

Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”

Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.

“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”

The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.

dchitnis@frontlinemedcom.com

Sofosbuvir and ribavirin treatments should be administered to patients with hepatitis C virus who undergo liver transplantations in order to significantly decrease the risks of posttransplant HCV recurrence, according to two new studies published in the January issue of Gastroenterology (10.1053/j.gastro.2014.09.023 and 10.1053/j.gastro.2014.10.001).

“In clinical trials, administration of sofosbuvir with ribavirin was associated with rapid decreases of HCV RNA to undetectable levels in patients with HCV genotype 1, 2, 3, 4, and 6 infections,” wrote lead author Dr. Michael P. Curry of the Beth Israel Deaconess Medical Center in Boston, and his coauthors on the first of these two studies. “In more than 3,000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions have been observed.”

In a phase II, open-label study, Dr. Curry and his coinvestigators enrolled 61 patients with HCV of any genotype, and cirrhosis with a Child-Turcotte-Pugh score no greater than 7, who were all wait-listed to receive liver transplantations. Subjects received up to 48 weeks of treatment with 400 mg of sofosbuvir, and a separate dose of ribavirin prior to liver transplantation, while 43 patients received transplantations alone. The primary outcome sought by investigators was HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients that had this level prior to the operation.

The investigators found that 43 subjects had the desired HCV-RNA levels; of that population, 49% had a posttransplantation virologic response, with the most frequent side effects reported by subjects being fatigue (38%), headache (23%), and anemia (21%). Of the 43 applicable subjects, 30 (70% of the population) had a posttransplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died.

“This study provides proof of concept that virologic suppression without interferon significantly can reduce the rate of recurrent HCV after liver transplantation,” the study says, adding that the results “compare favorably with those observed in other trials of pretransplantation antiviral therapy.”

In the second study, the authors ascertained that combination therapy consisting of sofosbuvir and ribavirin for 24 weeks is effective at preventing hepatitis C virus recurrence in patients who undergo liver transplantations.

“Recurrent HCV infection is the most common cause of mortality and graft loss following transplantation, and up to 30% of patients with recurrent infection develop cirrhosis within 5 years,” wrote the study’s authors, led by Dr. Michael Charlton of the Mayo Clinic in Rochester, Minn.

Using a prospective, multicenter, open-label pilot study, investigators enrolled and treated 40 patients with a 24-week regimen of 400 mg sofosbuvir and ribavirin starting at 400 mg, which was subsequently adjusted per patient based on individual creatinine clearance and hemoglobin levels. Subjects were 78% male and 85% white, with 83% having HCV genotype 1, 40% having cirrhosis, and 88% having been previously treated with interferon. The primary outcome investigators looked for was “sustained virologic response 12 weeks after treatment (SVR12).”

Data showed that SVR12 was achieved by 28 of the 40 subjects that received treatment, or 70%. The most commonly reported adverse effects were fatigue (30%), diarrhea (28%), headache (25%), and anemia (20%). No patients exhibited detectable viral resistance during or after treatment, and although two patients terminated their treatment because of adverse events, investigators reported no deaths, graft losses, or episodes of rejection.

“In contrast,” Dr. Charlton and his coauthors noted, “interferon-based treatments have been associated with posttreatment immunological dysfunction (particularly plasma cell hepatitis) and even hepatic decompensation in LT [liver transplant] recipients.”

The authors of the first study disclosed that Dr. Curry has received grants from and been affiliated with Gilead, which was a sponsor of the study. The authors of the second study reported no relevant financial disclosures.

dchitnis@frontlinemedcom.com

PHILADELPHIA – A 3-month course of levofloxacin after kidney transplant didn’t prevent BK virus from colonizing the urine, setting the stage for viremia in these immunosuppressed patients.

However, the antibiotic was associated with a significant 75% increase in the risk of developing a quinolone-resistant infection, compared with placebo, Dr. Greg A. Knoll and his colleagues reported in the Nov. 15 issue of JAMA (2014 [doi:10.1001/jama.2014.14721]).In a randomized trial of 154 kidney transplant patients, BK virus developed in 29% of those taking levofloxacin and in 33% of those taking placebo, a nonsignificant difference, coauthor Greg Knoll said at a late-breaking poster session during Kidney Week 2014, where the study was simultaneously presented.Levofloxacin, a quinolone antibiotic, has been shown to have some antiviral properties, especially against polyomaviruses – including BK virus, said Dr. Knoll of the University of Ottawa and the Ottawa Hospital.

Almost everyone harbors latent BK virus, Dr. Knoll said in an interview. It sometimes causes mild cold symptoms when first contracted, but often there’s no indication of illness at all. “If you’re otherwise healthy, it goes dormant and stays that way,” he noted.

But it can cause serious problems in immunocompromised patients, especially those with a kidney transplant. “BK virus tends to live in the bladder and urinary tract,” Dr. Knoll said, “So, when it reactivates, that’s the site where it does its damage.”

The virus will first appear in the urine, and then follow a logical progression through the ureters and into the kidney. If it remains unchecked, it causes very severe kidney inflammation. That inflammation “looks a lot like rejection,” Dr. Knoll said. “In fact, for years, we were very confused about this and ended up giving patients with BK viremia more immunosuppressants – when we actually should have been giving them less.”

It’s been tough to find the right balance of treatment to combat BK infections and immunosuppressants to maintain the allograft, he said.

Some retrospective studies suggested that quinolone antibiotics – including levofloxacin – could help fight cytomegalovirus infections and viral pneumonia, and decrease inflammatory markers in the urine of kidney transplant patients. “This was the little bit of evidence we needed to launch this study,” Dr. Knoll said.

The study investigators examined the time to first occurrence of BK viruria within the first year of transplant. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival.

Patients’ mean age was 48 years. They had undergone kidney transplant for a variety of reasons, including glomerulonephritis, polycystic kidney disease, diabetes, and hypertension. Comorbidities were common and included diabetes, history of cancer, cardiovascular disease, and hepatitis C and B infections. Most had received a living donor transplant (60%); the rest had kidneys from deceased donors.

Treatment began soon after transplantation. Patients were randomized to a target dose of 500 mg/day levofloxacin for 3 months. The mean length of follow-up was 46 weeks.

The primary outcome of BK viruria occurred in 46 patients – 29% of those in the levofloxacin group and 33.3% of those in the placebo group. That translated to a nonsignificant increased viruria risk of about 4%.

The time to viruria was not significantly different between the groups, with nearly 25% of each group developing it by 25 weeks. Nor was there a between-group difference in the occurrence of sustained viruria.

The secondary endpoint of BK viremia occurred in 7.9% of the levofloxacin group and 11.5% of the placebo group, also a nonsignificant finding. Infections were similar in both group, occurring in 59% of those taking levofloxacin and 45% of those taking placebo. The types of infections were similar: urinary tract/pyelonephritis (37% active vs. 38% placebo); cytomegalovirus (35% vs. 33%); pneumonia (3.5% vs. 1.7%); cellulitis (2.7% vs. 0.8%); and line infections and bacteremias, which were less than 1% in each group. No patient developed a Clostridium difficile infection.

However, patients taking levofloxacin developed significantly more quinolone-resistant infections (46.7% vs. 32.6%). Among isolates that are usually sensitive to quinolones, those patients taking the study drug were 75% more likely than were placebo patients to have a resistant strain (58.3% vs. 33.3%).

Because quinolones are an important part of infection prophylaxis in kidney transplant patients, “This would have significant implications for the management of common infections after transplantation,” Dr. Knoll said. “Our results don’t support the use of levofloxacin for preventing infections in patients with kidney transplants.”

The researchers were disappointed in the outcomes, “but there were people doing this already, and now we have the evidence to tell them to stop,” Dr. Knoll explained. “Of course, we are back to square one, with no proven treatment.”

He added that the quinolones remain critical antibiotics for kidney transplant patients – and that the study in no way suggests that should change.

“We were using these daily for 3 months, and that’s where we got into the resistance trouble,” he said. “That’s not anything like a 7- to 10-day course for a urinary tract infection.”

Dr. Knoll reported receiving investigator-initiated research grants from Astellas Canada and Pfizer Canada. The other coauthors had a number of financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – A 3-month course of levofloxacin after kidney transplant didn’t prevent BK virus from colonizing the urine, setting the stage for viremia in these immunosuppressed patients.

However, the antibiotic was associated with a significant 75% increase in the risk of developing a quinolone-resistant infection, compared with placebo, Dr. Greg A. Knoll and his colleagues reported in the Nov. 15 issue of JAMA (2014 [doi:10.1001/jama.2014.14721]).In a randomized trial of 154 kidney transplant patients, BK virus developed in 29% of those taking levofloxacin and in 33% of those taking placebo, a nonsignificant difference, coauthor Greg Knoll said at a late-breaking poster session during Kidney Week 2014, where the study was simultaneously presented.Levofloxacin, a quinolone antibiotic, has been shown to have some antiviral properties, especially against polyomaviruses – including BK virus, said Dr. Knoll of the University of Ottawa and the Ottawa Hospital.

Almost everyone harbors latent BK virus, Dr. Knoll said in an interview. It sometimes causes mild cold symptoms when first contracted, but often there’s no indication of illness at all. “If you’re otherwise healthy, it goes dormant and stays that way,” he noted.

But it can cause serious problems in immunocompromised patients, especially those with a kidney transplant. “BK virus tends to live in the bladder and urinary tract,” Dr. Knoll said, “So, when it reactivates, that’s the site where it does its damage.”

The virus will first appear in the urine, and then follow a logical progression through the ureters and into the kidney. If it remains unchecked, it causes very severe kidney inflammation. That inflammation “looks a lot like rejection,” Dr. Knoll said. “In fact, for years, we were very confused about this and ended up giving patients with BK viremia more immunosuppressants – when we actually should have been giving them less.”

It’s been tough to find the right balance of treatment to combat BK infections and immunosuppressants to maintain the allograft, he said.

Some retrospective studies suggested that quinolone antibiotics – including levofloxacin – could help fight cytomegalovirus infections and viral pneumonia, and decrease inflammatory markers in the urine of kidney transplant patients. “This was the little bit of evidence we needed to launch this study,” Dr. Knoll said.

The study investigators examined the time to first occurrence of BK viruria within the first year of transplant. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival.

Patients’ mean age was 48 years. They had undergone kidney transplant for a variety of reasons, including glomerulonephritis, polycystic kidney disease, diabetes, and hypertension. Comorbidities were common and included diabetes, history of cancer, cardiovascular disease, and hepatitis C and B infections. Most had received a living donor transplant (60%); the rest had kidneys from deceased donors.

Treatment began soon after transplantation. Patients were randomized to a target dose of 500 mg/day levofloxacin for 3 months. The mean length of follow-up was 46 weeks.

The primary outcome of BK viruria occurred in 46 patients – 29% of those in the levofloxacin group and 33.3% of those in the placebo group. That translated to a nonsignificant increased viruria risk of about 4%.

The time to viruria was not significantly different between the groups, with nearly 25% of each group developing it by 25 weeks. Nor was there a between-group difference in the occurrence of sustained viruria.

The secondary endpoint of BK viremia occurred in 7.9% of the levofloxacin group and 11.5% of the placebo group, also a nonsignificant finding. Infections were similar in both group, occurring in 59% of those taking levofloxacin and 45% of those taking placebo. The types of infections were similar: urinary tract/pyelonephritis (37% active vs. 38% placebo); cytomegalovirus (35% vs. 33%); pneumonia (3.5% vs. 1.7%); cellulitis (2.7% vs. 0.8%); and line infections and bacteremias, which were less than 1% in each group. No patient developed a Clostridium difficile infection.

However, patients taking levofloxacin developed significantly more quinolone-resistant infections (46.7% vs. 32.6%). Among isolates that are usually sensitive to quinolones, those patients taking the study drug were 75% more likely than were placebo patients to have a resistant strain (58.3% vs. 33.3%).

Because quinolones are an important part of infection prophylaxis in kidney transplant patients, “This would have significant implications for the management of common infections after transplantation,” Dr. Knoll said. “Our results don’t support the use of levofloxacin for preventing infections in patients with kidney transplants.”

The researchers were disappointed in the outcomes, “but there were people doing this already, and now we have the evidence to tell them to stop,” Dr. Knoll explained. “Of course, we are back to square one, with no proven treatment.”

He added that the quinolones remain critical antibiotics for kidney transplant patients – and that the study in no way suggests that should change.

“We were using these daily for 3 months, and that’s where we got into the resistance trouble,” he said. “That’s not anything like a 7- to 10-day course for a urinary tract infection.”

Dr. Knoll reported receiving investigator-initiated research grants from Astellas Canada and Pfizer Canada. The other coauthors had a number of financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – A 3-month course of levofloxacin after kidney transplant didn’t prevent BK virus from colonizing the urine, setting the stage for viremia in these immunosuppressed patients.

However, the antibiotic was associated with a significant 75% increase in the risk of developing a quinolone-resistant infection, compared with placebo, Dr. Greg A. Knoll and his colleagues reported in the Nov. 15 issue of JAMA (2014 [doi:10.1001/jama.2014.14721]).In a randomized trial of 154 kidney transplant patients, BK virus developed in 29% of those taking levofloxacin and in 33% of those taking placebo, a nonsignificant difference, coauthor Greg Knoll said at a late-breaking poster session during Kidney Week 2014, where the study was simultaneously presented.Levofloxacin, a quinolone antibiotic, has been shown to have some antiviral properties, especially against polyomaviruses – including BK virus, said Dr. Knoll of the University of Ottawa and the Ottawa Hospital.

Almost everyone harbors latent BK virus, Dr. Knoll said in an interview. It sometimes causes mild cold symptoms when first contracted, but often there’s no indication of illness at all. “If you’re otherwise healthy, it goes dormant and stays that way,” he noted.

But it can cause serious problems in immunocompromised patients, especially those with a kidney transplant. “BK virus tends to live in the bladder and urinary tract,” Dr. Knoll said, “So, when it reactivates, that’s the site where it does its damage.”

The virus will first appear in the urine, and then follow a logical progression through the ureters and into the kidney. If it remains unchecked, it causes very severe kidney inflammation. That inflammation “looks a lot like rejection,” Dr. Knoll said. “In fact, for years, we were very confused about this and ended up giving patients with BK viremia more immunosuppressants – when we actually should have been giving them less.”

It’s been tough to find the right balance of treatment to combat BK infections and immunosuppressants to maintain the allograft, he said.

Some retrospective studies suggested that quinolone antibiotics – including levofloxacin – could help fight cytomegalovirus infections and viral pneumonia, and decrease inflammatory markers in the urine of kidney transplant patients. “This was the little bit of evidence we needed to launch this study,” Dr. Knoll said.

The study investigators examined the time to first occurrence of BK viruria within the first year of transplant. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival.

Patients’ mean age was 48 years. They had undergone kidney transplant for a variety of reasons, including glomerulonephritis, polycystic kidney disease, diabetes, and hypertension. Comorbidities were common and included diabetes, history of cancer, cardiovascular disease, and hepatitis C and B infections. Most had received a living donor transplant (60%); the rest had kidneys from deceased donors.

Treatment began soon after transplantation. Patients were randomized to a target dose of 500 mg/day levofloxacin for 3 months. The mean length of follow-up was 46 weeks.

The primary outcome of BK viruria occurred in 46 patients – 29% of those in the levofloxacin group and 33.3% of those in the placebo group. That translated to a nonsignificant increased viruria risk of about 4%.

The time to viruria was not significantly different between the groups, with nearly 25% of each group developing it by 25 weeks. Nor was there a between-group difference in the occurrence of sustained viruria.

The secondary endpoint of BK viremia occurred in 7.9% of the levofloxacin group and 11.5% of the placebo group, also a nonsignificant finding. Infections were similar in both group, occurring in 59% of those taking levofloxacin and 45% of those taking placebo. The types of infections were similar: urinary tract/pyelonephritis (37% active vs. 38% placebo); cytomegalovirus (35% vs. 33%); pneumonia (3.5% vs. 1.7%); cellulitis (2.7% vs. 0.8%); and line infections and bacteremias, which were less than 1% in each group. No patient developed a Clostridium difficile infection.

However, patients taking levofloxacin developed significantly more quinolone-resistant infections (46.7% vs. 32.6%). Among isolates that are usually sensitive to quinolones, those patients taking the study drug were 75% more likely than were placebo patients to have a resistant strain (58.3% vs. 33.3%).

Because quinolones are an important part of infection prophylaxis in kidney transplant patients, “This would have significant implications for the management of common infections after transplantation,” Dr. Knoll said. “Our results don’t support the use of levofloxacin for preventing infections in patients with kidney transplants.”

The researchers were disappointed in the outcomes, “but there were people doing this already, and now we have the evidence to tell them to stop,” Dr. Knoll explained. “Of course, we are back to square one, with no proven treatment.”

He added that the quinolones remain critical antibiotics for kidney transplant patients – and that the study in no way suggests that should change.

“We were using these daily for 3 months, and that’s where we got into the resistance trouble,” he said. “That’s not anything like a 7- to 10-day course for a urinary tract infection.”

Dr. Knoll reported receiving investigator-initiated research grants from Astellas Canada and Pfizer Canada. The other coauthors had a number of financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Women who donate a kidney are almost two and a half times more likely than are nondonors to have preeclampsia or gestational hypertension in pregnancy, according to a study presented at Kidney Week 2014 and published online simultaneously in the New England Journal of Medicine.

“Information on this potential risk should be included in clinical practice guidelines, shared in the informed-consent processes for potential donors and their recipients when a woman has reproductive potential, and used to guide the care of pregnant donors,” wrote the study authors, led by Dr. Amit X. Garg at the London Kidney Research Unit in London, Ont. (N. Engl. J. Med. 2014 Nov. 14 [doi:10.1056/NEJMoa1408932]).

©Chuhail/thinkstockphotos.com

The Canadian retrospective study matched 85 living kidney donors in a 1:6 ratio with 510 healthy nondonors and followed them for almost 11 years. During this time, 131 pregnancies occurred in the donor group and 788 in the nondonor group.

Gestational hypertension or preeclampsia was diagnosed in 15 donors and 38 nondonors (11% vs. 5%, odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P = .01), the investigators reported.

No significant differences were observed between groups for other maternal or fetal outcomes, and there were no maternal or perinatal deaths in the study that was part of the Donor Nephrectomy Outcomes Research Network (DONOR).

However, they noted that the study included limitations, such as not recording body mass index, medication use, or the race of study participants.

Confidence intervals for risk estimates also were wide, and physicians used clinical judgment when applying accepted diagnostic criteria for gestational hypertension and preeclampsia.

“It remains possible that gestational hypertension and preeclampsia were more likely to be diagnosed and recorded among donors than nondonors despite similar clinical presentations in two groups,” the investigators wrote.

“There may be a role for government programs to cover the costs of recommended pregnancy care for donors who lack health insurance, including any costs related to the treatment of hypertension,” they added.

The meeting was sponsored by the American Society of Nephrology. The study was supported by a grant from the Canadian Institute of Health Research as well as several other research institutions. Dr. Garg received grants from Astellas and Roche outside this study. Several other authors received grants from a number companies outside this study, while the remainder of the authors had no relevant disclosures.

Women who donate a kidney are almost two and a half times more likely than are nondonors to have preeclampsia or gestational hypertension in pregnancy, according to a study presented at Kidney Week 2014 and published online simultaneously in the New England Journal of Medicine.

“Information on this potential risk should be included in clinical practice guidelines, shared in the informed-consent processes for potential donors and their recipients when a woman has reproductive potential, and used to guide the care of pregnant donors,” wrote the study authors, led by Dr. Amit X. Garg at the London Kidney Research Unit in London, Ont. (N. Engl. J. Med. 2014 Nov. 14 [doi:10.1056/NEJMoa1408932]).

©Chuhail/thinkstockphotos.com

The Canadian retrospective study matched 85 living kidney donors in a 1:6 ratio with 510 healthy nondonors and followed them for almost 11 years. During this time, 131 pregnancies occurred in the donor group and 788 in the nondonor group.

Gestational hypertension or preeclampsia was diagnosed in 15 donors and 38 nondonors (11% vs. 5%, odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P = .01), the investigators reported.

No significant differences were observed between groups for other maternal or fetal outcomes, and there were no maternal or perinatal deaths in the study that was part of the Donor Nephrectomy Outcomes Research Network (DONOR).

However, they noted that the study included limitations, such as not recording body mass index, medication use, or the race of study participants.

Confidence intervals for risk estimates also were wide, and physicians used clinical judgment when applying accepted diagnostic criteria for gestational hypertension and preeclampsia.

“It remains possible that gestational hypertension and preeclampsia were more likely to be diagnosed and recorded among donors than nondonors despite similar clinical presentations in two groups,” the investigators wrote.

“There may be a role for government programs to cover the costs of recommended pregnancy care for donors who lack health insurance, including any costs related to the treatment of hypertension,” they added.

The meeting was sponsored by the American Society of Nephrology. The study was supported by a grant from the Canadian Institute of Health Research as well as several other research institutions. Dr. Garg received grants from Astellas and Roche outside this study. Several other authors received grants from a number companies outside this study, while the remainder of the authors had no relevant disclosures.

Women who donate a kidney are almost two and a half times more likely than are nondonors to have preeclampsia or gestational hypertension in pregnancy, according to a study presented at Kidney Week 2014 and published online simultaneously in the New England Journal of Medicine.

“Information on this potential risk should be included in clinical practice guidelines, shared in the informed-consent processes for potential donors and their recipients when a woman has reproductive potential, and used to guide the care of pregnant donors,” wrote the study authors, led by Dr. Amit X. Garg at the London Kidney Research Unit in London, Ont. (N. Engl. J. Med. 2014 Nov. 14 [doi:10.1056/NEJMoa1408932]).

©Chuhail/thinkstockphotos.com

The Canadian retrospective study matched 85 living kidney donors in a 1:6 ratio with 510 healthy nondonors and followed them for almost 11 years. During this time, 131 pregnancies occurred in the donor group and 788 in the nondonor group.

Gestational hypertension or preeclampsia was diagnosed in 15 donors and 38 nondonors (11% vs. 5%, odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P = .01), the investigators reported.

No significant differences were observed between groups for other maternal or fetal outcomes, and there were no maternal or perinatal deaths in the study that was part of the Donor Nephrectomy Outcomes Research Network (DONOR).

However, they noted that the study included limitations, such as not recording body mass index, medication use, or the race of study participants.

Confidence intervals for risk estimates also were wide, and physicians used clinical judgment when applying accepted diagnostic criteria for gestational hypertension and preeclampsia.

“It remains possible that gestational hypertension and preeclampsia were more likely to be diagnosed and recorded among donors than nondonors despite similar clinical presentations in two groups,” the investigators wrote.

“There may be a role for government programs to cover the costs of recommended pregnancy care for donors who lack health insurance, including any costs related to the treatment of hypertension,” they added.

The meeting was sponsored by the American Society of Nephrology. The study was supported by a grant from the Canadian Institute of Health Research as well as several other research institutions. Dr. Garg received grants from Astellas and Roche outside this study. Several other authors received grants from a number companies outside this study, while the remainder of the authors had no relevant disclosures.