Liver Disease

The federal government on April 4 published a 3-year update of its viral hepatitis action plan that emphasizes the need to expand awareness of infection; improve surveillance, testing, and treatment; eliminate vaccine-preventable hepatitis; and reduce transmission of hepatitis C virus infection.

By 2020, the updated action plan calls for the United States to double the proportion of patients who know they have hepatitis B virus infection (from 33% to 66%); increase the percentage of patients who know they have HCV infection (from 45% to 66%); cut new HCV infections by 25%; and eliminate maternal-child HBV transmission.

Measures of progress include hepatitis B and C mortality and hepatitis B vaccination coverage among health care workers. The plan builds on recent strides in viral hepatitis prevention and treatment – including more widespread availability of safe, effective vaccines for hepatitis A and B and the development of highly effective direct-acting antivirals for chronic hepatitis C infection.

But despite these advances, 3.5-5.3 million Americans still have viral hepatitis, and most do not know they are infected. Sequelae of these infections cause 12,000-18,000 deaths annually – a higher death toll than that from HIV, according to the U.S. Department of Health & Human Services.

The agency authored the plan with input from the Department of Veterans Affairs, the Department of Justice’s Federal Bureau of Prisons, and the Department of Housing and Urban Development.

The federal government on April 4 published a 3-year update of its viral hepatitis action plan that emphasizes the need to expand awareness of infection; improve surveillance, testing, and treatment; eliminate vaccine-preventable hepatitis; and reduce transmission of hepatitis C virus infection.

By 2020, the updated action plan calls for the United States to double the proportion of patients who know they have hepatitis B virus infection (from 33% to 66%); increase the percentage of patients who know they have HCV infection (from 45% to 66%); cut new HCV infections by 25%; and eliminate maternal-child HBV transmission.

Measures of progress include hepatitis B and C mortality and hepatitis B vaccination coverage among health care workers. The plan builds on recent strides in viral hepatitis prevention and treatment – including more widespread availability of safe, effective vaccines for hepatitis A and B and the development of highly effective direct-acting antivirals for chronic hepatitis C infection.

But despite these advances, 3.5-5.3 million Americans still have viral hepatitis, and most do not know they are infected. Sequelae of these infections cause 12,000-18,000 deaths annually – a higher death toll than that from HIV, according to the U.S. Department of Health & Human Services.

The agency authored the plan with input from the Department of Veterans Affairs, the Department of Justice’s Federal Bureau of Prisons, and the Department of Housing and Urban Development.

The federal government on April 4 published a 3-year update of its viral hepatitis action plan that emphasizes the need to expand awareness of infection; improve surveillance, testing, and treatment; eliminate vaccine-preventable hepatitis; and reduce transmission of hepatitis C virus infection.

By 2020, the updated action plan calls for the United States to double the proportion of patients who know they have hepatitis B virus infection (from 33% to 66%); increase the percentage of patients who know they have HCV infection (from 45% to 66%); cut new HCV infections by 25%; and eliminate maternal-child HBV transmission.

Measures of progress include hepatitis B and C mortality and hepatitis B vaccination coverage among health care workers. The plan builds on recent strides in viral hepatitis prevention and treatment – including more widespread availability of safe, effective vaccines for hepatitis A and B and the development of highly effective direct-acting antivirals for chronic hepatitis C infection.

But despite these advances, 3.5-5.3 million Americans still have viral hepatitis, and most do not know they are infected. Sequelae of these infections cause 12,000-18,000 deaths annually – a higher death toll than that from HIV, according to the U.S. Department of Health & Human Services.

The agency authored the plan with input from the Department of Veterans Affairs, the Department of Justice’s Federal Bureau of Prisons, and the Department of Housing and Urban Development.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Information on the use of entecavir in children down to age 2 years has been added to the prescribing information for the chronic hepatitis B drug, the Food and Drug Administration has announced.

The changes include a revised indication, which now states that entecavir is indicated for treating chronic hepatitis B virus infection in adults and pediatric patients 2 years of age and older, who have evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (alanine aminotransferase or aspartate aminotransferase) or histologically active disease. The pediatric indication is based on "clinical trial data in nucleoside-inhibitor treatment–naive and in a limited number of lamivudine-experienced subjects with HbeAg [hepatitis B e antigen]-positive chronic HBV infection and compensated liver disease," according to the revised label.

Previously, the label included the statement that safety and effectiveness of entecavir in pediatric patients under age 16 have not been established. Now, the label states that the efficacy and safety have not been established in patients under age 2, and that the drug has not been studied in this age group because the need to treat children this young is rarely necessary.

Entecavir, a nucleoside analogue, was approved in 2005 and is marketed as Baraclude by Bristol-Myers Squibb. It is administered once-daily orally, in a tablet or solution formulation. The label says that the oral solution should be used for children who weigh up to 30 kg.

The revised label is available at http://packageinserts.bms.com/pi/pi_baraclude.pdf.

emechcatie@frontlinemedcom.com

Information on the use of entecavir in children down to age 2 years has been added to the prescribing information for the chronic hepatitis B drug, the Food and Drug Administration has announced.

The changes include a revised indication, which now states that entecavir is indicated for treating chronic hepatitis B virus infection in adults and pediatric patients 2 years of age and older, who have evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (alanine aminotransferase or aspartate aminotransferase) or histologically active disease. The pediatric indication is based on "clinical trial data in nucleoside-inhibitor treatment–naive and in a limited number of lamivudine-experienced subjects with HbeAg [hepatitis B e antigen]-positive chronic HBV infection and compensated liver disease," according to the revised label.

Previously, the label included the statement that safety and effectiveness of entecavir in pediatric patients under age 16 have not been established. Now, the label states that the efficacy and safety have not been established in patients under age 2, and that the drug has not been studied in this age group because the need to treat children this young is rarely necessary.

Entecavir, a nucleoside analogue, was approved in 2005 and is marketed as Baraclude by Bristol-Myers Squibb. It is administered once-daily orally, in a tablet or solution formulation. The label says that the oral solution should be used for children who weigh up to 30 kg.

The revised label is available at http://packageinserts.bms.com/pi/pi_baraclude.pdf.

emechcatie@frontlinemedcom.com

Information on the use of entecavir in children down to age 2 years has been added to the prescribing information for the chronic hepatitis B drug, the Food and Drug Administration has announced.

The changes include a revised indication, which now states that entecavir is indicated for treating chronic hepatitis B virus infection in adults and pediatric patients 2 years of age and older, who have evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (alanine aminotransferase or aspartate aminotransferase) or histologically active disease. The pediatric indication is based on "clinical trial data in nucleoside-inhibitor treatment–naive and in a limited number of lamivudine-experienced subjects with HbeAg [hepatitis B e antigen]-positive chronic HBV infection and compensated liver disease," according to the revised label.

Previously, the label included the statement that safety and effectiveness of entecavir in pediatric patients under age 16 have not been established. Now, the label states that the efficacy and safety have not been established in patients under age 2, and that the drug has not been studied in this age group because the need to treat children this young is rarely necessary.

Entecavir, a nucleoside analogue, was approved in 2005 and is marketed as Baraclude by Bristol-Myers Squibb. It is administered once-daily orally, in a tablet or solution formulation. The label says that the oral solution should be used for children who weigh up to 30 kg.

The revised label is available at http://packageinserts.bms.com/pi/pi_baraclude.pdf.

emechcatie@frontlinemedcom.com

Eligible patients who live farther away from a liver transplant center are less likely to be put on a waiting list, less likely to receive a transplant, and more likely to die within 5 years than are those who live closer, according to a report published online March 25 in JAMA.

These findings have broad implications beyond those for liver transplantation alone. "As complex, expensive medical technology evolves, certain services may be offered only at a limited number of sites" – an approach that may be more efficient but that increases the distance between patients and the centers at which they can receive care. "Our study is the first to demonstrate the adverse consequences of centralization of specialized care at a limited number of sites," said Dr. David S. Goldberg of the division of gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, and his associates.

The researchers assessed the medical records of 50,637 patients who were active users of Veterans Affairs outpatient care and had decompensated cirrhosis or hepatocellular carcinoma; of these, 2,895 were wait-listed for liver transplantation during 2003 and 2012. Liver transplantation is offered at only five VA transplant centers, which are located in Houston; Nashville, Tenn.; Pittsburgh; Portland, Ore.; and Richmond, Va.

Patients who lived farther away from these five centers and from non-VA transplant centers were significantly less likely to be wait-listed than were those who lived closer. For example, 66% of veterans who lived within 100 miles of a liver transplant center were wait-listed, compared with less than 51% of those who resided farther away.

Once patients were on the list, they were significantly less likely to receive a liver transplant if they resided far from a transplant center. For example, 70.4% of patients who lived within 100 miles of a transplant center received a transplant, compared with only 58.8% of those who lived 101-200 miles away, 57.3% of those who lived 201-300 miles away, and 53.5% of those who lived 301-500 miles away.

Overall survival also decreased as distance from a liver transplant center increased. For example, a wait-listed patient living 25 miles from a transplant center had a 62.9% probability of survival 5 years from the first hepatic decompensation event, while one who lived 100 miles from a transplant center had a 59.8% probability of surviving 5 years from the first hepatic decompensation event, Dr. Goldberg and his associates wrote (JAMA 2014;311:1234-43).

Several health services including proton-beam therapy, bariatric surgery, and treatment for complex or rare cancers currently are offered at a limited number of sites or are preferentially reimbursed by insurers if they are treated at designated "centers of excellence." The results of this study demonstrate that such centralized care may have the unintended consequence of excluding patients who live farther from these centers from treatment, the investigators added.

This study was supported in part by the U.S. Health Resources and Services Administration. No financial conflicts of interest were reported.

Eligible patients who live farther away from a liver transplant center are less likely to be put on a waiting list, less likely to receive a transplant, and more likely to die within 5 years than are those who live closer, according to a report published online March 25 in JAMA.

These findings have broad implications beyond those for liver transplantation alone. "As complex, expensive medical technology evolves, certain services may be offered only at a limited number of sites" – an approach that may be more efficient but that increases the distance between patients and the centers at which they can receive care. "Our study is the first to demonstrate the adverse consequences of centralization of specialized care at a limited number of sites," said Dr. David S. Goldberg of the division of gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, and his associates.

The researchers assessed the medical records of 50,637 patients who were active users of Veterans Affairs outpatient care and had decompensated cirrhosis or hepatocellular carcinoma; of these, 2,895 were wait-listed for liver transplantation during 2003 and 2012. Liver transplantation is offered at only five VA transplant centers, which are located in Houston; Nashville, Tenn.; Pittsburgh; Portland, Ore.; and Richmond, Va.

Patients who lived farther away from these five centers and from non-VA transplant centers were significantly less likely to be wait-listed than were those who lived closer. For example, 66% of veterans who lived within 100 miles of a liver transplant center were wait-listed, compared with less than 51% of those who resided farther away.

Once patients were on the list, they were significantly less likely to receive a liver transplant if they resided far from a transplant center. For example, 70.4% of patients who lived within 100 miles of a transplant center received a transplant, compared with only 58.8% of those who lived 101-200 miles away, 57.3% of those who lived 201-300 miles away, and 53.5% of those who lived 301-500 miles away.

Overall survival also decreased as distance from a liver transplant center increased. For example, a wait-listed patient living 25 miles from a transplant center had a 62.9% probability of survival 5 years from the first hepatic decompensation event, while one who lived 100 miles from a transplant center had a 59.8% probability of surviving 5 years from the first hepatic decompensation event, Dr. Goldberg and his associates wrote (JAMA 2014;311:1234-43).

Several health services including proton-beam therapy, bariatric surgery, and treatment for complex or rare cancers currently are offered at a limited number of sites or are preferentially reimbursed by insurers if they are treated at designated "centers of excellence." The results of this study demonstrate that such centralized care may have the unintended consequence of excluding patients who live farther from these centers from treatment, the investigators added.

This study was supported in part by the U.S. Health Resources and Services Administration. No financial conflicts of interest were reported.

Eligible patients who live farther away from a liver transplant center are less likely to be put on a waiting list, less likely to receive a transplant, and more likely to die within 5 years than are those who live closer, according to a report published online March 25 in JAMA.

These findings have broad implications beyond those for liver transplantation alone. "As complex, expensive medical technology evolves, certain services may be offered only at a limited number of sites" – an approach that may be more efficient but that increases the distance between patients and the centers at which they can receive care. "Our study is the first to demonstrate the adverse consequences of centralization of specialized care at a limited number of sites," said Dr. David S. Goldberg of the division of gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, and his associates.

The researchers assessed the medical records of 50,637 patients who were active users of Veterans Affairs outpatient care and had decompensated cirrhosis or hepatocellular carcinoma; of these, 2,895 were wait-listed for liver transplantation during 2003 and 2012. Liver transplantation is offered at only five VA transplant centers, which are located in Houston; Nashville, Tenn.; Pittsburgh; Portland, Ore.; and Richmond, Va.

Patients who lived farther away from these five centers and from non-VA transplant centers were significantly less likely to be wait-listed than were those who lived closer. For example, 66% of veterans who lived within 100 miles of a liver transplant center were wait-listed, compared with less than 51% of those who resided farther away.

Once patients were on the list, they were significantly less likely to receive a liver transplant if they resided far from a transplant center. For example, 70.4% of patients who lived within 100 miles of a transplant center received a transplant, compared with only 58.8% of those who lived 101-200 miles away, 57.3% of those who lived 201-300 miles away, and 53.5% of those who lived 301-500 miles away.

Overall survival also decreased as distance from a liver transplant center increased. For example, a wait-listed patient living 25 miles from a transplant center had a 62.9% probability of survival 5 years from the first hepatic decompensation event, while one who lived 100 miles from a transplant center had a 59.8% probability of surviving 5 years from the first hepatic decompensation event, Dr. Goldberg and his associates wrote (JAMA 2014;311:1234-43).

Several health services including proton-beam therapy, bariatric surgery, and treatment for complex or rare cancers currently are offered at a limited number of sites or are preferentially reimbursed by insurers if they are treated at designated "centers of excellence." The results of this study demonstrate that such centralized care may have the unintended consequence of excluding patients who live farther from these centers from treatment, the investigators added.

This study was supported in part by the U.S. Health Resources and Services Administration. No financial conflicts of interest were reported.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

Patients with HCV-HIV coinfections had significantly higher rates of hepatic decompensation vs. HCV-monoinfected patients, even when they received antiretroviral therapy and maintained low HIV RNA levels, researchers reported online March 17.

Decompensation rates in coinfected patients were significantly higher with concurrent advanced liver fibrosis, diabetes, or severe anemia or if patients were of nonblack race, reported Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, and his associates (Ann. Int. Med. 2014 Mar. 17 [doi:10.7326/M13-1829]).

The researchers conducted a retrospective cohort study of 4,280 Veterans Health Administration patients coinfected with HCV and HIV who initiated antiretroviral therapy (ART) and 6,079 HCV-monoinfected patients. Patients were treated between 1997 and 2010 and were HCV treatment naive.

The incidence of hepatic decompensation was 7.4% among coinfected patients and 4.8% among monoinfected patients at 10 years, the investigators reported. The difference was statistically significant (hazard ratio accounting for competing risks, 1.56; 95% confidence internal, 1.31-1.86), even when coinfected patients maintained HIV RNA levels of less than 1,000 copies/mL (HR, 1.44; 95% CI, 1.05-1.99).

The finding suggested that "suppression of HIV RNA with ART is an important factor in slowing progression of HCV-related liver fibrosis," the researchers wrote. "This observation supports current management guidelines that recommend initiation of ART among patients co-infected with HIV and HCV, regardless of CD4 cell count."

Hepatic decompensation in coinfected patients also was significantly associated with baseline advanced hepatic fibrosis, severe anemia (baseline hemoglobin level less than 100 g/L), diabetes mellitus, or being of nonblack race, with hazard ratios ranging between 1.88 and 5.45. "Clinicians should address modifiable risk factors and consider treatment of HCV infection in co-infected patients to reduce rates of hepatic decompensation," Dr. Lo Re and his colleagues wrote.

The study was supported by the National Institutes of Health. Investigator disclosures were not available.

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

msullivan@frontlinemedcom.com

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

msullivan@frontlinemedcom.com

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

msullivan@frontlinemedcom.com

A panel of California medical experts says two new, once-daily drugs for hepatitis C represent low-value treatment alternatives for the condition because of their high price tags.

The drugs, Gilead Sciences’ sofosbuvir (Sovaldi) and Johnson & Johnson’s simeprevir (Olysio), cost more than $1,000 per pill, pushing the price for the recommended 12-week course of treatment of sofosbuvir to close to $90,000 and treatment with simeprevir to around $66,000, according to the California Technology Assessment Forum (CTAF), an independent group originally convened by the insurance industry to evaluate costs and benefits of treatments.

Courtesy NIH

The Food and Drug Administration approved sofosbuvir and simeprevir late last year. CTAF, which met March 10 to consider the financial and clinical effects of the two new drugs, will issue its final report on the treatments in April.

The group acknowledged in its draft report that therapeutic regimens containing sofosbuvir, approved to treat hepatitis C genotypes 1 through 4, have the potential to "substantially increase" the number of patients achieving sustained virologic response. The drug also offers "the first effective interferon-free option" to patients who can’t take interferon.

"These advantages are considerable," the report said. However, it added, "the clinical advantages of newer treatment regimens would ... come with a substantial potential impact on health care budgets should a large number of patients be treated."

Replacing current care with sofosbuvir-based regimens would increase drug expenditures by $18-$29 billion per year in California alone, the report estimated. Gilead Sciences has maintained that the drug’s up-front costs are justified given that it could decrease the number of patients who ultimately suffer liver failure and need transplants. However, CTAF said it would take 20 years for payers to recoup two-thirds of the drug’s cost.

CTAF was less enthusiastic about simeprevir, which is approved only for treatment of hepatitis C genotype 1. The group said in its report that "use of simeprevir with pegylated interferon and ribavirin appear to provide limited benefit over the previous standard of care," mainly because that regimen decreased anemia and required patients to take fewer pills.

Originally funded and managed by the Blue Shield of California Foundation, in 2013 CTAF became a core program of the nonprofit Institute for Clinical and Economic Review, which includes representatives of payers, clinicians, and drug makers on its board.

Other groups also have complained about the high price of sofosbuvir and simeprevir. For example, in January, the AIDS Healthcare Foundation asked state Medicaid directors to keep sofosbuvir off its formulary because of its cost.

A panel of California medical experts says two new, once-daily drugs for hepatitis C represent low-value treatment alternatives for the condition because of their high price tags.

The drugs, Gilead Sciences’ sofosbuvir (Sovaldi) and Johnson & Johnson’s simeprevir (Olysio), cost more than $1,000 per pill, pushing the price for the recommended 12-week course of treatment of sofosbuvir to close to $90,000 and treatment with simeprevir to around $66,000, according to the California Technology Assessment Forum (CTAF), an independent group originally convened by the insurance industry to evaluate costs and benefits of treatments.

Courtesy NIH

The Food and Drug Administration approved sofosbuvir and simeprevir late last year. CTAF, which met March 10 to consider the financial and clinical effects of the two new drugs, will issue its final report on the treatments in April.

The group acknowledged in its draft report that therapeutic regimens containing sofosbuvir, approved to treat hepatitis C genotypes 1 through 4, have the potential to "substantially increase" the number of patients achieving sustained virologic response. The drug also offers "the first effective interferon-free option" to patients who can’t take interferon.

"These advantages are considerable," the report said. However, it added, "the clinical advantages of newer treatment regimens would ... come with a substantial potential impact on health care budgets should a large number of patients be treated."

Replacing current care with sofosbuvir-based regimens would increase drug expenditures by $18-$29 billion per year in California alone, the report estimated. Gilead Sciences has maintained that the drug’s up-front costs are justified given that it could decrease the number of patients who ultimately suffer liver failure and need transplants. However, CTAF said it would take 20 years for payers to recoup two-thirds of the drug’s cost.

CTAF was less enthusiastic about simeprevir, which is approved only for treatment of hepatitis C genotype 1. The group said in its report that "use of simeprevir with pegylated interferon and ribavirin appear to provide limited benefit over the previous standard of care," mainly because that regimen decreased anemia and required patients to take fewer pills.

Originally funded and managed by the Blue Shield of California Foundation, in 2013 CTAF became a core program of the nonprofit Institute for Clinical and Economic Review, which includes representatives of payers, clinicians, and drug makers on its board.

Other groups also have complained about the high price of sofosbuvir and simeprevir. For example, in January, the AIDS Healthcare Foundation asked state Medicaid directors to keep sofosbuvir off its formulary because of its cost.

A panel of California medical experts says two new, once-daily drugs for hepatitis C represent low-value treatment alternatives for the condition because of their high price tags.

The drugs, Gilead Sciences’ sofosbuvir (Sovaldi) and Johnson & Johnson’s simeprevir (Olysio), cost more than $1,000 per pill, pushing the price for the recommended 12-week course of treatment of sofosbuvir to close to $90,000 and treatment with simeprevir to around $66,000, according to the California Technology Assessment Forum (CTAF), an independent group originally convened by the insurance industry to evaluate costs and benefits of treatments.

Courtesy NIH

The Food and Drug Administration approved sofosbuvir and simeprevir late last year. CTAF, which met March 10 to consider the financial and clinical effects of the two new drugs, will issue its final report on the treatments in April.

The group acknowledged in its draft report that therapeutic regimens containing sofosbuvir, approved to treat hepatitis C genotypes 1 through 4, have the potential to "substantially increase" the number of patients achieving sustained virologic response. The drug also offers "the first effective interferon-free option" to patients who can’t take interferon.

"These advantages are considerable," the report said. However, it added, "the clinical advantages of newer treatment regimens would ... come with a substantial potential impact on health care budgets should a large number of patients be treated."

Replacing current care with sofosbuvir-based regimens would increase drug expenditures by $18-$29 billion per year in California alone, the report estimated. Gilead Sciences has maintained that the drug’s up-front costs are justified given that it could decrease the number of patients who ultimately suffer liver failure and need transplants. However, CTAF said it would take 20 years for payers to recoup two-thirds of the drug’s cost.

CTAF was less enthusiastic about simeprevir, which is approved only for treatment of hepatitis C genotype 1. The group said in its report that "use of simeprevir with pegylated interferon and ribavirin appear to provide limited benefit over the previous standard of care," mainly because that regimen decreased anemia and required patients to take fewer pills.

Originally funded and managed by the Blue Shield of California Foundation, in 2013 CTAF became a core program of the nonprofit Institute for Clinical and Economic Review, which includes representatives of payers, clinicians, and drug makers on its board.

Other groups also have complained about the high price of sofosbuvir and simeprevir. For example, in January, the AIDS Healthcare Foundation asked state Medicaid directors to keep sofosbuvir off its formulary because of its cost.

Glycerol phenylbutyrate significantly reduced the number of cirrhosis patients experiencing hepatic encephalopathy and the time to first event, a phase II trial has shown.

The randomized, double-blind placebo-controlled trial in 178 patients with cirrhosis found that only 21% of patients treated with glycerol phenylbutyrate (GPB) had a hepatic encephalopathy (HE) event compared with 36% of the placebo group (P =.02).

Treatment with 6 mL of oral GPB twice daily also significantly reduced the time to a first HE event (HR 0.56, 95% CI 0.32-0.99, P less than .05), in particular, more severe West Haven grade 2 events, according to a study published in the March issue of Hepatology.

The HE group also had significantly fewer total events (35 vs. 57, P less than .05), and treatment was associated with a nonsignificant reduction in HE hospitalizations (13 vs. 25; P = .06)

The treatment effect was more pronounced in the 119 patients not taking the antibiotic rifaximin at entry; among patients taking rifaximin there were no differences between the treatment arms in the number of patients experiencing an HE event, time to event, or total number of events (Hepatology 2014;59:1073-83).

Glycerol phenylbutyrate is currently approved for the treatment of urea cycle disorders and other inherited disorders characterized by an excess of ammonia in the blood.

This study followed a previous 4-week, open-label study that suggested this dose of GPB was well tolerated and lowered ammonia levels in patients with cirrhosis and HE.

"Though elevated blood ammonia has long been suspected as important, the evidence is largely correlative, other factors have been postulated, and evidence against ammonia has been reported," wrote Dr. Don C. Rockey of the Medical University of South Carolina, Charleston, and his colleagues.

In the current study, "GPB significantly lowered plasma ammonia and correlated strongly with HE events when assessed either at baseline or during the study."

Baseline ammonia levels were also higher among patients who subsequently experienced an HE event compared with those who did not, prompting the authors to suggest that elevated blood ammonia level does in fact play an important role in the pathogenesis of recurrent, overt HE.

Researchers reported similar types of adverse events in the two treatment arms and a similar frequency of these events, although serious adverse events and study drug discontinuations associated with adverse events occurred slightly more often in the GPB group.

"There were no treatment-related effects on liver biochemical tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, international normalized ratio (INR), or MELD [score]," the investigators wrote.

They concluced that "that GPB reduced the likelihood of HE events in patients with preexisting HE, and ... that it deserves further study as a potential therapeutic for these patients."

The study was funded by Hyperion Therapeutics. There were no other conflicts of interest declared.

Glycerol phenylbutyrate significantly reduced the number of cirrhosis patients experiencing hepatic encephalopathy and the time to first event, a phase II trial has shown.

The randomized, double-blind placebo-controlled trial in 178 patients with cirrhosis found that only 21% of patients treated with glycerol phenylbutyrate (GPB) had a hepatic encephalopathy (HE) event compared with 36% of the placebo group (P =.02).

Treatment with 6 mL of oral GPB twice daily also significantly reduced the time to a first HE event (HR 0.56, 95% CI 0.32-0.99, P less than .05), in particular, more severe West Haven grade 2 events, according to a study published in the March issue of Hepatology.

The HE group also had significantly fewer total events (35 vs. 57, P less than .05), and treatment was associated with a nonsignificant reduction in HE hospitalizations (13 vs. 25; P = .06)

The treatment effect was more pronounced in the 119 patients not taking the antibiotic rifaximin at entry; among patients taking rifaximin there were no differences between the treatment arms in the number of patients experiencing an HE event, time to event, or total number of events (Hepatology 2014;59:1073-83).

Glycerol phenylbutyrate is currently approved for the treatment of urea cycle disorders and other inherited disorders characterized by an excess of ammonia in the blood.

This study followed a previous 4-week, open-label study that suggested this dose of GPB was well tolerated and lowered ammonia levels in patients with cirrhosis and HE.

"Though elevated blood ammonia has long been suspected as important, the evidence is largely correlative, other factors have been postulated, and evidence against ammonia has been reported," wrote Dr. Don C. Rockey of the Medical University of South Carolina, Charleston, and his colleagues.

In the current study, "GPB significantly lowered plasma ammonia and correlated strongly with HE events when assessed either at baseline or during the study."

Baseline ammonia levels were also higher among patients who subsequently experienced an HE event compared with those who did not, prompting the authors to suggest that elevated blood ammonia level does in fact play an important role in the pathogenesis of recurrent, overt HE.

Researchers reported similar types of adverse events in the two treatment arms and a similar frequency of these events, although serious adverse events and study drug discontinuations associated with adverse events occurred slightly more often in the GPB group.

"There were no treatment-related effects on liver biochemical tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, international normalized ratio (INR), or MELD [score]," the investigators wrote.

They concluced that "that GPB reduced the likelihood of HE events in patients with preexisting HE, and ... that it deserves further study as a potential therapeutic for these patients."

The study was funded by Hyperion Therapeutics. There were no other conflicts of interest declared.

Glycerol phenylbutyrate significantly reduced the number of cirrhosis patients experiencing hepatic encephalopathy and the time to first event, a phase II trial has shown.

The randomized, double-blind placebo-controlled trial in 178 patients with cirrhosis found that only 21% of patients treated with glycerol phenylbutyrate (GPB) had a hepatic encephalopathy (HE) event compared with 36% of the placebo group (P =.02).

Treatment with 6 mL of oral GPB twice daily also significantly reduced the time to a first HE event (HR 0.56, 95% CI 0.32-0.99, P less than .05), in particular, more severe West Haven grade 2 events, according to a study published in the March issue of Hepatology.

The HE group also had significantly fewer total events (35 vs. 57, P less than .05), and treatment was associated with a nonsignificant reduction in HE hospitalizations (13 vs. 25; P = .06)

The treatment effect was more pronounced in the 119 patients not taking the antibiotic rifaximin at entry; among patients taking rifaximin there were no differences between the treatment arms in the number of patients experiencing an HE event, time to event, or total number of events (Hepatology 2014;59:1073-83).

Glycerol phenylbutyrate is currently approved for the treatment of urea cycle disorders and other inherited disorders characterized by an excess of ammonia in the blood.

This study followed a previous 4-week, open-label study that suggested this dose of GPB was well tolerated and lowered ammonia levels in patients with cirrhosis and HE.

"Though elevated blood ammonia has long been suspected as important, the evidence is largely correlative, other factors have been postulated, and evidence against ammonia has been reported," wrote Dr. Don C. Rockey of the Medical University of South Carolina, Charleston, and his colleagues.

In the current study, "GPB significantly lowered plasma ammonia and correlated strongly with HE events when assessed either at baseline or during the study."

Baseline ammonia levels were also higher among patients who subsequently experienced an HE event compared with those who did not, prompting the authors to suggest that elevated blood ammonia level does in fact play an important role in the pathogenesis of recurrent, overt HE.

Researchers reported similar types of adverse events in the two treatment arms and a similar frequency of these events, although serious adverse events and study drug discontinuations associated with adverse events occurred slightly more often in the GPB group.

"There were no treatment-related effects on liver biochemical tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, international normalized ratio (INR), or MELD [score]," the investigators wrote.

They concluced that "that GPB reduced the likelihood of HE events in patients with preexisting HE, and ... that it deserves further study as a potential therapeutic for these patients."

The study was funded by Hyperion Therapeutics. There were no other conflicts of interest declared.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Medicare officials propose to cover screening for hepatitis C virus for adults at high risk of infection as well as a one-time screening for Baby Boomers.

The plan, announced in a coverage memo on March 4, would provide Medicare coverage for all screening tests approved by the Food and Drug Administration when they are ordered by a primary care physician or other primary care clinician.

Officials at the Centers for Medicare & Medicaid Services initially floated the idea of hepatitis C (HCV) screening coverage last September. The response was overwhelmingly positive, with nearly all of the 65 public comments advocating in favor of coverage.

Courtesy US. Dept of Veterans Affairs

HCV screening is already recommended by the U.S. Preventive Services Task Force and the American Academy of Family Physicians. The AAFP recommends screening for HCV infection in high-risk adults. But the 2013 USPSTF recommendation goes further, calling on physicians to screen high-risk adults as well as to provide a one-time screening to all patients born between 1945 and 1965.

The Medicare proposal echoes the USPSTF recommendations.

For the proposal, the CMS deems the following patients as at high risk for HCV infection: adults who use illicit injection drugs or have a history of such drug use, as well as individuals who had blood transfusions before 1992. The proposal calls for coverage of an initial screening test for high-risk adults, followed by annual rescreening for those who continue to use illicit injection drugs after the first test.

“We acknowledge the limited evidence concerning health outcomes of HCV screening,” agency officials wrote in the coverage memo. “However, CMS believes that screening for HCV infection provides an opportunity for appropriate interventions to benefit the infected person by permitting for the early detection of, and potentially the prevention of, HCV-related liver disease.”

Treatment options for hepatitis C are expanding, the CMS noted in its coverage memo. Over the past several years, the FDA has approved three protease inhibitors, boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio), for the treatment of patients with genotype 1 infection. Each of these three drugs can be used in combination with pegylated interferon and ribavirin for the treatment of genotype 1 infection.

Last year, the FDA approved sofosbuvir (Sovaldi), which is indicated for the treatment of hepatitis C infection from genotypes 1, 2, 3, or 4. But access to that drug could be impacted by its hefty price tag, which is $1,000 a pill or about $84,000 for a 12-week course of treatment.

Comments on the CMS screening proposal can be made until April 3. The CMS is scheduled to issue a final decision on coverage in June.

mschneider@frontlinemedcom.com

On Twitter @maryellenny

Medicare officials propose to cover screening for hepatitis C virus for adults at high risk of infection as well as a one-time screening for Baby Boomers.

The plan, announced in a coverage memo on March 4, would provide Medicare coverage for all screening tests approved by the Food and Drug Administration when they are ordered by a primary care physician or other primary care clinician.

Officials at the Centers for Medicare & Medicaid Services initially floated the idea of hepatitis C (HCV) screening coverage last September. The response was overwhelmingly positive, with nearly all of the 65 public comments advocating in favor of coverage.

Courtesy US. Dept of Veterans Affairs

HCV screening is already recommended by the U.S. Preventive Services Task Force and the American Academy of Family Physicians. The AAFP recommends screening for HCV infection in high-risk adults. But the 2013 USPSTF recommendation goes further, calling on physicians to screen high-risk adults as well as to provide a one-time screening to all patients born between 1945 and 1965.

The Medicare proposal echoes the USPSTF recommendations.

For the proposal, the CMS deems the following patients as at high risk for HCV infection: adults who use illicit injection drugs or have a history of such drug use, as well as individuals who had blood transfusions before 1992. The proposal calls for coverage of an initial screening test for high-risk adults, followed by annual rescreening for those who continue to use illicit injection drugs after the first test.

“We acknowledge the limited evidence concerning health outcomes of HCV screening,” agency officials wrote in the coverage memo. “However, CMS believes that screening for HCV infection provides an opportunity for appropriate interventions to benefit the infected person by permitting for the early detection of, and potentially the prevention of, HCV-related liver disease.”

Treatment options for hepatitis C are expanding, the CMS noted in its coverage memo. Over the past several years, the FDA has approved three protease inhibitors, boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio), for the treatment of patients with genotype 1 infection. Each of these three drugs can be used in combination with pegylated interferon and ribavirin for the treatment of genotype 1 infection.

Last year, the FDA approved sofosbuvir (Sovaldi), which is indicated for the treatment of hepatitis C infection from genotypes 1, 2, 3, or 4. But access to that drug could be impacted by its hefty price tag, which is $1,000 a pill or about $84,000 for a 12-week course of treatment.

Comments on the CMS screening proposal can be made until April 3. The CMS is scheduled to issue a final decision on coverage in June.

mschneider@frontlinemedcom.com

On Twitter @maryellenny

Medicare officials propose to cover screening for hepatitis C virus for adults at high risk of infection as well as a one-time screening for Baby Boomers.

The plan, announced in a coverage memo on March 4, would provide Medicare coverage for all screening tests approved by the Food and Drug Administration when they are ordered by a primary care physician or other primary care clinician.

Officials at the Centers for Medicare & Medicaid Services initially floated the idea of hepatitis C (HCV) screening coverage last September. The response was overwhelmingly positive, with nearly all of the 65 public comments advocating in favor of coverage.

Courtesy US. Dept of Veterans Affairs

HCV screening is already recommended by the U.S. Preventive Services Task Force and the American Academy of Family Physicians. The AAFP recommends screening for HCV infection in high-risk adults. But the 2013 USPSTF recommendation goes further, calling on physicians to screen high-risk adults as well as to provide a one-time screening to all patients born between 1945 and 1965.

The Medicare proposal echoes the USPSTF recommendations.

For the proposal, the CMS deems the following patients as at high risk for HCV infection: adults who use illicit injection drugs or have a history of such drug use, as well as individuals who had blood transfusions before 1992. The proposal calls for coverage of an initial screening test for high-risk adults, followed by annual rescreening for those who continue to use illicit injection drugs after the first test.

“We acknowledge the limited evidence concerning health outcomes of HCV screening,” agency officials wrote in the coverage memo. “However, CMS believes that screening for HCV infection provides an opportunity for appropriate interventions to benefit the infected person by permitting for the early detection of, and potentially the prevention of, HCV-related liver disease.”

Treatment options for hepatitis C are expanding, the CMS noted in its coverage memo. Over the past several years, the FDA has approved three protease inhibitors, boceprevir (Victrelis), telaprevir (Incivek), and simeprevir (Olysio), for the treatment of patients with genotype 1 infection. Each of these three drugs can be used in combination with pegylated interferon and ribavirin for the treatment of genotype 1 infection.

Last year, the FDA approved sofosbuvir (Sovaldi), which is indicated for the treatment of hepatitis C infection from genotypes 1, 2, 3, or 4. But access to that drug could be impacted by its hefty price tag, which is $1,000 a pill or about $84,000 for a 12-week course of treatment.

Comments on the CMS screening proposal can be made until April 3. The CMS is scheduled to issue a final decision on coverage in June.

mschneider@frontlinemedcom.com

On Twitter @maryellenny