Liver Disease

Patients with chronic hepatitis C who develop cirrhosis with severe portal hypertension are at greater risk of progressing to liver decompensation within the first 5 years of treatment, even if they show a sustained virologic response to therapy, a cohort study has found.

The study of 100 patients with hepatitis C and compensated cirrhosis showed that the probability of developing a first episode of liver decompensation at 1, 5, and 7 years was 4%, 25%, and 28%, respectively, among patients with an hepatic venous pressure gradient (HVPG) value of 10 mm Hg or above, compared with 0, 0, and 16% in patients without cirrhosis with severe portal hypertension (CSPH).

Courtesy NIH

Nearly three-quarters of the patients in the study had CSPH at baseline and 35% achieved a sustained virologic response, while 19% developed liver decompensation, according to Dr. Sabela Lens of the Institut d’Investigacions Biomèdiques August-Pi-Sunyer, Barcelona, and coauthors.

“Although viral clearance was associated with a significant reduction in HVPG, this effect, at least 24 weeks after the end of treatment, was mild and only one-third of patients with a high-risk baseline situation with CSPH shifted to a condition of low risk for developing liver decompensation,” they wrote (Clin Gastro Hepatol. 2015. doi: 10.1016/j.cgh.2015.04.013).

“The results of our study show that baseline HVPG value before antiviral treatment is a strong predictor of liver decompensation on follow-up evaluation,” Dr. Lens and associates noted.

The study was funded by the Instituto de Salud Carlos III, and one author was funded by an unrestricted grant from Roche. There were no other conflicts of interest declared.

Patients with chronic hepatitis C who develop cirrhosis with severe portal hypertension are at greater risk of progressing to liver decompensation within the first 5 years of treatment, even if they show a sustained virologic response to therapy, a cohort study has found.

The study of 100 patients with hepatitis C and compensated cirrhosis showed that the probability of developing a first episode of liver decompensation at 1, 5, and 7 years was 4%, 25%, and 28%, respectively, among patients with an hepatic venous pressure gradient (HVPG) value of 10 mm Hg or above, compared with 0, 0, and 16% in patients without cirrhosis with severe portal hypertension (CSPH).

Courtesy NIH

Nearly three-quarters of the patients in the study had CSPH at baseline and 35% achieved a sustained virologic response, while 19% developed liver decompensation, according to Dr. Sabela Lens of the Institut d’Investigacions Biomèdiques August-Pi-Sunyer, Barcelona, and coauthors.

“Although viral clearance was associated with a significant reduction in HVPG, this effect, at least 24 weeks after the end of treatment, was mild and only one-third of patients with a high-risk baseline situation with CSPH shifted to a condition of low risk for developing liver decompensation,” they wrote (Clin Gastro Hepatol. 2015. doi: 10.1016/j.cgh.2015.04.013).

“The results of our study show that baseline HVPG value before antiviral treatment is a strong predictor of liver decompensation on follow-up evaluation,” Dr. Lens and associates noted.

The study was funded by the Instituto de Salud Carlos III, and one author was funded by an unrestricted grant from Roche. There were no other conflicts of interest declared.

Patients with chronic hepatitis C who develop cirrhosis with severe portal hypertension are at greater risk of progressing to liver decompensation within the first 5 years of treatment, even if they show a sustained virologic response to therapy, a cohort study has found.

The study of 100 patients with hepatitis C and compensated cirrhosis showed that the probability of developing a first episode of liver decompensation at 1, 5, and 7 years was 4%, 25%, and 28%, respectively, among patients with an hepatic venous pressure gradient (HVPG) value of 10 mm Hg or above, compared with 0, 0, and 16% in patients without cirrhosis with severe portal hypertension (CSPH).

Courtesy NIH

Nearly three-quarters of the patients in the study had CSPH at baseline and 35% achieved a sustained virologic response, while 19% developed liver decompensation, according to Dr. Sabela Lens of the Institut d’Investigacions Biomèdiques August-Pi-Sunyer, Barcelona, and coauthors.

“Although viral clearance was associated with a significant reduction in HVPG, this effect, at least 24 weeks after the end of treatment, was mild and only one-third of patients with a high-risk baseline situation with CSPH shifted to a condition of low risk for developing liver decompensation,” they wrote (Clin Gastro Hepatol. 2015. doi: 10.1016/j.cgh.2015.04.013).

“The results of our study show that baseline HVPG value before antiviral treatment is a strong predictor of liver decompensation on follow-up evaluation,” Dr. Lens and associates noted.

The study was funded by the Instituto de Salud Carlos III, and one author was funded by an unrestricted grant from Roche. There were no other conflicts of interest declared.

Researchers found an association between nonalcoholic fatty liver disease (NAFLD) and myocardial dysfunction and remodeling, according to a new study published in Hepatology.

“Both NAFLD and heart failure (particularly heart failure with preserved ejection fraction) are obesity-related conditions that have reached epidemic proportions. We know from epidemiologic studies that persons with NAFLD are more likely to die from cardiovascular disease than from liver-related death. This risk seems to be proportional to the amount of fat in the liver and is independent of the presence of nonalcoholic steatohepatitis (NASH). There have been numerous studies that have focused on the relationship between NAFLD and coronary artery disease, but very little work has been done to determine relationships with heart failure,” Dr. Lisa B. VanWagner of Northwestern University in Chicago noted. She continued, “There are several well-established major risk factors for the development of clinical heart failure, including coronary artery disease, diabetes, and hypertension, all of which are also closely associated with NAFLD. However, whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction that may lead to the development of clinical heart failure is unknown.”

Courtesy of Wikimedia /

NAFLD and heart failure are both associated with obesity. Likewise, there is evidence that NAFLD may also be related to endothelial dysfunction, coronary plaques, coronary artery calcifications, as well as being an independent risk factor for cardiovascular disease.

Dr. VanWagner and her colleagues conducted a cross-sectional study of 2,713 patients from the CARDIA (Coronary Artery Risk Development in Young Adults) study to understand any associations between NAFLD and abnormalities in left ventricular (LV) function and structure. Study participants completed CT quantification of liver fat and echocardiography with Doppler during the 25-year follow-up to the initial study (Hepatology 2015;62:773-83 [doi:10.1002/hep.27869]). Participants were excluded from analysis if they had missing or incomplete imaging, pregnancy, a history of MI or heart failure, cirrhosis, hepatitis, or chronic liver disease risk factors, or if they weighed more than 450 pounds,

Of the 2,713 subjects included in analysis, 48% were black and 58.8% were female. NAFLD was detected in 10% (n = 271) of participants. Those with NAFLD were more likely to be white males with metabolic syndrome and who were obese and had higher CT-measured levels of visceral adipose tissue, and an increased waist circumference and waist-to-hip ratio. Insulin resistance markers such as elevated fasting glucose, elevated C-reactive protein, and hypertriglyceridemia were more common in the participants with NAFLD.

Study participants with NAFLD had signs of myocardial remodeling such as more left ventricular wall thickness, LV end-diastolic volume, left aortic volume index, and LV mass index. Likewise, NAFLD was associated with more circumferential strain and global longitudinal strain but no differences in ejection fraction.

Subclinical systolic dysfunction (P less than .001 for the trend), subclinical diastolic dysfunction with impaired left ventricular relaxation (34.6% vs. 23.6%; P less than .0001), and elevated LV filling pressures (33.3% vs. 23.7%; P less than .001) was more common in NAFLD participants, compared with non-NAFLD subjects.

After researchers adjusted for health behaviors and demographic factors, evidence of NAFLD was associated with worse GLS (P less than .0001). Finally, NAFLD was associated with subclinical cardiac remodeling and dysfunction even after adjustment for body mass index and heart failure risk factors (P less than .01).

Dr. VanWagner summarized, “NAFLD may not necessarily be a ‘benign condition’ as previously thought. In our study, we determined liver fat by CT scan, which admittedly detects fat at a higher level (typically greater than 30%) than for example on MRI, which can detect fat as low as 5%. A fatty liver detected on CT or even on [ultrasound], which has similar sensitivity as CT for detecting liver fat should prompt evaluation for additional cardiovascular risk factors and treatment of identified abnormalities to reduce [atherosclerotic cardiovascular disease] and [heart failure] risk. Currently, our study only shows associations between liver fat and subclinical changes in the myocardium and causality cannot be determined. [On the basis] of our data, we cannot recommend screening for HF [heart failure] in this population, but future studies are needed to determine if NAFLD in fact lies in the casual pathway for the development of clinical HF.”

The investigators reported multiple supporting sources, including the National Institutes of Health, American Association for the Study of Liver Disease Foundation, and the American Heart Association. Dr. Lewis reported receiving grants from Novo Nordisk.

Researchers found an association between nonalcoholic fatty liver disease (NAFLD) and myocardial dysfunction and remodeling, according to a new study published in Hepatology.

“Both NAFLD and heart failure (particularly heart failure with preserved ejection fraction) are obesity-related conditions that have reached epidemic proportions. We know from epidemiologic studies that persons with NAFLD are more likely to die from cardiovascular disease than from liver-related death. This risk seems to be proportional to the amount of fat in the liver and is independent of the presence of nonalcoholic steatohepatitis (NASH). There have been numerous studies that have focused on the relationship between NAFLD and coronary artery disease, but very little work has been done to determine relationships with heart failure,” Dr. Lisa B. VanWagner of Northwestern University in Chicago noted. She continued, “There are several well-established major risk factors for the development of clinical heart failure, including coronary artery disease, diabetes, and hypertension, all of which are also closely associated with NAFLD. However, whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction that may lead to the development of clinical heart failure is unknown.”

Courtesy of Wikimedia /

NAFLD and heart failure are both associated with obesity. Likewise, there is evidence that NAFLD may also be related to endothelial dysfunction, coronary plaques, coronary artery calcifications, as well as being an independent risk factor for cardiovascular disease.

Dr. VanWagner and her colleagues conducted a cross-sectional study of 2,713 patients from the CARDIA (Coronary Artery Risk Development in Young Adults) study to understand any associations between NAFLD and abnormalities in left ventricular (LV) function and structure. Study participants completed CT quantification of liver fat and echocardiography with Doppler during the 25-year follow-up to the initial study (Hepatology 2015;62:773-83 [doi:10.1002/hep.27869]). Participants were excluded from analysis if they had missing or incomplete imaging, pregnancy, a history of MI or heart failure, cirrhosis, hepatitis, or chronic liver disease risk factors, or if they weighed more than 450 pounds,

Of the 2,713 subjects included in analysis, 48% were black and 58.8% were female. NAFLD was detected in 10% (n = 271) of participants. Those with NAFLD were more likely to be white males with metabolic syndrome and who were obese and had higher CT-measured levels of visceral adipose tissue, and an increased waist circumference and waist-to-hip ratio. Insulin resistance markers such as elevated fasting glucose, elevated C-reactive protein, and hypertriglyceridemia were more common in the participants with NAFLD.

Study participants with NAFLD had signs of myocardial remodeling such as more left ventricular wall thickness, LV end-diastolic volume, left aortic volume index, and LV mass index. Likewise, NAFLD was associated with more circumferential strain and global longitudinal strain but no differences in ejection fraction.

Subclinical systolic dysfunction (P less than .001 for the trend), subclinical diastolic dysfunction with impaired left ventricular relaxation (34.6% vs. 23.6%; P less than .0001), and elevated LV filling pressures (33.3% vs. 23.7%; P less than .001) was more common in NAFLD participants, compared with non-NAFLD subjects.

After researchers adjusted for health behaviors and demographic factors, evidence of NAFLD was associated with worse GLS (P less than .0001). Finally, NAFLD was associated with subclinical cardiac remodeling and dysfunction even after adjustment for body mass index and heart failure risk factors (P less than .01).

Dr. VanWagner summarized, “NAFLD may not necessarily be a ‘benign condition’ as previously thought. In our study, we determined liver fat by CT scan, which admittedly detects fat at a higher level (typically greater than 30%) than for example on MRI, which can detect fat as low as 5%. A fatty liver detected on CT or even on [ultrasound], which has similar sensitivity as CT for detecting liver fat should prompt evaluation for additional cardiovascular risk factors and treatment of identified abnormalities to reduce [atherosclerotic cardiovascular disease] and [heart failure] risk. Currently, our study only shows associations between liver fat and subclinical changes in the myocardium and causality cannot be determined. [On the basis] of our data, we cannot recommend screening for HF [heart failure] in this population, but future studies are needed to determine if NAFLD in fact lies in the casual pathway for the development of clinical HF.”

The investigators reported multiple supporting sources, including the National Institutes of Health, American Association for the Study of Liver Disease Foundation, and the American Heart Association. Dr. Lewis reported receiving grants from Novo Nordisk.

Researchers found an association between nonalcoholic fatty liver disease (NAFLD) and myocardial dysfunction and remodeling, according to a new study published in Hepatology.

“Both NAFLD and heart failure (particularly heart failure with preserved ejection fraction) are obesity-related conditions that have reached epidemic proportions. We know from epidemiologic studies that persons with NAFLD are more likely to die from cardiovascular disease than from liver-related death. This risk seems to be proportional to the amount of fat in the liver and is independent of the presence of nonalcoholic steatohepatitis (NASH). There have been numerous studies that have focused on the relationship between NAFLD and coronary artery disease, but very little work has been done to determine relationships with heart failure,” Dr. Lisa B. VanWagner of Northwestern University in Chicago noted. She continued, “There are several well-established major risk factors for the development of clinical heart failure, including coronary artery disease, diabetes, and hypertension, all of which are also closely associated with NAFLD. However, whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction that may lead to the development of clinical heart failure is unknown.”

Courtesy of Wikimedia /

NAFLD and heart failure are both associated with obesity. Likewise, there is evidence that NAFLD may also be related to endothelial dysfunction, coronary plaques, coronary artery calcifications, as well as being an independent risk factor for cardiovascular disease.

Dr. VanWagner and her colleagues conducted a cross-sectional study of 2,713 patients from the CARDIA (Coronary Artery Risk Development in Young Adults) study to understand any associations between NAFLD and abnormalities in left ventricular (LV) function and structure. Study participants completed CT quantification of liver fat and echocardiography with Doppler during the 25-year follow-up to the initial study (Hepatology 2015;62:773-83 [doi:10.1002/hep.27869]). Participants were excluded from analysis if they had missing or incomplete imaging, pregnancy, a history of MI or heart failure, cirrhosis, hepatitis, or chronic liver disease risk factors, or if they weighed more than 450 pounds,

Of the 2,713 subjects included in analysis, 48% were black and 58.8% were female. NAFLD was detected in 10% (n = 271) of participants. Those with NAFLD were more likely to be white males with metabolic syndrome and who were obese and had higher CT-measured levels of visceral adipose tissue, and an increased waist circumference and waist-to-hip ratio. Insulin resistance markers such as elevated fasting glucose, elevated C-reactive protein, and hypertriglyceridemia were more common in the participants with NAFLD.

Study participants with NAFLD had signs of myocardial remodeling such as more left ventricular wall thickness, LV end-diastolic volume, left aortic volume index, and LV mass index. Likewise, NAFLD was associated with more circumferential strain and global longitudinal strain but no differences in ejection fraction.

Subclinical systolic dysfunction (P less than .001 for the trend), subclinical diastolic dysfunction with impaired left ventricular relaxation (34.6% vs. 23.6%; P less than .0001), and elevated LV filling pressures (33.3% vs. 23.7%; P less than .001) was more common in NAFLD participants, compared with non-NAFLD subjects.

After researchers adjusted for health behaviors and demographic factors, evidence of NAFLD was associated with worse GLS (P less than .0001). Finally, NAFLD was associated with subclinical cardiac remodeling and dysfunction even after adjustment for body mass index and heart failure risk factors (P less than .01).

Dr. VanWagner summarized, “NAFLD may not necessarily be a ‘benign condition’ as previously thought. In our study, we determined liver fat by CT scan, which admittedly detects fat at a higher level (typically greater than 30%) than for example on MRI, which can detect fat as low as 5%. A fatty liver detected on CT or even on [ultrasound], which has similar sensitivity as CT for detecting liver fat should prompt evaluation for additional cardiovascular risk factors and treatment of identified abnormalities to reduce [atherosclerotic cardiovascular disease] and [heart failure] risk. Currently, our study only shows associations between liver fat and subclinical changes in the myocardium and causality cannot be determined. [On the basis] of our data, we cannot recommend screening for HF [heart failure] in this population, but future studies are needed to determine if NAFLD in fact lies in the casual pathway for the development of clinical HF.”

The investigators reported multiple supporting sources, including the National Institutes of Health, American Association for the Study of Liver Disease Foundation, and the American Heart Association. Dr. Lewis reported receiving grants from Novo Nordisk.

Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.

“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”

Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.

To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).

Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.

Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.

In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.

Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.

Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.

“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”

Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.

To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).

Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.

Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.

In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.

Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.

Combination treatment with ledipasvir, sofosbuvir, and ribavirin for chronic hepatitis C virus infection led to sustained viral response (SVR) rates of 86%-89% among nontransplanted patients and 60%-100% among transplant recipients, according to a study published in the September issue of Gastroenterology.

“Rates of SVR were over 85% in every group of patients with Child-Pugh class [CPC] B decompensated cirrhosis – in those who had and had not undergone liver transplantation, as well as those who were receiving 12 and 24 weeks of treatment,” said Dr. Michael Charlton of Intermountain Medical Center in Salt Lake City, and his associates. “Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation. Rates of response were numerically lower in liver transplant recipients with Child-Pugh class C disease, but the small sample size ... makes this a preliminary observation.”

Patients with chronic HCV infection and advanced liver disease have a poor prognosis because of their risk of liver failure and hepatocellular carcinoma and because they have very limited treatment options. Chances of reinfection are 100% if patients have detectable virus at transplantation, and reinfection increases rates of subsequent graft loss, morbidity, and mortality, the investigators noted.

To assess the recently approved sofosbuvir-ledipasvir regimen, they conducted an open-label, phase II trial (SOLAR-1) of the combination plus ribavirin in 337 HCV-infected patients with advanced liver disease, including transplant recipients. Nearly all (99%) of the patients had HCV genotype 1 infection, while 1% had genotype 4 infection. The investigators randomized patients to receive 90 mg ledipasvir and 400 mg sofosbuvir in a fixed-dose daily regimen for either 12 or 24 weeks in combination with ribavirin, which was dosed based on body weight, tolerance of side effects, and extent of liver disease. Patients with CPC C cirrhosis received lower doses of ribavirin because of increased risk of hemotoxicity (Gastroenterology 2015 May 15. doi:10.1053/j.gastro.2015.05.010).

Nontransplanted patients who had decompensated cirrhosis achieved SVR12 or SVR24 rates of 86%-89%, even if they had CPC C decompensated disease, the researchers reported. “Our results also demonstrate that SVR12 in patients with decompensated cirrhosis is associated with early improvements in CPC and MELD [Model for End-Stage Liver Disease] scores, suggesting that eradication of the virus can rapidly improve hepatic function by attenuating the injury and inflammation due to HCV replication,” they said. Patients with CPC B disease also had significant improvements in albumin and bilirubin levels after 4 weeks of treatment.

Among transplant recipients who were noncirrhotic or were in compensated cirrhosis, SVR rates ranged from 96% to 98%, regardless of treatment duration or presence of cirrhosis, Dr. Charlton and associates reported. Among transplant recipients with decompensated cirrhosis, SVR rates were 86%-88% for the subgroup with CPC B disease, but were 60% for CPC C patients who were treated for 12 weeks, and were 75% for CPC C patients who were treated for 24 weeks. In contrast, all six patients with fibrosing cholestatic hepatitis achieved SVR and also experienced large drops in total bilirubin levels within 2-4 weeks of starting treatment, the researchers said. Finally, among the seven patients who underwent liver transplantation either during treatment or before posttreatment week 12, six achieved virologic response after surgery, and one died of multiorgan failure and septic shock 1 day after testing negative for HCV RNA.

In all, 13 patients (4%) discontinued treatment because of adverse events, primarily liver decompensation, the researchers reported. Adverse events that led more than one patient to stop treatment included sepsis, renal failure, dyspnea, and gastrointestinal hemorrhage. Patients were more likely to stop taking ribavirin if they were treated for 24 weeks or had worsening disease. Ten patients died on study, but none of the deaths were thought to be related to treatment, the researchers wrote.

Dr. Charlton disclosed ties with Gilead Sciences, maker of sofosbuvir and ledipasvir. Gilead funded the study. Four coauthors reported having no conflicts; the other 25 investigators reported employment or other financial ties with numerous pharmaceutical companies.

More than 28% of patients with chronic hepatitis C (CHC) virus infection met at least one criterion for cirrhosis, while only 7% had biopsy confirmation of the condition, investigators reported in the August issue of the American Journal of Gastroenterology.

Furthermore, only half of the patients with a positive biopsy had been given an associated ICD-9-CM code, said Dr. Stuart Gordon at Henry Ford Health System in Detroit and his associates. Cirrhosis in CHC therefore might often go unreported, leading to “overly conservative” estimates of its prevalence, associated health care costs, and the cost-effectiveness of the newer HCV treatments, they said.

©Sebastian Kaulitzki/thinkstockphotos.com

The researchers analyzed data for 9,783 patients with CHC from the Chronic Hepatitis Cohort Study who were treated between 2006 and 2010. They compared the prevalence of biopsy-confirmed cirrhosis (Metavir stage 4 or pathologist’s report) with the proportion of patients who met at least one of four criteria: positive biopsy; Fibrosis-4 score of at least 5.88, or the presence of a diagnosis or procedural code for cirrhosis or hepatic decompensation. Patients averaged 55 years of age, and most were white males with health insurance, the researchers said (Am. J. Gastroenterol. 2015;110:1169-77).

In all, 28.5% of CHC patients met at least one of the four criteria, including 22% who met the Fibrosis-4 threshold, 6.8% who were biopsy positive, and 5.7% and 4.9% who had a diagnostic or procedural code for cirrhosis or hepatic decompensation, respectively, said the investigators. Patients had significantly greater odds of cirrhosis (P less than .05) if they were older, male, Asian, Hispanic, had genotype 3 HCV infection, HIV coinfection, or a history of antiviral treatment, alcohol abuse, or diabetes, they added. “Our findings are the first in the United States to attempt an accurate estimate of the prevalence of cirrhosis in the CHC patient population at large,” the researchers concluded. “Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.”

The CDC Foundation funds the Chronic Hepatitis Cohort Study. Dr. Gordon reported financial relationships with numerous makers of anti-HCV therapies. The other investigators reported having no conflicts of interest.

[email protected]

More than 28% of patients with chronic hepatitis C (CHC) virus infection met at least one criterion for cirrhosis, while only 7% had biopsy confirmation of the condition, investigators reported in the August issue of the American Journal of Gastroenterology.

Furthermore, only half of the patients with a positive biopsy had been given an associated ICD-9-CM code, said Dr. Stuart Gordon at Henry Ford Health System in Detroit and his associates. Cirrhosis in CHC therefore might often go unreported, leading to “overly conservative” estimates of its prevalence, associated health care costs, and the cost-effectiveness of the newer HCV treatments, they said.

©Sebastian Kaulitzki/thinkstockphotos.com

The researchers analyzed data for 9,783 patients with CHC from the Chronic Hepatitis Cohort Study who were treated between 2006 and 2010. They compared the prevalence of biopsy-confirmed cirrhosis (Metavir stage 4 or pathologist’s report) with the proportion of patients who met at least one of four criteria: positive biopsy; Fibrosis-4 score of at least 5.88, or the presence of a diagnosis or procedural code for cirrhosis or hepatic decompensation. Patients averaged 55 years of age, and most were white males with health insurance, the researchers said (Am. J. Gastroenterol. 2015;110:1169-77).

In all, 28.5% of CHC patients met at least one of the four criteria, including 22% who met the Fibrosis-4 threshold, 6.8% who were biopsy positive, and 5.7% and 4.9% who had a diagnostic or procedural code for cirrhosis or hepatic decompensation, respectively, said the investigators. Patients had significantly greater odds of cirrhosis (P less than .05) if they were older, male, Asian, Hispanic, had genotype 3 HCV infection, HIV coinfection, or a history of antiviral treatment, alcohol abuse, or diabetes, they added. “Our findings are the first in the United States to attempt an accurate estimate of the prevalence of cirrhosis in the CHC patient population at large,” the researchers concluded. “Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.”

The CDC Foundation funds the Chronic Hepatitis Cohort Study. Dr. Gordon reported financial relationships with numerous makers of anti-HCV therapies. The other investigators reported having no conflicts of interest.

[email protected]

More than 28% of patients with chronic hepatitis C (CHC) virus infection met at least one criterion for cirrhosis, while only 7% had biopsy confirmation of the condition, investigators reported in the August issue of the American Journal of Gastroenterology.

Furthermore, only half of the patients with a positive biopsy had been given an associated ICD-9-CM code, said Dr. Stuart Gordon at Henry Ford Health System in Detroit and his associates. Cirrhosis in CHC therefore might often go unreported, leading to “overly conservative” estimates of its prevalence, associated health care costs, and the cost-effectiveness of the newer HCV treatments, they said.

©Sebastian Kaulitzki/thinkstockphotos.com

The researchers analyzed data for 9,783 patients with CHC from the Chronic Hepatitis Cohort Study who were treated between 2006 and 2010. They compared the prevalence of biopsy-confirmed cirrhosis (Metavir stage 4 or pathologist’s report) with the proportion of patients who met at least one of four criteria: positive biopsy; Fibrosis-4 score of at least 5.88, or the presence of a diagnosis or procedural code for cirrhosis or hepatic decompensation. Patients averaged 55 years of age, and most were white males with health insurance, the researchers said (Am. J. Gastroenterol. 2015;110:1169-77).

In all, 28.5% of CHC patients met at least one of the four criteria, including 22% who met the Fibrosis-4 threshold, 6.8% who were biopsy positive, and 5.7% and 4.9% who had a diagnostic or procedural code for cirrhosis or hepatic decompensation, respectively, said the investigators. Patients had significantly greater odds of cirrhosis (P less than .05) if they were older, male, Asian, Hispanic, had genotype 3 HCV infection, HIV coinfection, or a history of antiviral treatment, alcohol abuse, or diabetes, they added. “Our findings are the first in the United States to attempt an accurate estimate of the prevalence of cirrhosis in the CHC patient population at large,” the researchers concluded. “Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.”

The CDC Foundation funds the Chronic Hepatitis Cohort Study. Dr. Gordon reported financial relationships with numerous makers of anti-HCV therapies. The other investigators reported having no conflicts of interest.

[email protected]

The newest guidelines for testing, managing, and treating hepatitis C infections in adults are part of a “living document” – a constantly updated online resource that reflects the ever-changing world of HCV research.

A joint venture of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), the document puts cutting-edge science in the hands of clinicians, Dr. Gary L. Davis wrote (Hepatology 2015 June 25 [doi:10.1002/hep.27950]). The continuously updated version may be accessed at any time at www.hcvguidelines.org.

“The pace of hepatitis C virus (HCV) drug development in recent years has accelerated dramatically,” wrote Dr. Davis, cochair for the AASLD/IDSA HCV Guidance writing group. “Such information and advice can be difficult to access readily given the diverse sources from which information is available, and the sometimes lengthy time needed for publication of original articles and scholarly perspectives. Traditional practice guidelines for more established areas of medicine and care often take years to develop and bring to publication. In the new era in hepatitis C treatment, such a process would not be nimble or timely enough to address the needs of patients with HCV infection, practitioners caring for these patients, or payers approving therapies for use.”

The online guidelines “will undergo real-time revisions as the field evolves,” Dr. Davis noted. A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations.

The new update contains recommendations for direct antiviral drug regimens in treatment-naive patients and for all six HCV genotypes. A second section examines the recommended regimens for patients who have failed treatment with PEG-interferon and ribavirin, with or without a direct antiviral agent.
The document also gives guidance for managing patients with and without a sustained viral response and concludes with a section on treating special patient populations (decompensated cirrhosis, post-transplant HCV infections, renal impairment, and coinfection with HIV).

[email protected]

AGA Resource
AGA offers a Hepatitis C Clinical Service Line through the AGA Roadmap to the Future of Practice to help you provide high-quality patient care. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

The newest guidelines for testing, managing, and treating hepatitis C infections in adults are part of a “living document” – a constantly updated online resource that reflects the ever-changing world of HCV research.

A joint venture of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), the document puts cutting-edge science in the hands of clinicians, Dr. Gary L. Davis wrote (Hepatology 2015 June 25 [doi:10.1002/hep.27950]). The continuously updated version may be accessed at any time at www.hcvguidelines.org.

“The pace of hepatitis C virus (HCV) drug development in recent years has accelerated dramatically,” wrote Dr. Davis, cochair for the AASLD/IDSA HCV Guidance writing group. “Such information and advice can be difficult to access readily given the diverse sources from which information is available, and the sometimes lengthy time needed for publication of original articles and scholarly perspectives. Traditional practice guidelines for more established areas of medicine and care often take years to develop and bring to publication. In the new era in hepatitis C treatment, such a process would not be nimble or timely enough to address the needs of patients with HCV infection, practitioners caring for these patients, or payers approving therapies for use.”

The online guidelines “will undergo real-time revisions as the field evolves,” Dr. Davis noted. A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations.

The new update contains recommendations for direct antiviral drug regimens in treatment-naive patients and for all six HCV genotypes. A second section examines the recommended regimens for patients who have failed treatment with PEG-interferon and ribavirin, with or without a direct antiviral agent.
The document also gives guidance for managing patients with and without a sustained viral response and concludes with a section on treating special patient populations (decompensated cirrhosis, post-transplant HCV infections, renal impairment, and coinfection with HIV).

[email protected]

AGA Resource
AGA offers a Hepatitis C Clinical Service Line through the AGA Roadmap to the Future of Practice to help you provide high-quality patient care. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

The newest guidelines for testing, managing, and treating hepatitis C infections in adults are part of a “living document” – a constantly updated online resource that reflects the ever-changing world of HCV research.

A joint venture of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), the document puts cutting-edge science in the hands of clinicians, Dr. Gary L. Davis wrote (Hepatology 2015 June 25 [doi:10.1002/hep.27950]). The continuously updated version may be accessed at any time at www.hcvguidelines.org.

“The pace of hepatitis C virus (HCV) drug development in recent years has accelerated dramatically,” wrote Dr. Davis, cochair for the AASLD/IDSA HCV Guidance writing group. “Such information and advice can be difficult to access readily given the diverse sources from which information is available, and the sometimes lengthy time needed for publication of original articles and scholarly perspectives. Traditional practice guidelines for more established areas of medicine and care often take years to develop and bring to publication. In the new era in hepatitis C treatment, such a process would not be nimble or timely enough to address the needs of patients with HCV infection, practitioners caring for these patients, or payers approving therapies for use.”

The online guidelines “will undergo real-time revisions as the field evolves,” Dr. Davis noted. A panel of 26 hepatologists and infectious diseases specialists and a patient advocate developed the original consensus recommendations.

The new update contains recommendations for direct antiviral drug regimens in treatment-naive patients and for all six HCV genotypes. A second section examines the recommended regimens for patients who have failed treatment with PEG-interferon and ribavirin, with or without a direct antiviral agent.
The document also gives guidance for managing patients with and without a sustained viral response and concludes with a section on treating special patient populations (decompensated cirrhosis, post-transplant HCV infections, renal impairment, and coinfection with HIV).

[email protected]

AGA Resource
AGA offers a Hepatitis C Clinical Service Line through the AGA Roadmap to the Future of Practice to help you provide high-quality patient care. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

The U.S. Food and Drug Administration has approved Daklinza (daclatasvir), a hepatitis C virus (HCV) drug that, when used in combination with sofosbuvir, does not require coadministration of interferon or ribavirin for the treatment of HCV genotype 3 infections, the agency announced in a statement on July 24, 2015.

In a clinical trial, 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks, and were monitored for 24 weeks post treatment; 98% of the treatment-naive participants with no cirrhosis of the liver (and 58% of the treatment-naive participants with cirrhosis) achieved a sustained virologic response. Among the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response.

“Today’s approval provides a new option for patients with genotype 3 HCV, including those patients who cannot tolerate ribavirin,” said Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

The most common side effects of Daklinza with sofosbuvir were fatigue and headache.

According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV of which approximately 10 percent are genotype 3.

Daklinza is marketed by Bristol-Myers Squibb, based in Princeton, N.J.

Read the full FDA statement at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm.

AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

The U.S. Food and Drug Administration has approved Daklinza (daclatasvir), a hepatitis C virus (HCV) drug that, when used in combination with sofosbuvir, does not require coadministration of interferon or ribavirin for the treatment of HCV genotype 3 infections, the agency announced in a statement on July 24, 2015.

In a clinical trial, 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks, and were monitored for 24 weeks post treatment; 98% of the treatment-naive participants with no cirrhosis of the liver (and 58% of the treatment-naive participants with cirrhosis) achieved a sustained virologic response. Among the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response.

“Today’s approval provides a new option for patients with genotype 3 HCV, including those patients who cannot tolerate ribavirin,” said Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

The most common side effects of Daklinza with sofosbuvir were fatigue and headache.

According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV of which approximately 10 percent are genotype 3.

Daklinza is marketed by Bristol-Myers Squibb, based in Princeton, N.J.

Read the full FDA statement at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm.

AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

The U.S. Food and Drug Administration has approved Daklinza (daclatasvir), a hepatitis C virus (HCV) drug that, when used in combination with sofosbuvir, does not require coadministration of interferon or ribavirin for the treatment of HCV genotype 3 infections, the agency announced in a statement on July 24, 2015.

In a clinical trial, 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks, and were monitored for 24 weeks post treatment; 98% of the treatment-naive participants with no cirrhosis of the liver (and 58% of the treatment-naive participants with cirrhosis) achieved a sustained virologic response. Among the participants who were treatment experienced, 92% with no cirrhosis of the liver and 69% with cirrhosis achieved sustained virologic response.

“Today’s approval provides a new option for patients with genotype 3 HCV, including those patients who cannot tolerate ribavirin,” said Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

The most common side effects of Daklinza with sofosbuvir were fatigue and headache.

According to the Centers for Disease Control and Prevention, approximately 2.7 million Americans are infected with HCV of which approximately 10 percent are genotype 3.

Daklinza is marketed by Bristol-Myers Squibb, based in Princeton, N.J.

Read the full FDA statement at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm.

AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

[email protected]

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

[email protected]

The first interferon-free treatment for people with genotype 4 hepatitis C infection has been approved by the Food and Drug Administration.

On July 24, the FDA approved a combination of three antivirals – ombitasvir, paritaprevir, and ritonavir – for use with ribavirin for treating hepatitis C virus (HCV) genotype 4 infections in people without cirrhosis, according to the agency’s statement announcing the approval. The combination tablet will be marketed as Technivie, by Abbvie. Ombitasvir is an HCV NS5A inhibitor, paritaprevir is an HCV NS3/4A protease inhibitor, and ritonavir is an HCV CYP3A inhibitor.

Technivie “is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for coadministration of interferon,” the statement said. It is administered orally. Technivie is a fixed-dose combination of paritaprevir/ritonavir (150/100 mg) co-formulated with ombitasvir (25 mg); it is dosed once a day and should be taken with a meal. It is co-administered with weight-based RBV (1000mg or 1200mg in divided doses, twice a day), taken with food, according to the company's statement announcing approval.

The FDA statement refers to that study of 135 people with chronic HCV genotype 4 infections and no cirrhosis, treated with the three antivirals plus ribavirin once a day for 12 weeks (91 patients), or without ribavirin (44 patients) for 12 weeks. All the patients on the three-drug combination plus ribavirin achieved a sustained virologic response (SVR12) 12 weeks after stopping treatment (no HCV detected in the blood) vs. 91% of those who did not take ribavirin. Fatigue, weakness, nausea, insomnia, pruritus and other skin reactions are among the most common adverse events associated with treatment with Technivie and ribavirin, according to the FDA statement.

The statement adds that the prescribing information includes a warning that elevations of liver enzymes up to greater than five times the upper limit of normal occurred in about 1% of the patients in clinical trials, which were more common among women taking contraceptives that contain ethinyl estradiol. Before starting treatment, women should discontinue contraceptives that containing ethinyl estradiol, and “hepatic laboratory testing should be performed during the first 4 weeks of treatment, and as clinically indicated thereafter,” the FDA statement said.

The three antivirals included in Technivie, plus dasabuvir (an HCV nonnucleoside NS5B polymerase inhibitor), are copackaged in the Viekira Pak, which was approved for the treatment of HCV genotype 1 chronic HCV infection, with or without ribavirin in 2014, and is also manufactured by Abbvie.

About 2.7 million people in the United States have chronic HCV infection, according to the Centers for Disease Control and Prevention. HCV genotype 4 is one of the least common types of HCV in the United States.


*This story was updated 7/24/2015.

AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

[email protected]

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

Patients treated with daclatasvir and sofosbuvir for hepatitis C who are coinfected with HIV have shown a significant virologic response, regardless of whether they had already been treated for their hepatitis C infection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment & Prevention.

The open-label ALLY-2 study – published simultaneously in the July 21 online edition of the New England Journal of Medicine – in 151 previously untreated patients with hepatitis C and HIV, and 52 previously treated patients, showed 12 weeks of treatment with NS5A inhibitor daclatasvir and sofosbuvir achieved a sustained virologic response in 96.4% of untreated patients and 97.7% of previously treated patients with HCV genotype 1, with no adverse effects on HIV-1 suppression.

Among previously untreated patients treated for 8 weeks, the response rate was 75.6%, and there were no study-drug discontinuations because of adverse events (N. Engl. J. Med. 2015 July 21 [doi:10.1056/NEJMoa1503153]).

“The lower efficacy observed after 8 weeks of treatment suggests that 12 weeks of therapy may be preferred for most patients with HIV-HCV coinfection,” wrote Dr. David L. Wyles of the University of California, San Diego, and his coauthors.

Bristol-Myers Squibb supported the study. Dr. Wyles reported serving as a scientific consultant to Bristol-Myers Squibb and Gilead Sciences. Some coauthors declared grants, personal fees, and speakers fees from pharmaceutical companies, including Bristol-Myers Squibb, and several authors are employees of Bristol-Myers Squibb.

The Global Health Justice Partnership and Treatment Action Group have filed a lawsuit against the Food and Drug Administration for access to data on the hepatitis C drugs sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni), according to a press release from Yale Law School, New Haven, Ct.

Sofosbuvir and sofosbuvir/ledipasvir were given Breakthrough Therapy Designation status by the FDA in December 2013 and October 2014, respectively, and since that time, have been used to treat more than 210,000 people. Both drugs are extremely effective, but their cost is tremendous, with the initial pricing of a 12-week treatment regimen at $84,000 and $94,500, respectively.

The two groups contacted Gilead Sciences for data on both drugs in November 2014, but received no response. In December 2014, GHJP and TAG submitted a Freedom of Information request to the FDA but were informed they would not get a response for 18-24 months and did not guarantee the data would ever be released.

“This lawsuit is about access and answers. The astronomical price of these drugs requires Medicaid programs and other providers to make hard choices about how to allocate their resources. They are making these decisions now. Crucial policy determinations about who has access to treatment are being made on incomplete information,” Karyn Kaplan, TAG’s International Hepatitis/HIV Policy and Advocacy director said in the press release.

Read the full press release on the Yale Law School website.

[email protected]

The Global Health Justice Partnership and Treatment Action Group have filed a lawsuit against the Food and Drug Administration for access to data on the hepatitis C drugs sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni), according to a press release from Yale Law School, New Haven, Ct.

Sofosbuvir and sofosbuvir/ledipasvir were given Breakthrough Therapy Designation status by the FDA in December 2013 and October 2014, respectively, and since that time, have been used to treat more than 210,000 people. Both drugs are extremely effective, but their cost is tremendous, with the initial pricing of a 12-week treatment regimen at $84,000 and $94,500, respectively.

The two groups contacted Gilead Sciences for data on both drugs in November 2014, but received no response. In December 2014, GHJP and TAG submitted a Freedom of Information request to the FDA but were informed they would not get a response for 18-24 months and did not guarantee the data would ever be released.

“This lawsuit is about access and answers. The astronomical price of these drugs requires Medicaid programs and other providers to make hard choices about how to allocate their resources. They are making these decisions now. Crucial policy determinations about who has access to treatment are being made on incomplete information,” Karyn Kaplan, TAG’s International Hepatitis/HIV Policy and Advocacy director said in the press release.

Read the full press release on the Yale Law School website.

[email protected]

The Global Health Justice Partnership and Treatment Action Group have filed a lawsuit against the Food and Drug Administration for access to data on the hepatitis C drugs sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni), according to a press release from Yale Law School, New Haven, Ct.

Sofosbuvir and sofosbuvir/ledipasvir were given Breakthrough Therapy Designation status by the FDA in December 2013 and October 2014, respectively, and since that time, have been used to treat more than 210,000 people. Both drugs are extremely effective, but their cost is tremendous, with the initial pricing of a 12-week treatment regimen at $84,000 and $94,500, respectively.

The two groups contacted Gilead Sciences for data on both drugs in November 2014, but received no response. In December 2014, GHJP and TAG submitted a Freedom of Information request to the FDA but were informed they would not get a response for 18-24 months and did not guarantee the data would ever be released.

“This lawsuit is about access and answers. The astronomical price of these drugs requires Medicaid programs and other providers to make hard choices about how to allocate their resources. They are making these decisions now. Crucial policy determinations about who has access to treatment are being made on incomplete information,” Karyn Kaplan, TAG’s International Hepatitis/HIV Policy and Advocacy director said in the press release.

Read the full press release on the Yale Law School website.

[email protected]