Wahajat Mehal, MD, DPhil

 

The development of therapies for chronic hepatitis C viral (HCV) infection has been a highlight of progress in hepatology and infectious disease over the last 25 years. From initial empiric approaches with interferon and ribavirin, to targeted and custom designed direct-acting antivirals (DAAs), there has been rapid improvement in efficacy and side effect profiles. Since we are dealing with a viral infection, loss of viremia after stopping therapy (sustained viral response, SVR) has been the marker of therapeutic success. SVR, however, is still a surrogate for clinical outcome and the analysis of 5-year follow-up in the December 2014 issue reported that in patients with SVR there was a reduction in risk of death, hepatocellular carcinoma, and liver transplantation.

Three years later, in the age of DAAs, can we say the same? The efficacy of DAAs is very clear with SVR in well over 90% of patients. The clinical trials in DAA’s, however, did not monitor mortality as an outcome because the natural history of liver disease from HCV is over many years. For these reasons, and because of the relatively short time that DAAs have been used, quality long-term data do not yet exist to conclusively answer if SVR as a result of DAAs reduces mortality, hepatocellular carcinoma, and liver transplantation.

Observational studies have the potential for significant biases as decisions to treat are frequently based on the likelihood of a successful outcome. A randomized clinical trial for DAAs compared to control would of course be unethical at this stage. The scale of use of DAAs should allow a clear answer to this question within the next 2 years.

Wahajat Mehal, MD, DPhil, is a hepatologist, an associate professor of medicine in the department of digestive diseases and hepatology, and the director of the Yale Weight Loss Program, Yale School of Medicine, New Haven, Conn. He is an Associate Editor for GI & Hepatology News.

 

The development of therapies for chronic hepatitis C viral (HCV) infection has been a highlight of progress in hepatology and infectious disease over the last 25 years. From initial empiric approaches with interferon and ribavirin, to targeted and custom designed direct-acting antivirals (DAAs), there has been rapid improvement in efficacy and side effect profiles. Since we are dealing with a viral infection, loss of viremia after stopping therapy (sustained viral response, SVR) has been the marker of therapeutic success. SVR, however, is still a surrogate for clinical outcome and the analysis of 5-year follow-up in the December 2014 issue reported that in patients with SVR there was a reduction in risk of death, hepatocellular carcinoma, and liver transplantation.

Three years later, in the age of DAAs, can we say the same? The efficacy of DAAs is very clear with SVR in well over 90% of patients. The clinical trials in DAA’s, however, did not monitor mortality as an outcome because the natural history of liver disease from HCV is over many years. For these reasons, and because of the relatively short time that DAAs have been used, quality long-term data do not yet exist to conclusively answer if SVR as a result of DAAs reduces mortality, hepatocellular carcinoma, and liver transplantation.

Observational studies have the potential for significant biases as decisions to treat are frequently based on the likelihood of a successful outcome. A randomized clinical trial for DAAs compared to control would of course be unethical at this stage. The scale of use of DAAs should allow a clear answer to this question within the next 2 years.

Wahajat Mehal, MD, DPhil, is a hepatologist, an associate professor of medicine in the department of digestive diseases and hepatology, and the director of the Yale Weight Loss Program, Yale School of Medicine, New Haven, Conn. He is an Associate Editor for GI & Hepatology News.

 

The development of therapies for chronic hepatitis C viral (HCV) infection has been a highlight of progress in hepatology and infectious disease over the last 25 years. From initial empiric approaches with interferon and ribavirin, to targeted and custom designed direct-acting antivirals (DAAs), there has been rapid improvement in efficacy and side effect profiles. Since we are dealing with a viral infection, loss of viremia after stopping therapy (sustained viral response, SVR) has been the marker of therapeutic success. SVR, however, is still a surrogate for clinical outcome and the analysis of 5-year follow-up in the December 2014 issue reported that in patients with SVR there was a reduction in risk of death, hepatocellular carcinoma, and liver transplantation.

Three years later, in the age of DAAs, can we say the same? The efficacy of DAAs is very clear with SVR in well over 90% of patients. The clinical trials in DAA’s, however, did not monitor mortality as an outcome because the natural history of liver disease from HCV is over many years. For these reasons, and because of the relatively short time that DAAs have been used, quality long-term data do not yet exist to conclusively answer if SVR as a result of DAAs reduces mortality, hepatocellular carcinoma, and liver transplantation.

Observational studies have the potential for significant biases as decisions to treat are frequently based on the likelihood of a successful outcome. A randomized clinical trial for DAAs compared to control would of course be unethical at this stage. The scale of use of DAAs should allow a clear answer to this question within the next 2 years.

Wahajat Mehal, MD, DPhil, is a hepatologist, an associate professor of medicine in the department of digestive diseases and hepatology, and the director of the Yale Weight Loss Program, Yale School of Medicine, New Haven, Conn. He is an Associate Editor for GI & Hepatology News.