Hepatitis C Therapy Update
Hepatitis C Therapy Update
Purpose of review We review here the recent literature regarding hepatitis C treatment through January 2012. We discuss newly approved therapies and their clinical trial data and discuss what can be expected in this rapidly changing field.
Recent findings Two new directly acting antiviral agents were approved in 2011 for use in hepatitis C treatment, bringing shortened treatment durations, and increased treatment success to some patients with genotype 1 hepatitis C. Additional drugs using different viral targets are in development to further improve response rates, tolerance, and increase access to therapy.
Summary Telaprevir and boceprevir were approved in 2011 for use against genotype 1 hepatitis C, in combination with pegylated interferon and ribavirin. In most populations of genotype 1 patients, response rates are much improved but increased treatment related anemia has been seen. Additional options for therapy, including interferon-free regimens, are still needed and are under development.
An estimated 130–170 million people are infected with hepatitis C virus (HCV) worldwide leading to significant morbidity, mortality, and financial burden on healthcare. Most of the patients in the United States, an estimated 3.2–3.5 million people, were born between 1945 and 1964 and likely contracted the virus in the 1970s and 1980s when transmission rates were highest. With the contribution of blood product screening, disposable medical equipment and public health education efforts, the US incidence of infection has been decreasing but in many parts of the world the virus remains unchecked due to unsafe medical practices, lack of public health education, and lack of funding for research and treatment. Currently, hepatitis C is the leading cause for liver transplantation worldwide. Out of 100 people that contract the infection, 75–85 people will develop chronic infection, 60–70 people will develop chronic liver disease, five to 20 people will develop cirrhosis over the course of their chronic infection and one to five people will die of complications including hepatocellular carcinoma (HCC). Perz et al. looked at 11 WHO-based regions in 2006 and estimated that globally 27% of cirrhosis was attributable to HCV and 25% of HCC was attributable to HCV. In addition to new infections, as the currently infected population ages, we are more likely to see increased consequences of the chronic infection. Studies confirming this have shown increases in HCV-related mortality and increasing prevalence of hepatitis C-related HCC and cirrhosis since the mid-1990s. A sustained viral response (SVR) to hepatitis C therapy reduces liver-related, as well as all-cause mortality for patients with hepatitis C. Failure to respond to treatment correlates with poor liverrelated outcomes including death and liver transplantation.
For the past 10 years, standard therapy has been some form of pegylated interferon and ribavirin for 24–48 weeks, based on genotype. The limitations of these medications are well known. For genotype 1, the most common genotype in the United States nd Europe, this has produced an SVR (equated with cure) rate of only about 40%. Pregnant patients or those with advanced renal disease are prohibited from using ribavirin. Likewise, interferon therapy excludes patients with autoimmune diseases, uncontrolled depression and mental illness, decompensated liver disease (Child-Turcotte-Pugh score more than 6), or decompensated cardiac or pulmonary disease. In addition to contraindications, side effects and low response rates have led to an aggressive search for treatment alternatives. Beginning in mid-2011, two new agents, known as direct-acting antivirals (DAA) were approved for use in conjunction with pegylated interferon and ribavirin.
Abstract and Introduction
Abstract
Purpose of review We review here the recent literature regarding hepatitis C treatment through January 2012. We discuss newly approved therapies and their clinical trial data and discuss what can be expected in this rapidly changing field.
Recent findings Two new directly acting antiviral agents were approved in 2011 for use in hepatitis C treatment, bringing shortened treatment durations, and increased treatment success to some patients with genotype 1 hepatitis C. Additional drugs using different viral targets are in development to further improve response rates, tolerance, and increase access to therapy.
Summary Telaprevir and boceprevir were approved in 2011 for use against genotype 1 hepatitis C, in combination with pegylated interferon and ribavirin. In most populations of genotype 1 patients, response rates are much improved but increased treatment related anemia has been seen. Additional options for therapy, including interferon-free regimens, are still needed and are under development.
Introduction
An estimated 130–170 million people are infected with hepatitis C virus (HCV) worldwide leading to significant morbidity, mortality, and financial burden on healthcare. Most of the patients in the United States, an estimated 3.2–3.5 million people, were born between 1945 and 1964 and likely contracted the virus in the 1970s and 1980s when transmission rates were highest. With the contribution of blood product screening, disposable medical equipment and public health education efforts, the US incidence of infection has been decreasing but in many parts of the world the virus remains unchecked due to unsafe medical practices, lack of public health education, and lack of funding for research and treatment. Currently, hepatitis C is the leading cause for liver transplantation worldwide. Out of 100 people that contract the infection, 75–85 people will develop chronic infection, 60–70 people will develop chronic liver disease, five to 20 people will develop cirrhosis over the course of their chronic infection and one to five people will die of complications including hepatocellular carcinoma (HCC). Perz et al. looked at 11 WHO-based regions in 2006 and estimated that globally 27% of cirrhosis was attributable to HCV and 25% of HCC was attributable to HCV. In addition to new infections, as the currently infected population ages, we are more likely to see increased consequences of the chronic infection. Studies confirming this have shown increases in HCV-related mortality and increasing prevalence of hepatitis C-related HCC and cirrhosis since the mid-1990s. A sustained viral response (SVR) to hepatitis C therapy reduces liver-related, as well as all-cause mortality for patients with hepatitis C. Failure to respond to treatment correlates with poor liverrelated outcomes including death and liver transplantation.
For the past 10 years, standard therapy has been some form of pegylated interferon and ribavirin for 24–48 weeks, based on genotype. The limitations of these medications are well known. For genotype 1, the most common genotype in the United States nd Europe, this has produced an SVR (equated with cure) rate of only about 40%. Pregnant patients or those with advanced renal disease are prohibited from using ribavirin. Likewise, interferon therapy excludes patients with autoimmune diseases, uncontrolled depression and mental illness, decompensated liver disease (Child-Turcotte-Pugh score more than 6), or decompensated cardiac or pulmonary disease. In addition to contraindications, side effects and low response rates have led to an aggressive search for treatment alternatives. Beginning in mid-2011, two new agents, known as direct-acting antivirals (DAA) were approved for use in conjunction with pegylated interferon and ribavirin.
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