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Management of Hepatitis C Infection

Stefan Zeuzem, MD
Program Director
Jordan J. Feld, MD, MPH
Hemant Shah, MD, MScCH HPTE
Released: June 17, 2019

Goals of Therapy

In patients with chronic HCV infection, the goal of therapy is virologic cure. Eradication of HCV RNA, which persists long-term off therapy, is referred to as a sustained virologic response (SVR). Although SVR is equivalent to virologic cure, the term cure has traditionally been avoided. Initially, there was concern that despite undetectable HCV RNA following treatment, there might potentially be dormant virus that could return in the future. However, long-term follow-up data show that patients with an SVR following treatment with peginterferon and ribavirin have a relapse rate < 1% after a mean of 1.8 years from the end of antiviral treatment.[1] A review of data from phase III trials of sofosbuvir-based regimens found a strong correlation between SVR rates at 12 weeks and 24 weeks posttreatment, suggesting evaluation at the later time point is not necessary even in the clinical setting.[2]

A further concern with the term cure is that underlying liver disease may not be fully reversed even if HCV infection is eradicated. Obtaining SVR is associated with decreases in all-cause mortality,[3] liver-related death, liver-related complications, the need for liver transplantation, and in the incidence of hepatocellular cancer.[4,5] In patients without advanced fibrosis before treatment, SVR represents cure. For those with advanced fibrosis, particularly cirrhosis, SVR is a virologic cure associated with improved outcomes, but adverse events, particularly the development of liver cancer, may still occur. The positive outcomes observed are an effect of permanent HCV RNA eradication, as viral suppression by long-term HCV therapy without SVR does not have the same impact on clinical outcomes.[6] SVR is associated with reduced long-term, all-cause mortality in chronic HCV–infected patients with advanced fibrosis.[7] A study of the use of sofosbuvir plus ribavirin in patients with cirrhosis and portal hypertension, some of whom had decompensated liver disease, demonstrated high SVR rates and improvements in clinical markers such as ascites and hepatic encephalopathy.[8] The long-term benefits of treating patients with decompensated liver disease remain to be determined. As in the HIV field, the prospect of highly effective, well tolerated antiviral regimens has prompted investigators to explore the potential role of HCV treatment in preventing onward HCV transmission and reducing HCV prevalence, particularly among people who inject drugs.[9,10]

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