Description of Treatment:
Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Acute infection from HCV is usually asymptomatic and evolves into chronic HCV infection in up to 85% of cases. In the United States about 4 million people (1.8%) are infected with HCV. Data suggest that there are about 10,000 to 12,000 deaths annually in the United States due to HCV or its sequelae. HCV transmission is mainly through exposure to infected blood. In the United States, transmission of HCV occurs primarily through injection drug use, resulting in 60% of new cases. Less common modes of transmission include needle-stick accidents, sexual contact, mother-to-infant transmission (either in utero or by breast feeding) and blood transfusions prior to 1990. Many cases of chronic hepatitis C are asymptomatic, and symptoms may not occur until the disease is advanced (up to 20 or more years since primary infection). Hepatitis C may eventually result in severe fibrosis and cirrhosis, ultimately with decompensation or liver failure. The purpose of treatment is to stop the progression of the disease and avoid cirrhosis and possible progression to hepatocellular carcinoma. The major antiviral drugs used for treatment include combination therapy with peginterferon-alfa2a/2b (PEG-IFN) and ribavirin, with treatment courses varying with the genotype of the virus. Genotypes 1, 2, 3 are the most common genotypes in the United States, with genotype 1 predominating.

A sustained virologic response (SVR) is the primary endpoint in many studies, and pertains to undetectable HCV levels 24 to 26 weeks after treatment completion. Patients achieving an SVR are generally considered at low risk for disease progression.

Committee Summary:
With regard to antiviral therapy for chronic hepatitis C, the ICSI Technology Assessment Committee finds that:

1. PEG-IFN and the combination of PEG-IFN and ribavirin are relatively safe when closely monitored by an experienced center. Serious side effects that may lead to discontinuation of treatment occur in 10% to 15% of patients and include neuropsychiatric effects (especially depression), influenza-like symptoms, and hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia.
   
2. HCV treatment with PEG-IFN plus ribavirin is presently the most efficacious treatment available for chronic HCV. (Conclusion Grade I)
   
3. For optimal treatment of HCV in genotype 1 patients, standard weekly dose PEG-IFN along with 1000 – 1200 mg/day ribavirin (depending on weight) given for a 48-week period leads to SVR in about 40% to 50% of patients.
   
4. For optimal treatment of HCV in genotypes 2 and 3, standard weekly dose PEG-IFN along with 800 mg/day ribavirin for 24 weeks is adequate for 73% to 78% conversion to SVR status. Longer courses of treatment have not further improved outcomes in this subgroup.
   
5. Long-term follow-up of HCV cases with an SVR shows regression of fibrosis, a significantly decreased rate of cirrhosis development, and lower HCC rates. However, the precise amount of risk reduction is unknown. (Conclusion Grade II)
   
6. Treatment non-responders (those who underwent previous treatment and did not achieve an SVR) show a low response rate on retreatment (15% to 20% SVR rate). Optimal selection criteria for treating non-responders are not known.
   
7. Predictors for a lower (worse) SVR rate include HCV genotype of 1, the presence of severe fibrosis or cirrhosis, advanced age, heavy alcohol use, obesity, and high viral load.