Treatment of Hepatitis C

Posted by Sara Fazio • January 19th, 2012

In a new study of 21 patients with hepatitis C virus genotype 1 infection who had had no response to prior treatment, sustained virologic responses were achieved in 4 of 11 who were treated with two antiviral agents alone and in 9 of 10 who were treated with the antiviral agents plus peginterferon and ribavirin.

Approximately 180 million people worldwide are infected with hepatitis C virus (HCV), including 4.1 million in the United States. HCV infection is the most common cause of chronic liver disease in the United States and a leading cause of cirrhosis and hepatocellular carcinoma globally. HCV is classified into six major genotypes; genotype 1 is predominant in the United States and is the most difficult to treat.

Clinical Pearls

What is the conventional treatment and associated outcomes for Hepatitis C genotype 1 infection?

Treatment of HCV genotype 1 infection with peginterferon alfa and ribavirin for 48 weeks results in sustained virologic response (undetectable HCV RNA 24 weeks after the end of therapy) in 40 to 50% of patients who have not received previous treatment. Patients are considered as not having had a response if they do not have a reduction in HCV RNA levels by at least 2 log10 IU per milliliter after a minimum of 12 weeks of treatment with peginterferon and ribavirin. Retreatment with triple therapy — a protease inhibitor, peginterferon, and ribavirin — yields rates of sustained virologic response of only 14 to 33%.

In patients with HCV genotype 1 infection who have not had a response to prior therapy, what new regimens may be effective?

In this week’s Journal, a preliminary study of patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents alone [the NS5A replication complex inhibitor BMS-790052 (60 mg once daily) and the NS3 protease inhibitor BMS-650032 (600 mg twice daily)]. In addition, a high rate of sustained virologic response at 24 weeks was achieved when the two direct-acting antiviral agents were combined with peginterferon and ribavirin.

Table 2. Virologic Response during and after Treatment.

Morning Report Questions

Q: What medication-related adverse effects were most commonly reported in patients receiving treatment in this study?

A: All the patients completed at least 24 weeks of therapy. The most common adverse events were diarrhea, fatigue, headache, and nausea, and were reported in both groups. Most adverse events were mild to moderate. There were no deaths, serious adverse events, or discontinuations due to adverse events during the analysis period.

Q: What was the pattern of resistance seen in patients treated only with direct-acting antiviral agents?

A: A high frequency of resistance to two classes of drugs was seen in patients with HCV genotype 1a infection who were treated with direct-acting antiviral agents alone. Although there were only two patients with HCV genotype 1b infection in this group, the observation that both of the patients had a sustained virologic response after treatment with two direct-acting antiviral agents alone may reflect a higher resistance barrier for this combination of drugs in patients with HCV genotype 1b infection than in patients  with HCV genotype 1a infection. In contrast to the former group, no viral breakthrough occurred in patients in the group receiving quadruple therapy.

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