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Hepatitis C (cont.)

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What are the goals of therapy for hepatitis C infection?

The ultimate goals of antiviral therapy are to eliminate HCV, prevent transmission, improve or normalize the liver tests and histology (microscopic appearance), prevent progression to cirrhosis and liver cancer, prolong survival, and improve the quality of life.

As already stated, only a sustained virologic response provides the possibility of achieving all of these goals since most patients who have a sustained response will remain in remission indefinitely. The rest of the patients (non-responders, partial responders and relapsers) may show improvement in blood tests with or without relief of symptoms.

What are the therapy options for previously untreated patients with chronic hepatitis C infection?

For previously untreated patients who are candidates for therapy, the optimal approach is combined treatment with pegylated interferon and ribavirin (Rebetol, Copegus). Patients who have reasons not to receive ribavirin may be treated solely with pegylated interferon. Older preparations (nonpegylated forms) of interferon are less effective and less commonly used.

Pegylated interferon: Interferons are a family of naturally occurring proteins that are produced by the body to fight viral infections. To produce pegylated interferon, the interferon is processed by attaching ethylene glycol to it. This process is called pegylation and it slows the elimination of interferon from the body so that its effects are more prolonged. There are currently two types of pegylated interferon: pegylated interferon alpha 2b (Peg-Intron A) and pegylated interferon alpha 2a (Pegasys). Both pegylated interferon alpha 2b and 2a; are given as a subcutaneous injection once a week.

Optimally, pegylated interferon therapy should be combined with ribavirin. In persons who cannot take ribavirin, monotherapy with pegylated interferon may be used. Monotherapy has been shown to achieve sustained virologic response rates of 23% to 25% in patients.

Ribavirin: The antiviral agent, ribavirin (Rebetol, Copegus), is a nucleoside analogue that is taken by mouth. Nucleoside analogues are man-made molecules that closely resemble the biochemical units that make up genetic material (RNA and DNA). Ribavirin works by fooling the virus into using it instead of the normal building blocks, thereby slowing viral reproduction. Ribavirin has not worked well when used alone for hepatitis C.

Combined pegylated interferon and ribavirin: Combined therapy with both pegylated interferon and ribavirin produces a sustained virologic response in 28% to 50% of patients with genotype 1. Genotype 1 is the most common genotype in the U.S., but also the most resistant to treatment. For unknown reasons, response rates are lower in African American persons and higher in Caucasians. In patients with genotype 2, sustained response rates are higher (76% to 82%).

  • The duration of therapy depends on the genotype of the HCV.
  • Hence the recommended duration of treatment for HCV genotype 2 and 3 is 24 weeks and for genotype 1 is 48 weeks.
  • Sustained virologic response usually is accompanied by a return to normal serum ALT levels and improvement in inflammation within the liver.

Combination therapy is associated with more side effects than therapy with single drugs (see below). In research studies, up to 20% of patients receiving combination therapy required a reduction in the doses or discontinuation of therapy because of the side effects. Nevertheless, combination therapy represents significant progress in the treatment of chronic HCV.

Some patients treated successfully with combination therapy still have detectable virus after 12 weeks of treatment but go on to have a sustained response. Therefore, patients on combination therapy should have hepatitis C virus RNA measured at 24 weeks of therapy. In those who are still positive for the virus at that time, consideration is given to stopping treatment, since the chance of sustained response is small.

Protease inhibitors: A new class of medications called protease inhibitors has been approved for the treatment of genotype 1HVC. These medications are telaprevir (Incivek  - this drug was withdrawn from the market by the manufacturer in August 2014) and boceprevir (Victrelis), and they are given along with pegylated interferon and ribavirin. Moreover, adding a protease inhibitor can shorten the overall duration of treatment for some patients.

Medically Reviewed by a Doctor on 2/2/2014


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