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The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 50% of these do not respond to therapy. There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5% to 0.74% per year). However, the majority of patients with chronic hepatitis C will not clear it without treatment.

The therapy of chronic hepatitis C has evolved steadily since alpha interferon was first approved for use in this disease more than ten years ago. At the present time, the optimal regimen appears to be a 24- or 48-week course of the combination of pegylated alpha interferon and ribavirin.

Alpha interferon is a host protein that is made in response to viral infections and has natural antiviral activity. Recombinant forms of alpha interferon have been produced, and several formulations (alfa-2a, alfa-2b, consensus interferon) are available as therapy of hepatitis C. These standard forms of interferon, however, are now being replaced by pegylated interferons (peginterferons). Peginterferon is alpha interferon that has been modified chemically by the addition of a large inert molecule of polyethylene glycol. Pegylation changes the uptake, distribution and excretion of interferon prolonging its half-life. Peginterferon can be given once weekly and provides a constant level of interferon in the blood, whereas standard interferon must be given several times weekly and provides intermittent and fluctuating levels. More importantly, peginterferon is more active than standard interferon in inhibiting HCV and yields higher sustained response rates with similar side effects. Because of its ease of administration and better efficacy, peginterferon has been replacing standard interferon both as monotherapy as well as combination therapy for hepatitis C.

Ribavirin is an oral antiviral agent that has activity against a broad range of viruses. By itself, ribavirin has little effect on HCV, but adding it to interferon increases the sustained response rate by two- to three-fold. For these reasons, combination therapy is now recommended for hepatitis C and interferon monotherapy is applied only when there are specific reasons not to use ribavirin.

Two forms of peginterferon have been developed and studied in large clinical trials: peginterferon alfa-2a (Pegasys®: Hoffman La Roche: Nutley, NJ) and peginterferon alfa-2b (Pegintron®: Schering-Plough Corporation, Kenilworth, NJ). These two products are roughly equivalent in efficacy and safety, but have different dosing regimens. Peginterferon alfa-2a is given subcutaneously in a dose of 180 mcg per week. Peginterferon alfa-2b is given subcutaneously weekly in doses of 1.5 mcg per kilogram per week (thus in the range of 75 to 150 mcg per week).

Ribavirin is an oral medication, given twice a day in 200-mg capsules for a total daily dose of 800 to 1,200 mg based upon body weight and the form of peginterferon. When combined with peginterferon alfa-2b, the recommended dose of ribavirin is 800 mg per day. When combined with peginterferon alfa-2a, the dose of ribavirin is 1,000 mg for patients who weigh less than 75 kilograms (165 pounds) and 1,200 mg for those who weight more than 75 kilograms. In all situations, ribavirin is given in two divided doses daily.

At the present, peginterferon alfa-2a has not been approved for use in chronic hepatitis C in the United States and is available only in clinical trials. Thus, only peginterferon alfa-2b is available for general use.

Combination therapy leads to rapid improvements in serum ALT levels and disappearance of detectable HCV RNA in up to 70 percent of patients. However, long-term improvement in hepatitis C occurs only if HCV RNA disappears during therapy and stays undetectable once therapy is stopped. Among patients who become HCV RNA negative during treatment, a proportion relapse when therapy is stopped. The relapse rate is lower in patients treated with combination therapy compared with monotherapy. Thus, a 48-week course of combination therapy using peginterferon and ribavirin yields a sustained response rate of approximately 55 percent. A similar course of peginterferon monotherapy yields a sustained response rate of only 35 percent. A response is considered “sustained” if HCV RNA remains undetectable for six months or more after stopping therapy.

The optimal duration of treatment varies depending on whether interferon monotherapy or combination therapy is used, as well as by HCV genotype. For patients treated with peginterferon monotherapy, a 48-week course is recommended, regardless of genotype. For patients treated with combination therapy, the optimal duration of treatment depends on viral genotype. Patients with genotypes 2 and 3 have a high rate of response to combination treatment (70 to 80 percent), and a 24-week course of combination therapy yields results equivalent to those of a 48-week course. In contrast, patients with genotype 1 have a lower rate of response to combination therapy (40 to 45 percent), and a 48-week course yields a significantly better sustained response rate. Again, because of the variable responses to treatment, testing for HCV genotype is clinically useful when using combination therapy.

Treatment isn’t always necessary
A diagnosis of hepatitis C infection doesn’t necessarily mean you need treatment. If you have only slight liver abnormalities, you may not need treatment because your risk of future liver problems is very low. Your doctor may recommend follow-up blood tests to monitor for liver problems.

Antiviral medications
Hepatitis C infection is treated with antiviral medications intended to clear the virus from your body. Your doctor may recommend a combination of medications taken over several weeks. Once you complete a course of treatment, your doctor will test your blood for HCV. If HCV is still present, your doctor may recommend a second round of treatment.

Antiviral medications can cause depression and flu-like signs and symptoms, such as fatigue, fever and headache. Some side effects can be serious enough that treatment must be delayed or stopped in certain cases.

Liver transplant
If your liver has been severely damaged, a liver transplant may be an option. During a liver transplant, the surgeon removes your damaged liver and replaces it with a healthy liver. Most transplanted livers come from deceased donors, though a small number come from living donors.

For people with hepatitis C infection, a liver transplant is not a cure. Treatment with antiviral medications usually continues after a liver transplant, since hepatitis C infection is likely to recur.

Vaccinations to protect against other forms of viral hepatitis
Your doctor will likely recommend that you receive vaccines against the hepatitis A and B viruses. These are separate viruses that also can cause liver damage and complicate treatment of hepatitis C.