Long-Term Therapy With Ribavirin for Chronic Hepatitis C

Up to 50 patients with chronic hepatitis C will be treated for up to eight years with ribavirin, an orally administered antiviral agent. Patients will be chosen who have moderate to severe chronic hepatitis C who previously failed to have a sustained virological response to the combination of alpha interferon and ribavirin or who were intolerant to interferon therapy or who have significant contraindications to the use of interferon. After medical evaluation and liver biopsy, patients will begin receiving ribavirin in a dose of 1000 mg (body weight less than 75 K) or 1200 mg daily (two or three capsules of 200 mg twice daily by mouth). Patients will be followed on therapy with visits to the outpatient clinic for medical interview, physical examinations and blood tests at 2 to 8 week intervals. After six months, the dose of ribavirin will be stopped or adjusted based upon changes in alanine aminotransferase (ALT) levels comparing the average of the three values from month 2, 4, and 6 to the baseline levels. A decrease by 50% or more will be considered a partial biomedical response and a decrease to within the normal range will be considered a complete biochemical response. In patients who do not respond by six months, therapy will be stopped, whereas, in patients who respond, therapy will be continued decreasing the dose in increments of 200 mg per day every 6 months as long as a biochemical response is maintained. The minimal dose will be 400 mg per day. In patients with a response, therapy will be continued for up to 8 years with repeat liver biopsies and evaluations at 2, 4 and 8 years. The primary criterion for success of therapy will be the degree of histologic improvement on liver biopsy at 2, 4 and 8 years; supportive, secondary criteria will be improvements in ALT levels and in symptoms done at the same time points. This open-label pilot study will allow for therapy of patients with resistant forms of chronic hepatitis C and will address whether long-term therapy with this agent is safe, as well as whether prolonged monotherapy with ribavirin leads to sustained improvements in serum ALT levels, whether these can be maintained using lower doses of ribavirin, and whether the improvements reflect amelioration of the underlying liver disease as judged histologically.