Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C.

Background/aims: Fatigue and other extra hepatic manifestations of hepatitis C have never been studied prospectively in a large cohort. The aim was to assess the prevalence of these symptoms prior to any treatment, and on prolonged follow-up in treated and untreated patients.

Methods: A single-center cohort of consecutive patients with chronic hepatitis C was investigated prior to any treatment. A questionnaire was completed every 6 months for 18 months of follow-up.

Results: Of 1614 patients, 431 met the inclusion criteria (56% male; age 49 years; 60% with significant fibrosis or cirrhosis; 46% with cryoglobulinemia). Seventy-six were untreated; of the treated patients, 83 were sustained responders, 47 relapsers and 225 non-responders. At baseline, fatigue and other extrahepatic manifestations were present in 254 (59%) and 225 (52%) patients. Fatigue was improved in 29 of 83 (35%) responders versus 75 of 348 (22%) patients with detectable hepatitis C virus (HCV)-RNA (P=0.01). The impact of virologic response on fatigue persisted after adjusting for age, gender, fibrosis stage, and depression (odds ratio: 0.34, P<0.001). A cryoglobulin was detectable in two of 34 (6%) responders versus 38 of 115 (33%) patients with detectable HCV-RNA (P<0.001).

Conclusions: In hepatitis C, a sustained virologic response is associated with a reduction in fatigue and cryoglobulin, but fatigue frequently persists despite a virologic response.