Report Fifteen from Dallas Liver Meeting, 50th AASLD, Nov 5-9

Starting HCV Treatment When Disease is Mild
Jules Levin, NATAP

JUSTIFICATION OF TREATING PATIENTS WITH "MILD" CHRONIC HEPATITIS C DISEASE WITH INTERFERON ALFA-2B AND RIBAVIRIN 

J WS Fang, I Yang, R Yao, J YN Lau, J J Garaud, J K Albrecht, Schering-Plough Res Institute, Kenilworth

Background: Whether patients with "mild" chronic hepatitis C disease should be treated or not is debatable. It is also controversial whether these patients should be treated with the recently approved combination therapy of interferon alfa-2b/ribavirin (Rebetron‘, SP) given the known side effects. 

Aim: To determine whether treating patients with "mild" chronic hepatitis C disease using the combination therapy is justified, based on virologic response and improvement in quality of life (QOL). 

Methods: Adult treatment-naive patients (n=1744) from two prospective, randomized, controlled clinical trials comparing the efficacy and safety of Rebetron‘ and interferon alfa-2b alone over 24 weeks and 48 weeks were categorized into having "mild" and "non-mild" disease based on their pretreatment liver biopsies. Those who have "mild" disease have METAVIR fibrosis scores of 0 of 1, and activity scores of 0 or 1. All other patients were grouped as having "non-mild" disease. Sustained virologic response (<100 copies/ml serum HCV RNA at 24 weeks of follow-up) was evaluated. The validated instrument SF-36 was used to measure QOL burden at baseline, throughout treatment/follow-up and at the end of follow-up (EOF). Baseline SF-36 scores were compared to the age-and gender-matched US norms and the mean changes in SF-36 before and after treatment were described in the context of virologic remission at EOF. 

Results: Of 1639 patients with baseline liver biopsies, 391 have "mild" disease and 1247 have "non-mild" disease. The patients with "mild" disease are younger (39.2 vs 43.3 yrs, p=0.001), less heavy (76.1 vs 79.5 kg, p=0.001), have lower baseline viral load (1.9 vs 2.8 x 106 copies/ml, p=0.001) and lower ALT (2.5 vs 3.8 x ULN, p=0.001) than those with "non-mild" disease. Virologic response: The rates of sustained virologic response to the combination therapy was similar between those with "mild" versus "non-mild" disease (I/R for 24 weeks: 34% vs 32%, p=NS; I/R for 48 weeks: 38% vs 43%, p=NS). QOL: When compared to the US normative values, patients with "mild" disease showed similar burden in QOL as those with "non-mild" disease, namely decrements in three SF-36 modalities: Role-physical, General Health and Vitality. These baseline decrements are consistent with the common but non-specific clinical features of patients with compensated HCV infection. Both groups shared similar QOL profiles throughout treatment and follow-up. At the end of follow-up, similar improvement in all three modalities was observed among responders in both groups of patients. 

Conclusions: Patients with "mild" and "non-mild" baseline liver disease responded equally to interferon alfa-2b/ribavirin in terms of virology and quality of life burden. Given the unpredictable natural history of chronic HCV infection in the individual patient, the combination therapy should be offered to the informed patient regardless of disease activity.