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Interferon therapy prolonged life expectancy among chronic hepatitis C patients: for both responders & perhaps nonresponders
Reported by Jules Levin
  GASTROENTEROLOGY 2002;123:483-491
Haruhiko Yoshida, M.D., Department of Gastroenterology, University of Tokyo
Graduate School of Medicine
Background & Aims: The effects of interferon therapy in chronic hepatitis C patients on survival are unclear. Our objective was to analyze survival among a large cohort of chronic hepatitis C patients. Methods: We used a retrospective cohort study design in the setting of 7 university hospitals and 1 regional core hospital in Japan. Our study included 2889 patients with histological-proven chronic hepatitis C: 2430 patients received interferon therapy, and 459 patients were untreated. For intervention, the median dose and duration of interferon administration was 480 million units and 137 days, respectively. For measurements, survival status was confirmed by medical records or direct questionnaires. The effect of interferon therapy on survival was assessed by standardized mortality ratio (SMR) based on published mortality among the Japanese general population and by risk ratio calculated by proportional hazards regression. Results: Thirty of 459 untreated patients, 7 of 817 virologic sustained responders, and 49 of 1613 nonresponders died in 5.4-years follow-up. Fifty-eight (67%) of 86 patient deaths were due to liver diseases (39 to hepatocellular carcinoma). Compared with the general population, overall mortality was high among untreated patients (SMR: 1.9; CI: 1.3-2.8) but not among interferon-treated patients (SMR: 0.9; CI: 0.7-1.1). The risk of death was reduced, compared with untreated patients, among interferon-treated patients (risk ratio for overall death: 0.367; CI: 0.236-0.596; for liver-related death: 0.284; CI: 0.164-0.494) and among sustained responders (risk ratios: 0.148; CI: 0.064-0.343 and 0.050; CI: 0.012-0.216). The risk of liver-unrelated deaths remained unchanged.
Conclusions: Interferon therapy improved survival of chronic hepatitis C patients by preventing liver-related deaths.
A sustained virologic response, defined as HCV RNA negativity more than 6 months after the termination of interferon therapy, was found in 817 (33.6%) patients. Positivity at the same time point, found in 1613 (66.4%) patients, was considered a nonsustained response. Four hundred fifty-nine patients did not receive interferon because of anxiety over adverse effects of interferon (11%), being busy during the scheduled treatment (22%), being not covered by health insurance (55%), or physician's judgment on patient's tendency toward depression (8%), severe diabetes mellitus (2%), pulmonary diseases (1%), or combined cardiovascular diseases (1%).
Interferon therapy significantly reduced the risk of overall death with a risk ratio of 0.375. When stratified into virologic-sustained and nonsustained responders, the virologic-sustained responders showed a further reduction in the risk of overall death (risk ratio: 0.148 compared with untreated patients), and the nonsustained responders had a higher but still significantly reduced risk (risk ratio: 0.472). Interferon therapy was associated with a reduced risk of overall deaths among the noncirrhotic patients but not among the cirrhotic patients. However, the risk was significantly reduced among the virologic-sustained responders with cirrhosis as well as among those without cirrhosis. Having an older age when being treated with IFN resulted in increased risk (but I don't think the p value was significant among cirrhotics with a nonsustained response).
Heavy alcohol consumption is known to worsen survival of chronic hepatitis C patients. However, we do not have sufficient data to allow evaluation of interferon therapy in face of heavy alcohol consumption because less than 2% of patients drank more than 80 g of alcohol daily during the follow-up. Although low-alcohol consumption (20 to 80 g/day) was reported by 25% of patients at entry, 90% of these patients stopped drinking alcohol after undergoing liver biopsy.
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