Long‐term administration of interferon‐α in non‐responder patients with chronic hepatitis C: follow‐up of liver fibrosis over 5 years

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Abstract
In chronic hepatitis C, previous data have shown that short‐term treatment with interferon‐α (IFN‐α) can reduce collagen deposition in the liver independently of the viral response. The aim of this work was to determine, in non‐responder patients, the long‐term effect of IFN‐α on liver fibrosis according to the total administered dose and the fibrotic stage. Fibrosis was investigated on liver biopsies from 24 non‐responder patients with chronic hepatitis C retreated with successive courses of IFN‐α. The degree of liver fibrosis was assessed on three successive biopsies, performed before IFN‐α treatment and 1 and 5 years later, in 13 and 11 patients, respectively, treated for less (mean: 7.5 months, 313 MU) and more (mean: 21.8 months, 791 MU) than 1 year. For each biopsy, fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining. Regardless of the dose and duration of IFN‐α therapy, a slight decrease of fibrosis was observed in patients 5 years after starting treatment. In cirrhotic patients, a short treatment induced an improvement followed by a relapse of fibrosis in 57%, and only 43% of patients showed constant collagen regression over the 5 years of follow‐up. On the contrary, after prolonged therapy, a progressive and significant decrease occurred throughout the follow‐up period in all patients (P = 0.045). Long‐term treatment with IFN‐α is therefore associated with regression of liver fibrosis, particularly in cirrhotic patients. These promising results need to be confirmed in a larger series of patients.