Long-term benefit of interferon α therapy of chronic hepatitis D: regression of advanced hepatic fibrosis

Abstract Background & Aims: Little is known about the long-term effects of interferon α on clinical outcome and survival of patients with chronic hepatitis D. Methods: Thirty-six patients with chronic hepatitis D who participated in a randomized controlled trial of a 48-week course of high (9 million units) or low (3 million units) doses of interferon α or no treatment were followed for an additional 2 to 14 years. Results: Long-term survival was significantly longer in the high-dose group than in untreated controls ( P = 0.003) or in the low-dose group ( P = 0.019) but did not differ between patients treated with 3 million units and controls. Among surviving patients at 12 years of follow-up, a biochemical response was present in 7 of 12 treated with 9 million units, in 2 of 4 who received 3 million units, and in none of 3 controls. Long-term alanine aminotransferase (ALT) normalization correlated with improved hepatic function and loss of IgM antibody to hepatitis delta antigen (anti-HD). Patients in the high-dose group had a sustained decrease in HDV replication ( P = 0.008), leading to clearance of HDV RNA and, eventually, hepatitis B virus (HBV) in some patients, as well as a dramatic improvement in liver histology with respect to activity grade ( P = 0.0004) and fibrosis stage ( P = 0.007). Strikingly, we documented an absence of fibrosis in the final biopsy of 4 patients with a long-term biochemical response and an initial diagnosis of active cirrhosis. Conclusions: High doses of interferon α-2a significantly improved the long-term clinical outcome and survival of patients with chronic hepatitis D, even though the majority had active cirrhosis before the onset of therapy.