Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-alpha) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-alpha. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-alpha for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had post-treatment liver biopsies. Patients were designated histologically responsive or non-responsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-alpha (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-alpha for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-alpha treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.