Treatment of Chronic Delta Hepatitis

Chronic delta hepatitis (CDH) remains the most progressive form of chronic viral hepatitis and as such its successful treatment is important. However, in striking contrast to the situation in chronic hepatitis B and C, no new drugs for its treatment have been introduced in the recent past and interferons remain the only evidence-based effective treatment of CDH. However, results are far from optimal. Overall, around 25 to 30% of patients may have a sustained response after one year of conventional or pegylated interferon (Peg-INF) treatment and such treatment may favorably affect the natural history of the disease. The superiority of Peg-INF over its conventional form is possible, but has not been demonstrated in a clinical trial. Several unanswered questions remain in the context of INF treatment such as (1) the need for standardization of HDV-RNA quantitation, the most widely used surrogate marker of treatment efficacy; (2) validation of this treatment end point as an index of long-term containment of HDV; (3) optimal duration of treatment; (4) baseline and on-treatment parameters of treatment efficacy; and (5) development of new markers of treatment efficacy. Nucleos(t)ide analogs (NAs) have been widely tested in CDH, but they appear to be ineffective when used for a duration of up to 2 years. Combination treatment of NAs with INFs also proved to be disappointing. New approaches to treatment are hepatocyte entry inhibitors and prenylation inhibitors to be hopefully tested in human CDH in the not-too-distant future.