Long-term therapy of chronic delta hepatitis with peginterferon alfa

Abstract

Background Chronic delta hepatitis (HDV) infection rapidly progresses to cirrhosis. Treatment with peginterferon for up to 2 years is often without durable response. Aim We examined the efficacy and safety of long-term peginterferon in achieving a durable response. Methods Treatment was initiated with 180 μg/wk of peginterferon alfa-2a with titration to a maximal tolerable dose, for up to 5 years. Liver biopsies and hepatic venous pressure gradients (HVPG) were evaluated at baseline, 1, 3, and 5 years. The primary endpoint was histological improvement or loss of serum HDV and HBsAg at 3 years. Results 13 patients were treated for a median of 140 weeks (6–260) with an average peginterferon dose of 180 μg/wk (90–270). At baseline, most had advanced disease (median Ishak fibrosis = 3) with portal hypertension (HVPG = 10.2 +/− 6 mm Hg). 5 of 13 patients (39%) achieved the primary endpoint, with 3 seroconverting for HBsAg after 24, 37 and 202 weeks of treatment. Histologic inflammation improved after one year, (median HAI: 10 vs. 7, p=0.01) with persistence in 4/5 patients at 3 years (median HAI: 7.5). Greatest improvements occurred in the first year. Baseline bilirubin and HBsAg levels were significantly lower in virologic responders than non-responders. After 12 weeks, virologic responders had a significant decline in HBsAg (1.5 log10 IU/mL, p=0.05). Conclusion Despite increased doses and duration of therapy, treatment of chronic HDV with peginterferon remains unsatisfactory. Quantitative measures of HBsAg may be an important biomarker of early response to peginterferon therapy in chronic HDV infection.

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial

“…Heller et al [13] studied prolonging therapy of chronic hepatitis D with PEGIFNα for up to 5 years. Only three of 12 patients treated achieved a complete virologic response, endpoint defined as the combination of undetectable HDV RNA with loss of HBsAg and anti HBsAg seroconversion in serum.…”

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…161,162 Several studies tried to increase efficacy by increasing treatment duration. 163,164 However, clear evidence is lacking to confirm that this approach is beneficial for most chronically HDV infected patients. Even after 96 weeks of PegIFNa therapy, alone or in combination with TDF, 24-week post-therapy relapses occurred in 36-39% of the patients with on-treatment response.…”

“…165 The likelihood of the long-term response to PegIFNa can be estimated to some extent by HDV RNA and HBsAg kinetics at weeks 12 and 24. 164,[166][167][168][169] However, stopping PegIFNa prematurely at this stage is not recommended, if treatment is well tolerated, as the negative predictive values of these markers are not very strong, and late responses may occur in patients with early non-response. Furthermore, long-term follow-up studies suggest that an IFNa based therapy per se can be taken as an independent factor associated with a lower likelihood of disease progression, and to develop clinical endpoints.…”

Diagnosis, management and treatment of hepatitis delta virus infection: Turkey 2017 Clinical Practice Guidelines

“…Various studies have been performed with the hypothesis that two years of treatment would be superior to one, but these did not yield the anticipated results. Meanwhile, expert opinions and certain case presentations and some previous studies suggested that that some patients might be benefit from long-term treatment (30)(31)(32)(33). In a retrospective study focusing on the delta hepatitis database of Ankara University School of Medicine, increasing the duration of treatment was shown to increase cumulative treatment response rates as well (33).…”