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Clinical Trial
. 2014 Jul;40(1):93-104.
doi: 10.1111/apt.12788. Epub 2014 May 11.

Long-term therapy of chronic delta hepatitis with peginterferon alfa

T Heller  1 , Y Rotman, C Koh, S Clark, V Haynes-Williams, R Chang, R McBurney, P Schmid, J Albrecht, D E Kleiner, M G Ghany, T J Liang, J H Hoofnagle
Affiliations
Clinical Trial

Long-term therapy of chronic delta hepatitis with peginterferon alfa

T Heller et al. Aliment Pharmacol Ther. 2014 Jul.

Abstract

Background: Chronic delta hepatitis virus (HDV) infection rapidly progresses to cirrhosis. Treatment with peginterferon for up to 2 years is often without durable response.

Aim: To examine the efficacy and safety of long-term peginterferon in achieving a durable response.

Methods: Treatment was initiated with 180 μg/week 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: Thirteen patients were treated for a median of 140 weeks (6-260) with an average peginterferon dose of 180 μg/week (90-270). At baseline, most had advanced disease (median Ishak fibrosis = 3) with portal hypertension (HVPG = 10.2 ± 6 mmHg). Five of 13 patients (39%) achieved the primary endpoint, with three seroconverting for HBsAg after 24, 37 and 202 weeks of treatment. Histological inflammation improved after 1 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 virological responders than nonresponders. After 12 weeks, virological 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 delta hepatitis virus infection.

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Figures

Figure 1
Figure 1
Patient flow throughout the study. Of the 19 patients screened, 13 were enrolled into the study. This figure shows the follow-up and responses of the patients enrolled in the study at years 1, 3 and 5.
Figure 2
Figure 2
This figure shows the fraction of patients becoming HDV RNA negative (red), HBsAg negative (black) or have ALT < 31 U/L (blue) during course of treatment out to 240 weeks.
Figure 3
Figure 3
This figure shows the effect of 1 year of peginterferon treatment on histological activity (a), fibrosis (b) and HVPG (c). At 1 year, histologic inflammation significantly improved (p=0.01) but fibrosis did not, and HVPG trended towards significance (p=0.085).
Figure 4
Figure 4
Examples of response patterns of individual patients. (a–c) complete responders, (d–e) response and breakthrough, (f–g) nonresponders.
Figure 5
Figure 5
Logarithmic decline in HBsAg level from baseline to week 12 according to virological response to treatment. Squares represent complete responders, while X represents patients who became HDV-RNA negative but broke through while on treatment. Compared to nonresponders, patients with response had a significantly different decline in HBsAg (p=0.05).
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References

    1. Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet. 2011;378:73–85. - PubMed
    1. Gudima S, Chang J, Moraleda G, Azvolinsky A, Taylor J. Parameters of human hepatitis delta virus genome replication: the quantity, quality, and intracellular distribution of viral proteins and RNA. Journal of virology. 2002;76:3709–19. - PMC - PubMed
    1. Glenn JS, Marsters JC, Jr, Greenberg HB. Use of a prenylation inhibitor as a novel antiviral agent. Journal of virology. 1998;72:9303–6. - PMC - PubMed
    1. Rizzetto M. Hepatitis D: thirty years after. Journal of hepatology. 2009;50:1043–50. - PubMed
    1. Rizzetto M, Ponzetto A, Forzani I. Hepatitis delta virus as a global health problem. Vaccine. 1990;8(Suppl):S10–4. discussion S21–3. - PubMed

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