Z Gastroenterol 2015; 53 - A2_9
DOI: 10.1055/s-0034-1397103

Early on-treatment HDV-RNA kinetics are not predictive for long-term response to a PEG-IFNa therapy of hepatitis delta

M Wöbse 1, C Yurdaydin 2, S Ernst 3, S Hardtke 1, B Heidrich 1, B Bremer 1, O Keskin 2, R Idilman 2, A Koch 3, MP Manns 1, H Wedemeyer 1
  • 1Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
  • 2Ankara University, Department of Gastroenterology, Ankara, Turkey
  • 3Hannover Medical School, Institute for Biometry, Hannover, Germany
  • 4German Center for Infection Research, Hannover, Germany

Introduction: PEG-Interferon alfa (PEG-IFNa) is the only currently available treatment option for hepatitis delta. One main goal of therapy is sustained HDV-RNA suppression which is achieved in less than 30% of cases. In PEG-IFNa therapy of HCV infection, early viral kinetics have high positive and negative predictive values for SVR, allowing individualization of treatment. Similar data are not available for HDV infection.

Aims: Analysis of early HDV-RNA kinetics during PEG-IFNa therapy of hepatitis delta to establish stopping rules to avoid unnecessary treatment.

Methods: In the HIDIT-2 study 120 HDV-RNA-positive patients were treated for 96 weeks with PEG-IFNa-2a in combination with tenofovir or placebo. Tenofovir had no significant effect on the post-treatment HDV RNA response. For this analysis all patients were selected who received at least 80 weeks of therapy and for whom HDV-RNA-values 24 weeks after the end of therapy were available (n= 91). HDV-RNA was measured in treatment weeks 4, 8, 12, 24 and 48.

Results: HDV RNA was undetectable at post-treatment week 24 in 28 of the 91 patients (31%). Early on-treatment mean HDV-RNA declines were 0.92, 1.61, 1.76, 2.49 and 2.78 log cop/ml at weeks 4, 8, 12, 24 and 48. An HDV-RNA reduction of at least 1 log was detected in 33% of patients at week 4, and in 64%, 68%, 74% and 79% at weeks 8, 12, 24 and 48. HDV RNA was negative in 5, 15, 19, 34 and 42 patients at the respective time points. Negative predictive values for long-term response to PEG-IFNA therapy for a 1log HDV RNA decline during treatment were clinically not useful with 73%, 75% and 54% until week 12 of therapy but increased to 85% and 95% at weeks 24 and 48. The corresponding positive predictive values were low with 13%, 12%, 16%, 30% and 37%. Undetectable HDV-RNA values at the respective time points were not associated with a HDV post-treatment week 24 response (week 4: 4/5; week 8: 7/15; week 12: 10/19 week 24: 20/34; week 48 26/42).

Conclusion: Early HDV-RNA viral kinetics do not allow individualization of PEG-IFNa therapy of hepatitis delta which is in contrast to hepatitis C. Treatment should be continued independently of the initial HDV-RNA response for at least 48 weeks but patients not achieving at least a 1log HDV RNA decline until week 48 should not prolong therapy.

Corresponding author: Wöbse, Michael

E-Mail: MichaelWoebse@gmx.de