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Background & Aims: Until recently, pegylated interferon‐alfa‐2a (PEG‐IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG‐IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short‐term relapses within 24 weeks. The virological and clinical long‐term effects after prolonged PEG‐IFNa‐based treatment of hepatitis D are unknown. Methods: In the HIDIT‐II study patients (including 40% with liver cirrhosis) received 180 μg PEG‐IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 μg PEG‐IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy). Results: Until the end of follow‐up, 16 (13%) patients developed liver‐related complications (PEG‐IFNa + TDF, n = 5 vs PEG‐IFNa + placebo, n = 11; p =.179). Achieving HDV suppression at week 96 was associated with decreased long‐term risk for the development of hepatocellular carcinoma (p =.04) and hepatic decompensation (p =.009). Including complications irrespective of PEG‐IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG‐IFNa (16/102, p >.999) but was associated with a higher chance of HDV‐RNA suppression (p =.024, odds ratio 3.9 [1.3–12]). Conclusions: Liver‐related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG‐IFNa treatment. PEG‐IFNa treatment should be recommended to HDV‐infected patients until alternative therapies become available. Retreatment with PEG‐IFNa should be considered for patients with inadequate response to the first course of treatment. Clinical Trial registration: NCT00932971. [ABSTRACT FROM AUTHOR]

Background & Aims: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient‐reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta. Methods: Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF‐36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG‐IFNa‐2a)‐based treatment in the HIDIT‐II trial. HIDIT‐II was a randomized prospective trial exploring PEG‐IFNa‐2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available. Results: Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG‐IFNa‐2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV‐RNA clearance was not associated with relevant changes in physical or social SF‐36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co‐treatment had no influence on QOL. Conclusions: Overall, our findings suggest that PEG‐IFNa‐2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF‐36 questionnaires. Of note, several patients may benefit from PEG‐IFNa‐2a‐based therapies with off‐treatment improvements in quality of life. [ABSTRACT FROM AUTHOR]

The role of low levels of HDV‐RNA during and after interferon therapy of hepatitis D is unknown. We re‐analysed HDV RNA in 372 samples collected in the HIDIT‐2 trial (Wedemeyer et al, Lancet Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in‐house assay (IA). We detected HDV‐RNA in one‐third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post‐treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. In contrast, the post‐treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment. [ABSTRACT FROM AUTHOR]