Poor clinical and virological outcome of nucleos(t)ide therapy in HBV/HDV co-infected patients

Background and aims Co-infection of Hepatitis B (HBV) and Delta viruses (HDV) represents the most severe form of viral hepatitis with high morbidity and mortality. While treatment with pegylated Interferon alpha (PEG-IFN-alpha) is well established, the role of concomitant therapy with nucleos(t)ide analogous (NA) against HBV has been a matter of debate. We aimed to investigate the role of NA treatment in HBV/HDV coinfected patients.

Method We retrospectively studied 53 HDV-RNA positive patients between 2000 and 2019. Patients were followed for at least 3 months (mean time of follow up 4.6 years; range 0.2 - 14.1 years). Patients who had liver transplantation or hepatocellular carcinoma (HCC) at time of presentation were excluded. 43% (n=23) were treated with nucleos(t)ide analogues, 43% (n = 23) received IFN-alpha-based therapies and 13% (n = 7) were untreated. Clinical endpoints were defined as hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding), HCC, liver transplantation and liver-related death.

Results Liver cirrhosis was already present in 47% (n = 25) of all patients at first presentation. During follow-up, liver-related endpoints developed in 23 patients (44%). NA-treatment was associated with a significantly worse clinical outcome (p = 0.01; OR = 4.92; CI = 1.51 - 16.01) compared to both untreated (p = 0.38; OR = 0.46; CI = 0.80 - 2.61) and IFN-alpha-based-treated patients (p = 0.04; OR = 0.29; CI = 0.89 - 0.94). HBsAg levels declined by more than 50% during NA-based therapy in only 5 cases (mean time of follow-up 8.7 years; range: 2.4 - 13.6 years). HDV RNA became undetectable during follow up in 7 patients receiving NA alone (mean time of follow-up 5.0 years; range 0.6 - 13.5 years).

Conclusion The therapeutic effect of HBV nucleos(t)ide analogous in patients with HBV-HDV coinfection is limited. Future studies need to elaborate on potential difference between tenofovir and entecavir. Alternative treatment options are urgently needed.

Abb. 1 Cumulative clinical endpoints-free survival

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Artikel online veröffentlicht:
08. September 2020