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
