Author information

1 1st Department of Internal Medicine, University Medical Hospital Hamburg-Eppendorf, Martinistr 52, 20246, Hamburg, Germany. j.bockmann@uke.de.

2 German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel site, Hamburg, Germany. j.bockmann@uke.de.

3 1st Department of Internal Medicine, University Medical Hospital Hamburg-Eppendorf, Martinistr 52, 20246, Hamburg, Germany.

4 School of Mathematics and Statistics, UNSW Sydney, Sydney, Australia.

5 Cancer Research Division, Cancer Council NSW, Sydney, Australia.

6 German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel site, Hamburg, Germany.

7 Center of Internal Medicine II, University Hospital Brandenburg, Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany.

8 Institute of Microbiology, Virology and Hygiene, University Medical Hospital Hamburg-Eppendorf, Hamburg, Germany.

Abstract

BACKGROUND: Chronic hepatitis delta virus (HDV) infection causes severe liver disease which often leads to cirrhosis and hepatocellular carcinoma (HCC). Aim of this study was to establish the disease severity and prognostic factors for disease outcome by analysing frequencies of clinical events and their correlation with baseline virological and biochemical parameters as well as interferon and nucleos(t)ide analogue treatment choice.

METHODS: We studied a single-centre cohort of 49 anti-HDAg-positive patients with HBsAg persistence for at least 6 months. Virological and biochemical parameters, interferon and nucleos(t)ide analogue treatment choice as well as clinical events during follow-up were analysed by retrospective chart review (mean follow-up time 3 years, range 0.25-7.67 years).

RESULTS: Severe clinical events occurred in 11/49 hepatitis D patients, including HCC (8/49), death (8/49) or liver transplantation (2/49). HCCs only occurred secondary to liver cirrhosis and their event rates in this cohort of hepatitis D patients did not differ from a matched HBV mono-infected cohort with comparable frequency of liver cirrhosis. A stepwise multivariate logistic regression revealed low platelet count (p = 0. 0290) and older age (p = 0.0337) correlating most strongly with overall clinical events, while serum HDV RNA positivity at baseline did not correlate with any clinical outcome. Interferon-free but not nucleos(t)ide analogue-free patient care correlated with the occurrence of HCC at logistic regression, although only 3/18 interferon-treated patients demonstrated repeatedly negative HDV PCR results post therapy.

CONCLUSIONS: Our data indicate that progressive liver disease at baseline plays a major role as predictive factor for overall clinical outcome of hepatitis D patients. In particular, HCC risk may not be underestimated in hepatitis D virusRNA negative hepatitis D patients with advanced liver fibrosis.