Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study

Abstract

Background & aims: Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years.

Methods: Prospective data were extracted from the HepNet.Greece Cohort-Study.

Results: Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p<0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p<0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)].

Conclusions: In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute >50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.

Keywords: ALT; Anti-HDV testing in HBsAg-positive patients; CHBe+; CHBe-; CHD; CI; Chronic HDV infection; Greece; HBV; HBV DNA; HBeAg; HBeAg-negative chronic hepatitis B; HBeAg-positive chronic hepatitis B; HBsAg; HCC; HDV; HDV RNA; HDV-PNALT; HDV-clinical course; HDV-epidemiology; HDV-infected patients with persistently normal ALT; HIV; IFN; IQR; IU/L; IU/ml; IVDU; NA(s); Treatment of HDV; alanine aminotransferase; alpha interferon (both recombinant or pegylated distinguished when necessary); chronic hepatitis D; confidence interval; hepatitis B surface antigen; hepatitis B viral DNA; hepatitis B virus; hepatitis B “e” antigen; hepatitis delta viral RNA; hepatitis delta virus; hepatocellular carcinoma; human immunodeficiency virus; illicit intravenous drug use(r); international units per liter; international units per milliliter; interquartile range; nucleos(t)ide analogue(s).