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

• Published in: Journal of hepatology Vol. 59; no. 5; pp. 949 - 956
• Main Authors: Manesis, Emanuel K, Vourli, Georgia, Dalekos, George, Vasiliadis, Themistoclis, Manolaki, Nina, Hounta, Athina, Koutsounas, Sotirios, Vafiadis, Irini, Nikolopoulou, Georgia, Giannoulis, Gregory, Germanidis, George, Papatheodoridis, George, Touloumi, Giota
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2013
• Subjects: Adolescent; Adult; Anti-HDV testing in HBsAg-positive patients; Child; Child, Preschool; Chronic HDV infection; Cohort Studies; Coinfection - epidemiology; Female; Follow-Up Studies; Gastroenterology and Hepatology; Greece; Greece - epidemiology; HDV-clinical course; HDV-epidemiology; Hepatitis B - blood; Hepatitis B - epidemiology; Hepatitis B Surface Antigens - blood; Hepatitis D - blood; Hepatitis D - epidemiology; Hepatitis Delta Virus; Humans; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Prevalence; Prospective Studies; Treatment of HDV; Young Adult; Greece; NA(s); nucleos(t)ide analogue(s); hepatitis B virus; Treatment of HDV; alanine aminotransferase; ALT; Anti-HDV testing in HBsAg-positive patients; interquartile range; IU/L; international units per liter; IU/ml; IFN; Greece; international units per milliliter; HDV-infected patients with persistently normal ALT; hepatitis B viral DNA; CHBe; HBV DNA; Chronic HDV infection; HDV; HBeAg-negative chronic hepatitis B; IVDU; HDV-clinical course; HBV; hepatocellular carcinoma; hepatitis delta virus; HBeAg-positive chronic hepatitis B; HDV-PNALT; hepatitis delta viral RNA; hepatitis B surface antigen; chronic hepatitis D; CI; HBeAg; HBsAg; HCC; HDV RNA; IQR; HDV-epidemiology; alpha interferon (both recombinant or pegylated distinguished when necessary); HIV; human immunodeficiency virus; confidence interval; hepatitis B “e” antigen; illicit intravenous drug use(r); CHD
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2013.07.005

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%, pLog-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.