title: Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Internal Medicine, Athens University Medical School, Greece. Electronic address: emanesis@med.uoa.gr.
authors.forename: Emanuel K
authors.initials: EK
authors.lastname: Manesis
authors.forename: Georgia
authors.initials: G
authors.lastname: Vourli
authors.forename: George
authors.initials: G
authors.lastname: Dalekos
authors.forename: Themistoclis
authors.initials: T
authors.lastname: Vasiliadis
authors.forename: Nina
authors.initials: N
authors.lastname: Manolaki
authors.forename: Athina
authors.initials: A
authors.lastname: Hounta
authors.forename: Sotirios
authors.initials: S
authors.lastname: Koutsounas
authors.forename: Irini
authors.initials: I
authors.lastname: Vafiadis
authors.forename: Georgia
authors.initials: G
authors.lastname: Nikolopoulou
authors.forename: Gregory
authors.initials: G
authors.lastname: Giannoulis
authors.forename: George
authors.initials: G
authors.lastname: Germanidis
authors.forename: George
authors.initials: G
authors.lastname: Papatheodoridis
authors.forename: Giota
authors.initials: G
authors.lastname: Touloumi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D060085:Coinfection / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006115:Greece / Q000453:epidemiology; D006509:Hepatitis B / Q000097:blood / Q000453:epidemiology*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D003699:Hepatitis D / Q000097:blood / Q000453:epidemiology*; D003698:Hepatitis Delta Virus; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D006514:Hepatitis B Surface Antigens
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)