title: Association between anti-HBc positivity and hepatocellular carcinoma in HBsAg-negative subjects with chronic liver disease: A meta-analysis.
abstract: A meta-analysis was performed to ascertain to what extent hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core (anti-HBc)-positive subjects with chronic liver disease are at a higher risk of developing hepatocellular carcinoma (HCC) than the anti-HBc-negative.All studies included had to fulfill the following characteristics and inclusion criteria: they investigated the relationship between HBsAg-negative/anti-HBc-positive serology and the occurrence of HCC, whether a case-control or cohort study, they provided relative risk (RR) or odds ratios (ORs) and 95% confidence intervals (CIs), were available as a full text written in English, and were published and indexed up to April 2015.Twenty-six original studies met the inclusion criteria, allowing a meta-analysis on 44,553 patients. The risk of HCC among the 9986 anti-HBc-positive subjects was 67% higher than in the 34,567 anti-HBc-negative (95% CI = 1.44-1.95, P < 0.0001). The results were similar when groups of patients with a different stage of liver disease (patients with chronic liver disease, patients with cirrhosis), with different ethnicity (Asian and non-Asian) and etiology (HCV and non-HCV) were considered. The risk of HCC was significantly higher in the 651 anti-HBs/anti-HBc-positive patients (RR = 1.36; 95% CI = 1.17-1.58, P = 0.03) and in the 595 anti-HBs-negative/anti-HBc-positive subjects (RR = 2.15; 95% CI = 1.58-2.92, P < 0.0001) than in the 1242 anti-HBs/anti-HBc negative. However, the RR from 8 studies indicated that the risk of HCC was 35% lower among the anti-HBs/anti-HBc-positive subjects compared to the anti-HBs-negative/anti-HBc-positive (RR = 0.65; 95% CI = 0.52-0.8, P < 0.0001).This meta-analysis shows that in HBsAg-negative subjects with chronic liver disease, anti-HBc positivity is strongly associated with the presence of HCC, an association observed in all subgroups according to the stage of the disease, etiology, and ethnicity.
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara" Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Onorato
authors.forename: Caterina
authors.initials: C
authors.lastname: Sagnelli
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
authors.forename: Italo F
authors.initials: IF
authors.lastname: Angelillo
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000821:virology*; D002908:Chronic Disease; D006509:Hepatitis B / Q000150:complications*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D008103:Liver Cirrhosis / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology* / Q000821:virology*; D012307:Risk Factors
chemical_list: D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens