Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study

• Published in: Oncotarget Vol. 7; no. 38; pp. 62706 - 62714
• Main Authors: Coppola, Nicola, Onorato, Lorenzo, Iodice, Valentina, Starace, Mario, Minichini, Carmine, Farella, Nunzia, Liorre, Giulia, Filippini, Pietro, Sagnelli, Evangelista, de Stefano, Giorgio
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20.09.2016
• Subjects: Aged; Biopsy; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Clinical Research Paper; DNA, Viral - blood; Female; Gene Deletion; Genotype; Hepatitis B - complications; Hepatitis B Surface Antigens - blood; Hepatitis B virus - genetics; Humans; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - virology; Liver Neoplasms - complications; Liver Neoplasms - genetics; Liver Neoplasms - virology; Male; Middle Aged; Mutation; Polymerase Chain Reaction; occult HBV infection; HBsAg mutants; anti-HBc positivity; hepatocellular carcinoma; liver cirrhosis
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10909

To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC. HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs. OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different. The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description.