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. 2016 Sep 20;7(38):62706-62714.
doi: 10.18632/oncotarget.10909.

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

Nicola Coppola  1 , Lorenzo Onorato  1 , Valentina Iodice  1   2 , Mario Starace  1 , Carmine Minichini  1 , Nunzia Farella  2 , Giulia Liorre  2 , Pietro Filippini  1   3 , Evangelista Sagnelli  1 , Giorgio de Stefano  2
Affiliations

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

Nicola Coppola et al. Oncotarget. .

Abstract

Aim: To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: HBsAg mutants; anti-HBc positivity; hepatocellular carcinoma; liver cirrhosis; occult HBV infection.

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Conflict of interest statement

All the authors of the manuscript declare that they have no conflict of interest in connection with this paper.

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