Clinical Research Papers:

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

Nicola Coppola _, Lorenzo Onorato, Valentina Iodice, Mario Starace, Carmine Minichini, Nunzia Farella, Giulia Liorre, Pietro Filippini, Evangelista Sagnelli and Giorgio de Stefano

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Oncotarget. 2016; 7:62706-62714. https://doi.org/10.18632/oncotarget.10909

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Nicola Coppola1, Lorenzo Onorato1, Valentina Iodice1,2, Mario Starace1, Carmine Minichini1, Nunzia Farella2, Giulia Liorre2, Pietro Filippini1,3, Evangelista Sagnelli1 and Giorgio de Stefano2

1 Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy

2 Ninth Interventional Ultrasound Unit for Infectious Diseases, Cotugno Hospital, Naples, Italy

3 Infectious diseases Unit, Caserta Hospital, Caserta, Italy

Correspondence to:

Nicola Coppola, email:

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

Received: May 07, 2016 Accepted: June 18, 2016 Published: July 28, 2016


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.

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