Abstract
AimTo evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC.MethodsHBV 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.ResultsOBI 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.ConclusionsThe 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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the ninth in women, with 554,000 and 228,000 new cases per year, respectively [1]
Liver cancer is strongly associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) chronic infection, liver cirrhosis being the morphologic substrate for HCC development in 80% of cases
An occult HBV infection (OBI)-defining condition was observed in HCC tissue of nearly 20% of the 68 hepatitis B surface antigen (HBsAg)-negative patients investigated in this study and more precisely in half of those with circulating anti-HBc alone, in nearly one-third of the anti-HBs/anti-HBc-positive and in only 5% of the anti-HBc-negative
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the ninth in women, with 554,000 and 228,000 new cases per year, respectively [1]. Liver cancer is strongly associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) chronic infection, liver cirrhosis being the morphologic substrate for HCC development in 80% of cases. The progressive application of universal HBV vaccination of newborn babies has significantly reduced the incidence of HBV-related HCC in developed countries, a reduction strengthened by the increasing use in the last decade of drugs suppressing HBV chronic infection in most patients treated. The increasing use in recent www.impactjournals.com/oncotarget years of directly acting antiviral agents that induce HCV eradication in nearly 95% of patients with chronic hepatitis C will significantly reduce, perhaps not fully eliminate, the risk of developing HCC [4]. The epidemiology of HCC in developed countries shows a reduced impact of both HBV and HCV chronic infections and an increasing role of non-alcoholic fatty liver diseases (NAFLD) [5]
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