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

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.

Eighteen‐month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy

“…The DNA extracted was analysed for the presence of HBV DNA by polymerase chain reaction (PCR) using sets of primers for core, as previously reported . In HBV DNA‐positive plasma, the HBV genotype and the mutations in the HBV pre‐S/S coding and pol regions were determined by automated sequencing, as previously described …”

Antigenicity reduction contributes mostly to poor detectability of HBsAg by hepatitis B virus (HBV) S‐gene mutants isolated from individuals with occult HBV infection

“…OBI is defined as the persistence of HBV DNA in the serum or liver of individuals with undetectable HBsAg using currently available assays . It has been suggested that OBI is related to misdiagnosis, disease progression, poor blood transfusion safety, HBV reactivation, and vaccination failure …”

Hepatitis C late relapse in patients with directly acting antiviral‐related sustained virological response at week 12

“…All patients had been treated with a DAA regimen according to the HCV genotype, international guidelines and local availability in 19 clinical centres in Campania, southern Italy. These centres had cooperated in several clinical investigations using the same clinical approach . In the study period, these 19 centres treated by DAA regimen 3259 anti‐HIV negative subjects, with virological failure in 129.…”