Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma.

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Hepatology. 2011 Jul 11. doi: 10.1002/hep.24551. [Epub ahead of print]

Occult hepatitis B infection and HBV replicative activity in patients with

cryptogenic cause of hepatocellular carcinoma.

Wong DK, Huang FY, Lai CL, Poon RT, Seto WK, Fung J, Hung IF, Yuen MF.

Source

Department of Medicine, University of Hong Kong, Queen Hospital, Hong Kong

SAR, China; State Key Laboratory for Liver Research, University of Hong Kong,

Queen Hospital, Hong Kong SAR, China.

Abstract

We aimed to investigate the incidence of occult hepatitis B infection (OBI) in

patients with " cryptogenic " hepatocellular carcinoma (HCC) and to study the HBV

replicative activity in these patients. Tumorous and adjacent nontumorous liver

tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with

identifiable causes (13 with chronic hepatitis B [CHB], six with chronic

hepatitis C, and nine alcohol-related). OBI was identified by nested polymerase

chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA

(cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and

reverse-transcription PCR (RT-PCR), respectively. OBI was identified in 24 (73%)

cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%)

patients with alcohol-related HCC. In HCC patients with OBI, HBV DNA were

detected in ™2 HBV genomic regions more often in nontumorous tissues than in

tumorous tissues (90% versus 57%, respectively; P = 0.007). Cryptogenic HCC

patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients

with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only

six (26%) cryptogenic HCC patients with OBI had detectable cccDNA (median:

<0.0002 copies/cell), which was significantly lower than that of the CHB

patients (median: 0.005 copies/cell; P < 0.0001). HBV pgRNA were detectable in

12 (52%) cryptogenic HCC patients with OBI (median: 0.0001 copies/cell), which

was significantly lower than that of the CHB patients (median: 2.90 copies/cell;

P < 0.001). Conclusion: 73% of patients with apparently unidentifiable causes

for HCC were HBV-related. The detection rate was higher in nontumorous tissues

than tumorous tissues. The low intrahepatic HBV DNA and pgRNA levels indicated

that persistent viral replication and possibly HBV integration are the likely

causes of HCC in OBI patients. (HEPATOLOGY 2011;).

Copyright ¿ 2011 American Association for the Study of Liver Diseases.

PMID: 21809355 [PubMed - as supplied by publisher]