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

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http://onlinelibrary.wiley.com/doi/10.1002/hep.24551/abstract

Viral Hepatitis

Occult hepatitis B infection and HBV replicative activity in patients with

cryptogenic cause of hepatocellular carcinoma†

Danny Ka Ho Wong1,2, Fung Yu Huang1, Ching Lung Lai1,2, Ronnie Tung Ping

Poon2,3, Wai Kay Seto1, Fung1, Ivan Fan Ngai Hung1, Man Fung Yuen1,2,*,‡

Article first published online: 21 JUL 2011

DOI: 10.1002/hep.24551

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Hepatology

Volume 54, Issue 3, pages 829–836, 2 September 2011

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;)