Occult hepatitis B infection and HBV replicative activity in patients with crypt

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<http://onlinelibrary.wiley.com/doi/10.1002/hep.24551/abstract;jsessionid=77EAFC5E3FC07F7BA9AF19F000C7511E.d03t03>

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, James 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
Early View (Online Version of Record published before inclusion in an
issue)

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;)