Occult hepatitis B infection and HBV replicative activity... : Hepatology (original) (raw)

Viral Hepatitis

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

Wong, Danny Ka Ho1,2; Huang, Fung Yu1; Lai, Ching Lung1,2; Poon, Ronnie Tung Ping2,3; Seto, Wai Kay1; Fung, James1; Hung, Ivan Fan Ngai1; Yuen, Man Fung1,2,*

1_Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China_

2_State Key Laboratory for Liver Research, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China_

3_Department of Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China_

*Address reprint requests to: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China

Email: [email protected]

Received 26 January 2011; accepted 28 June 2011

Potential conflict of interest: Nothing to report.

fax: 852-28162863

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;)

Abbreviations: anti-HBc, antibody-to-hepatitis B core antigen; anti-HBs, antibody-to-HBsAg; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B infection; DM, diabetes mellitus; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; hgDNA, human genomic DNA; NASH, nonalcoholic steatohepatitis; OBI, occult hepatitis B infection; pgRNA, pregenomic RNA; Pol, polymerase.