Occult Hepatitis B Infection May Be the Cause of Unexplained Liver Cancer

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Occult Hepatitis B Infection May Be the Cause of Unexplained Liver Cancer

Details Category: Occult HBV Published on Tuesday, 06 September 2011 00:00

Written by Liz Highleyman

Hepatitis B virus (HBV) infection may cause more cases of hepatocellular

carcinoma (HCC) than estimated if occult or " hidden " HBV is taken into account,

according to a study described in the September 2, 2011, issue of Hepatology.

Occult hepatitis B infection refers to the long-term persistence of covalently

closed circular HBV DNA (cccDNA) and ongoing low-level HBV replication in

hepatocytes (liver cells) of people who are hepatitis B surface antigen (HBsAg)

negative, with or without detectable plasma HBV DNA.

Danny Ka Ho Wong from the University of Hong Kong Queen Hospital and

colleagues explored the incidence of occult hepatitis B infection and HBV

replication among patients with " cryptogenic " or unexplained hepatocellular

carcinoma.

The researchers looked at tumor tissue and adjacent non-tumor liver tissue from

33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13

with chronic hepatitis B, 6 with chronic hepatitis C, and 9 with alcohol-related

liver disease).

Occult HBV was identified using a nested polymerase chain reaction (PCR) assay.

Intrahepatic (within the liver) HBV DNA, HBV cccDNA, and HBV pregenomic RNA

(pgRNA) -- all types of genetic material than can signal the presence of HBV --

were quantified by real-time PCR and reverse-transcription PCR.

Results

Occult HBV was identified in 24 HCC patients (73%) with cryptogenic cancer, 1

person (17%) with chronic hepatitis C, and 5 people with alcohol-related HCC.

Among HCC patients with occult hepatitis B, HBV DNA was detected in at least 2

HBV genomic regions significantly more often in non-tumor tissue than in tumor

tissue (90% vs 57%, respectively).

CryptogenicHCC patients with occult hepatitis B had lower intrahepatic total

HBV DNA levels than HCC patients with chronic hepatitis B (median 0.010 vs 3.19

copies/cell, respectively).

6 cryptogenic HCC patients (26%) with occult hepatitis B had detectable cccDNA,

at a significantly lower level than chronic hepatitis B patients (median <

0.0002 vs 0.005 copies/cell).

12 cryptogenicHCC patients (52%) had detectable HBV pgRNA, which again was

significantly lower than that of chronic hepatitis B patients (median 0.0001 vs

2.90 copies/cell).

Based on these findings, the study authors concluded that nearly three-quarters

of patients with apparently unidentifiable causes for HCC actually had

HBV-related liver cancer.

" The low intrahepatic HBV DNA and pgRNA levels indicated that persistent viral

replication and possibly HBV integration are the likely causes of HCC " in people

with occult hepatitis B, they suggested.

In an accompanying editorial, Abdirashid Shire and from the Mayo

Clinic in Rochester, MN, reviewed the current state of knowledge about occult

hepatitis B, noting that " [r]ecent studies have suggested that [occult hepatitis

B infection] has substantial clinical relevance and implicate [occult HBV] as an

important risk factor accelerating the progression of liver disease and the

development of cirrhosis and hepatocellular carcinoma. "

They added that [occult hepatitis B] also has clinical relevance for people with

prolonged severe immunosuppression, including transplant recipients, patients

receiving cancer chemotherapy or radiation, and people with HIV/AIDS, as they

may be at risk for reactivation of HBV infection from occult virus due to loss

of immune control.

While Wong's study did find occult hepatitis B in people with unexplained liver

cancer, a previously reported study by Lok and colleagues found no

association between prior HBV exposure or occult hepatitis B infection and

development of HCC among chronic hepatitis C patients in the HALT-C study who

did not achieve sustained response to interferon therapy.

Taken together, the editorial authors wrote, " the results from both studies also

highlight the insensitivity of current highly sensitive methods of serum HBV DNA

testing for the detection of [occult hepatitis B infection] and the importance

of studies of HBV infection and replication in liver tissue samples for

understanding the true prevalence and clinical relevance of [occult hepatitis

B]. "

These investigations, they continued, " will hopefully determine whether OBI is

truly a significant, important risk factor for advanced liver disease and HCC

and what interventions, if any, are needed to mitigate this risk. "

Investigator affiliations: 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;

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

SAR, China.

9/6/11

References

DKH Wong, FY Huang, CL Lai, et al. Occult hepatitis B infection and HBV

replicative activity in patients with cryptogenic cause of hepatocellular

carcinoma. Hepatology 54(3):829-836 (abstract). September 2, 2011.

AM Shire and LR . Occult hepatitis B virus infection: Bit player or role

player? Hepatology 54(3):760-763. September 2, 2011