Occult hepatitis B virus infection and its clinical implications

-Background -The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. Aims -To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. Methods -The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). Results -Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. Conclusion -Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confi rm that co-infection could determine a worse progress of chronic liver disease in this population.

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“…This fi nding is in agreement with other studies (7,20,30,31) demonstrating that HBsAg is more sensitive than HBcAg in liver tissue.…”

Section: Discussionsupporting

confidence: 93%

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

Branco

Mattos

Coral

et al. 2007

Arq. Gastroenterol.

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“…Hepatitis B virus infection determined by the detection of the virus by HBV DNA PCR but not by the current and otherwise sensitive immunoassays for HBsAg is defined as occult HBV infection (Hu, 2002;Torbenson and Thomas, 2002). Occult HBV infection has been found among people affected by liver disease in various parts of the world (Brechot et al, 2001;Hu, 2002;Torbenson and Thomas, 2002), and in a high proportion of subjects with cryptogenic chronic liver disease in one study (Chan et al, 2002).…”

Section: Occult Hepatitis B Virus Infectionmentioning

confidence: 99%

“…Occult HBV infection has been found among people affected by liver disease in various parts of the world (Brechot et al, 2001;Hu, 2002;Torbenson and Thomas, 2002), and in a high proportion of subjects with cryptogenic chronic liver disease in one study (Chan et al, 2002). Possible explanations for the seronegativity include mutations in the immunodominant loop of HBV surface antigen altering HBsAg antigenicity or strong suppression of viral replication and gene expression that can also involve wild-type strains.…”

Section: Occult Hepatitis B Virus Infectionmentioning

confidence: 99%

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

et al. 2006

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Hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol consumption are major causes of hepatocellular carcinoma (HCC) worldwide. We performed a systematic review of epidemiologic studies carried out on HCC aetiology in Southern Europe, an area with an intermediatehigh prevalence of these agents as well as of putative risk factors such as tobacco smoking, diabetes and obesity. To retrieve the articles, we performed a Medline search for titles and abstracts of articles. After the Medline search, we reviewed the papers and reference lists to identify additional articles. A synergism between HCV infection and HBV infection, overt (hepatitis B virus antigen (HbsAg) positivity) or occult (HBsAg negativity with presence of HBV DNA in liver or serum), is suggested by the results of some studies. The pattern of the risk for HCC due to alcohol intake shows a continuous dose-effect curve without a definite threshold, although most studies found that HCC risk increased only for alcohol consumption above 40-60 g of ethanol per day. Some evidence supports a positive interaction of alcohol intake probably with HCV infection and possibly with HBV infection. A few studies found that coffee has a protective effect on HCC risk due to various risk factors. Some data also support a role of tobacco smoking, diabetes and obesity as single agents or preferably cofactors in causing HCC. In countries with a relatively high alcohol consumption and intermediate levels of HCV and HBV infections (1-3% of population infected by each virus), such as Mediterranean countries, the three main risk factors together account for about 85% of the total HCC cases, leaving little space to other known risk factors, such as haemochromatosis, and to new, still unrecognised, factors as independent causes of HCC.

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“…[18][19][20][21] However, the results of these studies have been inconsistent, and some show that most occult HBV are caused by wild-type strains. 7,8,22 Further case control studies are needed to investigate pre-S and surface gene mutations to clarify the absence of detectable HBsAg.To elucidate these issues, this case control study investigated the clinical significance and prevalence of occult HBV infection in HCC patients without HBsAg or anti-hepatitis C virus (anti-HCV) (i.e. non-B non-C) in Taiwan.…”

mentioning

confidence: 99%

A study on sequence variations in pre‐S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non‐B, non‐C hepatocellular carcinoma patients in Taiwan

Chen

Changchien

Lee

et al. 2009

Intl Journal of Cancer

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This study was to investigate the clinical significance and virologic factors of occult hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) patients without hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (non-B, non-C) in Taiwan. Serum HBV DNA (occult HBV) was detected in 90 of 222 non-B, non-C HCC patients and 24 of 300 non-B, non-C controls without HCC. Of 90 occult HBV-infected HCC patients, the sequences of HBV pre-S/surface, X and enhancer II/core promoter/precore genes were analyzed from 40 patients. Direct sequencing of such genes was also performed in 24 non-B, non-C controls without HCC and 40 HBsAg-positive HCC controls. Compared with non-B, non-C controls without HCC, non-B, non-C subjects with HCC had significantly higher prevalence of occult HBV (p < 0.0001). Moreover, M1I and Q2K in pre-S2 gene and G1721A were more common in occult HBV-infected patients with HCC than in those without HCC. Compared with the HBsAg-positive HCC controls, occult HBV-infected HCC patients had higher frequencies of M1I and Q2K in pre-S2 gene, G185R and S210N in surface gene, A36T and A44L in X gene, and G1721A in enhancer II gene, and had lower rates of pre-S deletions and A1762T/G1764A, A1846T, G1896A and G1899A in core promoter/precore genes. Multivariate analysis showed Q2K in pre-S2 gene, G1721A and A1846T were independent factors for occult HBV-infected HCC. Our study suggested that the virological factors of HBV related to HCC were different between occult HBV-infected and HBsAgpositive patients. The G1721A, M1I and Q2K in pre-S2 gene may be useful viral markers for HCC in occult HBV carriers. ' UICCKey words: hepatitis B virus; occult hepatitis B virus; hepatocellular carcinoma; precore mutation; core promoter mutation Hepatitis B virus (HBV) infection is a major health problem associated with 1 million deaths annually worldwide. 1 A wide range of clinical manifestations has been established for chronic HBV infection from asymptomatic carriers to severe chronic liver disease, including those with cirrhosis and hepatocellular carcinoma (HCC). 2-4 Chronic HBV infection is characterized by persistent hepatitis B surface antigen (HBsAg) and viremia. 1,2 Early studies revealed that the clearance of HBsAg in HBV patients is associated with undetectable serum HBV DNA and disease remission. However, accumulating data indicate that a low level of HBV DNA remains detectable in serum and liver tissues in some patients cleared of HBsAg from either acute self-limited or chronic HBV infection. Occult HBV infection was detected even among family members of HBV carriers. 5 This so-called occult HBV infection has been identified by sensitive polymerase chain reaction (PCR) assays that detect low levels of HBV DNA in serum and/or liver tissue of HBsAg-negative subjects. [6][7][8] Since the early 1980s, several studies have reported the detection of HBV DNA in both tumorous and non-tumorous liver tissue of HBsAg-negative HCC patients. 9,10 However, whether occult HBV infection also contributes to the...

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Occult hepatitis B virus infection and its clinical implications

Cited by 289 publications

References 157 publications

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

A study on sequence variations in pre‐S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non‐B, non‐C hepatocellular carcinoma patients in Taiwan

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