Polymerase Chain Reaction to Detect Hepatitis B Virus DNA and RNA Sequences in Primary Liver Cancers from Patients Negative for Hepatitis B Surface Antigen

Paterlini, P.; Gerken, Guido; Nakajima, Etsuro; Terre, S.; d’Errico, Angelo; Grigioni, Francesco; Nalpas, Bertrand; Franco, Dominique; Wands, Jack R.; Kew, Michael C.; Pisi, E; Tiollais, Pierre; Bréchot, Christian

doi:10.1056/nejm199007123230202

Cited by 246 publications

(111 citation statements)

References 43 publications

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“…HBV-DNA may have been inserted into cellular DNA at an earlier stage, when the X gene or a truncated preS/S gene may have been responsible for initiating tumorigenesis (Galloway and McDougall, 1983;Kim et al, 1991). (2) Chronic HBV infection cannot be excluded in HBsAgnegative patients positive for anti-HBc, because it has been reported that HBV-DNA can be detected in their liver tissue and serum (Galloway and McDougall, 1983;Brechot et al, 1985;Paterlini et al, 1990;Sheu et al, 1992). Further studies focusing on the analysis of HBV-DNA in the liver and serum are needed to clarify this point.…”

Section: Discussionmentioning

confidence: 99%

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Okada

Sato²,

Okusaka

et al. 1998

Br J Cancer

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Summary The aim of the study was to determine whether past exposure to hepatitis B virus (HBV) influences the risk of the development of hepatocellular carcinoma (HCC) in Japanese patients with chronic liver disease (CLD). We conducted a hospital-based case-control study of 141 HCC patients with CLD and 151 controls with CLD but without HCC. Past exposure to HBV was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity. Ninety-two patients (65%) with HCC were anti-HBc positive compared with 65 patients (43%) with CLD alone (P < 0.01). A multivariate analysis using logistic regression modelling revealed that anti-HBc positivity significantly increased the rsk of the development of HCC [odds ratio (OR) 2.0, P= 0.01]. In the anti-HBc-positive patients, a significantly increased risk of HCC was seen among the patients positive for anti-HBc alone (OR, 2.6; P < 0.01). However, a significant OR was not obtained among the patients with a transient HBV infection implied by positivity for both antibody to hepatitis B surface antigen and anti-HBc (OR, 1.5; P = 0.48). These results indicate that past exposure to HBV is a risk factor for HCC in Japanese CLD patients, especially when they have no serological evidence of immunity to HBV.Keywords: hepatocellular carcinoma; chronic liver disease; hepatitis B virus; hepatitis C virus; case-control study In Japan, the vast majority of patients with hepatocellular carcinoma (HCC) have chronic liver disease (CLD) such as chronic hepatitis and liver cirrhosis, and CLD patients frequently develop HCC during the follow-up period; patients with CLD are at increased risk of developing HCC (Ikeda et al, 1993;Tsukuma et al, 1993). Many CLD patients are, therefore, followed up periodically using ultrasonography (US) and serum a-fetoprotein (AFP) measurements to detect HCC at an early stage (Tanaka et al, 1990). Evaluation of the risk factors for HCC in CLD patients is imperative. Identification of the individuals who are at higher risk of HCC would contribute to the early diagnosis of this disease and to effective implementation of strategies for chemoprevention.Numerous epidemiological and biological studies have indicated that a chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) plays an important role in hepatocarcinogenesis (Bruix et al, 1989;Saito et al, 1990;Kim et al, 1991). As for HBV, serum hepatitis B surface antigen (HBsAg) positivity, which indicates a chronic HBV carrier state, is a well-established risk factor for HCC (Beasley et al, 1981;Chen et al, 1991). However, only a few reports have addressed the relationship between past exposure to HBV and HCC and, as yet, no definite conclusion has been established (Chiba et al, 1996;Yu et al, 1997).This hospital-based case-control study was conducted to evaluate whether past exposure to HBV, which was assessed by antibody to hepatitis B core antigen (anti-HBc) positivity, influenced the risk of developing HCC in Japanese CLD patients. Study populationThe HCC patient group comprised 141 co...

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Section: Discussionmentioning

confidence: 99%

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Okada

Sato²,

Okusaka

et al. 1998

Br J Cancer

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“…Occult HBV infection has received much attention recently, since it has been detected in patients with hepatocarcinoma [18], in blood donors and transfused patients [19,20], and in patients infected with hepatitis C virus [21][22][23]. In chronic HCV patients on hemodialysis, the prevalence of occult HBV infection is not yet well known [22,24].…”

Section: Discussionmentioning

confidence: 99%

Occult hepatitis B virus infection in immunocompromised patients

Jardim¹,

Gonçales²,

Pereira³

et al. 2008

Braz J Infect Dis

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Occult hepatitis B infection is characterized by hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). We assessed occult HBV infection prevalence in two groups of immunocompromised patients (maintenance hemodialysis patients and HIV-positive patients) presenting HBsAgnegative and anti-HBc positive serological patterns, co-infected or not by HCV. Thirty-four hemodialysis anti-HIV negative patients, 159 HIV-positive patients and 150 blood donors who were anti-HBc positive (control group) were selected. HBV-DNA was detected by nested-PCR. Occult hepatitis B infection was not observed in the hemodialysis patients group but was found in 5% of the HIV-patients and in 4% of the blood donors. Immunosuppression in HIV positive patients was not a determining factor for occult HBV infection. In addition, no significant relationship between HBV-DNA and HCV co-infection in the HIV-positive patient group was found. A lack of significant associations was also observed between positivity for HBV-DNA and CD4 count, viral load and previous lamivudine treatment in these HIV-positive patients.

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“…The explanation for this fi nding may be in the fact that patients with occult B infection would be infected with low levels of viral particles incapable of stimulating the immune system to form its antibodies (28) , or that, following acute infection patients present a progressive decline of these markers until their becoming undetectable in the serum (35) . Another hypothesis is the existence of mutating HBV strains which do not express neither antigens nor antibodies in the blood of this population of patients (18,32) .…”

Section: Discussionmentioning

confidence: 99%

“…Identifi cation of the HBV genome has been reported in liver tumors of patients who are HCV-positive and HBsAg-negative in the serum (32,34,37,38) . The rate of occult infection in HCV-positive patients with HCC can be as high as 76% (24) .…”

Section: Introductionmentioning

confidence: 99%

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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-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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Polymerase Chain Reaction to Detect Hepatitis B Virus DNA and RNA Sequences in Primary Liver Cancers from Patients Negative for Hepatitis B Surface Antigen

Cited by 246 publications

References 43 publications

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Occult hepatitis B virus infection in immunocompromised patients

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

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