Detection of Hepatitis B Virus DNA in Pancreas, Kidney and Skin of Two Human Carriers of the Virus

Abstract

SUMMARYUsing the Southern blot technique, we have analysed the presence and state of hepatitis B virus (HBV) DNA in non-hepatic tissue from two human HBV carriers. HBV DNA sequences were detected in the pancreas, kidney and skin, demonstrating HBV infection of these organs. Moreover, the restriction DNA patterns were consistent with the integration of these viral sequences into high molecular weight DNA. These results demonstrate that HBV infection is not restricted to the liver.Hepatitis B virus (HBV) infects only humans and chimpanzees and is considered to be strictly hepatotropic. In the liver of chronic HBV carriers with or without hepatocellular carcinoma (HCC), integrated HBV DNA sequences have been observed (Br6chot et al., 1981 a;Shafritz et al., 1981; Chert et al., 1982). The restriction enzyme patterns obtained from cellular DNA showed the presence of delineated HBV-specific bands. HBV DNA is therefore a new marker in the study of the relationship between the viral infection and chronic liver diseases. Recent studies have demonstrated the presence of the hepatitis B surface antigen (HBsAg) in pancreatic secretions during pancreatic stimulation (Hoefs et al., 1980) and both the HBsAg and the hepatitis B core antigen (HBcAg) in the cytoplasm of pancreatic acinar cells (Shimoda et al., 1981). It was therefore of interest to investigate the possibility of HBV infection in non-hepatic tissues. For this purpose we have used the Southern blot technique (Southern, 1975;Wahl et al., 1979) with cloned viral DNA (Charnay et al., 1979) as a probe to detect HBV sequences in the DNA of various organs.Tissue samples were obtained at autopsy from two patients. Patient A was an 80 year old woman who died of cirrhosis with HCC. HBsAg, antibodies against the core antigen (anti-HBc) and the e antigen (anti-HBe) were present in her serum. The hepatitis e antigen (HBeAg) was not detected. Histological examination showed a normal pancreas and kidney without metastasis; of the liver only tumorous tissue was available. Patient B was a 67 year old man who died 5 months after the onset of a severe protracted acute hepatitis with massive renal failure due to glomerulonephritis. The acute hepatitis had occurred 2 months after blood transfusion during total pancreatectomy for a pancreatic adenocarcinoma. HBsAg, HBeAg and anti-HBc were present in the serum. A small pancreatic metastasis in the liver was carefully separated from the non-tumorous liver (as checked by histological examination). The kidney histology showed a membranous glomerulonephritis. HBsAg and HBcAg were detected in the tissues by an indirect immunoperoxidase technique using a murine monoclonal anti-HBs and human anti-HBc antibodies (Sternberger, 1979). Cellular DNAs extracted from various organs of the two patients were digested with either EcoRI, which cleaved most HBV genomes once, or HmdIII, which does not cut any of the HBV genomes so far analysed (Wain-Hobson et al., 1982). For patient A (HBsAg-positive, HBeAgnegative in the serum) the EcoRI fragment hybridiz...

ABO blood group, hepatitis B viral infection and risk of pancreatic cancer

“…There are some studies indicating that HBV antigens and viral DNA can be detected in pancreatic tissue, demonstrating HBV infection of these organs. 18,33,34 Replicative forms of HBV nucleic acids were identified in the pancreas in patients with acute HBV infection. 35,36 HBsAg was detected in pure pancreatic juice and bile in patients with acute and chronic HBV infection.…”

“…Findings from previous study indicated that HBV DNA sequences were detected in the pancreas, kidney and skin, demonstrating HBV infection of these organs. 18 Anatomically, liver and pancreas share common ducts and blood vessels may make the pancreas another potential target organ for infection with HBV. Nevertheless, epidemiological data investigating the relationship between infection with HBV and pancreatic cancer have shown inconsistent results so far.…”

A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus.

“…Replication of the viral genome and production of the 42-nm virion in infected liver tissues are frequently observed. However, the viral DNA and proteins have also been detected in many other tissues, including kidney, spleen, pancreas, bone marrow, and circulating blood cells (16,31,41,45). Furthermore, viral genes, including both the surface and the core genes, can be expressed in cultured systems of heterologous tissue type (18,46,49).…”

Chronic Hepatitis B Virus Infection and Risk of Pancreatic Cancer: A Meta-analysis

“…Several studies find that hepatitis B virus can replicate in human pancreatic tissue and that patients with hepatitis B infection have impairments of pancreatic function (Hoefs et al, 1980;Yoshimura et al, 1981;Dejean et al, 1984;Katakura et al, 2005). Also, some cohort and case-control studies (de Gonzalez et al, Lei Li 1,3 , Bo Wu 2 , Li-Bo Yang 3 , Guan-Cheng Yin 3 , Ji-Yong Liu 1 * 2008; Hassan et al, 2008;Iloeje et al, 2009;Gordon et al, 2009;Hong et al, 2010;Zhu et al, 2011;Wang et al, 2012;Ben et al, 2012) have been conducted to estimate the relationship between chronic hepatitis B virus infection and pancreatic cancer.…”