title: Hepatitis B virus DNA integration in tumour tissue of a non-cirrhotic HFE-haemochromatosis patient with hepatocellular carcinoma.
abstract: Co-existence of multiple causes of liver injury increases the risk of hepatocellular carcinoma (HCC) development. HCC usually develops in patients with cirrhosis although it may also occur in individuals with no or mild liver disease, in particular in cases with hepatitis B virus (HBV) infection. Here we report the case of a 43year-old man with HFE-haemochromatosis, seronegative for hepatitis B and C infections, who developed HCC in the absence of severe liver damage. Both tumoural and non-tumoural liver DNA extracts were tested by nested-PCR and primers specific for four different HBV genomic regions in order to evaluate the presence of occult HBV infection. Only X gene sequences were detected in tumour (but not in non-tumour) DNA extracts. HBV-Alu PCR showed a HBV integration involving a 5'-deleted X gene with an intact enhancer-II/basal-core promoter region. The viral-host junction sequencing revealed that this integrant was located upstream of the partitioning-defective-6-homolog-gamma gene (PARD6G) and real time-PCR quantification demonstrated that PARD6G was overexpressed in tumour compared to non-tumour liver tissues. In conclusion, the combination of HFE-haemochromatosis and occult HBV infection in this patient might have led to a sequel of cellular events that determined the development of HCC even in the absence of cirrhosis.
authors.affiliation: Division of Clinical and Molecular Hepatology, University Hospital of Messina, Italy. tpollicino@unime.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Pollicino
authors.forename: Alberto
authors.initials: A
authors.lastname: Vegetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Saitta
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrara
authors.forename: Elena
authors.initials: E
authors.lastname: Corradini
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Raffa
authors.forename: Antonello
authors.initials: A
authors.lastname: Pietrangelo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Raimondo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics / Q000821:virology*; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology*; D008297:Male; D016662:Virus Integration / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004279:DNA, Viral; C499657:PARD6A protein, human