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Summary   Background  A human betaretrovirus (HBRV) has been linked with primary biliary cirrhosis ( PBC ) following the detection of viral particles in biliary epithelium by electron microscopy and cloning of the betaretrovirus genome from biliary epithelium and peri‐hepatic lymph nodes. Evidence for viral infection was found in the majority of  PBC  patients' peri‐hepatic lymph node samples. However, less than a third of the liver samples had detectable HBRV, whereas others were unable to detect betaretrovirus infection or noted the presence of virus in the liver of patients with other diagnoses.    Aims  To address the hypothesis that the betaretrovirus may be below the limits of detection in the liver, biliary epithelial cells (BEC) were investigated for the evidence of infection.    Methods  Ligation‐mediated  PCR  and next generation sequencing were used to detect proviral integrations in liver, lymph nodes and BEC isolated from liver transplant recipients. Hybridisation‐based assays were used to detect betaretroviral  RNA  in BEC.    Results  Unique HBRV integrations and betaretrovirus  RNA  were detected in the majority of biliary epithelia derived from patients with  PBC , autoimmune hepatitis and cryptogenic liver disease but rarely in other liver transplant recipients with primary sclerosing cholangitis and other hepatic disorders. HBRV integrations were commonly found in  PBC  patients' lymph nodes but rarely in whole liver samples.    Conclusions  Human betaretrovirus infection is frequently observed at the site of disease in patients with  primary biliary cirrhosis  and also in biliary epithelium of patients with autoimmune hepatitis and cryptogenic liver disease.

Frequent proviral integration of the human betaretrovirus in biliary epithelium of patients with autoimmune and idiopathic liver disease