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Extrahepatic hepatitis B virus DNA sequences in patients with acute hepatitis B infection
Author(s) -
Yoffe Boris,
Burns Dennis K.,
Bhatt Harshika S.,
Combes Burton
Publication year - 1990
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840120202
Subject(s) - hepatitis b virus , virology , nucleic acid , virus , hepatitis , biology , hepatitis b virus dna polymerase , hepatitis b , hepatitis c virus , biochemistry
Recent studies have demonstrated the presence of hepadnavirus‐related nucleic acids in extrahepatic tissues in various animal models. The prevalence and biological significance of extrahepatic infection in humans remains undetermined. To characterize the tissue distribution and physical state of extrahepatic hepatitis B virus nucleic acids in acute hepatitis infection, we examined serum, liver and multiple extrahepatic tissues obtained at autopsy from two patients with fulminant hepatitis and one patient with resolving hepatitis who died of an unrelated cause. Southern‐blot hybridization analysis was used to analyze the physical state of hepatitis B virus‐related DNA. Hepatitis B virus‐related RNA sequences were examined by slot‐blotting total RNA extracted from corresponding tissues. Hepatitis B virus nucleic acids were demonstrated in lymph nodes, spleen, gonads, thyroid gland, kidneys, pancreas and adrenal glands. The most intense signal of hybridization was obtained with DNA extracted from lymph nodes. In general, the levels of hepatitis B virus RNA correlated with the amount of viral DNA. Fast‐migrating DNA sequences resembling replicative intermediates and ranging in size from 1 to 3.2 kb were detected in Eco RI digests. Faint high‐molecular‐weight smears suggesting random integration also were observed. Remarkably, little or no hepatitis B virus nucleic acid was detected in the serum or liver. In control specimens obtained from hepatitis B virus carriers, most hybridizable hepatitis B virus nucleic acid was present in liver, but hepatitis B virus DNA was also detected in extrahepatic tissues. Finally, no specific histological changes were observed in extrahepatic tissues harboring hepatitis B virus. These findings demonstrate hepatitis B virus nucleic acids in extrahepatic sites in humans during acute infection and provide new insights into the pathogenesis of fulminant hepatitis. (H EPATOLOGY 1990;12:187–192).