We assessed the presence of hepatitis B virus (HBV) DNA in liver or serum samples from 134 patients with hepatitis B surface antigen (HBsAg)-negative chronic liver disease, including 20 with hepatocellular carcinoma. HBV DNA sequences were detected in 52 of the 88 liver samples (59 per cent), including 17 of the 20 samples from patients with hepatocellular carcinoma. Presumably "replicative forms" of HBV DNA were detected in only 5 of the 88 liver samples, 3 of which were from patients with no serologic marker for HBV. In most of the liver samples the DNA patterns were consistent with the presence of HBV or a closely related virus. Of the 105 serum samples tested, HBV DNA sequences were identified in 10 (9.5 per cent), 6 of which had no HBV serologic marker. Moreover, HBsAg-associated determinants were detected in 5 of 17 patients who were positive for HBV DNA and in none of 14 patients who were negative. This study demonstrates the high frequency of HBsAg-negative HBV DNA-positive viral infection of the liver and suggests that multiplication of HBV may occur in the absence of any conventional serologic marker for HBV.

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...

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.

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