Years after infection with hepatitis B virus, chimpanzees may have manifestations of the carrier state as described in man. In addition to serologic evidence for persistent viral infection, percutaneous liver biopsy specimens showed hepatitis B virus surface antigen in the cytoplasm and hepatitis B virus core antigen in the nucleus. Four carrier animals had portal inflammatory reaction as seen in human chronic persistent hepatitis. Viral DNA was demonstrated in nucleic acid extracts of liver biopsy specimens by molecular hybridization to cloned plasmic pA01 containing hepatitis B virus DNA sequences. Although a viral molecule of length greater than the putative virus was identified, it did not appear to represent integration of viral DNA into the host genome. The chimpanzee model may serve as a means to study the mechanism of hepatitis B viral persistence and progression to chronic liver disease.

Animals↗

PubMed1980

[Bidermal hepatoblastoma in an adult (author's transl)].

Hepatoblastomas are more common in childhood but extremely rare in adults. A further case of hepatoblastoma in an adult is reported: The tumor consisted of two components, epithelial and mesenchymal ones. Both were well-separated from each other and showed different ways of metastasizing in to lymphatic vessels and lymph nodes or in to blood vessels and lung, respectively. It is concluded that hepatoblastomas of mixed type originate from two different cell types: The tubular and, sometimes, acinar malignant cells originate from the epithelium of the foregut and the osteo-osteoid-chondromatous malignant component is derived from mesenchymal cell of the coelomic wall.

Aged↗

PubMed1980

Histogenesis of alcoholic fibrosis and cirrhosis in the baboon.

Sequential liver specimens of 18 baboons exposed for up to 6 years to alcohol on a nutritionally adequate diet, as well as those of pair-fed controls, were examined by light microscopy. Whereas control animals failed to develop pathologic changes, in all baboons exposed, ethanol produced initial steatosis and subsequently fibrosis. Emphasis was on the pattern of the fiber accumulations as related to lesions of the hepatocytes. Segmented neutrophilic leukocytes were rarely observed, and the picture of frank alcoholic hepatitis was absent, but diffusely increased mononuclear sinusoidal cells and interstitial clusters of such cells with PAS-positive macrophages were abundant. Fibrosis proceeding to septum formation was associated mainly with large-droplet steatosis. Septum formation was initiated by excess layers of reticulin around steatotic hepatocytes or, more frequently, by linking of fiber accumulations around the clusters of mononuclear cells, in both instances with subsequent deposition of collagen fibers. Both processes were prominent in the centrolobular zone, creating a perivenous net-like fibrosis, but septum formation also started within the lobular parenchyma and eventually linked with the barely altered portal tracts. Fifteen alcohol-fed baboons developed septums, with diffuse septal fibrosis in 5; 4 proceeded to septal cirrhosis and 1 each to micronodular and to mixed micromacronodular cirrhosis. Cirrhosis in the baboons thus develops without the conspicuous polymorphonuclear inflammation characteristic of human alcoholic hepatitis. These observations indicate a pathway to cirrhosis over creeping fibrosis that might play a role also in man, instead of (or supplementing) the one proceeding over alcoholic hepatitis.

Animals↗

PubMed1980

The pathology of viral hepatitis in chimpanzees.

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Animals↗

PubMed1980

Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial.

The effects of azathioprine on the course of primary biliary cirrhosis were studied prospectively in a multinational, double-blind randomized clinical trial involving 236 patients, of which 124 received azathioprine and 112 placebo. No significant effects were seen on survival, clinical course, hepatic histologic features, hepatic tests, or immunologic abnormalities after a median follow-up period of 18 mo, but most of the trends observed were in favor of azathioprine. The results obtained so far indicate that the effect of azathioprine as a single treatment is limited and probably of little clinical importance, but more years of follow-up will be needed to provide a definite conclusion.

Actuarial Analysis↗

PubMed1980

Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients.

A prospective study of the clinical pattern and course of primary biliary cirrhosis based on the data of 236 patients (211 females, 25 males) in an international randomized trial has been performed mainly using life-table technique. The median follow-up period has been 18 mo. After the entry into the study, at which time the median duration of symptoms was 2.1 yr, the estimated 5-yr increase in the cumulative percentage of patients was for pruritus from 75% to 95%, jaundice 59% to 82%, hepatomegaly 54% to 86%, pigmentation 54% to 85%, xanthomas 27% to 50%, GI bleeding 17% to 46%, ascites 7% to 49%, and vertebral collapse 3% to 20%. The frequency of cirrhosis increased from 30% to 82% in 4 yr. The mitochondrial antibody titer showed a high rate of progression with time. In analysis of subgroups, age, histologic stage, and particularly the serum bilirubin level were important prognostic factors. Sex, duration of symptoms, and character of first symptom or sign had no independent prognostic influence. The most important indication of seriously progressive course was rapid development of severe cholestasis independent of the histologic stage.

Adult↗

PubMed1980

The significance of variations in the distribution of copper in liver disease.

Biopsy and autopsy specimens of liver from patients with Wilson's disease in various stages, chronic cholestatic conditions (including primary biliary cirrhosis, extrahepatic biliary obstruction, sclerosing cholangitis, and biliary atresia), chronic active hepatitis, and Indian childhood cirrhosis, as well as normal neonates, were examined by means of histochemical techniques for copper and copper-associated protein. The intracellular localization of copper and the lobular distribution of the metal and its associated protein differed in these conditions. Periportal hepatocytes containing granules (lysosomes) that were reactive for copper and for copper-associated protein were characteristic of cholestasis and neonatal liver. However, in cholestasis extralysosomal copper was often present in the hepatocellular cytoplasm. In contrast, in Wilson's disease, despite very high concentrations of copper in the early stages, the metal was diffuse in the cytoplasm, and the histochemical reactions for granular copper and its associated protein were usually negative. Therefore, a failure to stain for copper does not exclude the diagnosis of Wilson's disease. In the late stages of Wilson's disease staining varied in different nodules. In Indian childhood cirrhosis copper was present throughout the parenchyma, with periportal predominance. Differences in the distribution of copper and the cellular changes associated with its deposition suggest that different pathogenetic mechanisms and possibly different intracellular targets are susceptible to the toxic effects of the metal. For diagnosis, staining for copper and for copper-associated protein may assist in the differentiation of primary biliary cirrhosis from chronic active hepatitis.

Adolescent↗

PubMed1980

["Fatty neck." Symmetrical lipomatosis with Madelung's symptom (author's transl)].

The relatively rare disease of symmetrical lipomatosis is described on the basic of six own observations. For many years five patients worked with asphalt and one was a coal-miner. Because of this professional exposition oil and cole products are considered to be reason for this disease. The still unknown aetiology and pathogenesis are discussed and finally the surgical therapy is presented.

Head and Neck Neoplasms↗

PubMed1979

Hepatic angiosarcoma associated with androgenic-anabolic steroids.

A retrospective epidemiological study of deaths from hepatic angiosarcoma (HAS) in the U.S. showed that during 1964--74 there were 168 such cases, of which 37 (22%) were associated with previously known causes (vinyl chloride, 'Thorotrast', and inorganic arsenic) and 4 (3.1%) of the remaining 131 cases with the use of androgenic-anabolic steroids. It is suggested that the long-term use of androgenic-anabolic steroids is the fourth cause of HAS, the majority of cases still being of unknown aetiology. Moreover, the presented cases serve as a link in a spectrum of hepatic disorders recently recognised to be caused by environmental agents such as vinyl chloride, arsenic, and thorotrast, and by contraceptive and anabolic steroids. Similar precursor stages, usually not recognised by clinical laboratory tests and consisting of areas of hyperplasia of hepatocytes and sinusoidal cells and sinusoidal dilatation, lead potentially to hepatic adenoma, carcinoma, peliosis, and angiosarcoma.

Androstanes↗

PubMed1979

Cytoplasmic copper and its toxic effects. Studies in Indian childhood cirrhosis.

Morphological, histochemical, and chemical study of three necropsy specimens of liver in the terminal stage of Indian Childhood Cirrhosis revealed a strikingly high copper content. it is proposed that excess accumulation of copper in the cytoplasm of hepatocytes disturbs the microtubular system, causing hydropic swelling and the formation of Mallory's hyalin. Copper and copper-binding protein showed topographical association with Mallory's hyalin. Diffuse cytoplasmic staining and the lysosomal copper distribution also suggested that copper had a cytotoxic effect. The pattern of copper distribution in Indian Childhood Cirrhosis differs from that in Wilson's disease and in prolonged cholestasis with excessive hepatic copper deposition, indicating a different mechanism of the copper accumulation.

Child, Preschool↗

PubMed1979

Hepatic cancers in man: quantitative perspectives.

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Adenoma, Bile Duct↗

PubMed1979

Injury and repair of liver cells.

Alterations in hepatocytes, progressing to necrosis, are the morphologic basis for the main clinical manifestations and aberrations in hepatic test results in acute and chronic liver disease. The light-microscopic manifestations of hepatocellular injury, the mechanisms of necrosis, the light-microscopic features of repair and regeneration, and the applications of histologic alterations to the management and prognosis of liver disease are reviewed.

Biopsy↗

PubMed1979

Environmental liver tumors.

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Animals↗

PubMed1979

Veno-occlusive disease of the liver after allogeneic bone marrow transplantation: possible association with graft-versus-host disease.

Acute veno-occlusive disease of the liver developed in seven of 29 patients undergoing bone marrow transplantation for treatment of leukemia, aplastic anemia, or disseminated carcinomatosis. All seven died despite successful marrow engraftment. Hepatic failure was the principal cause of death in four and contributory in three. The veno-occlusive disease did not relate to the nature of the pretransplant immunosuppressive regimen, since it occurred in patients receiving irradiation alone, chemotherapy alone, or both. Twenty-two of the patients were autopsied. Among these, the lesion was found in seven of 11 in whom a graft-versus-host reaction developed but in none of the 11 without such a reaction who had received similar pretransplant immunosuppression (P less than 0.025). Hence, acute veno-occlusive disease of the liver appears to be a complication of allogeneic bone marrow transplantation related to the development of a graft-versus-host reaction.

Acute Disease↗