Oxyphilic granular hepatocytes. Mitochondrion-rich liver cells in hepatic disease.

In the course of examining liver biopsy specimens, certain larger than normal liver cells whose cytoplasm is finely granular and strikingly acidophilic have been seen. These cells are called "oxyphilic granular hepatocytes" (oxyphils) because of their similarities to the "oncocytes" of the salivary glands and other endocrine organs. Oxyphilic liver cells can be readily differentiated from acidophilic bodies and groundglass hepatocytes by light and electron microscpy, the latter showing them to be extraordinarily rich in mitochondria. A retrospective study of 214 consecutive liver biopsies was undertaken to determine the prevalence of oxyphilic cells in a variety of liver diseases. Oxyphils were identified in 15% of the biopsy specimens, and were most strongly associated with chronic active hepatitis and cirrhosis in hepatitis B surface antigen (HBsAg)-positive patients. Subsequent reevaluation of 77 biopsy specimens from HBsAg-positive patients showed oxyphils in 28.6%. Their pathogenesis and significance in chronic liver disease are unknown.

Hepatitis B surface antigen and alpha-fetoprotein secreting human primary liver cell cancer in athymic mice.

A human primary liver cancer cell line which retains the property of synthesizing hepatitis B surface antigen has been successfully transplanted into nude (athymic) mice. The morphology of the heterotransplanted tumor is similar to that of a well-differentiated human primary liver cell cancer. It produces hepatitis B surface antigen, but there is no evidence of hepatitis B virion production: Hepatitis B core antigen is not detected in the PLC tissue, and serum is negative for hepatitis B e antigen. The nude mouse exhibits a resistance to the transplantation of the human primary liver cancer cells which can be modified by sublethal total body irradiation, suggesting involvement of an immunologic rejection mechanism. The heterotransplanted primary liver cell cancer also produces alpha-fetoprotein, as did the original tumor in vivo, although this marker was not detected during in vitro cell culture. The serum level of alpha-fetoprotein rises exponentially, enabling quantitative evaluation of tumor growth. The human primary liver cell cancer in nude mice provides an in vivo model for determination of tumor response to chemotherapeutic agents.

Short incubation non-A, non-B hepatitis transmitted by factor VIII concentrates in patients with congenital coagulation disorders.

Ten cases are reported of short incubation (one to four weeks) non-A, non-B hepatitis occurring after infusion of various preparations of factor VIII concentrates into patients with coagulation disorders. Five patients were symptomatic and, in all, serum transaminase levels were increased for at least six months. These cases of chronic hepatitis exhibited none of the features of autoimmune chronic hepatitis: autoantibodies were negative and serum immunoglobulins were normal. Hepatic histology confirmed acute hepatitis in two cases biopsied early in the illness, and chronic active hepatitis (three) of chronic persistent hepatitis (two) in five cases studied later. Lobular inflammation was a prominent feature in all cases. Other features not commonly associated with type A or B hepatitis included fatty change and damaged bile ducts.

Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology.

Twenty-nine patients with primary sclerosing cholangitis were reviewed. Males predominated (2:1). Seventy-six per cent presented with cholestasis and cholangitis, 17% with cirrhosis and portal hypertension, and 7% were asymptomatic, presenting with a raised serum alkaline phosphatase. The serum immunoglobulin IgM concentration was raised in 45% of the patients, but no patient had serum mitochondrial antibody present. Seventy-two per cent had ulcerative proctocolitis. There was no relationship between either duration or severity of ulcerative proctocolitis and the development of primary sclerosing cholangitis. Four patients were not benefited by colectomy. None of the patients ahd Crohn's disease. The prognosis was variable. Corticosteriods and azathioprine were ineffective. Eleven patients (38%) had died with a mean survival time of seven years from diagnosis. Three patients with ulcerative proctocolitis developed bile duct carcinoma. The cholangiograms and liver biopsies were reported without reference to clinical information together with 41 patients with other biliary diseases. Cholangiography was diagnostic in 18/22 (82%). Hepatic histology was diagnostic in 8/22 (36%). Ten showed features of large bile duct disease and three were misdiagnosed as primary biliary cirrhosis. Reduced numbers of bile ducts, ductular proliferation, portal inflammation, and substantial copper deposition, in combination with piecemeal necrosis, are commonly seen in primary sclerosing cholangitis and indicate the need for cholangiography.