Non-A, non-B hepatitis: characterization of liver biopsy pathology.

We reviewed 40 liver biopsy specimens from 36 patients with non-A, non-B (NANB) hepatitis by light microscopy to characterize the histopathologic features associated with this condition. NANB hepatitis had been acquired from intravenous drug use (6 patients), transfusion (11 patients), sporadic (13 patients), and other routes (6 patients). The major pathologic diagnoses included acute hepatitis, chronic persistent hepatitis, chronic lobular hepatitis, chronic active hepatitis with or without cirrhosis, and hepatocellular carcinoma. Histopathologic changes seen in varied combinations in these specimens included acidophilic degeneration of hepatocytes (100%), fat (85%), formation of portal tract lymphoid aggregates or follicles (52%), bile duct damage (30%), and multinucleate giant hepatocytes (25%). Prominence of sinusoidal cells was variable, but often striking. Hepatocyte atypia (liver cell dysplasia) was noted in 17 specimens. These histologic parameters appear to be diagnostically useful when applied in appropriate clinical settings and will require reevaluation when serologic tests for NANB hepatitis become available.

Apolipoprotein A-IV synthesis in rat intestine: regulation by dietary triglyceride.

Apolipoprotein A-IV (apoA-IV) synthesis rates were measured in vivo in rat enterocytes by immunoprecipitation after administration of [3H]leucine into in situ loops of jejunum and ileum. Basal apoA-IV synthesis rates (percent total protein synthesis) were significantly higher in jejunal enterocytes (2.05 +/- 0.54%) compared with ileal enterocytes (0.48 +/- 0.32%) from the same fasted animals. After an acute triglyceride bolus, significant and sustained elevations of apoA-IV synthesis rates were seen in both jejunal and ileal enterocytes with maximal effects noted at 4-6 h. Animals fed diets containing 30% wt/wt triglyceride as saturated (SF) or polyunsaturated (UF) fats for 6 wk had similarly increased rates of apoA-IV synthesis in jejunal enterocytes with both SF (3.73 +/- 0.83%) and UF (3.33 +/- 0.64%) but no change in ileal enterocytes. By contrast, animals consuming a fat-free diet for 3 wk had jejunal apoA-IV synthesis rates indistinguishable from basal values (2.40 +/- 0.45%). Translatable intestinal mRNA levels for pre-apoA-IV after triglyceride increased in parallel to synthesis rates with a 50% increase in jejunum and a 350% increase in ileum observed at 4-6 h. These results suggest that apoA-IV synthesis by rat small intestine increases in response to acute and chronic dietary triglyceride, is maintained in the absence of dietary triglyceride, and may be under pretranslational control.

Liver cell dysplasia and hepatocellular carcinoma in non-A, non-B hepatitis.

Liver cell dysplasia (LCD) is a premalignant cytologic change of hepatocytes that has been statistically linked to cirrhosis, hepatocellular carcinoma (HCC), and chronic liver disease related to hepatitis B virus. The relationship of LCD to non-A, non-B (NANB) hepatitis is currently unknown. We studied liver biopsy and surgical resection specimens from 36 patients with NANB hepatitis, and identified LCD in 17 (42.5%) of 40 specimens, most often associated with cirrhosis. Dysplasia was present in individual hepatocytes, in clusters, and in a distinctive "spreading" pattern of hepatocytes about central veins. Three patients had HCC with a predominant giant cell pattern, as well as LCD. These findings suggest that LCD and HCC should be included among the potential pathologic sequelae of NANB hepatitis.

Acute liver biopsy lesions in early autoimmune ("lupoid") chronic active hepatitis.

We studied two female patients with autoimmune ("lupoid") chronic active hepatitis whose liver biopsies at initial presentation showed the unusual features of an acute hepatitis. Centrilobular hepatocyte swelling and multinucleation, acidophilic degeneration, cholestasis, mild fatty change and bile duct damage in one case resembled lesions of non-A, non-B hepatitis. Lobular and portal infiltrates of plasma cells with piecemeal necrosis suggested transition to chronicity as well as an autoimmune component. This was additionally supported by the presence of hypergammaglobulinemia and auto-antibodies in both patients. We conclude that liver biopsy features in the acute presentation of lupoid hepatitis may be difficult to distinguish from those seen in acute hepatitis due to virus or drugs.