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Activated liver macrophages are considered to play an important role in the development of liver injuries. Functional differences between activated and normal rat liver macrophages were investigated. In addition, from the therapeutic point of view, the effects of prostaglandin E1, prostaglandin I2 and E3330 ((2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2-nonyl-2-propenoic acid) on the functions of liver macrophages were also determined. Rat liver macrophages were primed by Propionibacterium acnes and activated by a small dose of lipopolysaccharide. Lipopolysaccharide uptake capacity was evaluated quantitatively by flow cytometric analysis. Tumor necrosis factor-alpha activities were measured by bioassay. There were no significant differences in lipopolysaccharide uptake capacity between activated and normal liver macrophages, while activated liver macrophages had a significantly (P < 0.01) higher capacity in the release of tumor necrosis factor-alpha. Prostaglandin E1 and E3330 inhibited tumor necrosis factor-alpha release without suppressing lipopolysaccharide uptake capacity. In this study we have clarified the functional differences between activated and normal liver macrophages. The beneficial effects of prostaglandin E1 and E3330 on the functions of liver macrophages were also demonstrated.

A 56-year-old man was admitted with obstructive jaundice. Abdominal computed tomography and endoscopic retrograde cholangiopancreatography showed circumferential stenosis with irregular wall in lower bile duct, but the cytology of biliary brushing was no malignancy. The patient was given a diagnosis of gastric carcinoma with bone and skin metastasis. He died 2 months after the first hospital admission and autopsy was performed. The histological findings of gastric and bile duct tumor revealed signet ring cell carcinoma. The immunohistological findings of both tumors were identical. We definitively diagnosed this case as metastasis of gastric carcinoma to the bile duct.

Secretin is known to stimulate bile flow from the bile duct epithelium. To investigate the effects of secretin in cholestasis, we studied the response of the bile flow and the excretion of biliary components to secretin using two cholestatic models with or without damage to the bile duct epithelium. The model without bile duct epithelial damage was a choledocho-caval (CC) fistula over a 24-hour period, and the model with bile duct damage was a bile duct ligation over a 48-hour period. Secretin was administered by intravenous infusion for 30 minutes and bile was collected for 120 minutes. Controls were given saline similarly. The bile flow and biliary bicarbonate excretion rate were significantly increased after secretin infusion in the CC fistula rats when compared with the control rats, but no stimulation by secretin was observed in the ligated rats. These data indicate that secretin-induced bile production was enhanced under cholestatic conditions with no bile duct epithelial disturbance.

Secretin is known to stimulate the flow of bicarbonate-rich bile from the bile-duct epithelium, but has no effect on hepatocytes. To investigate the effects of secretin on bile production during intrahepatic cholestasis, we infused secretin into rats with taurocholate-induced cholestasis. Secretin was given at 0.25 and 0.50 units·min −1 ·kg −1 to Wistar rats that simultaneously received a continuous infusion of taurocholic acid at above its maximum hepatic transport capacity to produce cholestasis. When taurocholic acid was infused at doses of 1.4 and 1.6 μ mol·min −1 ·100 g b.w. −1 , bile volume decreased in control rats. In contrast, the simultaneous infusion of secretin significantly increased bile flow and the biliary excretion of bile acids and bicarbonate. The serum taurocholic acid level at the end of the experiment was significantly lower in the secretin-treated groups than in the control group. These findings indicate that secretin prevents taurocholate-induced cholestasis and may enhance the biliary excretion of bile acids.

Using immunohistological methods, we studied the lymphoid follicles in liver biopsy specimens obtained from patients with chronic hepatitis C(CH-C) to determine whether they represented an autoimmune manifestation. In 84 specimens obtained by liver biopsy from 76 patients positive for C-100 antibody, we assessed the presence or absence of lymphoid follicles within the portal areas, and then compared the clinical and immunohistological profiles of the two groups defined on this basis. There were no significant differences in the serological and clinical profiles of the two groups, but the T4:T8 cell ratio within the portal areas differed significantly. A T4:T8 cell ratio > 1.0 was more common in the specimens containing lymphoid follicles. This finding resembled the distribution of T cell subpopulations in the portal areas of patients with autoimmune hepatitis, and suggested that lymphoid follicles may be worth investigating to elucidate the relationship between chronic hepatitis C and autoimmune hepatitis.

This study evaluated whether liver regeneration could take place after massive or submassive necrosis of liver cells in 25 patients with several kinds of hepatic failure by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). PCNA positivity was significantly higher (P less than 0.01) in the patients who survived than in the patients who died. Furthermore, PCNA-positive hepatocytes were recognized diffusely in the lobule of the liver in survivors. There was positive correlation between PCNA positivity and plasma concentration of AFP (alpha-fetoprotein), (r = 0.77, P less than 0.01). These results show that liver regeneration could take place after massive necrosis of liver cells in survivors from acute hepatic failure and that immunohistochemical staining for PCNA is useful for prognostic evaluation.

Many animal experiments have been studied on the choleretic effects of secretin. We intended to estimate secretin choleresis in human (15 patients) who had received PTCD or T-tube insertion into the common bile duct. Based upon these data of secretin and choleresis, secretin was administered to 11 patients with prolonged jaundice due to intrahepatic cholestasis in order to evaluate this as a new therapy for intrahepatic jaundice. As controls, eleven patients with intrahepatic cholestasis treated with steroid hormones and/or phenobarbital were used. In all cases with biliary drainage, secretin produced a remarkable choleretic effect with a high concentration of bicarbonate. In 9 out of 11 patients with intrahepatic cholestasis who were treated with secretin, levels of serum bilirubin decreased linearly and other liver function tests returned to the normal range. The mean values of T1/2 (number of days required for reduction by half) of serum bilirubin in 9 effective cases to secretin was 10.8 days. On the other hand, that in 11 effective cases treated with steroid hormones and/or phenobarbital was 23.2 days. These results suggest that secretin therapy may be an effective treatment for intrahepatic cholestasis.

Forty five patients were examined in order to evaluate the usefulness of glucagon and insulin as a therapy of fulminant hepatitis. Thirty patients were treated with simultaneous infusion of glucagon and insulin, whereas prednisolone was given at a daily dose of 60 to 90 mg in 15 cases. In the former group, 1 mg of glucagon and 10 units of regular insulin were infused over a period of 2 to 6 hours. Two such treatments were given per day in the early critical period of fulminant hepatitis. The therapeutic effect of glucagon and insulin was evaluated in comparison with that of prednisolone, and additionally, with a combination therapy of either blood exchange or plasmapheresis in both groups. The survival rate was superior in the group treated with glucagon and insulin (46%) and in the one with combined infusion of these hormones plus plasmapheresis (33%).