Yasushi Hasumura

Budd-Chiari syndrome associated with obstruction of the inferior vena cava: A report of seven cases

Abstract Seven patients with the Budd-Chiari syndrome associated with obstruction of the inferior vena cava are described. Six of these showed membranous obstruction. In these patients elevation of venous pressure in the lower limbs, abnormal bromsulfalein tests with minor changes in the other liver function tests, hepatomegaly and insidious onset of symptoms were the common features. Edema of the legs, ascites and dilation of the superficial veins were also found in most cases, but abdominal pain and jaundice were rarely observed. Duration from initial symptoms to admission was relatively long (one to seventeen years). Transcardiac membranotomy was successfully carried out in two cases in which the right hepatic vein was patent. After membranotomy, the signs of Budd-Chiari syndrome disappeared. Our observations indicate a poor prognosis in patients with occlusion of many hepatic veins and suggest the necessity of surgical treatment as soon as possible to prevent secondary obstruction of the patent hepatic veins by thrombi. The diagnosis of obstruction of the inferior vena cava is easy when venography is carried out. However, membranous obstruction was disclosed only by catheterization through both the femoral and antecubital routes, i.e., from above and below. Proteinuria is a clue to the presence of this syndrome at a very early stage. Estimation of venous pressures in the arm and leg, and liver biopsy, are also helpful in making the diagnosis.

A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.

SummaryA multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA - treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebotreated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentation showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.

Transcatheter arterial embolization of ruptured hepatocellular carcinoma associated with liver cirrhosis

Four cases of hepatocellular carcinoma treated by transcatheter arterial embolization have been reported. In three patients, the bleeding stopped completely after the procedure. Embolized tumor appeared to be necrotized in two cases. Transcatheter arterial embolization should be considered the treatment of choice for the emergency therapy of ruptured hepatocellular carcinoma.

Evaluation of hepatic fibrosis by serum proline and amino-terminal type III procollagen peptide levels in alcoholic patients

In patients with alcoholic liver disease, serum proline and amino-terminal type III procollagen peptide levels were evaluated as a marker of hepatic fibrosis. Thirty-one patients with alcoholic liver disease (2 with nonspecific change, 3 with alcoholic hepatitis, 17 with hepatic fibrosis without cirrhosis, and 9 with cirrhosis) and 15 controls were investigated. Hepatic fibrosis was estimated in each liver biopsy specimen by morphometric analysis, and the ratio of fibrotic change to total area (AREA-F) was calculated by morphometric analysis. In patients with hepatic fibrosis, serum proline levels and routine liver function tests were not significantly correlated to AREA-F value, while serum peptide levels showed a significant positive correlation to AREA-F value (r=0.733,P<0.001). These results suggest that the determination of serum amino-terminal type III procollagen peptide level may serve as a good marker for the diagnosis of liver fibrosis in the alcoholic.

Increased hepatotoxicity of acetaminophen by concomitant administration of caffeine in the rat

Since caffeine is frequently co-administered with acetaminophen, it is of clinical interest to study the effect of caffeine on the hepatotoxicity of acetaminophen. In male Sprague-Dawley rats fasted for 18 h, concomitant administration of caffeine (0.1 g/kg, i.p.) as judged by increased serum enzyme activities and increased incidence of hepatic necrosis. Careful observations on hepatotoxicity are suggested when acetaminophen is prescribed with caffeine.

Prostaglandin E-producing hepatocellular carcinoma with hypercalcemia

An autopsy case of prostaglandin E‐producing hepatocellular carcinoma with hypercalcemia is presented in this article. A 72‐year‐old man showed high serum calcium levels (14.2 to 17.3 mg/100 ml) and hypophosphatemia. The plasma level of immunoreactive parathyroid hormone was below the normal range. Administration of oral indomethacin 50 mg daily was effective in decreasing the serum calcium concentration. However, this effect lasted only 5 days, after which it returned to pretreatment levels. The patient died in a hypercalcemic coma. By an autopsy, hepatocellular carcinoma was found in the right lobe of the liver. However, no obvious bone metastases nor abnormalities in the parathyroid glands were detected. The immunoreactive prostaglandin E level assayed in the neoplastic tissue (2278 ng/g) was significantly high when compared with level in the nonneoplastic liver tissue (194 ng/g). The production of prostaglandin E by the tumor itself appears to be the most likely mechanism for the hypercalcemia in this patient.

Interaction of Ethanol with Drugs and Xenobiotics

Interaction of ethanol with drugs and xenobiotics has drawn much attention in clinical medicine. It is well known that alcoholic patients are tolerant to a variety of drugs, whereas they are susceptible to various hepatotoxins. Furthermore, in the presence of ethanol, drug action has been shown to be potentiated. However, the mechanisms of the observed effects of ethanol were not well understood until Lieber and his colleagues first showed that ethanol is metabolized not only via an alcohol dehydrogenase (ADH)-dependent pathway but also via a cytochrome-P-450-mediated pathway which is now known as the “microsomal ethanol-oxidizing system” (MEOS).

Differences of liver membrane antibody frequency in alcoholic liver disease: detection of IgG and IgA classes using radioimmunoassay

The presence of liver membrane antibody in IgG and IgA was investigated by radioimmunoassay using isolated rabbit hepatocytes as target cells. This technique was more sensitive than the immunofluorescent method. IgG liver membrane antibodies were positive in 24% of patients with alcoholic liver disease. IgA liver membrane antibodies were detected in 58% of patients with alcoholic liver disease, whereas they were detected only in 21% of those with nonalcoholic liver disease, except for cases of autoimmune chronic active hepatitis. In alcoholic liver disease, IgA liver membrane antibodies were detected at a high frequency in a group of patients with alcoholic hepatitis and active cirrhosis (94%) as compared with that of fatty liver, hepatic fibrosis, and inactive cirrhosis (42%). These results suggest that alcoholic liver disease is characterized in part by a humoral immune response of IgA liver membrane antibodies.

In vitro effect of corticosteroid on immunoregulatory functions in primary biliary cirrhosis

Primary biliary (PBC) has many features, suggesting immunopathogenic mechanisms involved in its etiology. However, none of the therapeutic modalities that are beneficial in many autoimmune diseases have been demonstrated to halt histologic progression of the disease or to induce a complete clinical, biochemical, and histologic remission on this disease. To investigate whether corticosteroids improve the abnormal immunoregulatory functions in PBC, the in vitro effect of corticosteroid on the activity of suppressor T cells and interleukin 2, an inducer of immunoregulatory cells, was evaluated in eight patients with PBC. Defective suppressor T cell activity was found in PBC; however, no clear improvement of T cell activity was observed after in vitro treatment of lymphocytes with corticosteroid. In PBC, interleukin 2 activity was normal, and the same decrease of activity as occurring in healthy controls was observed after corticosteroid treatment. These results suggest that a defect in the responsiveness of suppressor T cell activity to corticosteroid may play, at least in part, a role in the pathogenesis of corticosteroid ineffectiveness in PBC.

In vitro effect of prednisolone on peripheral blood suppressor T cell activity in patients with alcoholic hepatitis

An immunological process is suggested to play some role in the pathogenesis of alcoholic hepatitis; however, its nature has not been clarified. In the present study, we examined, in 30 patients with alcoholic liver disease, an in vitro effect of prednisolone on suppressor T cell activity to see whether an altered cellular immunoregulatory mechanism is affected by corticosteroid. Suppressor T cell activity, which was induced by concanavalin A (Con A), was assessed by inhibition of phytohemagglutinin-stimulated blast transformation of autologous lymphocytes, and prednisolone (10 micrograms/ml) was added when suppressor T cells were induced. Low suppressor T cell activity was found in alcoholic patients with hepatic fibrosis, alcoholic hepatitis, and cirrhosis with hepatitis; these reductions recovered to a normal range when lymphocytes were incubated in vitro with prednisolone, suggesting an improvement in the altered immunoregulation by prednisolone. Although immunotherapy is shown to be of no benefit in the treatment of alcoholic hepatitis, we propose a need to elucidate further the therapeutic modalities for correction of the immunoregulatory abnormalities in such patients.