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National surveillance studies on alcoholic liver disease (ALD) in Japan were performed in 1978 and 1985, by a previous Japanese study group for ALD (Takeuchi group). In the present study, a subsequent nationwide surveillance study was performed from 1986 to 1991 and the results were compared with the previous two studies. In order to clarify the etiological relationships between hepatitis C virus (HCV) infection and ALD, an analysis was also done according to the new diagnostic criteria of ALD which was proposed by this group (Takada group). By the criteria of the Takeuchi group, the incidence of ALD was not significantly different during 1986 to 1991. However, the incidence of hepatocellular carcinoma (HCC) in alcoholic cirrhosis (AL-LC) clearly increased during this period. The analysis including the results of the previous study indicate that incidence of ALD reached a plateau in 1980 and then features of ALD in Japan entered a stable stage. However, HCC in AL-LC continued to show a linear increase from 1976 to 1991. Analysis with the new criteria of the Takada group was done in cases of 1990 and 1991. Approximately 2 out of 3 cases of ALD were caused by alcohol alone, and the remaining cases were caused by a combination of alcohol and HCV. Cases caused only by HCV were very rare. The main etiology in patients with alcoholic hepatitis and fibrosis was alcohol alone and that in chronic hepatitis of heavy drinkers was a combination of alcohol and HCV. In half of the patients with AL-LC, the etiology was alcohol alone and in the other half patients, it was a combination of both factors. In most patients with HCC, the etiology was a combination of alcohol and HCV, indicating that HCV infection may be important for the development of HCC in alcoholics.

This paper reports a case with an undifferentiated carcinoma of the esophagus which primarily developed symptoms due to metastatic lesions. The case was a 59-year-old woman with a primary manifestation of an abdominal mass and with subsequent dysphagia. A protruding lesion with ulceration was found at the lower third of the thoracic esophagus by endoscopic examination and was histologically proved to be an undifferentiated carcinoma by biopsy. The abdominal mass was initially thought to be due to metastasis to an abdominal lymph node based on the diagnosis image finding at admission, but it was consequently found by autopsy to be a metastatic tumor in the liver. Therefore, undifferentiated carcinoma of the esophagus should be take into account for differential diagnosis of an abdominal mass.

Positivity for serum anti-HTLV-1 antibody (anti-HTLV-1) in 171 patients with various chronic liver diseases and 22 asymptomatic hepatitis B virus (HBV) carriers was compared with that of 200 healthy controls in the Chikugo district of Japan. The rate of anti-HTLV-1 positivity in patients with liver disease was 8.1% (14/171) and was higher than that (3.5%: 7/200) in healthy controls, but the difference was not significant. However, in patients with liver disease with a history of blood transfusion, the positive rate was 18.4% (7/38) which was significantly higher than that for healthy subject (P less than 0.001). On the other hand, in 133 liver disease patients without blood transfusion, anti-HTLV-1 positivity was significantly higher (P less than 0.05) in patients with hepatitis B surface antigen (11.3%: 6/53) than in those without it (1.3%: 1/80). These data suggest that the high incidence of anti-HTLV-1 in our patients with liver disease was due to the transmission of HTLV-1 by the same routes (maternal transmission and blood transfusion) and probably at the same time as the hepatitis viruses (HBV and hepatitis C virus).

Tissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n = 30); fulminant hepatitis (FH, n = 36); chronic inactive hepatitis (CIH, n = 57); chronic active hepatitis (CAH, n = 39); compensated liver cirrhosis (cLC, n = 78); decompensated liver cirrhosis (dLC, n = 84); hepatocellular carcinoma (HCC, n = 64); advanced hepatocellular carcinoma (aHCC, n = 28); and compared with that of a control group (n = 106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin alpha 1-plasmin inhibitor complex (PIC), plasminogen (Plg), FDP, AT III and alpha 2-plasmin inhibitor (alpha 2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

The significance of interleukin-6 (IL-6) in patients with inflammatory bowel disease (IBD) was studied by measuring the IL-6 level in serum and colonic tissue by means of an enzyme-linked immunosorbent assay (ELISA), and by examining its localization using an immunohistochemical method. The serum IL-6 level reflected the degree of disease activity, and the extent of affected area, and was also correlated with the serum C-reactive protein (CRP) level. In the colonic mucosa of active IBD, the tissue IL-6 level was markedly elevated, and immunoreactive products of anti-IL-6 antibody were present in infiltrative mononuclear cells in the lamina propria. This indicates that IL-6 production in these cells is enhanced at the site of affected intestine. These results, together with its biological activity and the type of cell producing it, suggest that IL-6 is an available marker to assess disease conditions of IBD and that it might be also involved in the pathophysiology of IBD.

The present study was intended to assess the incidence and the nature of gastric red spots (GRS) in patients with liver cirrhosis. Endoscopically, GRS was more frequently observed in patients with cirrhosis (n = 146) than those without cirrhosis (n = 103) (43.2% vs. 4.8%; P less than 0.001). There was no relationship between the incidence of GRS and the severity of cirrhosis or the size of varices. Portal venous pressure was higher in cirrhotics with GRS (n = 21) than those without GRS (n = 25) (33.7 +/- 6.0 mmHg vs. 28.2 +/- 4.8 mmHg; P less than 0.001). Morphometric analysis using the biopsied specimens was made in 16 cirrhotics with GRS, 12 cirrhotics without GRS, and 15 non-cirrhotics. The capillary bed occupation ratio (vascular area/mucosal area) was higher in cirrhotics with GRS (9.3 +/- 4.0%) than those without GRS 84.1 +/- 1.1%) or the non-cirrhotics (3.4 +/- 9.8%) (P less than 0.005, P less than 0.005), while there was no significant differences in the number of capillaries per unit area. Infiltrating inflammatory cell count was similar among the three groups. Extravascular red blood cell count per unit area was higher in cirrhotics with GRS (29.7 +/- 31.4) than those without GRS (5.4 +/- 5.1) or non-cirrhotics (5.4 +/- 6.3) (P less than 0.05, P less than 0.01). Furthermore, extravasation of red blood cells through defective portion of the endothelium and interposition of red blood cells in interepithelial spaces were observed electron microscopically in cirrhotics with GRS.(ABSTRACT TRUNCATED AT 250 WORDS)

We report the case of a 31-year-old female with extrahepatic portal vein obstruction. At the age of 16 she had developed hematemesis from esophageal varices. Trans-splenic portography failed to demonstrate the portal trunk, but showed instead well developed collateral circulation. She suffered from repeated hematemesis and ascites despite mesocaval shunt operation and resection of the esophagus for varices. Death resulted from gastrointestinal hemorrhage. Her family history revealed a 30-year-old sister with Takayasu's disease. On autopsy, the portal trunk and the portal vein at the hilus were indistinguishable due to proliferation of hyalinized connective tissue. Cavernous transformation was observed at the hilus. Histologically the presence of the portal trunk and the portal vein was confirmed, but they showed marked sclerosis, and were almost occluded by possible organized thrombus. The cavernous transformation consisted of numerous thin-walled vessels, which were also observed in the medium-sized portal tracts in the liver. The peripheral portal tracts showed no obvious narrowing nor occlusion of the portal vein branches, which are factors usually considered to play an important role in the genesis of portal hypertension in idiopathic portal hypertension. Even though the etiology is not clear, the portal trunk obstruction is concluded to be a significant factor in this case contributing to the development of protracted portal hypertension.

The significance of C-reactive protein (CRP) in acute viral hepatitis was studied by measuring the serum CRP level in patients with acute hepatitis type A (AHA), B (AHB), and non-A, non-B (AHNANB) and examining its localization in liver biopsy specimens by the immunohistochemical method. The mean value of the serum CRP level determined by enzyme immunoassay (EIA), was markedly increased in the acute phase of AHA and AHB, particularly the former. It decreased rapidly in both AHA and AHB during the convalescent phase, but was generally low in AHNANB with no marked difference between the acute phase and the convalescent phase. Under light microscopy, CRP was stained in the cytoplasm of hepatocytes, and immuno-reactive products were observed in the rough endoplasmic reticulum (RER) by electron microscopy. In the acute phase, the intensity of staining was slightly greater in AHA, decreasing during the convalescent phase in AHA and AHB, but only weak staining was observed in all patients with AHNANB. Evaluation of CRP may be useful for clarification of differences in clinical manifestations and the mechanisms of inflammation among different types of hepatitis.

Ursodeoxycholic acid (UDCA), 7beta hydroxy epimer of chenodeoxycholic acid (CDCA), has been used as a choleretica for 20 years in Japan. Recent report showing increased excretion of UDCA in bile after CDCA administration may suggest the possibility that UDCA has similar effects to CDCA on bile cholesterol unsaturation and on gallstone dissolution. The present paper describes the clinical usefulness of UDCA for gallstone patients during the past two years. Seventy-four gallstone patients with functioning gall-bladders, 19 men and 55 women with a mean age of 48 years, have been treated for 6 months or more. UDCA, supplied in tablets (Ursosan), was given 450 mg per day. The disappearance or the reduction of stone size or number, or both (dissolution effect) was recognized in 32 out of 74 patients (43%). In case of radiolucent stones, the overall effective rate was estimated for 24 of 46 patients (52%). There may be no significant difference in dissolution effect between CDCA and UDCA treatment, however, the merit of UDCA treatment seems to have its few side effects.

The efficacy of Shosaiko-to (SST) on 222 patients with chronic active hepatitis was studied in a double-blind multicenter clinical study. One hundred and sixteen patients received SST in a daily oral dose of 5.4 g for 12 weeks, followed by the same dose for a further 12 weeks. One hundred and six patients received a placebo containing 0.5 g of SST for 12 weeks, followed by a cross-over to SST for a further 12 weeks. Among the liver tests, serum AST and ALT values decreased significantly with the administration of SST. The difference of the mean value between the SST group and the placebo group was significant after 12 weeks. In patients with chronic active type B hepatitis, a tendency towards a decrease of HBeAg and an increase of Anti-HBe antibodies was also observed. No remarkable side effects were noticed.