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To compare the seroepidemiology of hepatitis C and hepatitis B between Bangladesh and Japan, we tested the second generation antibody to hepatitis C virus (anti-HCV-2) and hepatitis B surface antigen (HBsAg) in serum samples from 163 professional blood donors (161 males and 2 females, mean age 28.6 yr.) and 83 voluntary blood donors from Bangladesh, and 7479 Japanese voluntary blood donors (5036 males and 2443 females; mean age 37.1 yr.). In Bangladesh, anti-HCV-2 is detected in 2.4% of professional blood donors and 0% of voluntary blood donors, furthermore, HBsAg is detected in 29% and in 2.4% of professional and voluntary blood donors, respectively. In Japan, anti-HCV-2 is detected in 0.6% in voluntary blood donors, and HBsAg also in 0.6%. These results indicate that professional blood donors in Bangladesh are highly contaminated by hepatitis B virus and moderately by hepatitis C virus, while voluntary blood donors in both countries are not so highly contaminated by either hepatitis viruses.

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.

Three sisters with cystic dilatation of the intrahepatic bile ducts (Caroli's disease) are reported. The index case, a 41-year-old woman with remittent high fever and right upper quadrant abdominal pain, was diagnosed as Caroli's disease with hepatic lithiasis and cholangitis based on findings of ultrasonography, computed tomography and endoscopic retrograde cholangiography. Her two older sisters were also examined and found to have the same disease without clinical symptoms. Their symptoms, locations of the dilated ducts and complications all varied. The hereditary mode of Caroli's disease in 13 families (32 cases) reported in the world literature including our study was examined. While Caroli's disease is thought to be an autosomal recessive disease, a conclusion on the hereditary mode of transmission could not be made in this study because of an insufficient investigation of family members, especially the parents.

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)

A 48-year-old woman with Caroli's disease accompanied by hepatolithiasis, choledocholithiasis, and cholangiocarcinoma is reported. Magnetic resonance imaging was useful for the diagnosis of the cholangiocarcinoma. The relationship between cholangiocarcinoma and hepatolithiasis, choledocholithiasis, and chronic cholangitis in Caroli's disease is discussed.

We report a case of multiple cavernous hemangioma of the small intestine which was diagnosed definitively before operation. A 33-yr-old male was found to have multiple polypoid lesions in the small intestine during examination for recurrent iron deficiency anemia. Plain X-ray film of the abdomen revealed multiple calcifications in the middle to lower region, suggestive of cavernous hemangioma, which was further confirmed by angiography and scintigraphy with Tc 99m-labeled red blood cells. Endoscopy during surgery was used to determine the extent of surgical resection. Seventy-three cases of hemangioma of the small intestine were reported in Japan between 1953 and 1988 and their clinical features were reviewed.

Liver specimens were obtained from 21 non-A, non-B hepatitis patients when their serum transaminase levels were still elevated. The specimens were investigated by transmission electron microscope in order to investigate the presence of the structure relating to this type of hepatitis. Intranuclear electron-dense aggregates of virus-like particles were observed in 2 out of 21 cases. One was an unresolved acute hepatitis case with short-incubation posttransfusion type, and the other was a chronic persistent hepatitis case without bloodtransfusion. The size of these particles varied from 22 to 28 nm in diameter. The incidence of hepatocytes with the particles was approximately 2 to 3% of the cells investigated. These particles may represent an intranuclear alteration in close association with one type of non-A, non-B hepatitis.

In order to elucidate the functional states of the pancreas in the asymptomatic latent stage of chronic alcoholic pancreatitis, 45 chronic alcoholics with no obvious pancreatic structural abnormalities judged by endoscopic pancreatography were studied by pancreozymin-secretin test. We found three patterns of exocrine pancreatic function in alcoholics with or without cirrhosis: normal secretion (40%), hyposecretion (29%) and hypersecretion (31%). In the hyposecretory group, the amylase output proved to be impaired more frequently. In the hypersecretory group increases were observed in one or more of the following parameters, volume, bicarbonate output and amylase output. However, increase in volume was a fundamental condition in this hypersecretion. This study confirmed that exocrine pancreatic hyposecretion and hypersecretion were almost equally frequent in asymptomatic chronic alcoholics with no obvious pancreatographic abnormalities. These results suggest that ongoing exocrine pancreatic dysfunctions exist in the subclinical stage of chronic alcoholic pancreatitis.

Progression of acute non-A, non-B (NANB) posttransfusion hepatitis to liver cirrhosis has been well recognized as in hepatitis B infection, whereas no progression of acute NANB sporadic hepatitis to liver cirrhosis has yet been documented. We reported a 29-year-old male with prolonged transaminase elevations in whom acute NANB sporadic hepatitis progressed to histologically confirmed cirrhosis during follow-up of about 3 years. It is suggested that some of the cryptogenic cirrhosis of non-B type may develop from acute NANB sporadic hepatitis and long-term observation is also needed in patients with acute hepatitis of this category.

Hepatitis B surface antigen (HBs-Ag) and hepatitis B core antigen (HBc-Ag) in hepatic tissue of 3 cases with various liver diseases were investigated by immunofluorescent method. Virus-like particles were demonstrated by electron microscopy in the nuclei of these 3 cases. The localization of HBs-Ag was restricted in cytoplasma or on the surface of hepatocyte, while HBc-Ag was almost in the hepatocytic nuclei. However, there was unexplainable discrepancy between the distribution of HBs-Ag and that of HBc-Ag, as more the former in number and less that latter, of hepatocytes. The size of virus-like particles in nuclei was 22-27 nm in diameter. Most of them were hollow, but some of them were wholly electron dense. Their distribution was various from case to case. Discussion was made on the correlation between the presence of Hepatitis B virus and HBs-Ag or HBc-Ag.

Sixteen years follow-up was performed in a male of long-standing alcohol indulgence who had an alcoholic liver disease at the outset, followed by alcoholic pancreatitis which progressed finally to pancreatic calcification. During this course, the abnormalities of endoscopic pancreatogram were unremittingly progressive, whereas exocrine and endocrine pancreatic dysfunction remained fluctuating, but ultimately deteriorated. In contrast functional and histological abnormalities of the liver were not progressive but returned toward normal. The follow-up observations in this case suggest that some cases of typical alcoholic pancreatitis may have unremittingly progressive morphologic changes with fairly well reserved capacity of exocrine and endocrine pancreatic functions and their hepatic lesions may not be in parallel with pancreatic lesions.

IgM antibody to hepatitis B core antigen (anti-HBc) was assayed using a commercial kit in acute and chronic hepatitis B virus (HBV) infection and evaluated for its diagnostic and clinical significance. IgM anti-HBc was positive in all of 21 cases with type B acute hepatitis in the acute phase, and was also detected in 5 of 20 cases with type B chronic persistent hepatitis, in 4 of 20 patients with type B chronic active hepatitis and in one of 10 with type B liver cirrhosis. The absence of this marker was noted in all of 20 asymptomatic hepatitis B surface antigen (HBsAg) carriers and in 50 with HBsAg-negative patients with liver disease and in 200 healthy blood donors. The cut-off index of IgM anti-HBc was greater than 2.0 in all serum samples obtained in the acute phase of type B acute hepatitis, but was below 2.0 in type B chronic liver disease. A close relationship was found between the presence of IgM anti-HBc and the degree of inflammatory activity in patients with HBsAg-positive chronic liver disease. These data show that examination of IgM anti-HBc is useful in distingushing type B acute hepatitis from type B chronic liver disease, and also in evaluating the severity of disease in type B chronic liver disease.

A 73-year-old former soldier in whom a deposition of thorotrast had been detected 7 years previously was admitted to our hospital because of high fever and epigastric pain. He had been well with standard liver function tests within the normal range until 4 months before admission. Laboratory examination on admission showed marked abnormalities in the liver function tests and an elevated level of CEA. Abdominal ultrasonography and computerized tomography, which had shown no space-occupying lesion in the liver one year earlier, revealed an abnormal mass in the right hepatic lobe. Angiographic examination revealed low vascularity and encasement of the intrahepatic artery. The disease was diagnosed as thorotrast-induced cholangiocarcinoma. Despite chemotherapy, the patient's condition worsened rapidly and he died on the 78th day after admission. At autopsy, the primary tumor in the right hepatic lobe and metastatic nodular tumors throughout the liver were found. The histological diagnosis was cholangiocarcinoma. Thorotrast-induced liver cancers are inclined to grow rapidly, so early diagnosis of liver tumor accompanied by thorotrastosis is very difficult, as in this case. Repeated examinations at frequent intervals are required for early diagnosis.

In order to estimate age specific prevalence of Anti HA in Japan, 1757 serum samples from healthy subjects or patients with nonhepatic disease taken in 6 different districts of Japan were tested for Anti HA using HAVAB Kit. Very low prevalence, less than 10%, was observed in young adults or children. These facts indicate the young Japanese are quite susceptible to HAV infection and the effective preventive measures are urgently needed. Over all prevalence of Anti HA was 56.2%. Comparing the age specific prevalence of Anti HA in Japan with those in other countries, the situation in Japan was in intermediate between highly endemic South-East region and developed European countries.

A case of asymptomatic primary biliary cirrhosis (PBC) with an initial presenting feature of localized gastric varices is reported. The patient, 64 years old female, underwent a barium meal examination because of ill-defined abdominal complaints and was found to have gastric varices localized at the cardia but no esophageal varices. Her blood chemistry showed high values of biliary tract enzymes such as alkaline phosphatase and gamma-glutamyl transpeptidase, but the serum bilirubin level was almost normal. Serum anti-mitochondrial antibody was positive. Histological findings of the surgically biopsied liver specimen were compatible with PBC. The clinical implication of gastric varices in PBC is discussed.

Screening for pancreatic cancer was carried out by serum pancreatic oncofetal antigen (POA) tests in 440 out-patients with abdominal complaints, with concomitant assay of carcinoembryonic antigen, alpha-fetoprotein and ferritin. POA was positive in 13 patients, of whom 3 cases of pancreatic cancer, and 4 of other malignant diseases were diagnosed while the remaining 6 were non-malignant. Of these out-patients, 5 cases were finally diagnosed as having pancreatic cancer by further examinations. Of these 5 patients, POA was negative in 2, of whom one was positive for CEA and AFP. Accordingly, when POA test was applied concomitantly with the other 3 marker tests, the detection rate of pancreatic cancer was elevated to 4/5. Twenty-three patients were found to have malignant diseases and 20 of them were positive for at least one of the 4 markers tested. These results suggest that serum POA assay is useful for screening the pancreatic cancer, especially when the other tumor markers are assayed concomitantly.

e-antigen and anti-e were assayed in sera of asymptomatic HBs-Ag carriers and of patients with liver diseases. Thirteen out of 34 (38.2%) asymptomatic carriers were positive for e-antigen, which was in sharp contrast to the reports from USA and Europe. e-antigen was detected to a greater extent in patients with chronic active hepatitis, reversely anti-e in patients with chronic persistent hepatitis. However, e-antigen was found rarely in patients with cirrhosis and never in 23 cases with hepatoma positive for HBs-Ag. HBc-Ag in the liver was detected in 4 out of 8 e-antigen positive asymptomatic carriers and in 4 out of 5 patients with chronic liver diseases with e-antigen respectively, and moreover in 3 out of 14 anti-e positive cases, so that the presence of anti-e did not necessarily mean the negativity of HBc-Ag in the liver. Anti-HBc titer, however, was lower in anti-e positive sera than in e-antigen positive ones. This may implicate the decreased replication of HBV in cases with anti-e. These results emphasize that the investigation of e-antigen/anti-e is mandatory for the evaluation of the prognosis of asymptomatic carriers and of patients with chronic hepatitis.