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A 29-yr-old man with neurological symptoms that included tremor, dysarthria, and loss of consciousness was diagnosed as having variegate porphyria, because of increased urinary excretion of delta-aminolevulinic acid, porphobilinogen, uroporphyrin, and coproporphyrin, and increased fecal uro-, copro-, and protoporphyrins. He showed marked retention of indocyanine green (R15 min: 53%-78%) and bromosulfophthalein (R45 min: 24%-10%) as well. The kinetic analysis revealed that both hepatic uptake and hepatic excretion were decreased for both dyes. Results of other liver function tests were unremarkable except for intermittent hyperbilirubinemia (0.7-3.3 mg/100 ml), of which the ratio of conjugated and unconjugated fraction was between 0.7 and 1.2. Binding of serum protein and indocyanine green or bromosulfophthalein was normal. An angiographic and scintigraphic study of the liver was normal. A minimal deposition of hemosiderin pigment was found in liver biopsy specimen without other abnormalities. Deposition of porphyrin was not present in the liver. Plasma exchange and erythrocytapheresis did not show any beneficial effects on the clinical and laboratory abnormalities of the patient. A possible relationship between variegate porphyria and defective hepatic anion transport is discussed.

This study included 35 patients with liver cirrhosis, 23 patients with hyperthyroidism, 12 with hypothyroidism, and 2 with other endocrine disorders. In the various endocrine disorders an appreciable amount of triiodothyronine (T3) was excreted into the urine but the daily excretion was fairly constant in each patient. Urinary excretion of T3 was negligible or depressed in hypothyroidism, but increased with a rise in the serum level of T3. Serum and urinary T3 decreased in liver cirrhosis, but the serum thyroxine (T4) level was within the normal range. When the cirrhosis patients were divided into 3 groups according to the urinary excretion of T3, a decrease of urinary T3 was associated with a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of lh a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of lh a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of liver damage as judged by indocyanine green retention and a decreased urinary excretion of cyclic adenosine 3',5'-monophosphate. In vitro experiments indicated that rat liver, as compared to the kidney, heart and skeletal muscle, strongly converts T4 to T3, but this activity is greatly reduced by liver damage induced by ligation of the bile duct. It is suggested that patients with liver cirrhosis are, to some extent, in a state resembling subclinical hypothyroidism because of inability of the liver to metabolize a sufficient amount of T3 from T4.

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.

Plasma levels of human atrial natriuretic peptide (hANP) were investigated in patients with liver cirrhosis, and the relationships between plasma hANP levels and the following factors were studied: presence of ascites, serum and urine electrolytes, plasma renin activity, angiotensin I and II, aldosterone, catecholamines, prostaglandin derivatives, conventional liver function tests and circulating blood volume. Plasma hANP level was significantly (P less than 0.05) elevated in patients with ascites (mean = 58.6 pg/mL, s.e.m. = 8.8) compared with cases without ascites (mean = 36.6 pg/mL, s.e.m. = 2.6). With the disappearance of ascites, the level fell to normal in most cases. Urine sodium excretion was positively correlated with plasma hANP in patients without ascites, but not in patients with ascites. The plasma hANP level was disproportionately high for the rate of urinary Na excretion in cirrhotics with ascites. The plasma hANP level was not correlated with any of the other factors such as blood volume, renin-angiotensin-aldosterone levels, catecholamines and liver function tests. These results suggest that plasma hANP levels are elevated in cirrhotic patients especially with ascites, but the natriuretic response of the kidney to this raised hANP level can be impaired in patients with liver cirrhosis and ascites.

The intrahepatic expression of hepatitis-B core antigen (HBcAg) was investigated in 54 liver biopsy specimens from 24 chronic type-B hepatitis patients, by the peroxidase-anti-peroxidase technique. The HBcAg localization pattern in the hepatocyte correlated with the evolution of serum alanine aminotransferase (ALAT) values. The clinical course were classified into three phases, as follows: pre-exacerbation phase (A phase), with minimal abnormal range of ALAT (40-100 KU) for 6 to 12 months; exacerbation phase (B phase) with elevated ALAT (more than 100 KU) for 3 to 6 months; and post-exacerbation and subsiding phase (C phase) for 3 months after phase B, showing decreased ALAT values. Nineteen of the 54 biopsied specimens belonged to the A phase, 21 to the B phase, and 14 to the C phase. In the A phase the hepatocytic HBcAg was variably expressed as nuclear, cytoplasmic, and membranous in location in the same specimens. In the B phase, HBcAg expression decreased in the nucleus, but increased in the cytoplasmic-membranous pattern. The intrahepatic HBcAg expression in the C phase decreased in all patterns. The mean level of ALAT in cases of cytoplasmic-membranous HBcAg expression was higher than that in cases of nuclear HBcAg expression. Four of six patients who underwent liver biopsies in the A, B, and C phases showed remarkable decreases of cytoplasmic and membranous HBcAg expression in the C phase. These findings suggest that cytoplasmic and membranous localization of HBcAg can be related to both liver cell injury and active inflammatory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study is to evaluate the risk of infection of non-A, non-B acute hepatitis (NANB-AH) in hospital employees. Among 593 patients with acute viral hepatitis (AVH), hospital employees were 3/147 (2%) in type A, 19/174 (11%) in type B and 21/272 (8%) in non-A, non-B (NANB). All 43 patients were medical staffs such as doctors, nurses and laboratory technicians. Out of 21 patients with NANB hepatitis of hospital employees, 7 were doctors, 14 nurses and 6 laboratory technicians. Eight of them had preceding accidental needlestick exposures. Out of 17,290 employees of our hospital during 18 years, 27 medical persons developed AVH. They were 2 hepatitis A, 10 hepatitis B and 15 hepatitis NANB. No non-medical staff developed AVH. Out of 15 NANB hepatitis patients, 7 had needlestick accidents 4 to 6 weeks before development of the illness, and all donor patients showed liver diseases. During 3 years (1985 to 1987), there were 116 needlestick accidents in our hospital which happened in medical staffs alone, and 50 of them were NANB hepatitis-related accidents. Three ml of human immune serum globulin (ISG) was administered intramuscurally just after accidents to 23 persons but not to 27 persons. NANB hepatitis were developed in 2 doctors who were not treated with ISG. In conclusion, NANB hepatitis occurred in hospital employees especially in medical staffs.

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.

We report a case of successful surgical treatment of cholangiocarcinoma caused by a long standing thorotrastosis. Thorotrastosis should be recognized as a preliminary stage of malignancy. If early diagnosis of the tumor can be made, treatment may be successful.

Antibodies to the Ro/SSA antigen occur in patients with Sjögren's syndrome and other collagen diseases. In this study, we used ammonium sulfate precipitation, anti-Ro/SSA immunoaffinity chromatography and gel filtration to purify the Ro/SSA antigen from pig spleen. In addition, the normal human IgG affinity column chromatography was also used to adsorb nonspecific reacting materials as heterophile antigens which contaminated in preparations after immunoaffinity chromatography. On SDS-PAGE the purified Ro/SSA antigen migrated as 60K and 53K polypeptides bands and the antigenicity was observed on 60 K band. An enzyme-linked immunosorbent assay (ELISA) using the purified antigen was developed for quantitation of the antibody which was found to be sensitive, precise and specific. By the method, anti-Ro/SSA antibodies were detected in SLE (44%), MCTD (71%), PSS (50%), SjS (83%), RA (16%), PBC (23%), lupoid hepatitis (23%) but only 4% in normal controls. The purified antigen and ELISA method will provide beneficial tools for the investigation of autoimmune diseases.

In order to clarify the differences in past history, nutritional condition and, consumption of alcohol and tobacco, and liver dysfunction between the thorotrast patients who developed primary liver cancer and those who did not, 103 persons who had no primary liver cancer in January 1980 were studied. All subjects were military men who had undergone angiography with thorotrast between 1943 and 1946. Twenty persons developed hepatocellular carcinoma and 16 developed intrahepatic bile duct carcinoma by April 1987, whereas 67 are still alive without any cancer. There was no difference in age or period after thorotrast infusion between those two groups of patients in January 1980. A difference in history of hepatitis and/or jaundice and presence of hepatic dysfunction was found between the subjects who developed primary liver cancers and those who did not. These findings suggest that an anamnestic history of hepatitis and liver dysfunction are risks for development of thorotrast-induced liver cancer. On the basis of the above findings, early detection of liver dysfunction offers a possibility of early diagnosis of primary liver cancer.

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.

In order to search for some parameters that would make it possible to predict a potentially high risk of evolution from liver cirrhosis to hepatocellular carcinoma (HCC), the DNA content of hepatocytes in patients with liver cirrhosis with or without development to HCC was investigated by means of microspectrophotometry in Feulgen-stained specimens. In patients without development of HCC in more than 5 years of follow-up, 90% or more of tested hepatocytes were diploid, whereas in patients with liver cirrhosis who developed HCC within 3 years the frequency histogram of nuclear DNA content was widely spread from diploid to hyperpolyploid with a small peak of triploid. Furthermore, in the latter group of patients, many of the binucleate cells had different DNA contents in each paired nucleus. In non-cancerous portions of HCC, the ploidy histogram of nuclear DNA content was widely spread from diploid to polyploid with different DNA contents of each paired nucleus in binucleate cells, without the small peak of triploid. These results suggest that the deranged cell kinetics of hepatocytes in cirrhosis may be considered to be a state of potentially high risk for the evolution of HCC, and that a patient with liver cirrhosis with such an abnormal hepatocyte DNA content should be followed up carefully for the early diagnosis of HCC.

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.

Sera from 230 hepatocellular carcinoma patients were tested for antinuclear antibodies by anticomplement immunofluorescence in 16 types of transformed, diploid or primary cells of human, monkey, chimpanzee or rat origin. As controls, we tested 85 sera from patients with chronic liver diseases, 48 sera from patients with nonhepatic cancers and 164 sera of normal controls. Exactly 11.2% of all cancer patients but only 3.6% of noncancer patients had complement-fixing antinuclear antibody that reacted with all substrates. Only sera from hepatocellular carcinoma reacted with subsets of the tumor cell substrates. These sera reacted with hepatocellular carcinoma cells and nonhepatic cancer cells (antitumor) or only with one or more of the human hepatocellular carcinoma cell lines, PLC/PRF/5, Hep3B and Mahlavu, that were derived from HBsAg-positive patients (antihepatocellular carcinoma). Three of these reacted only with hepatitis B virus DNA-positive cells (PLC/PRF/5 and Hep3B) that contained "hepatitis B-associated nuclear antigen," 1 reacted only with hepatitis B virus DNA-negative Mahlavu cells, 1 reacted with PLC/PRF/5 and Mahlavu and 3 reacted with all 3 cells. The nuclear antigen in Mahlavu was expressed as a homogeneous fluorescence that spared the nucleoli, was present in a lower percentage of cells than hepatitis B-associated nuclear antigen and was more thermostable than hepatitis B-associated nuclear antigen. However, it resembled hepatitis B-associated nuclear antigen in kinetics of expression and susceptibility to digestion with DNase, RNase and proteinase K. The nature of the nuclear antigens in the hepatocellular carcinoma cells is poorly understood but one possibility is that they may represent the expression of viral or tumor-related genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Six hundred and fifty-one patients with acute viral hepatitis were identified serologically between January 1976 and December 1985. Of these, 109 (17%) had hepatitis A, 135 (21%) had hepatitis B, and 407 (62%) had hepatitis non-A, non-B. The possible infectious causes for acquisition of viral hepatitis occurring within 6 months before the onset of hepatitis were analysed. Approximately 80% of cases of hepatitis A and 70% of hepatitis B had no known risk factor, while in 67% of cases of hepatitis non-A, non-B possible risk factors for infection were documented. Infectious causes for hepatitis A were ingestion of raw shellfish (11%) and previous familial contact with patients with hepatitis A (10%). For hepatitis B, risk factors included medicare (24%), such as transfusion, surgical operation, accidental needle stick and acupuncture, and sexual contact (6%). For hepatitis non-A, non-B, the most important infectious cause was medical procedures (65%). The numbers of hospital employees were 2 (2%) with hepatitis A, 15 (11%) with hepatitis B and 14 (3%) with hepatitis non-A, non-B. These data suggest that hepatitis non-A, non-B can be a kind of nosocomial disease.

Serial assays for immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) were performed in 51 patients with antibody to hepatitis B e antigen (anti-HBe) in their sera. IgM anti-HBc was detected periodically and persistently in 8 (53%) of 15 patients with chronic hepatitis whose serum glutamic pyruvic transaminase (GPT) levels were elevated and was not detected in 36 patients with normal serum GPT levels. Antibody to delta agent was not detected in any of the patients. Of the eight patients positive for IgM anti-HBc, four had a high titer of IgM anti-HBc and either developed liver cirrhosis (three cases) or died due to massive hepatic necrosis (one case); the other four showed a low level of IgM anti-HBc and either recovered (two cases) or developed chronic persistent hepatitis (two cases). Of seven patients negative for IgM anti-Hbc, two had a fatty liver, and five, who had a history of blood transfusion, had chronic hepatitis. Thus, even though anti-HBe may be present, if the titer of IgM anti-HBc is high, the histological activity can be expected to increase, and the prognosis will be poor. If the titer of IgM anti-HBc is low, the histological activity may be expected to decrease, and the prognosis may be good. In patients with abnormally high serum GPT but without IgM anti-HBc, another type of hepatitis or a secondary form of liver disease should be considered.

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.

The antibody to hepatitis B core antigen (anti-HBc) is belived to be a marker for natural infection with hepatitis B virus (HBV). In order to study the etiological role of HBV in relation to primary hepatocellular carcinoma (PHC), the anti-HBc in sera of 31 PHC patients was surveyed by the immune adherence hemagglutination method which was about 10 times more sensitive than the complement fixation method. Twenty two out of 31 PHC cases were positive for anti-HBc (71.0%). The is a higher rate of incidence than that of HBs-Ag (51.6%). However, high anti-HBc titer above 2(10) which might reflect current infection with HBV was observed in 15 of these 22 cases. The remaining 7 cases had a titer lower than 2(8); 5 of these patients had neither HBs-Ag nor anti-HBs in their sera. As control, 37 anti-HBs positive blood donors with no definite liver disease were surveyed for anti-HBc titer. Thirty-four of them were positive, but in the majority of cases, the serum titer was less than 2(9), which might only reflect previous infection with HBV. These findings indicate that not only the prevalence of anti-HBc, but also the determination of its real titer is quite important for studying the relationship of HBV to PHC.

A case is reported in which non-A, non-B posttransfusion hepatitis was followed serially by chronic persistent hepatitis, chronic active hepatitis, and liver cirrhosis that finally developed into hepatocellular carcinoma. The patient died after a 19-year clinical course. During the last 8 years, repeated attempts to identify serum hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen were consistently negative. Liver biopsy was performed five times during the clinical course, and at autopsy, liver tissue was obtained from four different nontumor regions. These specimens were investigated by a peroxidase immunoenzyme method which failed to detect hepatitis B surface antigen and hepatitis B core antigen. Non-A, non-B posttransfusion hepatitis may become chronic and sometimes may advance to hepatocellular carcinoma.

We performed a follow-up study on 70 patients with acute non-A, non-B (NANB) posttransfusion hepatitis and a retrospective study on 283 chronic hepatitis, 70 cirrhosis and 53 hepatocellular carcinoma patients of type NANB. In acute NANB post-transfusion hepatitis, as judged by the transaminase levels, th duration of the disease exceeded 6 months in 46/70 = 65.7% and 1 year in 32/70 = 45.7%. The histological diagnosis of the 32 cases persisting for more than 1 year was chronic active hepatitis in 5, chronic persistent hepatitis in 2 and unresolved hepatitis in 6. The frequency of previous transfusion in chronic hepatitis, cirrhosis and hepatocellular carcinoma of type NANB was 42.8, 37.1 and 15.1%, respectively, whereas the incidence of early posttransfusion hepatitis was 8.5, 8.6 and 7.5%, respectively. in chronic liver diseases with a history of jaundice and/or hepatitis, previous transfusions are more frequently associated with type NANB than with type B disease. The present study demonstrates that NANB posttransfusion hepatitis tends to develop to chronic liver disease when analyzed prospectively as well as retrospectively.

Two hundred fifty-eight patients with clinically and serologically proven sporadic acute viral hepatitis during a period of past 7 years (January 1976-December 1982) were analyzed regarding epidemiology and outcome. The frequency of non-A, non-B (NANB) hepatitis was the highest among the three categories of viral hepatitis; 118 patients had hepatitis NANB (46%), 70 hepatitis A (27%), and 70 hepatitis B (27%). In NANB hepatitis, the mean age was older than in other categories of hepatitis and both sexes were equally affected, in contrast to the male predominance in types A and B. Chronic liver disease developed in 32% of patients with NANB hepatitis, but in none of patients with hepatitis type A or B. These results suggest that in Japan the infectious sources of hepatitis NANB virus(es) are more prevalent than those of hepatitis A and B viruses, and also suggest that one of the possible important factors for the high tendency to chronicity may be concerned with intimate contact with, or evolution from, asymptomatic NANB virus carriers.

Fifty-five Japanese HBV carriers under 15 yr of age were followed for 12 months or longer, during which time we investigated the evolution of HBeAg/anti-HBe status and clinical and histological aspects of the liver disease. Of 45 cases positive for HBeAg at the initial examination, 34 remained positive for HBeAg during the follow-up periods, while the remaining 11 lost HBeAg and eight of these seroconverted to anti-HBe. At the final observation, HBeAg positivity in serum was found in as many as approximately 90% of the HBV carriers under 6 yr, but had fallen to 48% in carriers between 12 and 15 yr. The serum transaminase values in 11 cases who lost HBeAg were abnormally elevated for variable periods, but eventually returned to normal. In six of these 11 who had liver dysfunctions, liver biopsy was performed during the HBeAg positive phase or shortly after the disappearance of HBeAg. The histologies of liver were chronic persistent hepatitis in two cases and chronic active hepatitis in four. Repeat liver biopsies of two cases with chronic active hepatitis at the first examination showed nonspecific reactive hepatitis 2 and 4 yr after seroconversion or disappearance of HBeAg. These results indicate that HBeAg-positive HBV carriers with overt liver dysfunctions in childhood are prone to lose HBeAg or to seroconvert to anti-HBe, followed by a marked histological regression, and therefore that special antiviral therapy is probably unnecessary.

Twenty-four patients with chronic non-A non-B hepatitis were randomly assigned to receive either human fibroblast interferon (HuIFN-beta) at doses of 1 or 3 million international units (MIU) per day for 4 or 12 weeks (12 patients) or to receive no therapy (12 patients), and were then compared with 5 patients with chronic type B hepatitis who were treated with HuIFN-beta. Elevated serum aminotransferase levels decreased more rapidly during the treatment of chronic non-A non-B hepatitis than of chronic hepatitis B. Variations in serum aminotransferases were not observed in any of the untreated chronic non-A non-B hepatitis patients. In 3 of the 9 patients with chronic non-A non-B hepatitis who responded to HuIFN-beta therapy, serum aminotransferase levels remained normal 15, 21 and 31 months after therapy was discontinued; liver biopsy specimens obtained after therapy from 2 patients showed marked histological improvement. In the six other patients aminotransferase activity levels became again elevated following cessation of interferon therapy. No response to HuIFN-beta was seen in the remaining 3 patients with chronic non-A non-B hepatitis.

To evaluate the prevalence of hepatitis virus markers and human T-cell lymphotropic virus infections among drug abusers in Japan, serum samples were collected from 91 male drug abusers at the Shinshu University Hospital and the rehabilitation facility in Matsumoto and from 519 healthy male blood donors as controls. Sera were tested for antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), immunoglobulin M anti-HBc (IgM anti-HBc), antibody to hepatitis D virus (anti-HDV), antibody to HTLV type 1 (anti-HTLV 1), and antibody to human immunodeficiency virus (anti-HIV). The prevalence of anti-HAV was 13.2% in drug abusers and 10.8% in controls (not significant). The prevalences of HBsAg, anti-HBs, anti-HBc and exposure rate to hepatitis B virus (HBV) were 4.4%, 24.2%, 31.9%, and 35.2%, respectively, in drug abusers and 0.8%, 6.7%, 9.6%, and 9.6% in controls. The exposure rate to HBV was significantly different (P less than 0.001). IgM anti-HBc and anti-HDV were not detected in any sera. Anti-HTLV I was detected in three drug abusers (3.3%) and in one (0.2%) of the controls (P less than 0.01). All sera were negative for anti-HIV in all subjects. Infection with HBV and HTLV I is more common among drug abusers than in the general population of blood donors in Japan.

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.

Sera and biopsied liver specimens from 45 hepatitis B surface antigen (HBsAg) carriers both with or without overt liver diseases and negative for anti-delta antibody, were examined for markers of hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA) in serum and hepatitis B core antigen (HBcAg) in liver. HBV-DNA in serum was assayed by the spot hybridization technique, and HBcAg in the liver was investigated by the peroxidase anti-peroxidase method. Among the parameters showing active replication of HBV, serum HBeAg, serum HBV-DNA and intrahepatic HBcAg were found in 27 (60%), 27 (60%) and in 22 (48.9%) of 45 HBsAg carriers, respectively. The presence of serum HBV-DNA and of intrahepatic HBcAg in HBeAg positive cases and the absence of serum HBV-DNA and of intrahepatic HBcAg in anti-HBe positive cases was the rule with few disparate cases among those with chronic liver disease. These parameters were not useful in predicting the histology on liver biopsy. The activity of hepatic inflammation in the HBsAg chronic carriers assessed by serum alanine aminotransferase level closely paralleled HBV-DNA in serum but not HBeAg in serum, HBcAg in liver or histologic picture on biopsy. HBV-DNA may be the most sensitive parameter of replication of hepatitis B virus and of the activity of inflammation in the liver.

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.