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Background & Aim Synchronous neoplasms ( SNs) are occasionally found in hepatocellular carcinoma ( HCC). We examined such cases and the efficacy of 18-fluoro-2-deoxyglucose positron-emission tomography computed tomography ( PET/ CT), retrospectively. Materials and Methods We investigated 687 naïve HCC, who were admitted to our hospitals, encountered from October 2006 to December 2010 and evaluated the clinical backgrounds. All study protocols, was approved by our Institutional Ethics Committee. The usefulness of detecting SNs by PET/ CT was evaluated in 234 patients who underwent PET/ CT ( PET group) and in 453 (non- PET group) examined in the same period. We noted the presence of SNs, defined as primary extrahepatic malignant neoplasms within 1 year of diagnosis of HCC. Results SNs were observed in 48 of 687 patients (54 tumours, 7.0%). SNs were detected by PET/ CT in 18, which was 7.7% of PET group. The detection rate for SNs, were increased to 11.1% (26/234) in PET group by using together with upper gastrointestinal endoscopy and routine enhanced CT for HCC, which was greater than that of non- PET group (22/453, 4.9%) ( P < 0.001). Conclusion SNs were pointed out more frequently in PET group than non- PET group (11.1% vs. 4.9%). FDG PET/ CT can enhance the detection ability for SNs in naïve HCC. [ABSTRACT FROM AUTHOR]

Background Biliary atresia is a progressive biliary injury which occurs only in infants. Aims To review the experience of patients surviving into adulthood without the need for liver transplantation in childhood. Methods A multicentre review of patients with biliary atresia treated surgically who survived into adulthood without the need for transplantation. Results Twenty-two patients were identified across four centres. Median age at the last follow-up was 25 years (range: 18-46), and 21 patients had clinical features of portal hypertension. At last follow-up values of liver enzymes varied from normal to 15 × the upper limit of normal ( ULN) for ALT (median 2.11 × ULN) and 9 × the ULN for ALP (median 2.02 × ULN). Six patients had a serum bilirubin > 50 μmol/l. Pruritus and jaundice were noted in 8 of 20 patients (40%) and 11 of 22 patients (50%) respectively. Thirteen patients (59.1%) were shown to have imaging features of sclerosing cholangitis, with strictures of intrahepatic bile duct(s) ( IHBD), dilatation of IHBD ( n = 8), or stone(s) within the IHBD ( n = 5). A history of presumed bacterial cholangitis was present in 11 patients (50%). Successful pregnancies were recorded in three of fourteen female patients. Four patients underwent transplant between the ages of 20-27 years. Twenty-one patients (95.5%) were alive, including 18 (81.8%) with their native liver at the time of last follow-up. Conclusions Some patients treated for biliary atresia will survive into adulthood with their native liver, but commonly with secondary biliary disease including cholangitis and portal hypertension. [ABSTRACT FROM AUTHOR]

im: Patients infected with hepatitis C virus (HCV) genotype 2 are more sensitive to interferon (IFN) therapy than those infected with genotype 1, but 10-20% of patients do not achieve a sustained viral response (SVR) to combination therapy with pegylated (PEG) IFN and ribavirin (RBV). This study examines the prognostic factors associated with SVR in patients infected with HCV genotype 2 treated with PEG IFN and RBV. Methods: We treated 149 patients with chronic hepatitis C caused by HCV genotype 2. The patients received s.c. PEG IFN-α-2b (1.5 µg/kg) and a weekly weight-adjusted dose of RBV (600, 800 and 1000 mg per <60, 60-80 and >80 kg, respectively) for 24 weeks and then prognostic factors associated with the SVR were examined. Results: Among the 149 patients, 138 completed the combination therapy and a sustained viral response was achieved in 71.8% of them. Univariate analysis showed that age, as well as mean RBV and PEG IFN doses were factors affecting the SVR ( P = 0.012, =0.021, =0.014). Multivariate analysis identified age and mean PEG IFN dose ( P = 0.021, =0.018, respectively) as factors involved in the SVR, but not mean RBV dose. Conclusion: The SVR of patients infected with HCV genotype 2 depended on the dosage of PEG IFN, but not of RBV. Selecting sufficient doses of PEG IFN for combination with RBV is critical for treating such patients. [ABSTRACT FROM AUTHOR]

Hypoglycemia caused by insulin-like growth factor II is difficult to control. A 77-year-old woman was diagnosed with gastric cancer and multiple liver metastases in September 2006 and underwent chemotherapy; however, at that time there were no symptoms of hypoglycemia. From January 2007 onwards, hypoglycemic comas and symptoms of hypoglycemia began to appear frequently. Her serum level of insulin was normal; thus, we suspected the presence of big insulin-like growth factor II was causing the hypoglycemia. This was proven by Western immunoblotting and we diagnosed non-islet cell tumor hypoglycemia associated with gastric cancer. Overnight nutrition provided via a central venous catheter port to prevent hypoglycemia allowed the patient to become ambulant and to remain free of hypoglycemic coma at follow-up until her death 7 months later. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). Methods: We assayed total branched-chain amino acids (BCAA), tyrosine (Tyr) levels and their ratio (BTR) in sera of 101 patients with CH (37 in fibrosis stage F1, 23 in F2, 21 in F3) and 20 with LC (F4) who were diagnosed by liver biopsy. Their levels in relation to the staging of liver fibrosis were analyzed. Results: The percentage of patients whose BTR was less than the normal range was 32.1% in CH and 75.0% in LC. The levels of BTR and BCAA were significantly lower ( P < 0.001, P < 0.05, respectively) and that of Tyr was significantly higher ( P < 0.001) in patients with LC than those in CH. The levels of BTR decreased according to the staging. The levels of Tyr increased according the staging, whereas the levels of BCAA deceased prominently in F4 (487 ± 103 in F1, 483 ± 122 in F2, 487 ± 111 in F3 and 423 ± 94 in F4). Conclusion: A considerable number of patients not only with LC but also with CH showed lower levels of BTR. It has been clarified that amino acid imbalance of Tyr was found in the early stage of liver disease, whereas decrease of BCAA was found mainly in F4 stage. [ABSTRACT FROM AUTHOR]

Background and Aim: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (≥ 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. Methods: Two hundred six patients with HCC, who were within the Milan criteria, with low-grade performance status (0 or 1) and a Child-Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e-HCC group; ≥ 75, n = 63) and non e-HCC group (< 75, n = 143), and their clinical data and survival rates were compared. Results: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA-II) were higher in the e-HCC group as compared with the non e-HCC group (78.3 ± 3.2 vs 64.2 ± 7.5 years, 676.3 ± 2643.7 vs 142.4 ± 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child-Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e-HCC group: 82.5% and 49.7%, respectively; non e-HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e-HCC group. Conclusions: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients. [ABSTRACT FROM AUTHOR]

Little is understood about worldwide changes in the epidemiological distribution of the etiology of liver cirrhosis (LC). The present study examines the etiology of liver cirrhosis in Japan using a nationwide survey. We analyzed data from 33,379 patients with LC at 58 hospitals and presented the findings in a poster symposium regarding the etiology and clinical features of LC in Japan that was included in the program of the 44th Annual Meeting of the Japan Society of Hepatology. We identified the distribution of the etiology of LC and compared the present with previous Japanese findings to estimate the future of etiological changes in LC. The etiological agents were as follows: hepatitis B virus (HBV) 13.9%, hepatitis C virus (HCV) 60.9%, alcohol 13.6%, primary biliary cirrhosis (PBC) 2.4% and autoimmune hepatitis (AIH) 1.9%. Cirrhosis was considered to be related to nonalcoholic steatohepatitis (NASH) in 2.1% of the patients. The ratio of HCV-related LC was significantly higher among patients with hepatocellular carcinoma (HCC) ( P < 0.0001) compared to those without, whereas the ratios of alcohol, PBC, AIH were lower. HCC was evident in 31.5% of NASH-related LC. The major etiology of liver cirrhosis in Japan remains HCV. Our survey revealed the prevalence of NASH-related LC in Japan and the frequency of HCC. Future changes in etiology must be considered in establishing preventive or educational strategies, as well as in developing new treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC). Aims: The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV. Methods: This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance. Results: Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and γ-glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis. Conclusions: A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV. [ABSTRACT FROM AUTHOR]

Fibrosing cholestatic hepatitis (FCH) is a serious disease in patients with recurrent hepatitis C after liver transplantation (LTx). Antiviral therapy is indicated in these patients; however, it is not always effective, and the prognosis of FCH is generally poor. Double filtration plasmapheresis (DFPP) has been shown to be effective at eliminating hepatitis C virus (HCV) in patients with chronic hepatitis C. We report a case of FCH with severe cholestasis (total bilirubin 34.2 mg/dl) after LTx. Combination therapy with interferon (IFN) and ribavirin (RBV) was unsuccessful for improving cholestasis; however, the addition of DFPP to IFN and RBV alleviated cholestasis and improved renal function. Although IFN and RBV with DFPP could not eliminate HCV, results of liver function tests improved and remained stable for several months. This treatment with DFPP combined with IFN and RBV would be useful for resolving cholestasis due to FCH. Moreover, treatment of DFPP could improve liver and renal function test results and could stop the worsening condition of patients with FCH. [ABSTRACT FROM AUTHOR]

Background: There is a lack of information regarding the laparoscopic features and interobserver variation of histological diagnosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Thirty-five patients with NAFLD were studied for laparoscopic and histological findings. For the study of interobserver variation of histological diagnosis, two pathologists from different hospitals independently observed the 35 liver samples with patient names blinded to the pathologists. Assessment of laparoscopic findings on the diagnosis of non-alcoholic steatohepatitis (NASH) was also investigated. Results: Histological diagnoses of the two pathologists were identical in 28 (five fatty liver, 23 NASH) patients, whereas they were not identical in seven patients (20%). The difference of diagnosis was mainly caused by the difference of judgment of minimal fibrosis and minimal necroinflammatory grade. Analysis of the laparoscopic findings revealed that small regular depressions were frequently found on the liver surface in patients with NASH. Scatter of dye on the liver surface facilitated the observation of this finding. Sensitivity and specificity of small depressions in the diagnosis of NASH was 73.9% and 80.0%, respectively. Conclusion: Interobserver variation of the diagnosis was found in 20% of patients with NAFLD. Small regular depressions were characteristic findings of NASH. Laparoscopy is assessed to be useful for diagnosis of NAFLD, especially of early stage of NASH. [ABSTRACT FROM AUTHOR]

Objective: Hepatitis B virus (HBV) genotypes B and C are predominant in Japan. Previously, we reported that approximately 9% of HBV carriers in the Ehime area of western Japan were infected with genotype D (HBV/D) and their sequences closely related. Recently, serum samples from 3 patients with chronic HBV/D infections living in Tokyo and the surrounding area became available for testing. The purpose of this study was to determine whether the HBV/D isolates from these different areas of Japan are closely related. Methods: Of the 3 Tokyo area patients infected with HBV/D, 2 had chronic hepatitis, and 1 had hemophilia with a history of frequent coagulation factor injections. The complete HBV/D genome sequences of each were determined, and compared with those of subjects from the Ehime area. Results: All 3 HBV/D sequences had a genomic length of 3,182 bases, and the hepatitis B surface antigen subtype was ayw3. Phylogenetic analysis revealed that the 1 of the HBV/D isolates was closely related to the isolates from Ehime Prefecture, while 1 was similar and 1 was clearly distinct. Conclusion: Our results indicate that HBV/D infections in Japan are heterogeneous. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually develops in middle-aged women. However, due to the increasing aging of the population and better diagnostic facilities, AIH is now diagnosed in older patients as well. This analysis compared the clinical and pathologic characteristics of older and middle-aged patients with AIH. Patients and methods: Thirteen older patients with AIH (mean age, 75.0±5.3 years; range, 70–89 years) and 27 middle-aged patients (mean age, 51.3±5.8 years; range, 41–60 years) were included in this study. In addition, the use of different treatment regimens, including prednisolone therapy and ursodeoxycholic acid (UDCA), was examined. Results: There were no significant differences in gender, complications of other autoimmune diseases, and liver function tests between groups. However, the degree of hepatic fibrosis was significantly higher in older patients compared with middle-aged patients (P <0.05). Four patients with AIH in the older age group were successfully managed by UDCA alone. Conclusion: This study shows that older patients with abnormal liver function should be checked for AIH. In addition, UDCA may be an effective drug for management of older patients with AIH. [Copyright &y& Elsevier]

Background. Variceal bleeding is a common, lifethreatening complication of primary biliary cirrhosis (PBC). Recently, several reports have suggested that the existence of esophageal varices in patients with PBC is a significant factor in the assessment of disease prognosis. However, there have been no reports on the recurrence of esophageal varices following treatment in patients with PBC. In this study, we investigated the recurrence of esophageal varices in PBC patients and attempted to identify predictive factors for the recurrence of esophageal varices. Methods. Between April 1993 and August 2003, 138 patients with esophageal varices who had been treated by endoscopic variceal ligation (EVL; 96 men and 42 women; age, 33-83 years; mean, 62.6 ± 10.1 years), were enrolled in the present study. The diagnosis of esophageal varices was made by upper gastrointestinal endoscopy, and the varices were graded according to the criteria of the Japanese Research Society for Portal Hypertension. The relationship between the recurrence of esophageal varices and factors such as biochemical and hematological parameters, as well as the etiology of the liver disease, was analyzed using the Kaplan-Meier method and the multivariate Weibull regression model. Results. PBC patients had an earlier recurrence of esophageal varices compared to non-PBC patients, and two factors, prothrombin time and etiology (PBC/non-PBC), were indicative of significantly earlier recurrence of esophageal varices. Conclusions. We should be extra careful in the follow-up of patients with PBC after therapy for esophageal varices. [ABSTRACT FROM AUTHOR]

Ultrasound (US)-guided ethanol injection therapy is becoming popular as a therapeutic tool for treating hepatocellular carcinoma (HCC); however, there are some HCCs seen on computed tomography (CT) and not visualized on US. The aim of this study was to learn whether ethanol could be injected into such tumors correctly using a specially designed needle-guide for intercostal puncture on US. We developed a new needle-guide attachment for US. In vitro experiments were done with gelatin gel and porcine liver to evaluate the accuracy of the puncture depth. We calculated the difference between the distance from the surface to the needle tip and the set depth as errors. Fifteen patients with HCC in which CT revealed a tumor but US did not were subjected to US-guided ethanol injection using this needle-guide, and the entry of ethanol into tumors was confirmed by subsequent enhanced CT. The errors were within 1.0 mm in the in vitro experiments using gelatin gel and porcine liver. In all HCC patients, ethanol was injected accurately. This new needle-guide may be useful for needle insertion to HCCs seen on CT and not visualized on US. [Copyright &y& Elsevier]

A 70-year-old man was admitted to our hospital with recurrent encephalopathy. Liver function tests, abdominal computerized tomography, ultrasonography, angiography, and laparoscopy revealed an intrahepatic portovenous shunt in a noncirrhotic liver. During follow-up, the intrahepatic portovenous shunt closed spontaneously. Subsequent liver function tests were markedly improved, with resolution of the patient's previously disturbed consciousness. In the elderly, intrahepatic portovenous shunt that can be managed with conservative therapy may spontaneously close, suggesting that management options should include watchful waiting. [ABSTRACT FROM AUTHOR]

Eighty-five Japanese patients with drug-induced liver injury were assessed by criteria of Consensus Meetings in Europe on causality assessment of drug-induced liver injury. Histopathological investigation was performed for all patients to confirm the diagnosis. We divided these patients into two groups by the date of disease onset. Cases before 1989 were defined as past cases, and those after 1990 as recent cases, because the clinical-pathological characteristics of drug-induced liver injury have changed due to the ability to diagnose hepatitis C virus infection since 1990. Fifty-seven patients with drug-induced liver injury were enrolled as past cases, and 28 as recent cases. For past cases, the results of assessment by the criteria of Consensus Meetings in Europe were as follows: ‘very likely’: 14 patients (25%), ‘likely’: 23 patients (40%), ‘possible’: 15 patients (26%), ‘dubious’: five patients (9%), and ‘unlikely’: none (0%). For recent cases, the results were as follows: ‘very likely’: six patients (22%), ‘likely’: 14 patients (42%), ‘possible’: six patients (22%), ‘dubious’: two patients (7%), and ‘unlikely’: none (0%). There were no differences between the past and recent cases in distribution of assessment. More than 90% of patients were assessed as ‘possible’ or more, and the remaining seven patients were assessed as ‘dubious’. No patients were assessed as ‘unlikely’. Five of seven patients assessed as ‘dubious’ had long-term cholestasis, and two had alcohol consumption. These results indicated that the criteria of Consensus Meetings in Europe were useful for diagnosing drug-induced liver injury in Japanese patients. [Copyright &y& Elsevier]

We report a case of peliosis hepatis associated with placental site trophoblastic tumor (PSTT) of the uterus. A 46-year-old woman was admitted to our hospital with complaints of leg edema, pleural effusion and ascites, complicated with esophageal varices. Peritoneoscopy did not show any evidence of liver cirrhosis and liver biopsy revealed peliosis hepatis. Later, uterine tumor was detected and, after a hysterectomy, peliosis hepatis and esophageal varices were dramatically improved. We suggest that the uterine tumor caused peliosis hepatis with fibrosis and that portal hypertension developed as a consequence of these lesions. The present case is of interest because esophageal varices were improved without ordinary treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to elucidate the morphometric changes occurring in hepatic lymphatics in primary biliary cirrhosis (PBC). The lymphatic vessels were stained intensely by enzyme-histochemistry for 5′-nucleotidase while blood vessels stained well for alkaline phosphatase (ALP). We performed a morphometric analysis to estimate the number of lymphatic and blood vessels and their areas, using computer graphics software (NIH Image). Both the number of lymphatics and their areas in specimens in patients with PBC at an early stage were found to have increased. Neither the number nor the areas of the blood vessels showed any obvious relationship with the degree of fibrosis of PBC. Our results clarified that the sizes and number of lymphatics are increased even in the early stage of PBC. This is thought to be due to increased lymph production, which is caused by disturbance of the microcirculation associated with portal hypertension. [Copyright &y& Elsevier]

Background/aims: The function and phenotype of antigen-presenting dendritic cells (DC) have been checked in patients with chronic hepatitis (CH) undergoing vaccine therapy to have insight about the mechanism of this immune therapy. Subjects and methods: Eleven patients with CH due to hepatitis B virus (HBV) were injected with vaccine containing 20 μg of hepatitis B surface antigen (HBsAg) once at every 2 weeks for 12 consecutive times. The serum interluekin-12 levels were estimated and the function and phenotype of peripheral blood DC were checked before, during and after the vaccine therapy. Results: Sustained normalization of DNA-polymerase activity and alanine aminotransferase were seen in six patients (complete responders [CR]) due to vaccine therapy. The levels of serum interleukin-12 (P<0.01), the stimulatory capacity of peripheral blood DC (P<0.05) and the numbers of CD83-positive mature DC and CD86-positive activated DC (P<0.05) were significantly increased due to vaccination in CH-B patients, especially in younger patients. Conclusions: A role of DC during vaccine therapy is shown. This study also indicates that more effective vaccine therapy can be developed by upregulating the function of DC in situ in younger patients. [Copyright &y& Elsevier]

In order to dissect the role of different subsets of antigen-presenting dendritic cell (DC) in autoimmune liver diseases, we analyzed the frequencies and phenotypes of DC1 and DC2 from patients with primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH). The numbers of DC, DC1 and DC2 in a fixed amount of peripheral blood (20 ml) from 14 patients with PBC (therapy [−]: 5, therapy [+]: 9), seven patients with AIH (therapy [−]): 4, therapy [+]: 3), nine patients with chronic hepatitis due to hepatitis C virus and 12 healthy subjects were estimated using three-color flow cytometry. The mean fluorescence intensities of HLA DR, CD11c and CD123 on DC subsets were evaluated from the flow cytometric profiles. The numbers of DC1 and DC2 did not differ significantly among patients and controls. The expression of HLA DR was lower on DC1 from patients with AIH, but not on PBC. However, the levels of HLA DR and CD 123 on DC2 were significantly decreased in patients with PBC (therapy [−]) and AIH (therapy [−]) compared with healthy subjects (P<0.05). Defective phenotype of DC2 in both AIH and PBC may have a relevance to the breakdown of tolerance to self antigen in these autoimmune diseases. Functional study of DC2 in autoimmune liver diseases is warranted. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV)-RNA titre has been regarded as a factor affecting the response to interferon (IFN) therapy of patients with chronic hepatitis C (CHC). The focus of our study is the investigation of the nucleotide sequence of HCV-RNA NS5B, which may code RNA-dependent RNA polymerase and NS5A in the sera of 33 patients with CHC prior to IFN therapy. Methods: Hepatitis C virus genotype and HCV-RNA titre were examined by polymerase chain reaction (PCR) and competitive reverse transcriptase-PCR. Results: The sequence for HCV-RNA NS5B (nt 8331–8600 in 1b and 8410–8679 in 2a) was determined by direct sequencing. The changes of the predicted amino acids in the genotype-specific sites of HCV-J, HCV-BK, HC-J4/83, HCV-JT, HCV-N, HC-J6 and HCV-K2a were examined, and the mutation was defined when changes of amino acids in sites specific to different reported genotypes were revealed. The mutations were observed in 6/19 (32%) in genotype 1b and 9/14 (64%) in 2a. In the 1b group, complete response (CR) was achieved in 5/6 of the mutant and in 2/13 of the wild type groups (P < 0.05). No relationship was observed between IFN effectiveness and HCV-RNA titre in the 1b wild type group. In the 2a group, CR was achieved in 4/9 of the mutant and in 4/5 of the wild type groups. An inverse relationship between IFN responsiveness and HCV-RNA titre was apparent in 1b mutant, 2a wild and 2a mutant. Conclusions: These data suggest the possible relationship between changes in the HCV-NS5B gene and the effect of IFN therapy in CHC patients with genotype 1b. [ABSTRACT FROM AUTHOR]

To study the intrafamilial transmission of hepatitis C virus (HCV), 36 family members of 16 patients with anti-HCV (anti-C100-3)-positive chronic liver disease were screened for anti-HCV by an enzymelinked immunosorbent assay (ELISA). Clusters of anti-HCV -positive individuals were observed in 2 of 16 families (12.5%). Four of 35 family members (11.4%) with no history of blood transfusion were positive for anti-HCV. Two of 17 offspring (11.8%) of anti-HCV-positive females were positive for anti-HCV, while 1 of 5 spouses (20.0%) was positive for anti-HCV. These data suggest that intrafamilial transmission is one of the possible routes of infection for HCV. [ABSTRACT FROM AUTHOR]

To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20% ), and in 5 out of 9 with multiple myeloma (56% ). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibodypositive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV -related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma. [ABSTRACT FROM AUTHOR]

ABSTRACT- The expression of intercellular adhesion molecule-1 (ICAM-1) on the hepatocyte membrane was studied in 27 patients with chronic hepatitis B and C (CHB, CHC) by immunostaining using a monoclonal antibody. ICAM-1 was expressed focally in a honeycomb-like pattern by hepatocytes in livers of 26/27 patients. The degree of ICAM-1 expression was closely related to the ALT level and the histological grade of liver damage. Abundant cytotoxic T cells (CD8 +, CD11b -) were found in ICAM-1-positive areas of the liver. Zones of focal necrosis contained both ICAM-1-positive hepatocytes and cytotoxic T cells. The expression of ICAM-1 was decreased in 4/6 CHB patients after interferon-α therapy. No relationship between the degree of hepatocyte ICAM-1 expression and viral replication markers (DNA polymerase activity and the presence of HBcAg in the liver) was observed in patients with CHB. In addition, no positive correlation was found between the distribution of ICAM-1-positive hepatocytes and HBcAg-positive hepatocytes. These results suggest that ICAM-1 may play an important role in the pathogenesis of hepatocellular injury mediated by cytotoxic T cells in CHB and CHC. [ABSTRACT FROM AUTHOR]

ABSTRACT- Hepatitis B virus (HBV) DNA was detected by in situ hybridization in 53 out of 74 liver specimens from patients with chronic HBV infection. The distribution of HBV DNA was classified into three patterns: diffuse (HBV DNA distributed diffusely, within the section of specimen), lobular (HBV DNA was present in 1/3-2/3 of the section) and spotty. All three specimens from asymptomatic HBV carriers showed the diffuse pattern. In the advanced stage of liver disease (chronic active hepatitis with severe activity and liver cirrhosis), a decreased number of specimens showed the diffuse pattern, whereas the number of specimens with the lobular pattern increased. From these data, we conclude that HBV may replicate diffusely in the liver in the early stage of chronic liver disease, and the site of HBV replication becomes localized in the advanced stage of the disease. The main target cells of immunocytes may be hepatocytes undergoing HBV replication, because HVB DNA was frequently detected in areas of focal, piecemeal and bridging hepatic necrosis. [ABSTRACT FROM AUTHOR]