Impaired lipopolysaccharide-inducible tumor necrosis factor production in vitro by peripheral blood monocytes of patients with viral hepatitis

We investigated lipopolysaccharide-induced tumor necrosis factor production in vitro by peripheral blood monocytes from patients with various liver diseases. Tumor necrosis factor production was found to be significantly reduced in patients with chronic hepatitis B (n = 17; 135 +/- 30 pg tumor necrosis factor/ml; mean +/- S.E.M.) and patients with chronic non-A, non-B hepatitis (n = 15; 212 +/- 22 pg tumor necrosis factor/ml) compared with healthy control individuals (n = 47; 411 +/- 40 pg tumor necrosis factor/ml; p less than 0.0005 and p less than 0.01, respectively). This reduced tumor necrosis factor production was not only seen with an optimal stimulating concentration of lipopolysaccharide (100 ng/ml) but also with suboptimal concentrations (0.1 ng/ml). In contrast to patients with chronic viral hepatitis, monocytes from patients with alcohol-induced cirrhosis (n = 26; 444 +/- 49 pg tumor necrosis factor/ml), primary biliary cirrhosis (n = 7; 412 +/- 81 pg tumor necrosis factor/ml) and alcohol-induced fatty liver changes (n = 5; 401 +/- 62 pg tumor necrosis factor/ml) produced normal amounts of tumor necrosis factor when stimulated with an optimal concentration of lipopolysaccharide. Lipopolysaccharide (0.1 ng lipopolysaccharide/ml)-stimulated peripheral blood monocytes of patients with chronic hepatitis B (n = 15; 102 +/- 32 pg/ml) or non-A, non-B hepatitis (n = 13; 97+/- 16 pg/ml) could not be induced to produce more tumor necrosis factor either when prestimulated with gamma-interferon (170 +/- 45 pg/ml and 149 +/- 32 pg/ml, respectively), a lymphokine known to activate monocytes, or with the cyclooxygenase inhibitor indomethacin to reduce the suppressive effect of prostaglandin E2 (148 +/- 40 pg/ml and 153 +/- 45 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunophenotyping of lymphocytes in liver tissue of patients with chronic liver diseases by flow cytometry.

Immunological factors are important in the pathogenesis of a spectrum of hepatobiliary diseases. To characterize the nature of specific immunological responses in liver disease, we determined lymphocyte changes in liver tissue and in blood using flow cytometry. A total of 113 liver biopsy specimens was collected from patients with the following diseases: 19 chronic hepatitis B; 39 chronic non-A, non-B hepatitis; 27 alcoholic liver disease; 10 hepatic malignancy; 8 autoimmune hepatitis; 6 fatty liver and 4 primary biliary cirrhosis. The lymphocytes were isolated from the liver biopsy specimens by mechanical and enzymatic methods. The lymphocyte yield was 7,901 +/- 575 cells/mg of liver tissue. The viability of lymphocytes was 97.7% +/- 0.3%. Lymphocytes were stained with four pairs of two-color mixed fluorescein-conjugated monoclonal antibodies, including T4-T8 (CD4/CD8), T11-B1 (CD2-CD20), NKH1-T8 (CD56-CD8), IL-2R1-T11 (CD25-CD2), and the ratios were determined by an Epics Profile flow cytometer. Immunophenotyping of lymphocytes in whole blood samples was simultaneously analyzed. Variability in lymphocyte yield and different patterns of lymphocyte subsets were found in the liver biopsy specimens. The yields of lymphocytes from patients with chronic non-A, non-B and autoimmune hepatitis were highest, and the lowest yield was from patients with fatty liver. Patients with primary biliary cirrhosis, fatty liver and hepatic malignancy had relatively high ratios of CD4/CD8, CD56/CD8 and CD25/CD2; whereas patients with chronic hepatitis B, autoimmune hepatitis and non-A, non-B hepatitis had lower ratios of CD4/CD8, CD56/CD8 and CD25/CD2. No difference in lymphocyte ratios between the patients with cirrhotic and noncirrhotic alcoholic liver disease was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relative Versus Absolute Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

BACKGROUND: Carbohydrate-deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate-deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis. METHODS: Absolute concentrations (U/I) and relative values (%) of carbohydrate-deficient transferrin determined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionnaire) in patients with acute alcoholic hepatitis (n = 19), alcoholic liver cirrhosis (n = 37), and nonalcoholic liver diseases (n = 16). RESULTS: The concentration of carbohydrate-deficient transferrin was increased (p < 0.001) in nonabstaining patients (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 +/- 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 +/- 7.8 U/l) despite higher alcohol consumption (median 130 g/d), nor in abstainers with alcoholic liver cirrhosis (19.4 +/- 6.0 U/l) or nonalcoholic liver disease (18.5 +/- 6.7 U/l). However, the relative values of carbohydrate-deficient transferrin were increased both in acute alcoholic hepatitis (7.9 +/- 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 +/- 2.8%), but not in abstainers with alcoholic liver cirrhosis (4.6 +/- 3.5%) or nonalcoholic liver disease (3.8 +/- 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, respectively, but 79% and 97% for relative values of carbohydrate-deficient transferrin. The concentrations of carbohydrate-deficient and total transferrin in serum were strongly correlated (r = 0.60; p = 0.008). CONCLUSIONS: The relative value (% of total), but not the absolute concentration, of carbohydrate-deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.     

Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease

We investigated the role of the interferon system in the pathogenesis of chronic liver disease. Interferon-gamma production by peripheral blood mononuclear cells was measured with an ELISA. While concanavalin A-stimulated and recombinant interleukin 2-stimulated production of interferon-gamma in patients with chronic active hepatitis and liver cirrhosis was significantly decreased when compared with that of controls (518 +/- 189 and 729 +/- 195 units per ml, mean +/- S.D.), there was also a lot of overlap. Addition of indomethacin to the cultures partially restored interferon-gamma production in patients with chronic active hepatitis and liver cirrhosis, indicating that suppressor function of monocytes was, in part, responsible for the diminished interferon-gamma production. Serial studies showed that interferon-gamma production rose during acute deterioration of illness, during treatment with interleukin 2 and with the improvement of clinical course. Interferon-gamma production was not different among hepatitis B e antigen or antibody positive, and non-A, non-B patients with chronic active hepatitis and liver cirrhosis. Our findings suggest that diminished interferon-gamma production is associated with disease severity in chronic liver disease, irrespective of the hepatitis B virus carrier state. It would be interesting to compare the efficacy of treatment with interferon-gamma or interferon-gamma inducers such as interleukin 2 in chronic hepatitis B patients with and without decreased in vitro interferon-gamma production.     

Establishment of a human T-cell clone cytotoxic for both autologous and allogeneic hepatocytes from chronic hepatitis patients with type non-A, non-B virus.

A human T-cell clone (TA-NB-2) that could lyse both autologous and allogeneic hepatocytes from chronic hepatitis patients with type non-A, non-B virus (NANB) was established. This clone produced CD3+ CD8+ cytotoxic T lymphocytes and expressed an antigen specific for alpha and beta subunits of T-cell receptor. The cytotoxic activity of the clone was abrogated by incubation with anti-CD3 monoclonal antibody. Anti-HLA monoclonal antibodies did not block the lysis of the target hepatocytes by TA-NB-2 cells. The cytotoxicity of TA-NB-2 clone against hepatocytes from patients with chronic NANB hepatitis was 39.8 +/- 13.2% (mean +/- SD; n = 17) (range, 14.2-60.5%), whereas that against hepatocytes from control patients with chronic type-B hepatitis, acute hepatitis B, acute hepatitis A, or alcoholic liver cirrhosis was 4.0 +/- 7.7% (n = 12) (range, -10.8 to 14.0%). The results suggest that TA-NB-2 cells specifically recognize a hepatitis NANB-related antigen expressed on hepatitis NANB-infected hepatocytes by T-cell receptor and that the recognition is not restricted by the major histocompatibility complex antigens. The results also suggest that most, if not all, cases of chronic hepatitis due to NANB are caused by one agent; TA-NB-2 clone may be useful as a tool to identify this particular hepatitis-related antigen.     

Chronic hepatitis with fatty change

Ten patients with clinical features of chronic hepatitis showed on liver biopsy histologic evidence of chronic hepatitis plus predominantly moderate to severe fatty change. No patient had a history of excess alcohol intake, or prolonged intake of hepatotoxic drugs and steroids, and were not obese or malnourished. These cases differ from the reported cases of non-alcoholic steatohepatitis resembling alcoholic hepatitis as they occurred in relatively young healthy adults, predominantly males, who were not diabetic or obese. Mallory's hyalin in liver was absent in all cases. Ingestion of toxic substances was possible but no history was obtained to account for it. While these could be unusual cases of chronic non-A, non-B hepatitis, this can be only speculation until a serologic test for non-A, non-B hepatitis becomes available. Follow-up of eight patients for 1–3 years with liver biopsy showed that they had a relatively benign course with no evidence of progression to cirrhosis.     

Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis

The in vitro production of interleukin-1 by peripheral blood monocytes derived from patients with various liver diseases was studied. An impaired production of immunoreactive interleukin-1 (IL-1) (mean±sem) by monocytes stimulated, with an optimal dose (100 ng/ml) of lipopolysaccharide was observed in patients with chronic hepatitis B (N= 13; 32±6 pg/ml) or chronic hepatitis C (N= 13; 61±12pg/ml) as compared to those of healthy control individuals (N=35; 166±24 pg/ml;P=0.0003 andP=0.015, respectively), whereas an unaltered, IL-1 production was seen in patients with alcoholic cirrhosis (N=23; 125±28 pg/ml) and primary biliary cirrhosis (N=6; 111±33pg/ml) Similar to the situation seen in chronic viral hepatitis, lipopolysaccharide-stimulated monocytes from patients with acute hepatitis also showed a decreased IL-1 production in the first week after onset of jaundice (N=17; 55±20 pg/ml;P=0.001) and a return to normal in the second and third week. An impaired production of IL-1 in chronic as well as acute viral hepatitis is a further example of the known disturbed immunoregulation in this disease.     

Long-term analysis of non-A, non-B hepatitis--clinical, histologic and immunologic findings

By means of a long-term analysis of histological and clinical-biochemical data taken of a group of patients (n = 38) having contracted an acute viral hepatitis non-A, non-B with a uniform parenteral source of infection evidence is given concerning the dynamic processes in the course of chronic non-A, non-B hepatitis. The analysis was therefore not based on the total biopsy material but on a section of 143 liver biopsies of patients who had been punctured at least 3 times (up to 6 times) in the 7 years of examination. A rate of 57,2% chronic persistent and 42,8% chronic lobular hepatitis was ascertained. A chronic active hepatitis or liver cirrhosis were not found. Both the histological activity degrees and ALAT-mean values were declining during the follow-up study though attacks (ALAT) and histological reactivations were observed in the 7th year, too. The data suggest that the chronic liver changes that developed in this type of non-A, non-B hepatitis proved to be extremely lingering but as a whole a regressive tendency could be observed.     

Low prevalence of hepatitis C antibodies in chronic liver disease in Finland.

High prevalence of hepatitis C antibodies (anti-HCV) have been found in the Middle- and Southern European countries in connection with chronic liver diseases. In a study of Finnish chronic liver disease patients no anti-HCV antibodies were found in 22 autoimmune chronic active hepatitis, in 5 chronic persistent hepatitis and in 38 alcoholic liver disease patients. 2/30 primary biliary cirrhosis patients were anti-HCV positive. As a comparison 3/9 patients with acute community acquired non-A non-B hepatitis and 28/48 i.v. drug addicts had anti-HCV antibodies. The results indicate that HCV infections in Finnish chronic hepatitis patients are rare.     

Role of hepatitis C virus in non-B chronic liver disease.

To assess the contribution of the recently identified hepatitis C virus to chronic liver diseases of unknown cause and chronic hepatitis attributed by exclusion to non-A, non-B hepatitis, we tested for antibody to hepatitis C in hepatitis B surface antigen-negative patients with a spectrum of chronic liver diseases. Antibody to hepatitis C virus, a marker of hepatitis C infection, was detected with a first-generation radioimmunoassay at the following frequencies in the following patient groups: 69% of transfusion-associated non-A, non-B hepatitis; 53% of non-transfusion-associated non-A, non-B hepatitis; 26% of hepatitis B surface antigen-negative hepatocellular carcinoma; 8% of cryptogenic cirrhosis; 5% to 7% of autoimmune chronic liver diseases; 19% of patients with miscellaneous types of chronic liver disease; and 0.67% of healthy controls. Among non-transfusion-associated cases, 81% with a history of intravenous drug use but only 18% with occupational exposure as health workers had antibody to hepatitis C virus. Among cases of hepatocellular carcinoma, 63% of Japanese patients but only 11% of American patients had evidence of hepatitis C infection. Comparison in a subgroup of 79 serum samples of a second-generation radioimmunoassay with the first-generation assay demonstrated a 12% increase in antibody frequency from 30% to 42%. We conclude that hepatitis C plays a substantial role in transfusion-associated and non-transfusion-associated non-A, non-B hepatitis as well as in hepatocellular carcinoma, especially in Japan, a limited role in cryptogenic cirrhosis, and essentially no role in autoimmune chronic liver diseases. Application of more sensitive immunoassays will increase the frequency of antibody seropositivity in all subgroups, but relative distinctions among risk groups are likely to remain.     

Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease

Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease.     

Prevalence of anti-HCV among Chinese patients with acute and chronic liver disease

To assess whether the hepatitis C virus plays an important role in Chinese patients with acute and chronic liver disease, antibodies to HCV (anti-HCV) were measured by enzyme immunoassay in 67 patients with type A and B acute viral hepatitis, 165 patients with non-A, non-B (NANB) hepatitis, 438 patients with chronic hepatitis, 200 patients with postnecrotic liver cirrhosis, 72 patients with alcoholic liver disease, 55 patients with non-alcoholic fatty liver, 24 patients with toxic and drug-induced hepatitis, and 20 patients with other chronic liver diseases. Anti-HCV was not detected in sera from patients with type A and B acute viral hepatitis, toxic and drug-induced hepatitis, primary biliary cirrhosis, Wilson's disease, or lupoid hepatitis. The anti-HCV prevalence was found to be highest in patients with NANB hepatitis (59% in sporadic and 73.2% in transfusion-associated), 16.4% in non-alcoholic fatty liver, 5.6% in alcoholic liver disease, 6.8% in chronic hepatitis, and 16% in postnecrotic liver cirrhosis. In patients with chronic hepatitis, the anti-HCV prevalence was significantly higher in HBsAg-negative (15/34, 44.1%) than in HBsAg-positive cases (15/404, 3.7%; P less than 0.0001). The results indicate that HCV is a major agent of NANB hepatitis and plays an important role in HBsAg-negative chronic liver disease in Taiwan.     

Clinical Significance of Serum and Urinary Neopterin Levels in Patients with Various Liver Diseases

Serum and urinary neopterin levels were measured by radioimmunoassay in 120 healthy controls, 16 asymptomatic HBsAg carriers, 12 patients with acute hepatitis, 13 with chronic inactive hepatitis, 35 with chronic active hepatitis, 46 with liver cirrhosis, 18 with hepatocellular carcinoma, and 6 with alcoholic liver disease. Serum and urinary neopterin levels were significantly higher in almost all patients than in normal subjects. Neopterin levels were highest in acute hepatitis and correlated with the results of liver function tests, but did not show this correlation in chronic liver disease. In chronic liver disease, the levels of serum neopterin in non-A non-B viral patients was significantly increased, compared with those in B viral and alcoholic patients. The rate of abnormal urinary neopterin levels in chronic liver disease was higher than the rate of abnormal serum neopterin levels, but no difference was observed between the rates of abnormal serum and urinary levels in acute hepatitis and asymptomatic HBsAg carriers. These results indicate that serum and urinary neopterin levels may be useful markers for cell-mediated immunity in liver disease, and that the immune system response in chronic liver disease may be different for different pathogens.     

Long-term follow-up of chronic post-transfusion non-A, non-B hepatitis: clinical and histological outcome

A chart review of chronic hepatitis cases at the Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institute, Stockholm, Sweden, revealed 37 patients with chronic non-A, non-B hepatitis, caused by blood transfusions or intravenous gammaglobulin infusions. They had been followed up long-term, mean 46 months (range 10-149). During the initial hepatitis episode most patients had been anicteric and 13/37 (35%) asymptomatic. Yet, the majority developed progressive liver disease with chronic active hepatitis, with or without histological signs of cirrhosis. Thus, 10/18 (56%) on whom a liver biopsy had been performed within 7-12 months had chronic active hepatitis, four (22%) with histological signs of cirrhosis, and of the five patients biopsied after greater than or equal to 5 years of follow-up, three (60%) had histological signs of cirrhosis. Accordingly, as the duration of follow-up increases, an increasing number of patients with post-transfusion non-A, non-B hepatitis seem to develop cirrhosis.     

Histological changes of the liver by treatment of chronic non-A,non-B hepatitis with recombinant leukocyte interferon alpha

We have treated 17 patients with non-A, non-B chronic hepatitis by recombinant interferon alpha (0.3-9 megaunits for 4-28 weeks). In six patients, serum aminotransferase levels fell to normal or near-normal range during treatment. The mean levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 17 patients fell from 156 +/- 80 (mean +/- SD) and 213 +/- 135 at the beginning of treatment to 94 +/- 49 and 112 +/- 71, respectively, at the end of treatment. In 12 patients, liver biopsies were performed before and after (or during) the treatment, and histological activity indices (HAI) were blindly examined by two independent observers. For comparison, we examined histological changes of pre- and posttreatment liver biopsies of 19 patients who were treated by recombinant interferon for chronic hepatitis B. Mean HAI scores improved from 10.0 to 5.4 after treatment in non-A, non-B chronic hepatitis. The most marked reduction was noted in scores of portal inflammation and hepatocellular degeneration and/or necrosis. No such reduction was observed in B-viral chronic hepatitis. These data indicated that rapid biochemical resolution by the treatment was related to histological improvement of the liver in our patients with non-A, non-B hepatitis.     

Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis.

The long-term outcome of non-A, non-B post-transfusion hepatitis was evaluated in 21 patients who developed the illness after open-heart surgery and could be followed thereafter up to five years. Histological chronic sequelae were documented in 13 patients, and consisted of chronic persistent hepatitis in one case, chronic lobular hepatitis in two and chronic active hepatitis in 10, five of whom also developed superimposed cirrhosis. Progression to these chronic states was in most cases symptomless, independently of the severity of liver lesions; one patient, however, died of gastrointestinal bleeding due to cirrhosis of the liver. During follow-up the biochemical pattern of chronic non-A, non-B hepatitis was unique, while striking fluctuations of transaminase levels. Liver histology proved essential to identify the severity of chronic liver lesions, as clinical and biochemical features were uniform and not indicative of it. Our results suggest that cirrhosis may develop, often with an asymptomatic course, in a significant number of patients who do not recover after acute post-transfusion non-A, non-B hepatitis.     

Serum dolichols in chronic cholestatic liver diseases

BACKGROUND/AIMS: Dolichols are long-chain polyisoprenoid alcohols. It has been suggested that they modify membrane fluidity, stability and permeability. Some lysosomal diseases are associated with elevated serum dolichol levels. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol, however, is not known. METHODS: We therefore studied the effect of early or intermediate primary biliary cirrhosis, primary sclerosing cholangitis and alcoholic liver cirrhosis on serum dolichol concentration. Furthermore, serum dolichol content was measured in patients with end-stage primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis, waiting to be transplanted. RESULTS: As compared to age-adjusted controls, serum dolichol was significantly increased in early and intermediate primary biliary cirrhosis (451+/-56 ng/ml vs. 225+/-13 ng/ml, p<0.0001) and primary sclerosing cholangitis (315+/-16 ng/ml vs. 224+/-7 ng/ml, p<0.0001). However, in alcoholic liver cirrhosis serum dolichol was unaffected. Serum dolichol content was also significantly elevated in patients with end-stage primary biliary cirrhosis (844+/-210 ng/ml vs. 225+/-13, p<0.001) and chronic active hepatitis (594+/-198 vs. 224+/-7 ng/ml, p<0.02). Furthermore, in patients with liver diseases serum dolichol concentration correlated positively with serum high density lipoprotein (HDL)-cholesterol (r = +0.50, p<0.0001). CONCLUSIONS: Serum dolichol levels are elevated in all stages of chronic cholestatic liver diseases but not in alcoholic liver cirrhosis. Impaired biliary excretion of dolichols appears to be the primary explanation for this finding.     

The characteristics of alcoholic liver disease in Japan. Clinicopathologic comparison with alcoholic liver disease in the United States

Alcoholic liver disease (ALD) in Japan was compared clinicopathologically with the occurrence in the U.S.A. ALD found in Japan was more frequently complicated by other hepatic diseases including non-A, non-B chronic hepatitis than ALD found in the U.S.A. (9.9% versus 21.9%). Patients with such complications were excluded from this study. The chief complaints of the total of 51 alcoholics studied in the U.S.A. were abdominal distension or jaundice and those of 98 alcoholics studied in Japan were non-specific: general fatigue, weakness or appetite loss. The U.S. patients exhibited more elevated levels of serum bilirubin (8.1 +/- 7.5 versus 1.9 +/- 2.4 mg/dl, mean +/- SD) and a higher incidence of leukocytosis (49.0% versus 5.1%). While the serum glutamic-oxalacetic transaminase (GOT) levels were not significantly different between the two groups (146.5 +/- 116.8 versus 140.8 +/- 147.7 IU/L), the serum glutamic-pyruvic transaminase (GPT) levels among Japanese alcoholics were higher (38.6 +/- 31.4 versus 87.4 +/- 99.1 IU/L) and in about one quarter of these patients, serum GPT was higher than serum GOT, a feature not seen in the patients in the U.S.A. Comparative histopathologic study of 337 U.S. patients and 210 Japanese patients disclosed a higher frequency of cirrhosis (46.9% versus 33.8%), the presence of Mallory bodies (58.5% versus 13.8%) and marked neutrophilic exudation (45.1% versus 6.2%). Thus, the majority of Japanese alcoholics exhibited progression of liver disease, eventually leading to cirrhosis, due to hepatocellular drop-out and fibrosis caused by a mechanism different from alcoholic hepatitis. In addition, ALD in the U.S.A. revealed more striking extension of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histomorphologic picture of chronic non-A, non-B hepatitis

Basing on several international studies on the light microscopic pattern of acute non-A, non-B hepatitis we tried to discover the histological criteria of its chronic course by means of a detailed analysis of 181 liver biopsies of 94 patients suffering from chronic non-A, non-B hepatitis (a homogeneous group without competing noxious agents). In accordance with the relevant literature we found a rate of chronic courses of about 60% with chronic persistent hepatitis (2/3) and chronic lobular hepatitis (1/3) predominating. A transition into liver cirrhosis was not stated. As changes typical of the chronic non-A, non-B hepatitis cell ballooning (89%), changes of cell nuclei (88%), eosinophilic changes of cytoplasm (73%), focal sinusoidal cell activation (92%) and microvesicular steatosis (59%) were ascertained with the chronological analysis showing that there were no changes of these criteria up to the 6th year of disease. Its cause is seen in an incomplete elimination of the hepatitis viruses as a result of inefficient immune defence.     

Hepatitis C in patients undergoing liver transplantation.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) among patients undergoing liver transplantation and the relation between anti-HCV and post-transplant hepatitis. DESIGN: Retrospective cohort. PATIENTS: Serum samples from 128 patients who underwent liver transplantation. Sixty-six patients who had 6 months of follow-up and for whom both pretransplant and post-transplant serum samples were available were included in a study to asses the relation between anti-HCV and post-transplant hepatitis. MEASUREMENTS: Sera were tested for anti-HCV using an enzyme-linked immunosorbent assay (ELISA) and, if positive, two confirmatory tests were done. Patients had a biopsy every week until two specimens showed no abnormal findings. MAIN RESULTS: Only patients with chronic non-A, non-B hepatitis (15 of 30; 50%), alcoholic cirrhosis (7 of 19; 37%), and chronic hepatitis B infection (3 of 11; 27%) were anti-HCV positive. No patient with another form of chronic liver disease or with acute liver failure due to non-A, non-B hepatitis was anti-HCV positive. After transplantation, loss of anti-HCV was frequent and acquisition rare. Hepatitis developed in the graft in 17% of patients, but the incidence was similar among anti-HCV negative and anti-HCV-positive patients. CONCLUSIONS: Hepatitis C virus is a common cause of chronic liver disease in patients requiring liver transplantation, but anti-HCV is rarely found in patients with acute liver failure. Previous HCV infection, based on detection of anti-HCV, is not an independent risk factor for post-transplant hepatitis.