A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease

To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B. The majority of alcoholics with chronic hepatitis C virus infection displayed virus-related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (83.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority. These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver disease.     

Alcoholism, hepatitis B and C viral infections, and impaired liver function among Taiwanese aboriginal groups

Viral hepatitis and alcoholism prevail in four major Taiwanese aboriginal groups. To study the relative importance of the acquisition of hepatitis B virus or hepatitis C virus infection and alcoholism to the presence of impaired liver function in these groups, the authors conducted a semistructured clinical interview for alcoholism and test for seromarkers for viral hepatitis among 993 cohort members enrolled in 1990-1992 in an ongoing prospective study (Taiwan Aboriginal Study Project). The subjects' blood specimens were tested for serum alanine aminotransferase/aspartate aminotransferase levels and for the presence of hepatitis B surface antigen and anti-hepatitis C virus antibody. The prevalence of a combination of an alanine aminotransferase level of > 35 IU/liter and an aspartate aminotransferase level of > 40 IU/liter, implying impaired liver function or advanced liver disease, was 4.3% overall. Univariate and multiple logistic regression analysis showed that, rather than chronic hepatitis B virus infection, hepatitis C virus infection and alcoholism were the two dominant risk factors that signalled the risk of liver damage among these Taiwanese aborigines. In addition, these two contributing factors were able to act synergistically to cause impaired liver function.     

Fifth-year hemodynamic performance of the prima stentless aortic valve

In patients infected with the hepatitis C virus (HCV), 20% to 30% will progress to cirrhosis in over two to three decades. Viral and host factors that are important in the clinical and histologic progression of HCV infection are not entirely certain. It has been suggested that liver disease is worse in alcoholics infected with HCV. In the present retrospective study, we examined the effect of moderate alcohol intake on the histologic and clinical progression of HCV infection and assessed whether other variables such as gender, length of exposure, mode of exposure, HCV RNA levels, and ferritin levels also independently impacted disease progression. Liver biopsies were analyzed for the degree of fibrosis, presence of cirrhosis, and histologic activity by using the Histologic Activity Index of Knodell. Patients were divided into two groups based on whether their alcohol intake was significant or not significant. Significant alcohol intake was defined as > 40 g alcohol/day in women and > 60 g of alcohol/day in men for > 5 years. Groups were further divided based on the decades of exposure to HCV. There was no difference in the age or length of exposure to HCV in the alcohol and the alcohol-free group. HCV RNA serum levels, ferritin levels, and viral genotypes were similar in both groups. There was a two- to threefold greater risk of liver cirrhosis and decompensated liver disease in the alcohol group. Also, the rate to which subjects developed cirrhosis was faster in the alcohol group with 58% being cirrhotic by the second decade as opposed to 10% being cirrhotic in the nonalcohol group by the second decade. The histologic and clinical acceleration of liver disease was independent of the mode of exposure or sex. In summary, alcohol intake is an independent risk factor in the clinical and histologic progression of HCV infection.     

Chronic hepatitis C infection. A disease ideally suited to management in the primary care setting

BACKGROUND: The currently sub-optional efficacy of therapy for chronic hepatitis C infection makes other management modalities a priority. OBJECTIVE: To address issues in overall management of hepatitis C infection through case studies. DISCUSSION: Management of hepatitis C infection should cover discussion of hepatitis C transmission, natural history (prognosis) and therapy. A polymerase chain reaction (PCR) for detection of hepatitis C RNA should be ordered in those patients with persistently normal liver function tests to determine the presence or absence of chronic infection. Other measures include assessment and counselling in relation to alcohol intake, and vaccination against both hepatitis A and hepatitis B. In patients with abnormal liver function tests a liver biopsy should be considered in order to determine the stage of disease, thus enabling targeting of therapy to those at highest risk of progression to advanced liver disease.     

Attributable risk for symptomatic liver cirrhosis in Italy. Collaborative Groups for the Study of Liver Diseases in Italy

BACKGROUNDS/AIMS: Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports. METHODS: The proportion of newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989-1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection. The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk. RESULTS: Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5-7.6) for hepatitis B virus. The three factors together explained 98.1% (95% CI: 81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women. CONCLUSIONS: Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the well-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis should become a rare disease.     

Hepatitis B virus occult infection in subjects with persistent isolated anti-HBc reactivity

The aim of this study was to investigate the presence of hepatitis B virus occult infection in asymptomatic subjects with persistent anti-HBc reactivity but no other hepatitis B virus serological markers, including HBsAg, anti-HBs, IgM anti-HBc and HBV-DNA. For this purpose we used both polymerase chain reaction assays in sera and immunohistochemistry for HBsAg and HBcAg in liver biopsy specimens. Twenty-four cases were studied: 15 were drug abusers or homosexuals (eight with normal alanine aminotransferase levels) and nine were heterosexuals with raised alanine aminotransferase levels (> 45 U/l) but with no history of blood transfusion or ethanol intake (< 80 g daily). In all but five cases, liver biopsy was performed in subjects with persistent elevated alanine aminotransferase levels. In 10 out of 24 cases (41.66%) hepatitis B virus infection was demonstrated by polymerase chain reaction or immunohistochemistry, and when results from both procedures were available (n = 11) hepatitis B virus infection was detected in 63.63% of the subjects. The only clinical feature associated with HBV infection was the presence of persistent elevated alanine aminotransferase levels (p < 0.05). In conclusion, persistent isolated anti-HBc reactivity may be a relatively common serologic pattern for hepatitis B virus occult infection, at least in patients with chronic liver disease.     

On the experimental distinction between ssbs and dsbs in circular DNA

Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) have been reported in 10-66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto-antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and HCV genotype) were compared between patients with and without serum auto-antibodies. Fifty-eight (48%) patients were associated with positive serum auto-antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto-antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not correlated to the presence of serum auto-antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.     

Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups

BACKGROUND: Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression. METHODS: We recruited 2235 patients from the Observatoire de l'Hépatite C (OBSVIRC) population, the Cohorte Hépatite C Pitié-Salpétrière (DOSVIRC) population, and the original METAVIR population. All the patients had a biopsy sample compatible with chronic hepatitis C as assessed by the METAVIR scoring system (grades the stage of fibrosis on a five-point scale, F0 = no fibrosis, F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity, A3 = severe activity). No patient had received interferon treatment before the liver biopsy sample was obtained. We assessed the effect of nine factors on fibrosis progression: age at biopsy; estimated duration of infection; sex; age at infection; alcohol consumption; hepatitis C virus C (HCV) genotype; HCV viraemia; cause of infection; and histological activity grade. We defined fibrosis progression per year as the ratio between fibrosis stage in METAVIR units and the duration of infection (1 unit = one stage, 4 units = cirrhosis). FINDINGS: The median rate of fibrosis progression per year was 0.133 fibrosis unit (95% CI 0.125-0.143), which was similar to the estimates from previous studies (0.146 to 0.154). Three independent factors were associated with an increased rate of fibrosis progression: age at infection older than 40 years, daily alcohol consumption of 50 g or more, and male sex. There was no association between fibrosis progression and HCV genotype. The median estimated duration of infection for progression to cirrhosis was 30 years (28-32), ranging from 13 years in men infected after the age of 40 to 42 years in women who did not drink alcohol and were infected before the age of 40. Without treatment, 377 (33%) patients had an expected median time to cirrhosis of less than 20 years, and 356 (31%) will never progress to cirrhosis or will not progress for at least 50 years. INTERPRETATION: The host factors of ageing, alcohol consumption, and male sex have a stronger association with fibrosis progression than virological factors in HCV infection.     

The influence of muscular lengthening on cramps

The risks of acquisition of hepatitis C infection, the histological spectrum of liver disease, and the presence of viraemia were investigated in anti-hepatitis C virus (HCV) antibody positive blood donors. All 357 (0.64%) blood donors to the South Australian Red Cross Transfusion Service found to have anti-HCV antibody during the first seven months of testing in 1990 were assessed, and 70 (19.6%) were found to have elevated alanine transaminase levels. These subjects were referred for participation in the study; 31 presented for enrollment. Sixteen (52%) of the 31 patients had previously used intravenous drugs, four (13%) had been transfused, two (6%) had a history of occupational exposure to blood, and three (10%) had tattoos and ear-piercing as possible risk factors for acquisition of hepatitis C. There was no history of parenteral exposure in six (16%). None of these donors had clinical evidence of liver disease, but in all 24 of the 31 who had a liver biopsy there was histological evidence of significant liver damage. Twelve had evidence of chronic active hepatitis. All 24 subjects biopsied were viraemic as judged by the presence of HCV RNA in serum.     

Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients

BACKGROUND/AIMS/METHODS: The aim of this study was to elucidate the rate of development to cirrhosis and the rate of appearance of hepatocellular carcinoma in chronic viral hepatitis and to assess the risk factors for the development of disease in 2215 consecutive patients with viral hepatitis who were prospectively studied for a median observation period of 4.1 years. RESULTS: The rates of development to cirrhosis were 7.6%, 21.7%, and 32.2%, at the 5th, 10th, and 15th year, respectively. The carcinogenesis rates were 3.4%, 10.5%, and 22.4% at the 5th, 10th, and 15th year, respectively. The appearance rates of cancer in 645 patients with only hepatitis B surface antigen and in 1500 patients with only anti-hepatitis C virus antibodies were 2.1% and 4.8% at the 5th year, 4.9% and 13.6% at the 10th year, and 18.8% and 26.0% at the 15th year, respectively. The proportional hazard model identified that the amount of alcohol intake (p= 0.0002) and the indocyanine green retention rate (p= 0.022) were independently associated with carcinogenesis in hepatitis type B; and stage of hepatitis (p<0.0001), gamma-glutamyl transpeptidase (p= 0.0046), history of blood transfusion (p=0.0093), albumin (p=0.012), and amount of alcohol intake (p= 0.031) were independently associated with the carcinogenesis rate in hepatitis type C. Although the severity of portal fibrosis was closely correlated with the future disease development and carcinogenesis in chronic hepatitis C, it was not a good predictor in chronic hepatitis B. CONCLUSION: These epidemiological results suggest that there are some differences in the activity and modes of disease progression and cancer promotion between hepatitis B virus infection and hepatitis C virus infection.     

Chronic hepatitis in children after liver transplantation: role of hepatitis C virus and hepatitis G virus infections

BACKGROUND/AIMS: Chronic graft hepatitis occurs in 20-30% adults after liver transplantation but the prevalence and causes in children are not known. In adults, hepatitis C virus infection is prevalent prior to transplantation and recurrent infection is a frequent cause of graft dysfunction. The significance of the recently described hepatitis G virus infection remains unproven. The aim of this study was to examine the role of hepatitis C virus and hepatitis G virus infection in chronic graft hepatitis after paediatric liver transplantation. METHODS: The prevalence of graft hepatitis and the role of hepatitis C virus and hepatitis G virus infections in 80 children after liver transplantation have been studied, with a median follow up of 4.4 years (range 0.4 to 10.7), and the persistence of hepatitis G infection in the presence of immunosuppression has been determined. RESULTS: Chronic graft hepatitis was diagnosed in 19/80 (24%) children and was most frequently seen in children transplanted for cryptogenic cirrhosis (71%). There was no significant difference in the prevalence of chronic hepatitis in those transplanted before or after donor anti-HCV screening. Hepatitis C infection occurred in three children transplanted prior to donor screening but in only one was associated with chronic hepatitis. Hepatitis G infection was found in 22/79 (28%) transplant recipients but was not associated with graft hepatitis. In 17/21 children hepatitis G infection persisted for a median of 5.2 years after transplantation. CONCLUSION: Chronic hepatitis occurred in 24% of children after liver transplantation, a similar prevalence to that in adults. Cryptogenic liver disease predisposed to graft hepatitis, but neither hepatitis C nor hepatitis G infection was associated. Hepatitis G virus caused a frequent and usually persistent infection after transplantation.     

Hepatitis C virus c100 antigen in liver tissue from patients with acute and chronic infection

A pool of murine monoclonal antibodies developed against c100 antigen, a hepatitis C virus-associated protein encoded by the NS3/NS4 virus genome, was used to detect hepatitis C virus in liver biopsy specimens from patients with acute and chronic hepatitis C virus infection. The antigen was present in the cytoplasm of liver cells only. The immunoreactive signal appeared as large, distinct, brilliant fluorescent granules with no clear relationship to cellular structures. No obvious membrane c100 antigen accumulation was observed. Distribution of c100-containing hepatocytes was directly correlated with viral replication in acute hepatitis. All three acute-hepatitis patients were positive for hepatitis C virus RNA (as detected on polymerase chain reaction) in serum and displayed c100 antigen in 50% to 70% of hepatocytes, with a distinct topographical relationship with necrotic areas and inflammatory cell accumulation. Conversely, very low numbers of infected cells and no relationship between tissue c100 antigen expression and sites of liver cell necrosis and inflammation were found in 14 chronic hepatitis C virus infection patients. Furthermore, though all patients had measurable levels of serum hepatitis C virus RNA, only eight (57%) had detectable c100 antigen in liver sections. Indeed, these two distinct immunopathological patterns were inversely related to the development of c100 antibody in serum. Specificity of hepatocellular c100 antigen deposits was established through extensive absorption experiments using structural and nonstructural hepatitis C virus recombinant proteins. However, tissue processing was found to be a crucial step in the demonstration of hepatitis C virus antigen in fresh frozen liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study

OBJECTIVES: To estimate the incidence of HIV and hepatitis C virus and risk factors for seroconversion among a cohort of injecting drug users. DESIGN: Retrospective cohort study. SETTING: Primary healthcare facility in central Sydney. SUBJECTS: Injecting drug users tested for HIV-1 antibody (n=1179) and antibodies to hepatitis C virus (n=1078) from February 1992 to October 1995. MAIN OUTCOME MEASURES: Incidence of HIV-1 and hepatitis C virus among seronegative subjects who injected drugs and underwent repeat testing. Demographic and behavioural risk factors for hepatitis seroconversion. RESULTS: Incidence of HIV-1 among 426 initially seronegative injecting drug users was 0.17/100 person years (two seroconversions) compared with an incidence of hepatitis C virus of 20.9/100 person years (31 seroconversions) among 152 injecting drug users initially negative for hepatitis C virus. Incidence of hepatitis C virus among injecting drug users aged less than 20 years was 75.6/100 person years. Independent risk factors for hepatitis C virus seroconversion were age less than 20 years and a history of imprisonment. CONCLUSIONS: In a setting where prevention measures have contributed to the maintenance of low prevalence and incidence of HIV-1, transmission of hepatitis C virus continues at extremely high levels, particularly among young injecting drug users.     

Nested polymerase chain reaction (PCR) and multiple cloned antibody capture PCR for the examination of serum hepatitis B virus DNA in negative hepatitis B surface antigen patients suffering from liver diseases

In order to find out rapidly the causes of the liver diseases suffered by patients with negative hepatitis B surface antigen (HBsAg), nested polymerase chain reaction (PCR) and multiple cloned antibody capture PCR techniques were established to examine serum hepatitis B virus (HBV) DNA. By using both techniques along with the examination of hepatitis C virus (HCV) infection, the causes of chronic liver diseases with negative HBsAg were studied. It is found that nested-PCR can increase the sensitivity of single PCR more than 1,000 fold and multiple cloned antibody capture-PCR can detect concentration of HBV DNA as low as 0.1-0.01 pg/L. HBV DNA positive patients were found in 45.5%, 30.8%, 13.3% and 100% respectively of the patients suffering from liver cirhosis with negative HBsAg (group A, 22 cases), chronic hepatitis with negative HBsAg (group B, 13 cases), normal subjects with negative HBsAg and positive hepatitis B core antibody (HBcAb, group C, 30 cases) and liver cirhosis with positive HBsAg and negative HBeAg (group D, 12 cases). HBV DNA can be also found in the serum of HBsAb positive patients and subjects supposed to be healthy, 81.8% and 53.8% of the patients were infected with HBV and/or HCV in group A and group B respectively. All these results suggest that nested-PCR and multiple cloned antibody capture-PCR are rapid and highly sensitive methods for detection of serum HBV DNA. HBV infection is an important cause of chronic liver diseases in patients with negative HBsAg. The causes of most of the HBsAg-negative chronic liver diseases are related with infection of viruses. The clinical significance of serum HBsAb in naturally infected patients should be reconsidered.     

The prevalence of hepatitis C in patients admitted with acute hepatitis to Fairfield Infectious Diseases Hospital, 1971-1975

OBJECTIVE: To identify and determine trends in the prevalence of hepatitis C virus (HCV) antibody in stored sera from 1971 to 1975 and to determine associations with HCV seropositivity, including markers for other hepatitis infections and possible routes of transmission. DESIGN: A retrospective cross-sectional study. PATIENTS AND SETTING: 1511 adults admitted to Fairfield Infectious Diseases Hospital, Victoria, with a clinical and biochemical diagnosis of hepatitis between 1 January 1971 and 31 December 1975. MAIN OUTCOME MEASURES: Prevalence over study period of hepatitis A virus antibody (anti-HAV) IgM, hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) in stored sera; sociodemographic data and risk factors for blood-borne viruses documented in original medical records. RESULTS: Anti-HCV was detected in 17% of adults admitted with hepatitis from 1971 through 1975. Prevalence increased significantly over this period. Most cases were in young men who had a history of injecting drug use. HCV seropositivity was also significantly associated with markers for hepatitis B infection. CONCLUSIONS: Given the 20-30-year period between infection with hepatitis and the development of liver disease, our findings predict significant liver-related morbidity in Australia in the next decade. The increase in prevalence over the five years studied suggests rapid spread of HCV through susceptible populations, principally injecting drug users.     

Correlation between serum levels of alanine aminotransferase and ferritin in male blood donors with antibody to hepatitis C virus

Chronic hepatitis C has been demonstrated to be associated with hepatic iron overload, and the hypothesis that the disease activity of hepatitis C is associated with iron cytotoxicity was tested in male volunteer blood donors. Sera with either antibody to hepatitis C virus or hepatitis B surface antigen were selected for determination of ferritin concentration and alanine aminotransferase activity. A correlation between serum ferritin concentration (Y; microgram/l) and alanine aminotransferase activity (X; IU/l) was found in donors with antibody to hepatitis C (log Y = 0.65 x log X + 0.98, r = 0.53, and P < 0.01). The correlation was lower in donors with hepatitis B surface antigen (r = 0.37; P < 0.01). Hepatitis C virus infection probably induces time-dependent iron accumulation associated with the progression of disease activity, while hepatitis B virus infection results in a variety of iron loads with different clinical features. The high disease activity related to hyperferritinemia suggests the presence of iron-induced liver damage in donors with hepatitis C.     

Prevalence of liver abnormalities in the general population of Okinawa, Japan

A total of 2,825 Japanese over 20 years of age living in the Yaeyama District of Okinawa, Japan were investigated in 1983 and 1984 to determine the prevalence and risk factors of liver abnormalities. Obesity index, hepatitis B virus markers, hepatitis C virus marker and serum transaminase were measured and the history of alcohol intake was recorded. People with elevated transaminase levels were assumed to have abnormalities of the liver. The overall prevalence of liver abnormalities was 3.6% and was significantly higher in men than in women (p < 0.001). Logistic regression analysis showed that the strongest predictors of liver abnormalities were alcohol for the men and obesity for the women. Hepatitis B virus was the second most prevalent risk factor in both sexes.     

Genetic counseling in autism and pervasive developmental disorders

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables. a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.     

Human fascioliasis: comparison of a fasciolicidal effect of bithionol and praziquantel

BACKGROUND: The frequency of gliadin antibody (GA) positivity has been found to be increased among patients with chronic liver disease, as has that of coeliac disease (CD). CD has also been found to be increased among patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). METHODS: To investigate these relationships further, a micro-enzyme-linked immunosorbent assay and immunofluorescence tests for GAs and endomysial antibodies (EMAs) were performed in large subgroups of patients representing various chronic liver diseases and in healthy blood donors. RESULTS: As compared with blood donors (among whom it was 5%) the frequency of IgA GA positivity was higher in all patient subgroups: alcoholic liver disease, 20% (22 of 110, P < 0.001); PBC, 16% (16 of 101, P < 0.001); PSC, 24% (19 of 80, P < 0.001); chronic hepatitis, 19% (13 of 70, P < 0.001); and hepatitis C virus infection, 11% (11 of 104, P < 0.01). Two patients with autoimmune chronic hepatitis were EMA-positive, and in both cases the presence of CD was verified by small-bowel biopsy. CONCLUSIONS: IgA GA positivity generally occurs at increased frequency among patients with chronic liver disease and may represent non-specific immune activation. In liver disease GA testing is not useful in screening for CD, whereas the EMA test seems to be highly specific. CD is more prevalent than expected among patients with autoimmune chronic hepatitis but not among those with PBC or PSC.