BACKGROUND: Type-2 autoimmune hepatitis is a subgroup of chronic hepatitis characterized by the presence of liver/kidney microsomal autoantibodies type 1 (LKM-1). A frequent association with chronic hepatitis C suggests that hepatitis virus might trigger autoimmune reactivity. LKM-1-positive chronic hepatitis is not uncommon in southern Europe but is rarely seen in the USA and the UK. The prevalence in Scandinavia is hitherto unknown. METHODS: We used an automated prototype LKM-1 immunometry-based assay (IMx) to detect LKM-1 antibodies in sera from 350 Swedish patients with chronic liver diseases (100 with primary biliary cirrhosis, 80 with primary sclerosing cholangitis, 100 with hepatitis C, and 70 patients with various forms of chronic hepatitis, including 36 autoimmune cases), and from 17 children with autoimmune hepatitis. Sera reactive in the IMx assay were subjected to immunofluorescence testing. RESULTS: No clearly LKM-reactive sera were detected. Serum samples from 29 patients were borderline reactive in the IMx assay but tested negative in the confirmatory immunofluorescence test. Positive tests in the former assay were likely caused by reactivity against microsomal antigens other than LKM-1/cytochrome P450IID6. CONCLUSIONS: LKM-1-positive type-2 autoimmune hepatitis is very rare in Sweden. Furthermore, chronic hepatitis C did not trigger this type of autoimmune reactivity in our patients, probably owing to genetic insusceptibility.
To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994-2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score with transplant-free deaths as a positive outcome.
Adult patients in Sweden with international normalized ratio (INR) of >or=1.5 due to severe liver injury with and without encephalopathy at admission between 1994-2003 were included.
A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive-predictive value (PPV) of 67%, negative-predictive value (NPV) of 84% in the acetaminophen group. Positive-predictive value and negative-predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score>30 had a positive-predictive value of 21%, negative-predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively.
Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score
A cohort of 559 patients in Sweden who satisfied predetermined criteria for the diagnosis of primary biliary cirrhosis was followed with respect to the incidence of cancer during the period of 1958 to 1988. The mean follow-up time from the time of primary biliary cirrhosis diagnosis was 9.0 +/- 5.4 yr. During the follow-up period, 148 patients died and the primary cause of death was liver insufficiency. An overall excess risk for cancer, standardized incidence ratio 1.6; 95% confidence interval, 1.1 to 2.2, was found in the cohort. In contrast to previous reports, we found no excess risk for breast cancer (standardized incidence ratio, 0.9; 95% confidence interval, 0.3 to 2.1). The number of hepatocellular cancers in the primary biliary cirrhosis cohort did not significantly differ from expected (standardized incidence ratio, 2.91; 95% confidence interval, 0.4 to 10.5).
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
Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p
We analysed the presence of hepatitis C virus (HCV) antibodies in 566 patients undergoing liver biopsy. While over 20% of the patients were anti-HCV positive according to ELISA, only 13.8% had HCV antibodies when tested with a four-antigen recombinant immunoblot assay (RIBA 2). At the time of inclusion in the study, most patients were asymptomatic, irrespective of whether they were HCV-positive. Histological findings in anti-HCV-positive patients were chronic persistent hepatitis, chronic active hepatitis or cirrhosis in greater than 75% of cases. Only four of the patients who were anti-HCV-positive according to the RIBA 2 had autoimmune chronic active hepatitis. Risk behaviour could be identified in the majority of cases. Community-acquired sporadic cases were rare (12%). Of the 153 patients who died during follow-up, 23 subjects were anti-HCV positive. Although age- and sex-adjusted survival was not shorter in anti-HCV-positive patients than in anti-HCV-negatives, the risk of hepatocellular cancer was higher (P = 0.01). We conclude that HCV infection is associated with chronic liver disease, even when critical evidence of viral aetiology is slight. Truly sporadic cases are rare. Patients infected with HCV are at increased risk of developing hepatocellular cancer.
Genetic susceptibility to PBC can, at least in part, be ascribed to the major histocompatibility complex. The relevance of immunogenetic markers for the clinical presentation and course, however, is unclear. Thus, the aim of this study was to investigate the contribution of HLA class II genes to susceptibility, clinical presentation and course of disease in PBC patients. HLA genotyping for HLA-DRB1, -DQB1 and -DPB1 was carried out in a total of 99 Swedish PBC patients and 158 controls. Clinical parameters including epidemiologic variables, signs and symptoms of PBC-related liver disease and histologic data were collected and analyzed in 92 patients at study entry and at follow-up five years later. Significant clinical heterogeneity was seen among PBC patients upon study entry. Although a significant disease association was seen for HLA DRB1*08 and DQB1*0402, immunogenetic markers identified neither a particular subset of patients nor an association with the clinical course of the disease. HLA-DRB1*08 and DQB1*0402 provide the strongest immunogenetic influence in PBC. However, this association is not restricted to any particular, clinically defined subgroup of patients and it is not predictive for the course of the disease.
In Sweden, the most common causes of liver cirrhosis are alcohol overconsumption and hepatitis C. However, recent data on the clinical characteristics of Swedish patients with cirrhosis are scarce.
To determine the incidence, clinical presentation, aetiological spectrum and survival rates of liver cirrhosis in Southern Sweden from 2001 to 2011.
We used population-based medical registries to conduct a cohort study of all patients with liver cirrhosis in the southernmost region of Sweden with a population of 1.17 million. Medical records and histopathology data were reviewed. Patients were classified according to aetiology, and clinical parameters were registered. Patients were followed until death or December 2014.
A total of 1317 patients with cirrhosis were identified. The crude annual incidence of cirrhosis was estimated at 14.1/100 000. The most common aetiology was alcohol overconsumption with or without additional causes of cirrhosis (58%) followed by HCV alone (13%) and cryptogenic cirrhosis (12%). At diagnosis, ascites occurred in 43%, variceal bleeding in 6% and overt encephalopathy in 4%. The median follow-up was 4.3 years. The total 1-, 5- and 10-year survival rates were 79%, 47% and 27% respectively. Survival rates were better for women than for men. A 10-year cumulative incidence of transplantation was 7.3%. Mortality was worst for alcoholic cirrhosis with concomitant HCV when adjusted for age and gender.
Sweden continues to have a low incidence of cirrhosis compared with other European countries. Mortality varies with gender, aetiology and severity at diagnosis. Patients with alcoholic cirrhosis with concomitant HCV infection fare worst.
BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important causative factor in the development of liver cirrhosis and hepatocellular cancer (HCC), the strength of this correlation has been difficult to confirm in low-prevalence areas. METHODS: Stored serum samples from 987 consecutive (1978-88) patients with chronic liver disease were tested with an enzyme-linked immunosorbent assay for anti-HCV and further confirmed by immunoblot. To evaluate the long-term outcome, the cohort was followed up until 1995, for a median observation time of 10 years. RESULTS: Anti-HCV, confirmed by immunoblot, was found in 9.5% (94 of 987) of the patients, and at inclusion most patients were asymptomatic irrespective of anti-HCV status. Of the 445 patients who died during the study period, 44 were HCV-positive. A liver-related cause of death was far commoner and the age-adjusted survival shorter among HCV-positive patients than among HCV-negative ones. At death 68% (30 of 44) of the HCV-positive subgroup had developed cirrhosis, and 30% (13 of 44) had concurrent HCC, as compared with 36% (142 of 393) (P = 0.001) and 8% (31 of 393) (P = 0.001), respectively, of the HCV-negative subgroup. HCV infection (P
We studied 33 patients with primary biliary cirrhosis representative of a well-defined population (240,000) during the decade 1973-82. Mean annual incidence was 13.7 per 10(6) and point prevalence, 92 per 10(6) inhabitants in 1982. An accumulation of asymptomatic cases, constituting 45% of all patients, with a normal life expectancy accounted for this high prevalence. During the study period no disease progress was seen in asymptomatic patients, in contrast to a 50% mortality in the symptomatic group. Disease progress in the latter group was reflected by deterioration of N-demethylating capacity and increasing bilirubin levels. Although our data confirm an increasing prevalence of primary biliary cirrhosis, the mortality rate during the study period was almost identical to that in an earlier period, 1951-60.