HLA class II markers and clinical heterogeneity in Swedish patients with primary biliary cirrhosis

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

Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC)

Background/Aims: This study aims at describing the natural history and outcome of small duct primary sclerosing cholangitis (PSC). Methods: Thirty-two patients with small duct PSC were studied. The average time taken for diagnosis was 69 (1-168) months. The median follow-up time was 63 (1-194) months. Results: All patients including one who underwent liver transplantation because of end-stage liver disease and hepatocellular carcinoma were alive at follow-up. None developed cholangiocarcinoma. In 27 patients repeated cholangiographic examinations were done after a median time of 72 (12-192) months from first ERCP. Four developed features of large duct PSC. Conclusions: Small duct PSC rarely progresses to large bile duct PSC and it seems to have a benign course in most patients and no development of cholangiocarcinoma was found. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved

Acute liver failure in Sweden: etiology and outcome

Wei G, Bergquist A, Broome U, Lindgren S, Wallerstedt S, Almer S, Sangfelt P, Danielsson A, Sandber-Gertzen H, Loof L, Prytz H, Bjomsson E (Sahlgrenska University Hospital, Gothenburg; Karolinska University Hospital, Huddinge, Stockholm; University Hospital MAS, Malmo; University Hospital, Linkoping; University Hospital, Uppsala; University Hospital, Umea; University Hospital, Orebro; Central Hospital, Vasteras; and University Hospital, Lund; Sweden). Acute liver failure in Sweden: etiology and outcome. J Intern Med 2007; 262: 393-401. Objective. 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. Research design and methods. Adult patients in Sweden with international normalized ratio (INR) of >= 1.5 due to severe liver injury with and without encephalopathy at admission between 1994-2003 were included. Results. 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 nonacetammophen 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. Conclusions. 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 < 30 predicts a good prognosis in acetaminophen patients without transplantation

Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives

Background & Aims: Iron overload may be carcinogenic. Patients with hereditary hemochromatosis (HH) are reportedly at a 20-200-fold risk of intrahepatic cancer, but the reported risks for nonhepatobiliary cancers are conflicting. The risk of cancer in heterozygous individuals (estimated allele frequency, 1/10 to 1/20) is unknown. This study aimed to better assess these risks. Methods: We performed a population-based cohort study of 1847 Swedish patients with HH and 5973 of their first-degree relatives using nationwide, population-based health and census registers. We used standardized incidence ratios (SIRs) as relative risk. Results: With 62 liver cancers and 128 nonhepatobiliary cancers, patients with HH were at a 20-fold risk of liver cancer (SIR, 21; 95% confidence interval [Cl], 16-22) but an almost unaltered risk of all other cancers (SIR, 1.2; 95% Cl, 1.0-1.4), including nonelevated risks for several gastrointestinal tract cancers. At 10 years of follow-up, the absolute risk of liver cancer was 6% among men and 1.5% among women. With 21 liver cancers and 508 nonhepatobiliary cancers, first-degree relatives were at an unaltered risk of extrahepatic cancer (SIR, 1.0; 95% Cl, 0.9-1.1, including unelevated risks for gastrointestinal cancers) but at a modest and historic increased risk of hepatobiliary cancer (SIR, 1.5; 95% Cl, 1.0-2.4), the histopathologic spectrum of which differed from the patients. Conclusions: Patients (particularly men) with HH are at increased risk for hepatocellular cancer, although the magnitude of the risk is lower than previous estimates. Overall cancer risk in first-degree relatives does not seem to be increased