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).
The northern part of Sweden is sparsely populated and must be regarded as a rural region. An investigation into the incidence and prevalence of primary biliary cirrhosis was conducted and the course of the disease was followed. In total, 111 patients with primary biliary cirrhosis were identified for the 10-yr period 1973 to 1982 in the northern health region of Sweden. The mean annual incidence amounted to 13.3 per million and the point prevalence was 151 per million, which is the highest reported so far. There was a significantly higher prevalence in the most northern county of Sweden, both with respect to total number of primary biliary cirrhosis patients and symptomatic patients. Asymptomatic patients amounted to 37%. During the study period 25 patients out of the 111 died (23%), 14 as a direct consequence of the liver disease. Three patients died of primary hepatocellular carcinoma, one having an asymptomatic liver disease without cirrhosis. Primary biliary cirrhosis seems to be more common in Sweden, especially in the northern part, than it is elsewhere. A high frequency of extrahepatic symptoms (85%), mainly musculoskeletal, was recorded. These symptoms may lead to the first contact with the health service, rather than signs of liver disease. Thus, an increasing number of patients are diagnosed with asymptomatic liver disease, who must be followed to check for the eventual development of symptoms.
Twenty-six consecutive patients with primary biliary cirrhosis (PBC) from northern Sweden were studied regarding the occurrence and features of Sjögren's syndrome (SS). In more than 50% of the patients the rose bengal dye test showed conjunctival and/or corneal staining. In six patients keratoconjunctivitis sicca (KCS) was present with positive rose bengal and Schirmer tests. In a further three patients only the results of the Schirmer tests were abnormal. Radiological findings of sialectasia were demonstrated in six patients, five of whom had KCS. Two of the seven patients who fulfilled our criteria for Sjögren's syndrome were HLA-B8 positive. A high prevalence of increased immune globulins and rheumatic factor was found, but this did not correlate with the presence of Sjögren's syndrome. Some features of Sjögren's syndrome were found in 73% of PBC patients, and keratoconjunctivitis sicca and/or sialectasia were found in 27% of PBC patients. This constitutes a high frequency of secondary manifestations of the liver disease.
Hereditary transthyretin (TTR) amyloidosis is a rare often fatal form of systemic amyloidosis, that until recently was considered intractable, with the patients dying from the disease 5-15 years after onset. The phenotype of the disease varies according to the type of mutation, but generally the heart and/or the nervous system is affected. Liver and in some cases heart transplantation has now been shown to stop the progress of the disease, but the outcome depends on the patients' status at the time of operation, as no substantial improvement of the patients' symptoms has been noted after the procedure. Thus an early diagnosis is of importance for the outcome. In the following, we summarize our knowledge of the amyloidogenic TTR mutations found in the Scandinavian countries, their symptoms, how to settle the diagnosis and the outcome of transplantation. Besides, the problems arising from our capability to genetically test asymptomatic members of affected families for the trait will be discussed.
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.
Liver transplantation is the only effective treatment of familial amyloidotic polyneuropathy type I (FAP). The aim of the present investigation was to identify factors at the time of submission for transplantation that had impact on survival, with special reference to gastrointestinal disturbances. All 28 liver-transplanted FAP patients evaluated at Umeå University Hospital were included in the study. A modified body mass index was used to assess nutritional status. Intestinal examinations were performed to diagnose bile acid malabsorption, gastric retention, and bacterial contamination of the small bowel. A significantly improved survival rate was found for patients in a good nutritional state (P = 0.002). Peripheral neurological symptoms were unrelated to survival, whereas increased mortality was found for patients with bile acid malabsorption (P
To study the natural course of primary biliary cirrhosis (PBC) in order to be able to design accurate clinical pharmacological studies and evaluate the need for liver transplantation.
A cohort of 86 patients with PBC living in northern Sweden was followed for a 10-year period during 1983-93. No patients received therapy with ursodeoxy cholic acid or other drugs during the follow-up period.
At start all patients were investigated personally by the authors. At follow-up medical notes were scrutinized and special questionnaires to the current responsible physician were applied. Endpoints were the time of dropout, liver transplantation, death or end of the study period.
At follow-up data were available for 84 patients (97%). During the study period 34 patients died, of whom 28 were symptomatic; 15 deaths had no direct connection to PBC. Nineteen deaths were related to PBC of whom two were asymptomatic, the most common cause being end-stage liver disease with liver coma. During the study period in all eight patients were subjected to liver transplantation.
The survival rate of the 32 asymptomatic PBC patients at the start of the study was the same as a sex- and age-matched standard background population. Those patients with symptomatic PBC from the beginning of study had a survival rate at 10 years of 50%, and the most ominous sign was a bilirubin greater than 35 micromol L(-1) . Liver transplantation was performed in almost 10% in this cohort until 1993. Since then, the indications and referral practice for liver transplantation has changed and is now higher.