OBJECTIVES: Autoimmune hepatitis (AIH) is a liver disease which, if untreated, may lead to liver cirrhosis and hepatic failure. Limited data exist regarding factors predicting the long-term outcome. The aims of this study were to investigate symptoms at presentation, prognostic features, management and treatment in relation to long-term outcome of AIH. MATERIAL AND METHODS: A cohort of 473 Swedish patients with AIH was characterized regarding initial symptoms and signs, factors predicting death and future need for liver transplantation. Survival and causes of death were retrieved from Swedish national registers. RESULTS: At diagnosis, fatigue was a predominant symptom (69%), 47% of the patients were jaundiced and 30% had liver cirrhosis. Another 10% developed cirrhosis during follow-up. Markedly elevated alanine aminotransferase levels at presentation were correlated with a better outcome. A high international normalized ratio (INR) at diagnosis was the only risk factor predicting a need for later liver transplantation. Histological cirrhosis, decompensation and non-response to initial treatment were all factors that correlated with a worse outcome. Overall life expectancy was generally favourable. However, most deaths were liver-related, e.g. liver failure, shock and gastrointestinal bleeding. CONCLUSIONS: Cirrhosis at diagnosis, a non-response to initial immune-suppressive treatment or elevated INR values were associated with worse outcome and a need for later liver transplantation. In contrast, an acute hepatitis-like onset with intact synthetic capacity indicated a good response to treatment and favourable long-term prognosis. Lifetime maintenance therapy is most often required.
BACKGROUND: The prevalence of coronary artery disease (CAD) has been reported to be low in patients with liver cirrhosis. Previous studies have, however, included mostly patients with cirrhosis due to hepatitis C. We aimed to determine the prevalence and predictive factors of CAD in a cohort of consecutive patients with cirrhosis of various etiologies compared to the general population. METHODS: A total of 127 patients with cirrhosis were evaluated for a history of CAD and cardiovascular risk factors. Arterial blood pressure, fasting plasma glucose, and serum cholesterol were measured. Nutritional status was assessed by anthropometry and estimation of recent weight change. A group of 203 subjects from the general population with similar age and gender distribution, as well as smoking habits as the cirrhotic patients, served as controls. RESULTS: CAD was more common in cirrhotics compared to controls (20% vs. 12%, P = 0.001). Compared to controls, cirrhotics had lower mean arterial blood pressure and serum cholesterol and a higher prevalence of diabetes, but did not differ significantly in the prevalence of hypertension or family history for CAD. In regression analysis, CAD was independently related to diabetes (odds ratio [OR] 5.47, 95% confidence interval [CI] 2.44-12.28), but not to liver cirrhosis. In the cirrhosis group, only alcoholic cirrhosis (OR 9.50, 95% CI 1.08-83.4) and age (OR 1.23 per year, 95% CI 1.06-1.43) were independently related to CAD. CONCLUSIONS: Liver cirrhosis, per se, does not seem to confer a protective effect against CAD. In cirrhotics, older age and alcoholic etiology were independently related to CAD.
OBJECTIVE: There are only a few data on the prevalence of drug-induced liver injury associated with fatal outcome. The aim of this study was to determine the nature and number of suspected adverse drug-induced liver disease associated with fatalities and/or liver transplantation since reporting of adverse drug reactions (ADRs) started in Sweden. MATERIAL AND METHODS: All reports of suspected hepatic ADRs with fatal outcome received by the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) from 1966 to 2002 were reviewed and causality assessed. RESULTS: The SADRAC received 151 reports of suspected ADRs with fatal outcome from liver injury; 48 cases were either unlikely or excluded. Of the remaining 103 cases, 13 (13%) were highly probable, 48 (47%) probable and 42 (41%) possible. The median age of the 103 patients was 64 years (47-77 interquartile range (IQR)) and 59 (57%) were males. The majority of cases were classified as hepatocellular (75%), with only 15% cholestatic and 10% mixed. Halothane, paracetamol, flucloxacillin, sulfamethoxazole/trimethoprim and diclofenac were the most common drugs associated with fatal outcome. Seventeen patients underwent liver transplantation, most commonly because of paracetamol and disulfiram toxicity. CONCLUSIONS: A wide range of suspected ADRs are associated with fatalities. Antibiotics and analgesics are associated with the greatest number of reports of deaths.
OBJECTIVE: Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. MATERIAL AND METHODS: Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. RESULTS: The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (p
Limited data exist on drug-induced liver injury (DILI) associated with statins.
Reports on adverse reactions suspected to be due to statins received by the Swedish Adverse Drug Reactions Advisory Committe 1988-2010 were analyzed. Only cases with >5×upper limit of normal (ULN) in aminotransferases and/or alkaline phosphatase >2×ULN were included.
The most common types of ADRs suspected were DILI in 124/217 (57%) cases. A total of 73/124 (59%) cases had at least possible relationship, median age 64 years (57-73), 55% males, whereas 25/124 cases (20%) were excluded due to mild elevations of liver tests and 26 due to unlikely relationship and/or lack of data. A statin-related DILI episode was reported in 1.2/100,000 users. Atorvastatin was implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin (15%), and others. Two patients died of acute liver failure, one underwent liver transplantation and 25 (34%) had jaundice. Three patients were rechallenged with the same statin producing similar patterns of liver injury. The median duration of therapy was 90 days (30-120), 120 (39-248) for atorvastatin, and 75 (30-150) for simvastatin (NS). Cholestatic/mixed injury was more common with atorvastatin, 17/30 (56%) than with simvastatin, 7/28 (24%) (p=0.018).
Idiosyncratic liver injury associated with statins is rare but can be severe. After recovery, a similar pattern of liver injury can be reproduced on re-exposure. Most patients experience liver injury 3-4 months after start of therapy. Atorvastatin is mostly associated with cholestatic liver injury whereas hepatocellular injury is more common with simvastatin.
Patients with jaundice are looked after by many different specialists: general internists, general surgeons, specialists in infectious diseases and gastroenterologists. Overuse of radiological methods has been demonstrated recently in patients hospitalized for jaundice in Sweden probably due to a lack of experience in interpretation of pathological liver tests especially in patients with hepatocellularjaundice. Two cases of hepatocellular jaundice with a diagnosis of autoimmune hepatitis are described. This condition led in one case to severe liver failure and to severe jaundice in the other case. These cases illustrate the consequences of delayed diagnosis and lack of treatment early in the course of autoimmune hepatitis. Furthermore the common delay in contact with a liver transplant center in patients with severe liver failure is discussed. It is concluded that specialized units should investigate patients with jaundice and a medical gastroenterologist should be contacted early in the hospitalization of these patients.
OBJECTIVE: No systematic evaluation has been performed previously in the Scandinavian countries on patients transplanted for alcoholic liver disease (ALD). Data are limited on the impact of structured management of the alcohol problem on the risk of recidivism following transplantation in ALD. MATERIAL AND METHODS: A total of 103 ALD patients were compared with a control group of patients with non-alcoholic liver disease (NALD). The recidivism rates for ALD patients transplanted between 1988 and 1997 as well as after 1998 (institution of structured management) were compared. RESULTS: The median follow-up was 31 (6-60) months in the ALD group and 37 (12-63) months in the control group (NS). The overall survival rates at 1- and 5 years were, respectively, 81% and 69% for the ALD group and 87% and 83% for the non-alcoholic group. The proportion of patients with Child-Pugh C (75%) was higher in ALD patients than in NALD patients (44%) (p
1 Institute of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 2 Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland. 3 Transplant institute, Sahlgrenska University Hospital, Gothenburg, Sweden. 4 Department of Gastroenterology, Skåne University Hospital, Lund, Sweden. 5 Address correspondence to: Axel Josefsson, M.D., Institute of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, 41345 Göteborg, Sweden.
Cardiovascular disease and renal impairment are common in cirrhotic transplant candidates. We aimed to investigate potential association between pretransplant renal function impairment and cardiac events after liver transplantation.
Adult cirrhotic patients undergoing first-time liver transplantation between 1999 and 2007 in a single institution with available glomerular filtration rate (GFR), assessed by Cr-EDTA clearance at pre-transplant evaluation, were retrospectively enrolled (n=202). Impaired renal function was defined as GFR less than 60 mL/min/1.73 sqm. Pretransplant QT-time corrected by heart rate (QTc) and left-ventricular dysfunction was also registered. Mortality and cardiac events were analyzed, until death or last follow-up (end 2009).
Renal impairment was present in 24% (48/202). Cardiac events occurred in 28% (56/202) after transplantation, mean follow-up time of 3.8 years (2.2). Events were more common in patients with renal impairment compared with those without (48% versus 21%, P0.05). A pretransplant score comprising renal impairment, prolonged QTc interval, and age older than 52 was developed for prediction of 3- and 12-month cardiac events (c-statistic 0.73 and 0.75, respectively).
Pretransplant renal impairment is a predictor of cardiac event after liver transplantation together with prolonged QTc interval.