严重药物性肝病的后果及其预后指标

The combination of high aminotransferases (hepatocellular injury) and jaundice has been reported to lead to a mortality rate of 10% to 50% for different drugs, a phenomenon known as “ Hy’s rule." However, Hy’s rule has never been validated, and limited data exist on predictors for outcome in hepatocellular and other forms of drug-induced liver disease. All reports of suspected hepatic adverse drug reactions received by the Swedish Adverse Drug Reactions Advisory Committee (1970- 2004) were reviewed. Cases with bilirubin levels 2 or more times the upper limit of normal (ULN) were analyzed. A total of 784 cases were retrieved-409 with hepatocellular injury, 206 with cholestatic injury, and 169 with mixed liver injury. The mortality/transplantation rate was 9.2% , and bilirubin (median 18.7 × ULN [IQR 12.6- 25]; range 4.5- 42) was higher (P < .0001) in the deceased/transplant recipients compared with the surviving patients (median 5.5 × ULN [IQR 3.3- 9.5]; range 2.0- 38). A total of 7.8% with cholestatic and 2.4% with a mixed pattern died. The mortality rate in hepatocellular injury for different drugs varied from 40% (6 of 15) for halothane to 0% (0 of 32) for erythromycin, in total 12.7% . Using logistic regression analysis, age, aspartate aminotransferase (AST) and bilirubin were found to independently predict death or liver transplantation in the hepatocellular group, whereas among patients with cholestatic/mixed liver injury, bilirubin was the only independent predictor. In conclusion, hepatocellular jaundice has a high but variable mortality rate, depending on the drug involved. The AST and bilirubin levels are the most important predictors of death or liver transplantation.

戒酒硫导致肝损伤的临床特征和预后指标

Background/Aims:Limited systematic data exists on the incidence of drug-induced hepatotoxicity due to disulfiram and the most important prognostic markers.We aimed to determine the nature and frequency of suspected disulfiram hepatotoxicity in Sweden.Methods:All reports of suspected hepatic adverse drug reactions(ADR)associated with disulfiram received by the Swedish Adverse Drug Reactions Advisory Committee(SADRAC)1966-2002 were reviewed.Causality assessment was based on the International Consensus Criteria.Results:A total of 82 reports of disulfiram suspected ADRs had at least a possible causal relationship.Eight patients died or underwent liver transplantation(Tx).Mortality or Tx was 16%in patients with jaundice.The median age of the patients(65%males)was 45 years with a median duration of treatment of 42 days.Bilirubin was higher(P < 0.0001)in the deceased/transplanted patients compared to surviving patients.No difference was observed in age or duration of therapy between deceased and transplanted and those who recovered.Eosinophilic infiltration in liver biopsies was associated with a favourable outcome,hepatocyte drop-out with a poor outcome.Conclusions:Disulfiram associated hepatitis has a considerable mortality risk.Histological signs of immunoallergy seem to be common.Bilirubin and hepatocyte drop-out were the only predictors for death or transplantation.

瑞典大学医院中1994—1999年间食管静脉曲张患者的特点、预后及转归

Objective. Patients with liver cirrhosis, portal hypertension and oesophageal varices are known to have high morbidity and mortality. The knowledge of incidence, aetiology and outcome in Sweden in recent years is limited. Material and methods. All patients with oesophageal varices diagnosed for the first time at Sahlgrenska University Hospital during the 6-year period 1994-1999 were retrospectively studied. Information about the aetiology of liver cirrhosis and oesophageal varices, as well as about the proportion of bleeding and non-bleeding varices, endoscopic and pharmacological treatment and outcome, was analyszed. Results. 312 patients were retrieved, 297 with liver cirrhosis (197 diagnosed before first bleeding (P), 92 after bleeding (B) and 8 at autopsy) and 15 with portal vein thrombosis without cirrhosis. Fifty-four percent had alcoholic liver disease. Fifty-five percent in group B and 13%in group P had at least one bleeding episode during follow-up (p < 0.001). There was no significant difference in survival between groups B and P. Twenty-six percent of the cirrhotics died of liver failure and 19%from variceal bleeding. In a multivariate analysis, variables predicting mortality were: Child-Pugh class, group B, age and bilirubin levels. Conclusions. Variceal bleeding is still a strong risk factor for recurrent bleeding, but few die from their first bleeding. This concurs with studies indicating declining mortality from variceal bleeding. However, this patient group still has a high mortality from other causes.

原发性硬化性胆管炎患者的疲乏感

Background: The occurrence of fatigue in primary sclerosing cholangitis (PSC), its impact on quality of life and the role of concomitant inflammatory bowel disease (IBD) and coexisting irritable bowel syndrome (IBS) is unexplored. Methods: Ninety three patients with PSC, associated with IBD in 80%of cases and 77 patients with IBD alone, were enrolled in the study. The patients completed the following questionnaires: the Fatigue Impact Scale (FIS), the Psychological General Well Being Index (PGWB), the Gastrointestinal Symptom Rating Scale (GSRS), the Beck Depression Inventory (BDI) and diagnostic criteria for IBS. Questionnaire data were related to liver tests and the latest liver biopsy in the PSC patients. Two sex and age matched controls from the general population (GP) were assigned to each PSC patient and these controls completed the FIS and the BDI. Results: Total fatigue score did not differ significantly between patients with PSC and IBD alone. Median total fatigue score among GP subjects was 39 (13-72), which was higher than in PSC (19 (6-52) (P = 0.02)) and in IBD patients (19 ( 5-35 ) ( P < 0.0001)). PGWB and GSRS scores did not differ between patients with PSC and IBD alone. Depression and general health (PGWB) were independent predictors for total fatigue score in PSC. No correlation was observed between fatigue in PSC and the severity of the liver disease. Conclusions: Fatigue in patients with PSC is related to depression but not to the severity of the liver disease. Both the PSC and IBD patients had lower total fatigue scores than subjects from the general population. This argues against fatigue as a specific symptom of PSC and IBD patients.

瑞典人群迟发性皮肤卟啉症的风险因素和并发症

There are varying reports on the prevalence of risk factors in porphyria cutanea tarda (PCT). We reviewed 84 patients with PCT in a restricted uptake area in Gothenburg, Sweden and evaluated different potential risk factors for the disease and complications. Besides a thorough medical history, the patients were investigated with urinary porphyrin analyses, transferrin saturation, ferritin and liver tests. Subsamples of patients were tested for antibodies to hepatitis C virus (n=68), haemochromatosis gene mutations (n=58) and with the oral glucose tolerance test (n=31). We found a prevalence of about 1 patient with PCT in 10 000 inhabitants. Nineteen (23%) patients reported heredity for PCT. Identified risk factors were alcohol abuse (38%of male patients), oestrogen treatment (55%of female patients), anti-hepatitisC virus positivity (29%ofmale patients), diabetes (17%) or impaired glucose tolerance (45%of tested patients) and haemochromatosis gene mutations (57%of tested patients). All patients positive for anti-hepatitis C virus belonged to the non-hereditary group. During follow-up we observed a high incidence of stroke, no case of hepatocellular carcinoma and a normal life expectancy.