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.

原发性硬化性胆管炎患者小肠内渗透压与细菌生长

Objective. Animal studies show that small intestinal bacterial overgrowth and infusion of bacterial antigens into portal blood cause hepatic histological changes similar to those seen in primary sclerosing cholangitis in man. It has been suggested that a similar mechanism involving bacterial overgrowth with increased small-bowel permeability may play a pathogenic role in patients with primary sclerosing cholangitis. Material and methods. Twenty-two patients with primary sclerosing cholangitis (13 M, 9 F, median age 37 years, range 21-74 years), 19 of whom (83%) had quiescent inflammatory bowel disease, were included in the study along with 18 healthy volunteers (9 F, 9 M, median age 36 years, range 23-80 years). Small-bowel bacterial overgrowth was denned as the presence of colonic flora > 105 colony-forming units (cfu)/ml from duodenal aspirations. Small-bowel intestinal permeability was assessed as the differential urinary excretion of lactulose/L-rhamnose. Results. Bacterial overgrowth was evident in one patient with primary sclerosing cholangitis (4.5%) (Enterobacter) and in none of the controls. Intestinal permeability in patients with primary sclerosing cholangitis (0.034 (0.026-0.041) (median, interquartile range (IQR)) did not differ significantly from that of the controls (0.033 (0.025-0.041). Conclusions. Small intestinal bacterial overgrowth and increased intestinal permeability does not seem to play an important pathogenic role in patients with primary sclerosing cholangitis.

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.

肝硬化伴和不伴腹水患者的肠道通透性研究

Objective.It has been suggested that increased intestinal permeability plays a pathogenic role in bacterial infections,such as spontaneous bacterial peritonitis,in patients with liver cirrhosis.The aim of this study was to assess whether intestinal permeability is altered in cirrhotic patients with and without ascites.Material and methods.Intestinal permeability was assessed by a 51Cr-EDTA permeability test in 20 cirrhotic patients(10 with and 10 without ascites)along with 20 age-and gender-matched healthy controls.In six patients with ascites,the test was performed before and after therapeutic paracentesis.Results.The median(IQR)24-h urinary excretion of 51Cr-EDTA was higher in patients with cirrhosis(1.94%(1.21-2.70%))compared with that in controls(1.40%(1.09-1.99%);p < 0.05).Patients with(2.05%(1.50-3.46%);p < 0.05)but not those without ascites(1.94%(1.13-2.53%);p > 0.1)had significantly higher excretion values compared with those of controls.Only one patient without ascites and a total of four patients with ascites had increased intestinal permeability(51Cr-EDTA excretion > 95%confidence than that of controls;p > 0.1).Paracentesis did not affect urinary 51Cr-EDTA excretion significantly(1.69%(1.16-2.86%)versus 1.30%(1.08-1.79%)before and after,respectively;p > 0.1).No significant correlation was found between clinical severity scores for liver disease and intestinal permeability.Conclusions.Only a small proportion of patients with liver cirrhosis have increased intestinal permeability and it is unlikely that this plays any major role in predisposing these patients to infections.