FULMINANT-HEPATITIS IN A TROPICAL POPULATION - CLINICAL COURSE, CAUSE, AND EARLY PREDICTORS OF OUTCOME

The profiles of patients with fulminant hepatic failure (FHF) from dev eloping countries have not been reported earlier. The current study wa s conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural cour se, and causative profile of-patients with FHF as well as to define si mple prognostic markers in these patients. Four hundred twenty-three c onsecutive patients with FHF admitted from January 1987 to June 1993 w ere included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, m ultivariate Cox's proportional hazard regression, stepwise logistic re gression, and Kaplan-Meier survival analysis were done to identify ind ependent predictors of outcome at admission. All patients presented wi th encephalopathy within 4 weeks of onset of symptoms. Hepatotropic vi ruses were the likely cause in most of these patients. Hepatitis A (HA V), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular d rugs could be implicated as the cause of FHF in 1.7% (n = 7), 28% (n = 117), 3.8% (n = 16), and 4.5% (n = 19) patients, respectively, In the remaining 62% (n = 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepat otoxins. FHF was presumed to be caused by non-A, non-B virus(es) infec tion Sera of 50 patients from the latter group were tested for hepatit is E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 ( 19%). Two hundred eighty-eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quart er of the female patients with FHF were pregnant. Mortality among preg nant females, nonpregnant females, and male patients with FHF was simi lar (P > .1). Univariate analysis showed that age, size of the liver a ssessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothromb in time prolongation over controls at admission were related to surviv al (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression s howed age greater than or equal to 40 years, presence of cerebral edem a, serum bilirubin greater than or equal to 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with thre e or more of the above prognostic markers died. The sensitivity, speci ficity, positive predictive value, and the negative predictive value o f the presence of three or more of these prognostic factors for mortal ity was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accu racy of 87.3%. We conclude that most of our patients with FHF might ha ve been caused by hepatotropic viral infection, and non-A, non-B virus (es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the on set of symptoms. Pregnancy, cause, and rapidity of onset of encephalop athy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission.