Search

The aim of this study was to define factors predictive of the onset of the terminal phase, defined by hyperbilirubinemia or the occurrence of a severe clinical complication, in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. The 97 primary biliary cirrhosis patients in this study participated in a 2-yr clinical trial. Four of the 49 patients treated with ursodeoxycholic acid (13 to 15 mg/kg/day) entered the terminal phase of the disease, compared with 9 of the 48 patients assigned to placebo. In addition to clinical, conventional biological and histological parameters, we analyzed three serum markers of connective tissue components--type III procollagen aminoterminal peptide, hyaluronic acid and laminin. In the ursodeoxycholic acid-treated group, hyaluronic acid, type III procollagen aminoterminal peptide, bilirubin and splenomegaly were the factors most closely associated with entry into the terminal phase of the disease. In multivariate analysis, after adjustment for age, the hyaluronic acid level was the only predictive factor. In the placebo-treated group, the bilirubin level, total bile acid level, Mayo score, type III procollagen aminoterminal peptide, hyaluronic acid, splenomegaly and pruritus were associated with aggravation of disease. In multivariate analysis, high bilirubin level, high type III procollagen aminoterminal peptide or hyaluronic acid levels and low prothrombin time independently implied poor prognosis. In conclusion, when patients with primary biliary cirrhosis are treated with ursodeoxycholic acid, bilirubinemia loses, in part, its predictive value. It is replaced by hyaluronic acid and type III procollagen aminoterminal peptide. This suggests that models used in deciding on the need for liver transplantation require adaptation for patients receiving ursodeoxycholic acid.

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)

The fact that only a small percentage of excessive drinkers develop cirrhosis may be due to a genetic susceptibility to the disease. In order to identify possible genetic risk factors for cirrhosis, we studied mixed-race (Negroid-Caucasian) inhabitants of the French West Indies and compared: (1) the frequency of 51 HLA-A, -B, -C and -DR antigens in 41 subjects with alcoholic cirrhosis and in two control groups consisting of 41 excessive drinkers free of liver disease and 51 healthy non-drinkers; and (2) the frequency of Gm and Km haplotypes in the same groups. Analysis of the Gm system also determined the patients' ethnic origins. The frequency of the HLA-A2 antigen was significantly higher in the cirrhotic patients than in the control group of excessive drinkers (chi 2 = 4.47; P less than 0.05), while that of the HLA-B15 antigen was significantly lower (chi 2 = 5.14; P less than 0.05). The frequency of the Cw4 antigen was significantly higher in the cirrhotics than in the non-drinkers (chi 2 = 5.59; P less than 0.05). However, these differences did not persist when the number of comparisons was taken into account. The frequency of Gm and Km haplotypes was not significantly different in the three groups. In conclusion, complementary studies are required to determine the value of the Gm-Km system as a marker of susceptibility to alcoholic cirrhosis. Our results do not identify an association between HLA antigens and cirrhosis specific to a negroid ethnic group and support the notion that such an association is weak.