Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731 .).

for the Foie-Alcool group of the Association Française pour l'Etude du Foie (AFEF)** Tumor necrosis factor-␣ (TNF-␣) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score >32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% ؎ 11%) than in group B (18% ؎ 9%). The study was stopped by the follow-up committee and the sponsor (Assistance Publique-Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B (P < .002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections.

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory and hemostatic responses to heat stress, suggesting that immunomodulation may improve outcome. We postulated that an experimental baboon model of heatstroke will reproduce human responses and clinical outcome to allow testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio hamadryas) were subjected to heat stress in an incubator maintained at 44-47 degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0 and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic inflammation and activated coagulation, indicated by increased plasma IL-6, prothrombin time, activated partial thromboplastin time, and D-dimer levels, and decreased platelet count. Biochemical markers and/or histology evidenced cellular injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase, lactic dehydrogenase, and alanine aminotransferase were increased, and varying degrees of tissue damage were present in liver, brain, and gut. No baboon with severe heatstroke survived. Neurological morbidity but no mortality was observed in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater coagulopathy, inflammatory activity, and tissue injury than survivors. Sham-heated animals had an uneventful course. Heat stress elicited distinct patterns of inflammatory and hemostatic responses associated with outcome. The baboon model of heatstroke appears suitable for testing whether immunomodulation of the host's responses can improve outcome.