Early switch to pentoxifylline in patients with severe alcoholic hepatitis is inefficient in non-responders to corticosteroids.

BACKGROUND/AIMS: In severe alcoholic hepatitis (AH), 40% of patients will obtain no benefit from corticosteroids. Improvement in management of non-responders is warranted and only pentoxifylline can be considered an alternative. A two-step strategy was evaluated consisting of early withdrawal of corticosteroids and a switch to pentoxifylline for 28 additional days in non-responders identified using early change in bilirubin level. METHODS: One hundred and twenty-one patients with AH were treated prospectively with corticosteroids, and the two-step strategy was proposed to 29 non-responders treated according to a two-step strategy who were compared to 58 matched non-responders treated with corticosteroids only. RESULTS: Clinical and biological features of the two groups were similar. There was no survival improvement at 2 months in patients treated with the two-step strategy compared to controls: 35.5+/-6.3% vs 31+/-8.6%. After 21 days, biological evolution was similar for prothrombin time (-0.25s vs +0.2s), bilirubin (0.8 mg/dl vs 2.03 mg/dl) and creatinine (+0.16 mg/dl vs -0.7 mg/dl). In multivariate analysis, only age, evolution of bilirubin during the first week, creatinine and DF were associated with 2-month survival. CONCLUSIONS: Non-responders to corticosteroids do not obtain any benefit from an early switch to pentoxifylline. Thus, the issue of management of non-responders remains unresolved.

The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids.

UNLABELLED: Early identification of patients with severe (discriminant function > or = 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies. Three hundred twenty patients with AH prospectively treated by corticosteroids were included in the development cohort and 118 in its validation. Baseline data and a change in bilirubin at day 7 were tested. The model was generated by logistic regression. The model combining six reproducible variables (age, renal insufficiency, albumin, prothrombin time, bilirubin, and evolution of bilirubin at day 7) was highly predictive of death at 6 months (P < 0.000001). The area under the receiver operating characteristic (AUROC) curve of the Lille model was 0.89 +/- 0.02, higher than the Child-Pugh (0.62 +/- 0.04, P < 0.00001) or Maddrey scores (0.66 +/- 0.04, P < 0.00001). In the validation cohort, its AUROC was 0.85 +/- 0.04, still higher than the other models, including MELD (0.72 +/- 0.05, P = 0.01) and Glasgow scores (0.67 +/- 0.05, P = 0.0008). Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival as compared with others: 25% +/- 3.8% versus 85% +/- 2.5%, P < 0.0001. This cutoff was able to identify approximately 75% of the observed deaths. CONCLUSION: In the largest cohort to date of patients with severe AH, we demonstrate that the term "nonresponder" can now be extended to patients with a Lille score above 0.45, which corresponds to 40% of cases. Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies.

Evaluation of amantadine in chronic hepatitis C: a meta-analysis.

BACKGROUND/AIMS: The benefit of amantadine combination therapy, either with interferon (IFN) alone (double therapy) or with ribavirin and IFN (triple therapy) is unknown. METHODS: We analyzed the effect of amantadine on the end-of-treatment virological response and the sustained response using meta-analysis of 31 randomized controlled trials. RESULTS: Overall analysis revealed a significant effect of amantadine. Triple therapy was the best regimen for improving the sustained response (mean difference: 8.4%, 95% CI: 2.4-13.8%, P=0.002). In subgroup analysis, amantadine did not have a significant effect upon naive patients or relapsers. In non-responders, combination therapy with amantadine was associated with a significant effect on the sustained response (mean difference: 8.3%, 95% CI: 1.9-14.6%, P=0.01). In sensitivity analysis, double therapy did not improve virological responses. Conversely, triple therapy tended to improve the end-of-treatment virological response and was associated with a significant effect upon the sustained response (mean difference: 12.7%, 95% CI: 3.8-21.6%, P=0.005). CONCLUSIONS: Combination therapy with amantadine is of no effect upon naive patients or relapsers. In non-responders, triple therapy with amantadine improved the sustained response. New randomized controlled trials are required to confirm this meta-analysis.

[Membranous glomerulonephritis complicating hepatocellular carcinoma]. / Glomérulonéphrite extra-membraneuse paranéoplasique compliquant un carcinome hépato-cellulaire.

We report the case of a 65-Year-old man with advanced hepatocellular carcinoma related to alcoholic cirrhosis who was hospitalised for oliguric renal failure. Investigations showed a severe nephrotic syndrome related to paraneoplastic membranous glomerulonephritis. The patient's course was temporarily stabilized with loop diuretics and dialysis but the patient died of hemoperitoneum from a ruptured tumor.