Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis.

UNLABELLED: Autoimmune hepatitis (AIH) typically responds to treatment in 90% of patients. Early prediction of treatment outcome would be advantageous in clinical practice. We evaluated whether parameters at initiation of therapy or changes in these parameters at day 3 and day 7 following corticosteroid initiation predicted treatment failure. Treatment-naive, jaundiced patients presenting to our tertiary unit between 1999-2009 were identified and mathematical models of prognosis in liver disease scores calculated at day 0, day 3, and day 7. Overall, 72 patients were identified (48 women, 24 men). Treatment failure occurred in 18% (13/72) of patients. At diagnosis, higher median bilirubin (451 µmol/L versus 262 µmol/L, P = 0.02), INR (1.62 versus 1.33, P = 0.005), model for endstage liver (MELD) score (26 versus 20, P = 0.02), MELD-sodium (Na) score (27 versus 22, P = 0.03) and United Kingdom endstage liver disease score (UKELD) score (59 versus 57, P = 0.01) significantly correlated with treatment failure. Analysis of area under the receiver operator characteristic curve (AUROC) values at day 7 identified change (Δ) bilirubin (AUROC 0.68), Δ creatinine (0.69), Δ MELD (0.79), Δ MELD-Na (0.83) and Δ UKELD (0.83) best predicted treatment failure. Specifically, a fall in UKELD of less than 2 points predicted treatment failure with a sensitivity of 85% and specificity of 68%. Of 13 treatment failures, nine required second-line immunosuppression, three required emergency transplant, and one died of sepsis. In total, four patients died in the treatment failure group compared with one in the responder group (4/13 = 31% versus 1/59 = 1.7%, P = 0.003). CONCLUSION: Approximately 20% of icteric AIH presentations fail corticosteroid therapy. This is associated with significant mortality and the need for emergency transplantation. Treatment failure is best predicted by change in MELD-Na and UKELD at day 7. Early identification of nonresponders may allow timely escalation of immunosuppression to prevent clinical deterioration.

Biliopancreatic diversion: long-term effects on gonadal function in severely obese men.

BACKGROUND: This study investigated hormonal parameters of gonadal function in severely obese men before and 1 year after undergoing biliopancreatic diversion (BPD). METHODS: This observational 1-year postoperative study conducted at medical and surgical clinics at an academic medical center in Italy followed 20 severely obese men age 21 to 63 years, with a mean (+/- standard deviation) body mass index (BMI) of 47.3 +/- 13.1. The following parameters were evaluated: body composition, using body impedance analysis (BIA), and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, estradiol 17beta, and leptin. RESULTS: At a mean 12 +/- 1 months after surgery, the patients showed a significant decrease in weight, from 132.1 +/- 36.9 before surgery to 93.5 +/- 20 kg (P < .0001), and BMI, from 47.3 +/- 13.1 before surgery to 33.5 +/- 7 (P < .0001). LH increased from 2.42 +/- 1.59 to 4.97 +/- 2.6 mIU/ml (P < .0001), FSH increased from 2.85 +/- 1.85 to 4.9 +/- 4.2 mIU/mL (P = .021), and total testosterone increased from subnormal presurgical values to within normal range (2.81 +/- 1.08 to 9.12 +/- 1.37 ng/mL; P < .0001), whereas estradiol 17beta decreased from elevated basal levels of 44.0 +/- 29 to 16.7 +/- 6.9 pg/mL (P < .0001). The basal leptin level dropped from 33.0 +/- 9.23 to 16.6 +/- 5.12 ng/mL (P < .0001), reflecting the decrease in body fat. Subjective improvement in sexual performance was reported by 80% of patients. CONCLUSIONS: Severe obesity is coupled with some significant alterations of the gonadotropin-testicular axis and estradiol 17beta and leptin blood levels. These derangements were substantially corrected by 1 year after BPD.