Strong predictors for alcohol recidivism after liver transplantation: non-acceptance of the alcohol problem and abstinence of <3 months.

OBJECTIVE: Alcohol-toxic liver cirrhosis (ALC) is one of the main indications for liver transplantation (LT). The aim of the study is to define predictors for alcohol recidivism and to identify the outcome and quality of life of such patients. MATERIAL AND METHODS: From March 2003 to July 2009, 226 patients underwent LT in our centre. In 53% liver cirrhosis was caused by alcohol abuse (sole/cofactor). Outcome and alcohol recidivism were assessed using patients' records, laboratory tests and interviews (patient, family members and family doctor). Furthermore, patients received an SF-36 quality of life and a self-designed questionnaire anonymously. RESULTS: Mean follow-up after LT was 31 + 23 months. The 5-year survival rate after LT in patients with ALC was significantly better compared to patients with other indications (78 vs. 64%; p = 0.016). Quality of life of both patient groups was comparable. After LT, alcohol recidivism rate was 16%. Patients with an alcohol abstinence of <3 months before LT had a significantly higher (p = 0.012) rate of alcohol recidivism in comparison to those with an abstinence of >3 months. Another predictor for alcohol recidivism was the patients' non-acceptance of having an alcohol problem before LT (p = 0.001). CONCLUSIONS: ALC is a good indication for LT. An alcohol abstinence of <3 months before LT and a non-acceptance of having an alcohol problem are strong predictors for alcohol recidivism after LT.

Improved outcome after 'bottom-up' immunosuppression in liver transplant recipients with preoperative renal impairment.

BACKGROUND: Most patients with high MELD scores have impaired renal function prior to transplantation. PATIENT AND METHODS: A retrospective case control study was conducted with initial low immunosuppression, which was increased when patients rejected or were clinically stable beyond day 30 ('bottom-up'). RESULTS: Thirty patients with impaired renal function were included. Fifteen were treated with de novo cyclosporine A (CsA; group A), and 15 had 'bottom-up' immunosuppression (group B). Baseline renal function was similar: serum creatinine (SCr) median 1.8 mg/dl (range: 1.5-4.0 mg/dl; group A) versus 2.4 mg/dl (range: 1.5-4.0 mg/dl; group B; p = 0.24). The requirement for renal replacement therapy was significantly lower in group B (p = 0.032). Ten received 'bottom-up' immunosuppression [4 CsA/1 sirolimus (Sir) 'on demand' after rejection, 5 Sir (stable)] beyond day 30. By months 6 and 12 (1.6 mg/dl vs. 1.2 mg/dl), SCr values were significantly better in group B (p = 0.006). Renal function in group B did not differ between patients receiving CsA or Sir. Overall complication rates, survival and biopsy-proven acute rejection were similar, although BANFF scores were higher in group B (p = 0.004). CONCLUSION: Successful implementation of 'bottom-up' immunosuppression in liver transplant recipients with high lab-MELD scores and renal dysfunction at the time of transplantation has the potential to substantially improve short- and long-term outcomes.

Calcineurin Inhibitor Free De Novo Immunosuppression in Liver Transplant Recipients With Pretransplant Renal Impairment: Results of a Pilot Study (PATRON07).

BACKGROUND: Renal impairment and high model of end-stage liver disease scores before liver transplantation (LT) are increasingly common. PATIENTS AND METHODS: This was a single-arm, 2-step prospective trial of bottom-up calcineurin inhibitor (CNI)-free de novo immunosuppressive treatment (mycofenolate mofetil, steroids, basiliximab) with delayed introduction of sirolimus in patients with renal impairment. Primary endpoint was immunologic safety assessed by the incidence of steroid-resistant rejection within the first 30 days after liver transplantation. RESULTS: Twenty-seven patients were included with a median age of 56 years and labMELD of 28. Baseline glomerular filtration rate was 38 (Cockroft-Gault) and 24 mL/min (modification of diet in renal disease). No steroid-resistant rejections occurred within 30 days. Incidence of biopsy proven acute rejection was 18.5%. Sirolimus was started on day 10 (range, day 1 to day 48). The rate switched to CNI treatment by 1 year was 44%; 1-year overall survival was 93%. Renal function improved significantly, reflected by a Δglomerular filtration rate of 31 mL/min from baseline to 1 year (P = 0.006). Per protocol analysis revealed freedom from CNI, but not presence of sirolimus within the first 30 days, as critical for renal recovery. CONCLUSIONS: Initial de novo CNI-free immunosuppressive bottom-up treatment is safe in selected patient groups. The critical period for relevant recovery of renal function seems to be the early period (first 30 days), independent from presence of sirolimus.