Screening for alcohol-induced liver injury by patient self-report after liver transplantation

Despite widespread concern about the magnitude of alcohol consumption and/or recidivism after liver transplantation (LT), no universal agreement exists regarding the tools to assess problem alcohol drinking. We performed a single-center, cross-sectional study to assess the performance of the CAGE questionnaire in discriminating between LT recipients with and without post-transplant alcohol-induced liver injury. A total of 316 adult, consenting, maintenance patients between 6 months and 5 years after LT received the CAGE (Cut down, Annoyed, Guilty, Eye-opener) screening questionnaire. Calculation of the sensitivity, specifi city, receiver operating characteristic (ROC) curve, and likelihood ratio for CAGE scores of 0 to 4 was performed using as gold standard the biopsy-proven evidence of alcohol-induced liver injury (BPAI). One-hundred-ninety-fi ve patients responded to the questionnaire, and among them 45 (23%) had a CAGE score ≥1 (mean 2.13 ± 0.9). Among patients with a CAGE score = 0 there were 11 (7.3%) cases of BPAI, as compared with 24 (53.3%) among patients with a CAGE score of ≥1 (p<0.0001). A CAGE score ≥1 was associated with a sensitivity and a specifi city of 68.5% and 86.8%, and an area under ROC curve of 0.79 (95% CI 0.70-0.87). The likelihood ratios for scores of 0 to 4 were 0.3, 5.2, 7.8, 9.9, and 100, respectively. These ratios were associated with posterior probabilities for BPAI of 7.3%, 53.3%, 63.3%, 87.5%, and 100%, respectively. Based on these data, transplant physicians can improve their ability to predict the probability for alcohol-related liver injury using likelihood ratios for CAGE scores, in the setting of either recurrent or de novo post-transplant alcohol disorder

How to achieve optimal trough levels when switching calcineurin inhibitors (CNI) to everolimus (EVER): the 50%-per-week rule

Scanty data are available on the best schedule for switching calcineurin-inhibitors (CNI) to everolimus (EVER) in liver transplant (LT) patients. We explored prospectively introduction of EVER at a dosage of 0.75 mg b.i.d.with overnight withdrawal of antimetabolites and reduction of CNI by 50% per week to a complete stop after 4 weeks (the 50%-per-week rule). Adult, consenting recipients of LT from a deceased donor with a minimum follow-up of 12 months were included if they had a C0 ≤150ng/mL, and/or C2 ≤650ng/mL or a TAC trough level ≤8ng/mL. EVER trough levels were obtained 7, 14, 21, 28 days after switch and each month thereafte for 6 months. Target EVER trough levels were 3-8ng/mL. Twenty-seven patients were enrolled (mean age 56.4 ± 9.6 years; M/F=18/9) at a mean follow-up of 42.9 ± 29.3 months from LT. Twenty-one patients (77.8%) were on CsA; 6 patients (22.2%) were on TAC. At baseline, mean CsA dose was 131.6 ± 41.4mg/day and mean TAC dose was 2.8 ± 1.4 mg/day. Mean baseline C0 was 86.8 ± 70.9 ng/mL and mean baseline TAC trough level 6.7 ± 1 ng/mL. Seven days after switch, mean EVER trough level was 6.5 ± 3.2 ng/mL (2.2/14 ng/mL) and 21 patients (77.7%) were within the target range. In 2 patients (7.4%) EVER trough level was 8 ng/mL (3 CsA; 1 TAC). EVER at a dosage of 0.75 mg b.i.d. with 50% reduction of CNI allows to achieve trough levels between 3 and 8 ng/mL in 77.7% of cases, provided that patients have C0 ≤ 150ng/mL and/or C2 ≤ 650 ng/mL, or a TAC trough level ≤8 ng/mL at the time of switch

Switch to everolimus in maintenance liver transplant patients: preliminary results of a prospective, single-center trial

Renal function is often impaired after liver transplantation (LT). We present the preliminary results of a prospective trial on efficacy and safety of switching from calcineurin inhibitors (CNI) to everolimus (EVER) in maintenance LT recipients. Adult, consenting deceased donor LT recipients with a minimum follow-up of 12 months were included. EVER was introduced at 0.75 mg b.i.d. with overnight withdrawal of antimetabolites and a 50%-per-week reduction of CNI to a complete stop after 4 weeks. Steroids were kept at pre-switch levels. EVER target levels were 3-8ng/mL. Twenty-seven patients (mean age 56.4±9.6 years; M/F=18/9) on cyclosporine (21) or tacrolimus (6) were enrolled at a mean of 42.9±29.3 months post-LT. Native disease was HCV in 10 patients (37%). Indications were CrCl ≤80mL/min in 26 (96.3%) and CNI-related peripheral neuropathy in 1 (3.7%). At baseline, mean CrCl was 57.2±16.1mL/min (range 38.6/120.5). At a mean follow-up of 110.9±34.9 days, 17 (62.9%) patients had EVER-related complications: hypercholesterolemia/hypertriglyceridemia requiring medication in 5 (18.5%); oral ulcers in 4 (14.8%); acne in 2 (7.4%); eczema in 2 (7.4%); headache, urticaria, psoriasis, relapse of zoster infection in 1 patient each (3.7%). All cases were amenable to medication/EVER dose reduction. Two (7.4%) patients presented 1 episode of treated biopsy proven rejection each (1 RAI 6; 1 RAI 8), one of them (3.7%) dropped treatment. One further patient (3.7%) dropped treatment at 14 days for increase in HCV-RNA. Among the 17 patients (62.9%) with a minimum follow-up of 3 months, mean CrCl increased from 53.1±6.6mL/min (95% CI 49.6/56.5) to 58.7±12.3mL/min (95% CI 52.4/65.1). Preliminary data suggest that switching from CNI to EVER-based immunosuppression is feasible and associated with improvement in CrCl. Larger series and longer follow-ups are favored to tailor EVER on patients’ immunologic profile