Improving Patient Safety in Medication Management by Medication Reconciliation and Pharmaceutical Care Process in Post-Liver Transplant Clinic.

INTRODUCTION: Liver transplant recipients receive many medications for anti-rejection, infection prophylaxis, and treatment of comorbidities. Most of them also receive medications from multiple sources. Therefore, these patients are prone to drug-related problems (DRPs) and medication errors. This study aimed to study the effect of medication reconciliation (MR) and pharmaceutical care processes by transplant pharmacists in the post-liver transplant clinic. METHODS: This study was a retrospective study in Siriraj Liver Transplant Center, Mahidol University, Thailand. Patients who received pharmaceutical care from transplant pharmacists were compared before and after the implementation of MR (October 2020-September 2021 vs October 2021-September 2022) to assess the prevalence of medication errors and identify DRPs between the 2 groups. RESULTS: Before implementation of MR, in a total of 797 visits, 69 medication errors (8.7%) were found. The most errors were medication omissions (44.9%, n = 31). After the implementation of MR, in a total of 879 visits, 44 medication errors (5.0%) were found. Most were medication omission and incorrect strength (31.8%, n = 14). Medication errors significantly decreased by 36.2% (P < .001) after the implementation of MR. Regarding DRPs, transplant pharmacists could significantly detect more DRPs after implementation of MR, 66 DRPs before implementation of MR vs 111 DRPs after implementation of MR (P < .001). The most DRPs were non-adherence (34 vs 41). CONCLUSIONS: MR can reduce medication errors and assist transplant pharmacists in identifying DRPs that will lead to active intervention by attending physicians and/or patients to improve medication management and patient safety in post-liver transplant care.

Incidence and Risk Factors Associated With Chronic Kidney Disease After Liver Transplantation: A Review of a 20-Year Experience at a Single Center.

BACKGROUND: Chronic kidney disease (CKD) is one of the major complications after liver transplantation (LT), with a significant impact on patient outcomes. This study aims to investigate the incidence and risk factors of CKD in LT recipients at Siriraj Hospital over the past 20 years. METHODS: There were 366 adult patients undergoing LT at Siriraj Hospital between January 2002 and December 2021. After excluding patients with pretransplant CKD stages 4 to 5, simultaneous liver-kidney transplantation, and patients who died after LT within 90 days, we retrospectively reviewed a total of 288 patients. Univariable and multivariable binary logistic regression analyses were used to identify the risk factors of post-transplant CKD. RESULTS: Of the 288 patients, 171 (59.4%) developed CKD after LT. The median time to develop CKD was 5.8 months (IQR, 3.8-15.3). Univariable and multivariable analyses revealed that age ≥55 years (odds ratio [OR] = 2.44; 95% CI, 1.34-4.42; P = .003), pretransplant kidney dysfunction defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 (OR = 2.23; 95% CI, 1.16-4.27; P = .016), and postoperative acute kidney injury (OR = 3.06; 95% CI, 1.73-5.42; P < .001) were significantly associated with post-transplant CKD. Patients with preexisting kidney dysfunction who received delayed calcineurin inhibitor introduction without antibody induction protocol had a significantly lower incidence of post-transplant CKD (OR = 0.28; 95% CI, 0.11-0.70; P = .007). CONCLUSIONS: Advanced age, pre-transplant kidney dysfunction, and postoperative acute kidney injury are risk factors for CKD after LT. Importantly, delayed calcineurin inhibitor introduction can protect patients with pretransplant kidney dysfunction from developing post-transplant CKD. These results may have important clinical implications in reducing the incidence of CKD after LT.

Delayed Calcineurin Inhibitor Introduction Without Antibody Induction in Liver Transplantation Is Safe and Helps Preserve Kidney Function.

INTRODUCTION: Acute kidney injury (AKI) is common after liver transplantation and affects outcome after liver transplantation. Antibody induction is commonly used to reduce dose and/or to delay introduction of calcineurin inhibitor (CNI) but is very expensive. We propose a modified immunosuppressive protocol that delays administration of CNI for 48 to 72 hours without antibody induction. This study evaluates the results of our new protocol. MATERIAL AND METHODS: A retrospective case-control study was performed. Study patients had induction with steroid and mycophenolate mofetil without antibody induction, and CNI administration was delayed for 48 to 72 hours. Control patients received CNI and steroid induction without antibody induction, and CNI was continued posttransplant. AKI was defined as an increase in serum creatinine level of at least 1.5 times the pretransplant baseline within the first postoperative week. RESULTS: Sixty liver transplant recipients from 2013 to 2015 were included in this study (30 in the delayed CNI group and 30 in the control group). The patient characteristics and intraoperative factors were comparable in both groups. AKI developed in 11 patients in the study group and in 20 patients in the control group (37% vs 66.7%; P = .02). There was no acute rejection observed in the first month in either group. CONCLUSION: We have demonstrated that delayed CNI introduction without antibody induction is safe and helps preserve kidney function. Antibody induction can be omitted safely in a delayed CNI introduction protocol to reduce the cost of liver transplantation without increasing the risk of acute rejection.

Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker.

BACKGROUND: Gallbladder cancer (GBC) is a rare and fatal biliary tract malignancy. Genetic derangements are one of many factors that determine the prognosis of GBC. In this study, the expression of the stratifin (SFN) gene encoding 14-3-3 sigma protein, which is reported to be associated with the metastatic property of cholangiocarcinoma cells, was investigated in GBC. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded cancer (n = 37) and non-cancer control tissues (n = 14) of gallbladders from patients who underwent surgical resection from January 2006 to May 2015 were retrieved. The expression of SFN normalized with that of ACTB was determined using RT-qPCR. Multivariate analysis of factors affecting disease-free survival (DFS) and overall survival (OS) including the type of SFN expression was performed. RESULT: The average expression level of SFN in cancer was higher than that in control tissues (p = 0.002). The relative SFN expression in cancer tissue was classified as overexpression (n = 14) and control level expression (n = 23) according to the receiver operating characteristic (ROC) curves for discriminating early GBC recurrence or metastasis after surgery. The SFN overexpression group was associated with lower rates of distant metastasis and early tumor recurrence following resection. The univariate analysis demonstrated factors affecting DFS, including resection margin (p < 0.001), lymphovascular invasion (p = 0.040), perineural invasion (p = 0.046), and SFN expression (p < 0.001). The multivariate analysis revealed that the resection margin (p = 0.019) and SFN expression (P = 0.040) were independent prognostic factors of DFS. CONCLUSION: To achieve the longest survival, margin-free resection is recommended. The overexpression of SFN in GBC is associated with better prognosis, lower rates of early cancer recurrence, and distant metastasis following resection. SFN expression might be a novel prognostic biomarker in GBC treatment. Further studies to elucidate the role of SFN might unveil its clinical benefit in cancer treatment regimens.

Liver transplantation in children using organ donation after circulatory death: a case-control outcomes analysis of a 20-year experience in a single center.

IMPORTANCE: While orthotopic liver transplantation (OLT) is a durable life-saving treatment for patients with irreversible liver disease, the waiting list mortality rate for children younger than 6 years is 4 times higher than for children aged 11 to 17 years and adults owing to scarce availability of size-appropriate grafts for transplantation. OBJECTIVE: To compare long-term outcomes for children (aged ≤18 years) undergoing OLT using grafts from donation after circulatory death (DCD) and donation after brain death (DBD). DESIGN, SETTING, AND PARTICIPANTS: Retrospective study using case-control matched groups at a university transplant center. All patients aged 18 years and younger who underwent OLT using DCD organs between February 1, 1990, and November 30, 2010, at the University of California, Los Angeles, were matched in a 1 to 3 ratio with patients who received primary OLT from DBD donors within a 12-month period. Other matching criteria included recipient age, weight, cause of liver disease, and acuity of illness. Outcomes after OLT were compared for DCD (n = 7) and DBD (n = 21) donors. The median follow-up was 4.5 years. MAIN OUTCOMES AND MEASURES: The primary outcome measure was graft failure-free survival; the secondary end point was the development of ischemic cholangiopathy. RESULTS: Comparing DCD and DBD groups, recipient median age (28.4 vs 20.1 months, respectively; P = .80), weight (12.0 vs 11.6 kg, respectively; P = .87), Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score (19 vs 11, respectively; P = .48), and donor age (24.0 vs 13.1 months, respectively; P = .72) were similar. For the DCD donors, the median donor warm ischemia duration was 24 minutes. Liver test results were similar for both groups at 1 week and 3, 6, and 12 months following OLT. Ten-year patient and graft survival rates for both DCD and DBD were 100%. Neither ischemic cholangiopathy nor vascular complications occurred in the DCD group. Biliary anastomotic strictures occurred in 1 DCD patient and 3 DBD patients. CONCLUSIONS AND RELEVANCE: Our study showed excellent long-term outcomes with liver transplantation in children using DCD organs. Use of liver grafts procured after circulatory death is an effective approach to expand the donor pool and remains an untapped resource for children with end-stage liver disease.

Liver transplantation using organ donation after cardiac death: a clinical predictive index for graft failure-free survival.

OBJECTIVE: To define a prognostic scoring system for risk stratification of patients undergoing orthotopic liver transplantation (OLT) using grafts from donation after cardiac death (DCD). DESIGN: Retrospective study. SETTING: University transplant center. PATIENTS: Eighty-one patients underwent OLT using DCD grafts from March 1, 1994, to November 30, 2010. The mean follow-up was 2 years. Independent risk factors for graft failure after OLT were identified using Cox model and assigned risk score points. Points were summed and assigned to predictive index categories: 0 or 1 for low risk, 2 to 4 for intermediate risk, and 5 to 9 for high risk. RESULTS: Six multivariate factors predictive for graft failure after OLT using DCD grafts included the following: for recipients, (1) diagnosis of hepatitis C virus with malignancy, non-hepatitis C virus with malignancy, or hepatitis C virus only, (2) previous OLT, and (3) body mass index (calculated as weight in kilograms divided by height in meters squared) greater than 30; for donors, (4) hepatitis B core antibody positivity and (5) mean arterial pressure lower than 60 mm Hg for longer than 20 minutes after withdrawal of life support; and for grafts, (6) cold ischemia time longer than 6 hours. Five-year graft failure-free survival was significantly higher for the low-risk group (83%) compared with the intermediate-risk (62%) and high-risk (0%) groups (P < .001). Overall biliary complications occurred in 24 patients (29%), with ischemic cholangiopathy in 8 patients (9.9%). CONCLUSIONS: Our study showed superior long-term patient survival with liver transplantation using DCD organs in highly selected donors and recipients. We propose a practical risk stratification system highly predictive of long-term survival outcomes after OLT using DCD grafts. Application of this predictive index for transplant candidates receiving DCD liver grafts would improve patients' outcomes and optimize use of scarce resources.

Predictive index for long-term survival after retransplantation of the liver in adult recipients: analysis of a 26-year experience in a single center.

OBJECTIVE: To develop a prognostic scoring system for risk stratification of patients with hepatic graft failure (GF) undergoing retransplants of the liver (ReLT) and improve patient selection. SUMMARY OF BACKGROUND DATA: Retransplantation of the liver remains controversial because of inferior outcomes compared with the primary orthotopic liver transplantation (OLT) and raises concerns of inappropriate utilization of a scarce donor organ resource. Data on risk stratification of ReLT patients for long-term survival outcomes are limited. METHODS: We conducted an analysis from our prospective database of 466 adults' ReLT between February 1984 and September 2010. Mean follow-up was 3 years. Each independent predictor for allograft failure was assigned risk score (RS) points of 1 or 2, proportional to the corresponding parameter estimate under the Cox model: Predictive index category (PIC) 1, RS = 0; PIC II, RS = 1 to 2; PIC III, RS = 3 to 4; and PIC IV, RS = 5 to 12. RESULTS: Eight risk factors predictive for GF after ReLT included recipient age greater than 55 years, Model for End-Stage Liver Disease score greater than 27, history of prior OLT greater than 1, pre-ReLT requirement for mechanical ventilation, serum albumin less than 2.5 g/dL, donor age greater than 45 years, intraoperative requirement of packed red blood cell transfusion greater than 30 units, and performance of ReLT between 15 and 180 days from the prior OLT. Five-year GF-free survival was significantly higher in PIC I (65%) than in PIC II (53%), PIC III (43%), and PIC IV (20%) groups (P < 0.001). CONCLUSIONS: This risk-stratification model was highly predictive of long-term outcome after liver retransplantation in adult recipients. This formula provides a practical guide for selection of candidates for retransplantation of the liver that can lead to improved patient outcomes and optimal utilization of a scarce resource.