Incidence, Outcomes, and Risk Factors of Intraoperative Cardiac Arrest During Orthotopic Liver Transplantation.

BACKGROUND: Intraoperative cardiac arrest (ICA) during liver transplantation (LT) is a rare surgical complication that results in devastating outcomes. Moreover, previous worldwide studies have found inconsistencies in the risk factors associated with ICA in LT. METHODS: This was a retrospective cohort study of adult patients who underwent LT between January and October 2021 at Siriraj Hospital, a tertiary care hospital. The incidence of ICA and outcomes of patients who experienced ICA were examined. Risk factors associated with ICA were investigated as a secondary objective. RESULTS: Among 342 patients, the incidence of ICA was 3.5% (95% CI 1.8%-6.1%). Of these, 33.3% died intraoperatively. Among patients with ICA, 41.7% died within 30 days, compared with only 7.6% in those without ICA (P = .002). Moreover, the in-hospital mortality rate of those with ICA was 58.3%, which was significantly higher than that of those without ICA (9.7%, P < .001). However, 41.7% of patients with ICA were discharged alive with long-term survival. Because ICA is a rare event, we found only 2 independent factors significantly associated with ICA. These factors include intraoperative temperature below 35°C, with an odds ratio (OR) of 6.07 (95% CI:1.32-27.88, P = .02) and elevated intraoperative serum potassium, with an OR of 4.57 (95% CI:2.15-9.67, P < .001). CONCLUSIONS: ICA is associated with high perioperative and in-hospital mortality. However, our findings suggest that with effective management of ICA, more than 40% of these patients could be discharged with excellent long-term outcomes. Hypothermia and hyperkalemia were independent risk factors significantly associated with ICA.

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.

Predictive score for immediate extubation after liver transplantation.

INTRODUCTION: Evidence suggests that immediate extubation after liver transplantation provides graft and economic benefits without compromising patient outcomes. This study tried to determine the incidence of immediate extubation, demonstrate related factors, and develop a predictive model from the significant factors. METHODS: This retrospective descriptive study included 240 out of 271 liver transplantation patients in the hospital liver transplant registry between 2004 and 2016. Extubated and non-extubated groups were statistically compared. RESULTS: The incidence of immediate extubation was 32.1%. It was associated with a MELD score ≤ 25 (adjusted OR, 5.17; 95% CI, 1.64-16.24; p = .005); packed red cells (PRC) transfusion ≤1600 ml (adjusted OR, 3.45; 95% CI, 1.82-6.53; p < .001); and no requirement for post-operative vasopressors (adjusted OR, 5.83; 95% CI, 2.30-14.77; p < .001). The immediate-extubation group had fewer complications and shorter hospital stays. A Siriraj Liver transplant Extubation Score (SLES) of 5 yielded the best prediction of safe immediate extubation. CONCLUSIONS: An incidence of 32.1% was found for immediate extubation following liver transplantation. Associated factors were a MELD score ≤ 25, a lower amount of transfused blood, and no requirement for post-operative vasopressors. An SLES score of 5 predicted safe immediate extubation.

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.

Time spent in hospital after liver transplantation: Effects of primary liver disease and comorbidity.

AIM: To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS: A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS: In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION: The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS.

Time-varying impact of comorbidities on mortality after liver transplantation: a national cohort study using linked clinical and administrative data.

OBJECTIVE: We assessed the impact of comorbidity on mortality in three periods after liver transplantation (first 90 days, 90 days-5 years and 5-10 years). DESIGN: Prospective cohort study using records from the UK Liver Transplant Audit (UKLTA) linked to Hospital Episode Statistics (HES), an administrative database of hospital admissions in the English National Health Service (NHS). Comorbidities relevant for liver transplantation were identified from the 10th revision of the International Classification of Diseases (ICD-10) codes in HES records of admissions in the year preceding their operation. Multivariable Cox regression was used to estimate HRs for three different time periods after liver transplantation. SETTING: All liver transplant centres in the NHS hospitals in England. PARTICIPANTS: Adults who received a first elective liver transplant between April 1997 and March 2010 in the linked UKLTA-HES database. OUTCOMES: Patient mortality in three different time periods after transplantation. RESULTS: Among 3837 recipients, 45.1% had comorbidities. Recipients with cardiovascular disease had statistically significantly higher mortality in all three periods after transplantation (first 90 days: HR=2.0; 95% CI 1.4 to 2.9, 90 days-5 years: 1.6; 1.2 to 2.2, beyond 5 years: 2.8; 1.7 to 4.4). Prior congestive cardiac failure (3.2; 2.1 to 4.9) significantly increased mortality only in the first 90 days. History of non-hepatic malignancy appeared to increase risk over all periods, but significantly only in the first 90 days (1.9; 1.0 to 3.6). A diagnosis of connective tissue disease, dementia, diabetes, chronic pulmonary and renal disease did not have a significant impact on mortality in any period. CONCLUSIONS: The impact of comorbidities present at the time of transplantation changes with time after transplantation. Renal disease, pulmonary disease and diabetes had no impact on mortality in contrast to previous reports.

Linkage of a national clinical liver transplant database with administrative hospital data: methods and validation.

INTRODUCTION: The UK Liver Transplant Audit (UKLTA) database contains clinical information on all liver transplants carried out in the UK. To expand its potential for research and service evaluation, we linked it to the Hospital Episode Statistics (HES), an administrative database of all admissions to English National Health Service (NHS) hospitals. MATERIALS AND METHODS: In the UKLTA database, we identified the linkable records of first liver transplantation between April 1997 and March 2010. We linked UKLTA records to HES records on the basis of NHS number, gender, date of birth, and postcode, as well as procedure codes for liver transplantation and dates of transplant. In linked records, agreement of primary liver disease diagnoses according to both databases was expressed as a proportion of the linked records and using kappa statistic. RESULTS: There were 5,815 linkable records in the UKLTA database, of which 4,959 records were successfully linked with HES (85.3%). Among these, 4,922 records (99.3%) had at least one diagnosis coded in HES relevant to an indication for liver transplantation. The overall agreement of primary liver disease diagnoses between UKLTA data and HES was 77.8% (95% CI 76.6%-79.0%) with a kappa of 0.75 (0.74-0.76). Diagnostic agreement can be further improved by using broader groupings of clinically related diagnoses. CONCLUSION: Linkage of clinical data and administrative hospital data provides a rich resource for the study of liver transplantation.

Comparison of staging systems of hepatocellular carcinoma.

Many staging systems of hepatocellular carcinoma (HCC) were established; however, there is no consensus on which is proper in predicting prognosis. This study aims to evaluate various commonly used staging systems of HCC. Patients who underwent surgery during 2001-2007 were included. All patient data were retrospectively staged using six staging systems, that are American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM), Okuda staging, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), Chinese University Prognostic Index (CUPI), and Japan Integrated Staging (JIS). Child-Pugh classification was also evaluated. The staging systems were compared by mean of overall and disease-free survival. Total of 99 patient data were enrolled in the analyses. All staging systems except Okuda were significant in determining overall survival in univariate analyses. In multivariate analyses, TNM and Child-Pugh demonstrated better predictive power for overall survival. In terms of disease-free survival, univariate analyses revealed that TNM, CLIP, BCLC, CUPI, and JIS were significant, and TNM was the best predictive staging system in multivariate analyses. In our study, TNM and Child-Pugh are the representative systems in predicting survival of HCC patients who undergo surgical resection. Moreover, they are practical and easily assessable in clinical practice.