Post-liver Transplant Outcomes Research Articles

S1979 MELD-Psoas: A New Composite Predictive Score for Post-liver Transplant Outcomes

S1979 MELD-Psoas: A New Composite Predictive Score for Post-liver Transplant Outcomes

402.2: Association of macrovascular invasion and poor tumor differentiation on post-liver transplant outcomes in patients with hepatocellular carcinoma.

402.2: Association of macrovascular invasion and poor tumor differentiation on post-liver transplant outcomes in patients with hepatocellular carcinoma.

P.398: Evaluating post-liver transplantation outcomes in hepatorenal syndrome: Insights from a small volume center study.

P.398: Evaluating post-liver transplantation outcomes in hepatorenal syndrome: Insights from a small volume center study.

Racial and ethnic disparities in post-liver transplant outcomes for patients with acute-on-chronic liver failure: An analysis of the UNOS database.

The incidence of hospitalisations related to acute-on-chronic liver failure (ACLF) is increasing. Liver transplantation (LT) remains the definitive treatment for the condition. To evaluate the influence of race and ethnicity on LT outcomes in ACLF. We conducted a retrospective analysis utilising LT data from the United Network for Organ Sharing (UNOS) database. White patients served as the control group and patients of other races were compared at each ACLF grade. The primary outcomes assessed were graft failure and all-cause mortality. Blacks exhibited a higher all-cause mortality (Grade 1: aHR 1.36, 95% CI 1.18-1.57, p < 0.001; Grade 2: aHR 1.27, 95% CI 1.08-1.48, p = 0.003; Grade 3: aHR 1.19, 95% CI 1.04-1.37, p = 0.01) and graft failure (Grade 1: aHR 2.05, 95% CI 1.58-2.67, p < 0.001; Grade 2: aHR 1.91, 95% CI 1.43-2.54, p < 0.001; Grade 3: aHR 1.50, 95% CI 1.15-1.96, p = 0.002). Hispanics experienced a lower all-cause mortality at grades 1 and 3 (Grade 1: aHR 0.83, 95% CI 0.72-0.96, p = 0.01; Grade 3: aHR 0.80, 95% CI 0.70-0.91, p < 0.001) and Asians with severe ACLF demonstrated decreased all-cause mortality (Grade 3: aHR 0.55, 95% CI 0.42-0.73, p < 0.001). Black patients experienced the poorest outcomes and Hispanic and Asian patients demonstrated more favourable outcomes compared to Whites.

Impact of Sarcopenia on Post-Liver Transplant Hospitalization: Insights From a South Asian Cohort

BackgroundSarcopenia's impact on post-liver transplant outcomes remains a subject of debate, with limited data from South Asia on its association with post-liver transplant hospital stays. This study aims to investigate sarcopenia's influence on post-transplant hospitalization duration in South Asians. MethodsIn this retrospective study, patients with liver cirrhosis who underwent living-donor liver transplantation at Shifa International Hospital in Islamabad, Pakistan, between January 2022 and January 2023 were included. Computed Tomography (CT) images were used to assess the skeletal muscle index (SMI). The areas of the psoas, erector spinae, multifidus, quadratus lumborum, rectus abdominis, transverse abdominis, and internal/external oblique muscles were quantified at the level of L3. The data was analyzed using SPSS v. 29.0 (IBM Chicago, IL). ResultsThere was a total of 84 patients. Mean age was 47.4 ± 12.0 years. There were 62 (73.8%) males and 22 (26.2%) females. Hepatitis C was noted in 36 (42.9%) patients. 22 (26.2%) patients had hepatocellular carcinoma. Sarcopenia was identified in 58 (69.0%) patients. No significant association was observed between sarcopenia and ICU or general floor stays. Regression analysis identified pre-transplant MELD-Na score as the sole significant factor associated with both ICU and total length of stay (p-value 0.002; p-value 0.009). ConclusionIn our population, sarcopenia did not correlate with post-transplant ICU or overall hospital stay. The pre-transplant MELD-Na score emerged as the most influential predictor of length of stay. Therefore, delaying liver transplant procedures based on muscle mass estimations may not be a practical clinical approach for South Asian patients.

Should advanced perfusion be the standard of care for donation after circulatory death liver transplant?

As an alternative to static cold storage (SCS), advanced perfusion techniques such as normothermic regional perfusion and ex-situ perfusion (normothermic or hypothermic) have emerged as a way to improve the ischemic injury suffered by donation after circulatory death (DCD) livers. Multiple studies have been published that have demonstrated superior post-DCD liver transplant outcomes when using advanced perfusion compared with SCS. In particular, these studies have shown lower rates of ischemic cholangiopathy with advanced perfusion. In addition to the improved post-liver transplant outcomes, studies have also demonstrated higher rates of liver utilization from DCD donors when advanced perfusion is used compared with SCS. Given the high rates of graft loss in patients who develop ischemic cholangiopathy, the significant reduction seen in DCD donor livers that have undergone advanced perfusion represents a key step in more broad utilization of these livers. With such compelling evidence from multiple trials, it seems reasonable to ask the question: should advanced perfusion be the standard of care for DCD liver transplant?

Reversing malnutrition and low muscle strength with targeted enteral feeding in patients awaiting liver transplant: A randomized controlled trial.

Most patients with decompensated cirrhosis fail to meet their nutrition targets. The impact of nasogastric feeding (NGF) on malnutrition in cirrhosis remains unknown. This study aims to assess the impact of pretransplant NGF on pre-liver transplant and post-liver transplant outcomes. This single-center, prospective randomized controlled trial of 55 patients with severe malnutrition and low handgrip strength (HGS) compared a standard high-energy high-protein diet to diet plus supplemental nocturnal NGF while awaiting transplant. The primary outcome was a change in HGS. The median age was 58.5 years (IQR: 51.1-64), median MELD was 24 (20-28.5), and 32 (58%) patients were male. The median duration of NGF was 63.0 days (34.5-127), following which time the median between-group difference in HGS was 3.6kg (95% CI: 1.7-5.2, p <0.001), an increase of 20% from baseline. Mid-upper-arm circumference, triceps skinfold, and immune function all increased significantly with NGF. Muscle and nutritional parameters continued to improve with increasing duration of feeding. NGF significantly increased daily energy intake between groups by 1285kcal (95% CI: 860-1677) and protein intake by 51g (95% CI: 32-71) (both p <0.001). All NGF patients met >100% of their measured nutritional requirements. Posttransplant clinical outcomes were similar between groups. Targeted enteral feeding before liver transplant improves HGS, anthropometry, and immune function in severely malnourished patients with cirrhosis. These findings provide a strong rationale for early consideration of NGF to reverse malnutrition and improve muscle strength. Appropriately powered studies should explore whether NGF can also impact clinically relevant outcomes including pretransplant and posttransplant mortality.

Point-of-care device for the noninvasive assessment of hepatic macrosteatosis in liver donors

BackgroundQuantification of macrosteatosis (MS) in the liver is important given that it has shown to directly correlate with adverse post-liver transplant (LT) outcomes. With advances in medical technology and an implicit understanding of pathology, noninvasive methods of quantitatively assessing MS are in various stages of development. Each of these methods is based on the physical principles of differences between a fat-laden hepatocyte and a normal one. MethodsIn this regard, after a proof-of-concept study on a prototype for a simple, real-time, handheld device using the principle of diffuse reflectance spectroscopy, this study presents an upgraded point-of-care (POC) device for the noninvasive assessment of hepatic MS in liver donors. ResultsThe device was validated on cohort of donor livers and showed a sensitivity (0.0021 V/% fat) and highly correlated (r = 0.9868, P < .0001) with gold-standard liver biopsy. Results showed that this upgraded POC device provides a reliable method for the noninvasive assessment of hepatic MS, which is crucial for selecting suitable donor livers for LT. ConclusionThe device has the potential to be an invaluable apparatus at the hands of the organ-retrieving surgeon. It is noninvasive, portable (handheld), and economic; provides real-time readings of the percentage of MS; and can be efficaciously handled by any member of the organ-retrieving team.

The role of donor sex on the post-liver transplant outcomes in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) can result in hepatic decompensation and require liver transplantation (LT). This study investigates the effect of the sex of the donor and recipient as a prognostic risk factor for adverse outcomes after LT in patients with PSC. UNOS registry was used to select LT patients with PSC from 1987 to 2019. The study cohort was stratified based on the sex of the recipient and further subdivided based on the sex of the donor. The primary endpoints of this study were all-cause mortality and graft failure, which were evaluated using a sequential Cox regression analysis. This study included 2829 patients; 906 female recipients were transplanted from 441 male donors and 465 female donors. 1923 male recipients were transplanted from 1194 male donors and 729 female donors. Within the mismatch analyses, the male-to-male recipients also had a significantly reduced hazard ratio of graft failure compared to female-to-male transplants [aHR 0.51, 95% confidence interval (CI) 0.33-0.79, P = 0.003]. No difference in graft failure was observed in the mismatched female recipient subgroup. The mismatched male recipient group also showed a decreased hazard ratio of mortality from graft rejection and respiratory causes. No differences in specific mortality causes were identified in the mismatched female recipient group. This study demonstrated an increase in the risk of graft failure and mortality secondary to graft failure in male recipients of female donor livers. No differences in mortality or graft failure were identified in female recipients of male livers.

The impact of socioeconomic deprivation on liver transplantation.

Despite global expansion, social disparities impact all phases of liver transplantation, from patient referral to post-transplant care. In pediatric populations, socioeconomic deprivation is associated with delayed referral, higher waitlist mortality, and reduced access to living donor transplantation. Children from socially deprived communities are twice as much less adherent to immunosuppression and have up to a 32% increased incidence of graft failure. Similarly, adult patients from deprived areas and racial minorities have a higher risk of not initiating the transplant evaluation, lower rates of waitlisting, and a 6% higher risk of not being transplanted. Social deprivation is racially segregated, and Black recipients have an increased risk of post-transplant mortality by up to 21%. The mechanisms linking social deprivation to inferior outcomes are not entirely elucidated, and powered studies are still lacking. We offer a review of the most recent evidence linking social deprivation and post-liver transplant outcomes in pediatric and adult populations, as well as a literature-derived theoretical background model for future research on this topic.

The Lower Survival in Patients With Alcoholism and Hepatitis C Continues in the DAA Era.

Alcohol liver disease (ALD) may coexist with hepatitis C (HCV) in many transplant recipients (alcoholic cirrhosis with hepatitis C [AHC]). Our objective was to determine whether there were differences in postliver transplantation outcomes of patients with AHC when compared with those with alcoholic cirrhosis (AC) and/or alcoholic hepatitis (AH). Using UNOS explant data sets (2016-2020), the survival probabilities of AC, AH, and AHC were compared by Kaplan-Meier survival analysis. Cox proportional-hazard regression analysis was used to determine outcomes after adjusting for disease confounders. The outcomes were also compared with predirect antiviral agent (DAA) period. During study period, 8369 biopsy-proven ALD liver transplant recipients were identified. Of those, 647 had AHC (HCV + alcohol), 353 had AH, and 7369 had AC. MELD-Na score (28.7 ± 9.5 versus 23.8 ± 10.7; P < 0.001) and presence of ACLF-3 (19% versus 11%; P < 0.001) were higher in AC + AH as compared with AHC. AHC and AC+AH has similar adjusted mortality at 1-y, but 3-y (hazard ratios, 1.76; 95% confidence intervals, 1.32-2.35; P < 0.0001) and 5-y (hazard ratios, 1.64; 95% confidence intervals, 1.24-2.15; P = 0.0004) mortality rates were higher in AHC. Survival improved in the DAA era (2016-2020) compared with 2009 to 2013 in AHC, but remained worse in AHC group versus AC and/or AH. Malignancy-related mortality was higher in AHC (15% versus 9.3% in AC) in the DAA era. AHC was associated with lower 3- and 5-y post-LT survival as compared with ALD without HCV and the worse outcomes in AHC group continued in the DAA era.

The predictive role of autonomic neuropathy in pre- and post-liver transplantation outcomes: a systematic review and meta-analysis.

Autonomic neuropathy (AN) in cirrhotic patients has been linked to a higher risk of cirrhosis-related complications and worse outcomes before, during or after liver transplantation (LT). However, only a few studies exist with inconsistent results. We searched for all articles published until September 2023 that described a diagnosis of AN based on cardiovascular autonomic reflex tests (CARTs), assessment of the rate-corrected QT interval (QTc), heart rate variability (HRV), and baroreflex sensitivity (BRS) tests, in order to evaluate the predictive role of AN in cirrhosis and/or peri-/post-LT prognosis. Twenty-five studies were included: 5, 12, 9, and 1 study, respectively, assessed the predictive role of CARTs, prolonged QTc, HRV indices, and BRS in cirrhosis or peri-/post-LT prognosis. In CARTs-based analysis, the pre-LT pooled mortality rate was significantly higher in cirrhotics with AN compared to those without AN (20% vs. 6%; P=0.01). However, no difference was found between patients with and without pre-LT prolonged QTc in the pre-LT pooled mortality rates (41% vs. 18%; P=0.08), pooled peri-transplant risk of major complications (29% vs. 17%; P=0.08) or post-LT pooled mortality rates (15% vs. 12%; P=0.36). In HRV-based analysis, the standard deviation of normal-to-normal intervals was significantly lower in non-survivors, compared to survivors with cirrhosis: standardized mean difference -2.59, 95% confidence interval -4.75 to -0.43; P=0.04. The presence of CARTs- and HRV-based AN was a good predictor of mortality in the pre-LT setting. Preoperative prolonged QTc did not seem to be associated with the outcome before or after LT.

Association of body mass index with post-liver transplant outcomes.

Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. Recipientwere categorized by body mass index (BMI, kg/m2 ): non-obese (BMI<30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI≥35).Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p=.047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p=.02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p=.01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p=.002; 9 (6-14) vs. 8 (6-11) days]. Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p>.05). Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

Severe hepatic encephalopathy with mechanical ventilation may inform waitlist priority in acute liver failure: A UNOS database analysis.

Patients with acute liver failure (ALF) awaiting liver transplantation (LT) may develop multiorgan failure, but organ failure does not impact waitlist prioritization. The aim of this study was to examine the impact of organ failure on waitlist mortality risk and post LT outcomes in patients with ALF. We studied adults waitlisted for ALF in the United Network for Organ Sharing (UNOS) database (2002-2019). Organ failures were defined using a previously described Chronic Liver Failure modified sequential organ failure score assessment adapted to UNOS data. Regression analyses of the primary endpoints, 30-day waitlist mortality (Competing risk), and post-LT mortality (Cox-proportional hazards), were performed. Latent class analysis (LCA) was used to determine the organ failures most closely associated with 30-day waitlist mortality. About 3212 adults with ALF were waitlisted, for hepatotoxicity (41%), viral (12%) and unspecified (36%) etiologies. The median number of organ failures was three (interquartile range 1-3). Having ≥3 organ failures (vs. ≤2) was associated with a sub hazard ratio (HR) of 2.7 (95%CI 2.2-3.4)) and a HR of 1.5 (95%CI 1.1-2.5)) for waitlist and post-LT mortality, respectively. LCA identified neurologic and respiratory failure as most impactful on 30-day waitlist mortality. The odds ratios for both organ failures (vs. neither) were higher for mortality 4.5 (95% CI 3.4-5.9) and lower for delisting for spontaneous survival .5 (95%CI .4-.7) and LT .6 (95%CI .5-.7). Cumulative organ failure, especially neurologic and respiratory failure, significantly impacts waitlist and post-LT mortality in patients with ALF and may inform risk-prioritized allocation of organs.

The impact of recipient and donor gender-match and mismatch on the post-liver transplant outcomes of patients with primary biliary cholangitis.

In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC). The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis. There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n=1581), those with gender-mismatch (male donors, n=769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n=304), no associations were found between gender-mismatch (female donors, n=108) and all-cause mortality or graft failure. This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort.

Predicting post–liver transplant outcomes in patients with acute-on-chronic liver failure using Expert-Augmented Machine Learning

Liver transplantation (LT) is a treatment for acute-on-chronic liver failure (ACLF), but high post-LT mortality has been reported. Existing post-LT models in ACLF have been limited. We developed an Expert-Augmented Machine Learning (EAML) model to predict post-LT outcomes. We identified ACLF patients who underwent LT in the University of California Health Data Warehouse. We applied the RuleFit machine learning (ML) algorithm to extract rules from decision trees and create intermediate models. We asked human experts to rate the rules generated by RuleFit and incorporated these ratings to generate final EAML models. We identified 1384 ACLF patients. For death at 1 year, areas under the receiver-operating characteristic curve were 0.707 (confidence interval [CI] 0.625-0.793) for EAML and 0.719 (CI 0.640-0.800) for RuleFit. For death at 90 days, areas under the receiver-operating characteristic curve were 0.678 (CI 0.581-0.776) for EAML and 0.707 (CI 0.615-0.800) for RuleFit. In pairwise comparisons, both EAML and RuleFit models outperformed cross-sectional models. Significant discrepancies between experts and ML occurred in rankings of biomarkers used in clinical practice. EAML may serve as a method for ML-guided hypothesis generation in further ACLF research.

Factors associated with a positive phosphatidylethanol test during liver transplantation evaluation.

Early identification of alcohol use is crucial for informing recommendations of appropriate follow-up treatment pre-liver transplant and optimizing post-liver transplant outcomes. The purpose of the study was to investigate whether there are psychosocial factors associated with a positive PEth test. All patients who underwent a routine pre-surgical psychological evaluation for liver transplant listing (all etiologies, including acute liver failure, dual organ, and re-transplantation) at a single health care system in 2020 were included in a retrospective chart review. Data extraction included results from PEth testing and information from the psychological evaluation (i.e., demographic, psychiatric symptoms, and cognitive functioning). There were 158 patients (73.8%) who had a PEth test, of whom 21.5% had a positive result (n=34). Younger age was associated with a positive PEth (p<.001). ALD status and type of ALD (hepatitis vs. cirrhosis) were also associated with a positive PEth test. Other demographic characteristics and psychiatric symptoms were not associated with a positive PEth result (p>.05). Younger age was the only significant demographic variable associated with a positive PEth test. Given the difficulty of predicting who may be using alcohol, it may be useful to use PEth testing for all patients during the pre-liver transplant evaluation and while patients are listed for liver transplant. Early identification of alcohol use through routine PEth testing will help identify patients who are using alcohol and need further treatment for alcohol use to optimize health and post-transplant outcomes.

Physical function in children and adolescents pre- and 1-year post-liver transplant.

Several studies describe poorer motor developmental motor outcomes post-liver transplant (LT) in younger children. Limited studies examine physical function in older children and adolescents pre- and post-LT. Retrospective review of standard of care physical function outcome measures pre- and 1-year post-LT in children ≥6 years at LT. Measures include: 6-minute walk test (6MWT), grip strength, Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2) components, Physical Activity Questionnaire (PAQ), and Paediatric Quality of Life Multidimensional Fatigue Scale. Association of medical variables with outcomes was explored. The study cohort included 23 (8 male, median (interquartile range) age 11.67 (8.25, 13.92) years at LT) participants. Top two primary diagnoses included biliary atresia (30.4%) and fulminant hepatic failure (21.7%). At 1-year post-LT, over one-third (36%) were overweight or obese. Compared with healthy norms, children had significantly lower pre-LT PAQ scores (p = .002), pre- and post-6MWT scores (p < .001) and post-LT BOT-2 strength and agility scores (p < .001). Pre-LT, lower balance scores were associated with abdominal distention/ascites (p = .009) and splenomegaly (p = .017). Lower pre-LT platelet count correlated with poorer balance (r = .532, p = .017) and lower strength and agility scores (r = .446, p = .043). Significant moderate inverse correlations were found between weight/body mass index z-scores and BOT-2 components. Post-LT children continue to demonstrate decreased levels of motor proficiency and functional capacity but report less fatigue and increased physical activity. Older children and adolescents undergoing LT are at risk of decreased physical function, highlighting the need for pre- and post-LT rehabilitation to optimize long term outcomes.

Impact of Inflammatory Bowel Disease Subtypes on the Post-liver Transplant Outcomes of Patients with Primary Sclerosing Cholangitis.

Liver transplant patients with primary sclerosing cholangitis often present with concurrent inflammatory bowel disease. The effect of comorbid conditions on post-transplant prognosis was evaluated. The 2005-2019 United Network of Organ Sharing Standard Transplant Analysis and Research database was used to identify patients with primary sclerosing cholangitis. Patients were categorized as having Crohn's Disease, ulcerative colitis, unclassified inflammatory bowel disease, or no inflammatory bowel disease. Baseline characteristics were assessed between cohorts, and outcomes were examined using Cox regression. Outcomes included all-cause mortality, graft failure, infection-induced mortality, and organ system-delineated mortality. Supplementary analyses with unique exclusion and stratification criteria were also performed. Among 2829 patients undergoing transplant, 1360 were considered to have ulcerative colitis, 372 were considered to have Crohn's Disease, and 69 were considered to have an unclassified form of inflammatory bowel disease. Primary sclerosing cholangitis patients with some form of inflammatory bowel disease had no increased risk for any outcomes. However, patients with ulcerative colitis had lower risks of general infectious (aHR 0.65 95%CI 0.44-0.95) and sepsis-induced (aHR 0.56 95%CI 0.35-0.91) mortality, whereas patients with Crohn's Disease had higher risks of sepsis-induced mortality (aHR 2.13 95%CI 1.22-3.70). Supplementary analyses showed effect modification by abdominal surgery history and era. The type of inflammatory bowel disease in liver transplant patients with primary sclerosing cholangitis was found to portend risk difference for infection-induced mortality, with ulcerative colitis found to be protective and Crohn's Disease predictive of increased mortality secondary to infectious etiologies. These associations warrant further investigation.

Long Term Complications of Immunosuppression Post Liver Transplant

Improvement in immunosuppression has led to a remarkable improvement in short-term and long-term outcomes post-liver transplant (LT). However, with improvements in long-term survival, complications related to immunosuppressive drugs, either directly or indirectly, have also increased. The adverse events could be drug-specific, class-specific, or generic. Calcineurin inhibitors (cyclosporine and tacrolimus) are the backbone of the immunosuppression after LT and the main culprit associated with most of the complications, including renal failure, post-transplant diabetes mellitus (PTDM), and metabolic syndrome. Steroids are also implicated in the development of diabetes, osteoporosis, and metabolic syndrome post-LT. The development of infections and de novo malignancies (DNMs) is a generic effectlinked to the overall cumulative immunosuppression. The development of these complications significantly hampers the quality of life and leads to increased morbidity and mortality post-LT. Thus, it is important to minimize the cumulative immunosuppression dosewhile simultaneously preventing allograft rejection. This review provides up-to-date, comprehensive knowledge of the complications of long-term immunosuppression post-LT along with associated risk factors and strategies to minimize the risk of complications.