Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

This national survey sought to determine the practices and policies pertaining to opioid and opioid substitution therapy (OST) use in the selection of liver transplant (LT) candidates. Of 114 centers, 61 (53.5%) responded to the survey, representing 49.2% of the LT volume in 2016. Only two programs considered chronic opioid (1 [1.6%]) or OST use (1 [1.6%]) absolute contraindications to transplant, while 63.9% and 37.7% considered either one a relative contraindication, respectively. The majority of programs did not have a written policy regarding chronic opioid use (73.8%) or OST use (78.7%) in LT candidates. Nearly half (45.9%) of centers agreed that there should be a national consensus policy addressing opioid and OST use. The majority of responding LT centers did not consider opioid or OST use in LT candidates to be absolute contraindications to LT, but there was significant variability in center practices. These surveys also demonstrated a lack of written policies in the assessment of the candidacy of such patients. The results of our survey identify an opportunity to develop a national consensus statement regarding opioid and OST use in LT candidates to bring greater uniformity and equity into the selection of LT candidates.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

INTRODUCTION: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. METHODS: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010–2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). RESULTS: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04–1.4 and 1.37, 95% CI 1.08–1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15–1.3; sHR 2.99, 95% CI 1.76–5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00–1.13). DISCUSSION: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.

Introduction The increased demand for clinician-educators in academic medicine necessitates additional training in educational skills to prepare potential candidates for these positions. Although many teaching skills training programs for residents exist, there is a lack of reports in the literature evaluating similar programs during fellowship training. Aim To describe the implementation and evaluation of a unique program aimed at enhancing educational knowledge and teaching skills for subspecialty medicine fellows and chief residents. Setting Fellows as Clinician-Educators (FACE) program is a 1-year program open to fellows (and chief residents) in the Department of Internal Medicine at the University of Iowa. Program Description The course involves interactive monthly meetings held throughout the academic year and has provided training to 48 participants across 11 different subspecialty fellowships between 2004 and 2009. Program Evaluation FACE participants completed a 3-station Objective Structured Teaching Examination using standardized learners, which assessed participants' skills in giving feedback, outpatient precepting, and giving a mini-lecture. Based on reviews of station performance by 2 independent raters, fellows demonstrated statistically significant improvement on overall scores for 2 of the 3 cases. Participants self-assessed their knowledge and teaching skills prior to starting and after completing the program. Analyses of participants' retrospective preassessments and postassessments showed improved perceptions of competence after training. Conclusion The FACE program is a well-received intervention that objectively demonstrates improvement in participants' teaching skills. It offers a model approach to meeting important training skills needs of subspecialty medicine fellows and chief residents in a resource-effective manner.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post‐TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined “post‐TIPS renal dysfunction” as a change in estimated glomerular filtration rate (ΔeGFR) ≤−15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post‐TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD‐Na was 17. After 30 days post‐TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post‐TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00‐4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01‐1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16‐3.61; P = 0.01) were associated with post‐TIPS renal dysfunction. Competing risk regressions showed that those with post‐TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18‐2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post‐TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Checkpoint inhibitor therapy with monoclonal antibodies against programmed cell death protein 1 (PD1) has been implemented in the treatment of numerous malignancies. Pembrolizumab is one such medication. While severe toxicities are very rare, mild immune-mediated reactions with a variety of end organ injuries are among the most commonly encountered adverse events attributed to these medications. Acute liver injury manifesting as biochemical abnormalities with or without synthetic dysfunction is one such potential adverse reaction. Rarely, a relatively severe hepatitis can occur. While such severe adverse events are often successfully managed with systemic corticosteroids and drug discontinuation, our patient was refractory to standard management. We present a case of pembrolizumab-induced hepatitis in a patient with squamous cell carcinoma and prior orthotopic liver transplantation. Through a combination of serial plasmapheresis and intravenous immunoglobulin(IVIG) infusion, the patient’s hepatitis resolved as evidenced by virtual normalization of his liver indices. This illustrates the effectiveness of a relatively novel treatment strategy for this rare side effect of checkpoint inhibitor antineoplastic therapy.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a ‘multiple hit’ hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury. AIM To examine the genetic expression of NAFLD and non-alcoholic steatohepatitis (NASH) tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis. METHODS We employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology. For NAFLD, we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies; for NASH, we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies. RESULTS Our results from the NAFLD analysis reinforce the role of altered metabolism, inflammation, and cell survival in pathogenesis and support recently described contributors to disease activity, such as altered androgen and long non-coding RNA activity. The top upstream regulator was found to be sterol regulatory element binding transcription factor 1 (SREBF1), a transcription factor involved in lipid homeostasis. Downstream of SREBF1, we observed upregulation in CXCL10, HMGCR, HMGCS1, fatty acid binding protein 5, paternally expressed imprinted gene 10, and downregulation of sex hormone-binding globulin and insulin-like growth factor 1. These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver. Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis. Top canonical pathways, disease networks, and disease functions were related to cholesterol synthesis, lipid metabolism, adipogenesis, and metabolic disease. Top upstream regulators included pro-inflammatory cytokines tumor necrosis factor and IL1B, PDGF BB, and beta-estradiol. Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism, extracellular matrix deposition, and tumor suppression. Lastly, we found riciribine (an AKT inhibitor) and ZSTK-474 (a PI3K inhibitor) as potential drugs that targeted the differential gene expression in our dataset. CONCLUSION In this study we describe several molecular processes that may correlate with NAFLD disease and progression. We also identified ricirbine and ZSTK-474 as potential therapy.