Reduced metabolic flexibility is a predictor of weight gain among liver transplant recipients.

Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (ß-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (ß-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (ß-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.

Locked Posterior Shoulder Dislocation with a Large Bone Defect in an Active Patient Treated with Autograft.

Introduction: Posterior glenohumeral joint dislocations are uncommon injuries. The disease often goes undiagnosed and untreated despite positive clinical signs. In the event of a large humeral bone defect, the outcome may be worse. Case Report: This case report presents a 47-year-old man with a 2-year-old locked posterior shoulder dislocation with a large segmental bone defect involving 40% of the humeral head's articular surface. We decided to treat the patient with an open reduction of the shoulder dislocation and reconstruction of the articular surface with iliac crest autograft. We observed an improvement in shoulder mobility and range of motion on all planes, which were beneficial to the patient's daily activities; at follow-up, no pain was reported. Conclusion: Our case report demonstrates that locked posterior shoulder dislocations with a large bone defect and viable humeral head can be treated using an autograft. This will result in optimal clinical results and avoid early prosthetic replacement surgery. Autograft may be a preferred method in the presence of economic constraints or due to the unavailability of allografts or implants.

Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients.

NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.

Derivation and Validation of a Model to Predict Clinically Significant Portal Hypertension Using Transient Elastography and FIB-4.

BACKGROUND: Liver biopsy and hepatic venous pressure gradient (HVPG), the gold standard for assessing advanced fibrosis (AF) and clinically significant portal hypertension (CSPH), are invasive, costly, and time-consuming. GOAL: We investigated if the combination of fibrosis index based on 4 factors (FIB-4) and liver stiffness measure (LSM) can identify AF and more importantly, CSPH. PATIENTS AND METHODS: Patients with chronic liver disease referred for transjugular liver biopsy were analyzed retrospectively. FIB-4 and LSM were compared with liver histology for diagnosing AF. FIB-4, LSM, and platelet count were compared with HVPG for diagnosing CSPH. Optimal cutoffs for predicting CSPH were determined by grid search. A composite log-odds to predict CSPH was derived from logistic regression using LSM, FIB-4, and gender. Internal bootstrap validation and external validation were performed. RESULTS: A total of 142 patients were included in the derivation; 42.3% had AF, and 11.3% had CSPH using the current gold standards. The area under the receiver operating characteristic curve (AUROC) for LSM, FIB-4, and their combination to predict AF were 0.7550, 0.7049, and 0.7768, respectively. LSM, FIB-4, and platelet count predicted CSPH with AUROC 0.6818, 0.7532, and 0.7240, respectively. LSM plus FIB-4 showed the best performance in predicting CSPH with AUROC 0.8155. Based on LSM, FIB-4, and gender, a novel model-the Portal Hypertension Assessment Tool (PHAT)-was developed to predict CSPH. PHAT score ≥-2.76 predicted CSPH with sensitivity 94%, specificity 67%, positive predictive value 27%, negative predictive value 99%, and accuracy 70%. In internal and external validation, AUROCs for the model were 0.8293 and 0.7899, respectively. CONCLUSION: A model consisting of FIB-4, LSM, and gender can identify CSPH among patients with chronic liver disease.

Glomerular filtration rate early after liver transplantation independently predicts atherosclerotic events.

Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three-point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow-up of 74 months (interquartile range 46-111), 94 (17%) LT recipients died and CVD-associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95-0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95-0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE-3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation.

Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease.

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS: Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS: The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION: Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.

Early laboratory values after liver transplantation are associated with anastomotic biliary strictures.

BACKGROUNDS/AIMS: The aim of this study was to evaluate longitudinal changes of post-liver transplantation (LT) biliary anatomy and to assess the association of increased laboratory values after LT with the development of post-LT anastomotic biliary stricture (ABS). METHODS: Adult deceased donor LT recipients from 2008 and 2019 were evaluated. ABS was defined after blinded review of endoscopic cholangiograms. Controls were patients who underwent LT for hepatocellular carcinoma who did not have any clinical or biochemical concerns for ABS. RESULTS: Of 534 patients who underwent LT, 57 patients had ABS and 57 patients served as controls. On MRI, ABS patients had a narrower anastomosis (2.47 ± 1.32 mm vs. 3.38 ± 1.05 mm; p < 0.01) and wider bile duct at 1-cm proximal to the anastomosis (6.73 ± 2.45 mm vs. 5.66 ± 1.95 mm; p = 0.01) than controls. Association between labs at day 7 and ABS formation was as follows: aspartate aminotransferase hazard ratio (HR): 1.014; 95% confidence interval (CI): 1.008-1.020, p = 0.001; total bilirubin HR: 1.292, 95% CI: 1.100-1.517, p = 0.002; and conjugated bilirubin HR: 1.467, 95% CI: 1.216-1.768, p = 0.001. Corresponding analysis results for day 28 were alanine aminotransferase HR: 1.004, 95% CI: 1.002-1.006, p = 0.001; alkaline phosphatase HR: 1.005, 95% CI: 1.003-1.007, p = 0.001; total bilirubin HR: 1.233, 95% CI: 1.110-1.369, p = 0.001; and conjugated bilirubin HR: 1.272, 95% CI: 1.126-1.437, p = 0.001. CONCLUSIONS: Elevation of laboratory values early after LT is associated with ABS formation.

Neurological safety and efficacy of darifenacin and mirabegron for the treatment of overactive bladder in patients with history of cerebrovascular accident: A prospective study.

OBJECTIVES: To evaluate the neurological safety and clinical efficacy of darifenacin and mirabegron in patients with a history of cerebrovascular accident (CVA) who had overactive bladder (OAB) symptoms. METHODS: This prospective randomized study, approved by the institute's ethics committee, was carried out at a tertiary care center from December 2018 to June 2020. Treatment naïve adult patients with a past history of CVA with stable neurological status for atleast past 3 months with symptoms of OAB for 3 or more months were included. Eligible patients received either darifenacin or mirabegron for a period of 3 months and various parameters on the 3-day International Consultation on Incontinence Questionnaire (ICIQ) bladder diary, the Montreal Cognitive Assessment-Basic score (MoCA-B), and the adverse events at 3 months posttreatment were compared to that at the baseline. RESULTS: A total of 60 patients were included, 30 in each arm. After 3 months of treatment with darifenacin or mirabegron, the majority of the ICIQ bladder diary parameters improved and there was no deterioration in the cognitive function as noted on the MoCA-B score in either of the arms. On intergroup comparison, the mean change in bladder diary parameters and the MoCA-B scores was similar between the two groups. CONCLUSION: Darifenacin and mirabegron, in the short term, do not adversely affect the cognitive function in patients with a history of CVA with OAB symptoms. Both are safe and effective treatment options in patients with OAB post-CVA.

Gut Microbial Signature of Hepatocellular Cancer in Men With Cirrhosis.

The gut microbiome is altered in cirrhosis. Recent evidence has suggested a key role for the gut microbiota in the progression of cirrhosis and the development of hepatocellular carcinoma (HCC). We studied the differences in the microbial composition in patients with cirrhosis with prior and future HCC in the context of other complications (eg, infections, hepatic encephalopathy). The following 2 cohorts were recruited prospectively: the prior HCC cohort, in which outpatients with HCC within 2 years were age-matched, sex-matched, and Model for End-Stage Liver Disease (MELD) score-matched with those without HCC; and the future HCC cohort, in which patients were followed for 2 years and divided into future HCC versus no HCC after age, sex, and MELD-score matching and other complications were also recorded. Microbiota composition and predicted function were analyzed with ribosomal RNA sequencing and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PiCRUST)and compared between (1) prior HCC versus none and (2) future HCC versus none, and in the future cohort, comparisons were also made between those patients who developed (1) HCC only versus without complications, (2) HCC only versus non-HCC complications only, and (3) HCC + other complications versus non-HCC complications only. A total of 142 men (76 total in the prior cohort [38 with/38 without HCC] and 66 total in the future cohort [33 with/33 without future HCC]) were included. The groups had similar etiology, lactulose/rifaximin/proton pump inhibitor use, diabetes mellitus, and non-HCC complications. Microbial diversity was similar between prior HCC/not or future HCC/not. On DESeq2 higher Clostridium sensu stricto and Anaerotruncus were significantly associated with protection from HCC, whereas the reverse was seen with Raoultella and Haemophilus regardless of prior/future HCC comparisons. Functions focused on urea cycle, bioenergetics, tryptophan, and toluene metabolism were different between the groups. Rothia was specific for other complications. Despite age, sex, and MELD-score matching and accounting for other complications, gut microbiota composition and the predicted function are different in men with cirrhosis with and without prior HCC and can be extended toward future HCC development.

Progression to Cirrhosis Leads to Improvement in Atherogenic Milieu.

INTRODUCTION: The prevalence of coronary artery disease (CAD) is high among patients with cirrhosis; however, the impact of it on cardiovascular disease (CVD) is not known. The aim of the current study was to evaluate CVD events in patients with cirrhosis and impact of cirrhosis on biomarkers of atherogenesis. METHODS: The study included 682 patients with decompensated cirrhosis referred for liver transplantation (LT) evaluation between 2010 and 2017. All patients were followed until they experienced a CVD event, non-cardiac death, liver transplantation or last follow-up. To evaluate mechanistic link, patients with NASH cirrhosis were propensity matched 1:2 to non-cirrhosis NASH patients and biomarkers of atherogenic risk were compared. RESULTS: The composite CVD outcome occurred in 23(3.4%) patients after a median follow-up period of 585 days (IQR 139, 747). A strong association between presence of any CAD and CVD event was noted (HR = 6.8, 95% CI 2.9, 15.9) that was independent of age, gender, BMI, and MELD score. In competing risk model, the combined rate of LT and non-cardiac was significantly higher when compared to the rate of CVD events. Marker of insulin resistance and inflammation-related markers were similar in patients with and without cirrhosis. Patients with cirrhosis were more likely to have reduced VLDL, sdLDL-C, LDL-C, and triglycerides. Interestingly, patients with cirrhosis had an increase in serum HDL-2, the anti-atherogenic lipoprotein, and adiponectin, a protective serum adipokine. CONCLUSION: The risk of CVD events in patients with cirrhosis is low and may potentially be due to improvement in markers of atherogenic risk.

Diagnostic Performance of Vibration-Controlled Transient Elastography in Liver Transplant Recipients.

BACKGROUND & AIMS: Vibration-controlled transient elastography (VCTE) is a non-invasive tool for detecting hepatic steatosis and fibrosis in patients who have not received liver transplants. We aimed to evaluate the diagnostic performance of VCTE in detection of hepatic steatosis and fibrosis in patients who have undergone liver transplantation. METHODS: We performed a prospective study of 99 liver transplant recipients assessed by VCTE using a standard protocol. Controlled attenuation parameter cutoff values for pairwise steatosis grade and liver stiffness measurements (LSM) and cutoff values for pairwise fibrosis stage were determined using cross-validated area under the receiver operating characteristics (AUROC) curve analyses. We calculated sensitivity (fixed at 90%) and specificity (fixed at 90%) values. RESULTS: A controlled attenuation parameter cutoff value of 270 dB/m detected any hepatic steatosis with an AUROC of 0.88 (95% CI, 0.78-0.93). VCTE detected steatosis grades 2-3 vs 0-1 with an AUROC of 0.94 (95% CI, 0.89-0.99) and steatosis grade 3 vs 0-2 was similar and AUROC of 0.89 (95% CI, 0.83-0.96). When we used an LSM cutoff value of 10.5 kPa, VCTE identified patients with advanced fibrosis (fibrosis stages ≥ 3) with an AUROC of 0.94 (95% CI, 0.88-0.99). At fixed sensitivity, the cutoff LSM value of 10.5k Pa excluded advanced fibrosis with a negative predictive value of 0.99. At fixed specificity, the cutoff LSM value of 16.9 kPa detected advanced fibrosis with a sensitivity of 0.86, a positive predictive value (PPV) of 0.40, and a negative predictive value of 0.99. CONCLUSIONS: VCTE accurately detects hepatic steatosis and fibrosis in recipients of liver transplants. This non-invasive method might be used to identify patients in need of confirmatory liver biopsy analysis.

Association Between Lipoprotein Particles and Atherosclerotic Events in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease,1 is independently associated with increased risk of cardiovascular disease (CVD), which is the leading cause of mortality in patients with NAFLD.2 This is likely caused by the centrality of the liver in lipid homeostasis. Prior cross-sectional studies have shown that NAFLD is associated with perturbations in lipid profile and atherogenic lipoprotein subparticles.3 Although statins improve lipid profile and CVD-associated mortality, residual CVD risk has been demonstrated in major statin trials.4,5 A key contributor to this residual risk is the limited ability of the standard lipid profile to precisely quantify atherogenic lipoprotein subparticles, such as small dense low-density lipoprotein (sdLDL), which might confer higher atherogenic risk. There are currently no studies evaluating the longitudinal impact of sdLDL on atherosclerotic events in NAFLD. Thus, we conducted a prospective study in patients with histologically confirmed NAFLD to better define the relationship among NAFLD, residual CVD risk, and sdLDL.

A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach. APPROACH AND RESULTS: In this phase 1, double-blind, randomized clinical trial, patients with AUD-related cirrhosis with problem drinking (AUDIT-10 > 8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. Six-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine), quality of life, cognition, serum IL-6 and lipopolysaccharide-binding protein, plasma/stool short-chain fatty acids (SCFAs), and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse event (SAE) analysis was performed. Twenty patients with AUD-related cirrhosis (65 ± 6.4 years, all men, Model for End-Stage Liver Disease 8.9 ± 2.7) with similar demographics, cirrhosis, and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day 15 (P = 0.02) with lower urinary ethylglucuronide/creatinine (P = 0.03) and improved cognition and psychosocial quality of life. There was reduction in serum IL-6 and lipopolysaccharide-binding protein and increased butyrate/isobutyrate compared with baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFAs, producing taxa following FMT but not placebo, which were linked with SCFA levels. At 6 months, patients with any SAEs (8 vs. 2, P = 0.02), AUD-related SAEs (7 vs. 1, P = 0.02), and SAEs/patient (median [interquartile range], 1.5 [1.25] vs. 0 [0.25] in FMT, P = 0.02) were higher in placebo versus FMT. CONCLUSIONS: This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-associated cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6 months in patients assigned to FMT.

Training of hepatology providers improves the screening and resultant interventions for alcohol use disorder.

Alcohol use disorder (AUD) screening is important but focused training with using AUDIT-10 with counselling/mental health (MH) referral may be needed. We aimed to compare the effect of training on AUD screening/intervention in hepatology clinics in pre vs post-training phases of a quality-improvement initiative. Pre-training encounters were evaluated for inquiry into AUD, AUDIT-10 and MH referrals. Dedicated AUD-related training was provided to hepatology providers and analyses repeated post-training. Pre-training (n = 378) and post-training patients(n = 318) had similar demographics and disease characteristics. Post-training there was higher inquiry about alcohol(92% vs 80%, P < .0001), counselling (82% vs 68%, P < .0001). This led to higher diagnosis of drinkers (49% vs 31%, P < .0001) of whom higher proportion had AUDIT-10 administered(91% vs 34%, P < .0001) and referred to MH(29% vs 8%, P < .0001). On regression presumed alcohol-related aetiology, younger age and post-training period were associated with AUDIT-10 administration. AUD-focused training significantly improves rates of screening and MH referral for problem drinking in a hepatology clinic population.

CReSCENT: CanceR Single Cell ExpressioN Toolkit.

CReSCENT: CanceR Single Cell ExpressioN Toolkit (https://crescent.cloud), is an intuitive and scalable web portal incorporating a containerized pipeline execution engine for standardized analysis of single-cell RNA sequencing (scRNA-seq) data. While scRNA-seq data for tumour specimens are readily generated, subsequent analysis requires high-performance computing infrastructure and user expertise to build analysis pipelines and tailor interpretation for cancer biology. CReSCENT uses public data sets and preconfigured pipelines that are accessible to computational biology non-experts and are user-editable to allow optimization, comparison, and reanalysis for specific experiments. Users can also upload their own scRNA-seq data for analysis and results can be kept private or shared with other users.

Why Do Lifestyle Recommendations Fail in Most Patients with Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease has been recognized as a major health burden. The efficacy and safety profile of pharmacotherapy in the treatment of nonalcoholic fatty liver disease remains uncertain; therefore, lifestyle modification is the first line of treatment. Based on available data, patients should optimally achieve at least a 5% to 10% weight reduction for histologic improvement. There is no clear consensus on the optimal diet or exercise regimen. Sustainability of any intervention is key to success; however, compliance has been a major issue in clinical trials. This finding underscores the importance of multidisciplinary strategies to achieve targeted weigh loss.

Office-Based Weight Loss Counseling Is Ineffective in Liver Transplant Recipients.

BACKGROUND: Weight gain after liver transplantation (LT) is a predictor of major morbidity and mortality post-LT; however, there are no data regarding weight loss following LT. The current study evaluates the effectiveness of standard lifestyle intervention in LT recipients. METHODS: All adult LT recipients with body mass index (BMI) ≥ 25 kg/m2 who followed up in post-LT clinic from January 2013 to January 2016 were given standard lifestyle advice based on societal recommendations which was reinforced at 24 weeks. Patients were followed for a total of 48 weeks to assess the impact of such advice on weight. Primary outcome was achieving weight loss ≥ 5% of the body weight after 48 weeks of follow-up. RESULTS: A total of 151 patients with 86 (56.0%) overweight and 65 (44.0%) obese patients were enrolled in the study. The mean BMI at baseline increased from 30.2 ± 3.7 to 30.9 ± 4.3 kg/m2 at 48-week follow-up (p = 0.001). Over the course of study, 58 (38.4%) patients lost any weight and weight loss greater than 5% and 10% occurred in only 18 (11.9%) and 8 (5.3%) of the entire cohort, respectively. Higher level of education was associated with increased likelihood of weight loss (OR 9.8, 95% CI 2.6, 36.9, p = 0.001), while nonalcoholic steatohepatitis as etiology of liver disease (HR 3.7, 95% CI 1.4, 9.7, p = 0.007) was associated with weight gain. CONCLUSION: The practice of office-based lifestyle intervention is ineffective in achieving clinically significant weight loss in LT recipients, and additional strategies are required to mitigate post-LT weight gain.

Range of Normal Serum Aminotransferase Levels in Liver Transplant Recipients.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are used to monitor liver transplant recipients (LTR) but the reference range and context of its use is not well defined. We aimed to determine the healthy ranges in LTR without chronic liver disease. METHODS: One hundred and three LTR without chronic liver disease based on serology, transient elastography with controlled attenuated parameter, and ultrasound were included. A healthy range of aminotransferases was set to 95th percentile. An updated normal aminotransferase range was used to detect recurrence in post-liver transplantation (LT) with hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD). RESULTS: The normal ALT and AST range was 0 to 57 and 0 to 54 IU/L, respectively, in LTR and was not affected by age, sex, obesity, or choice of immunosuppressant. The diagnostic performance of serum ALT and AST to detect recurrence of NAFLD by a controlled attenuated parameter was poor with area under the receiver operating characteristic curve of 0.573 (95% confidence interval 0.493, 0.655; P = .08) and 0.537 (0.456, 0.618; P = .4), respectively. In contrast, the diagnostic performance of ALT and AST to detect recurrence of HCV after LT was 0.906 (0.868, 0.944; P < .001) and 0.925 (0.890, 0.959; P < .001), respectively. CONCLUSION: The updated aminotransferase range in LTR is higher than the general population and accurate for detecting recurrent HCV, but not NAFLD.

The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation.

Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre-LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new-onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow-up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre-LT evaluation. The presence or severity of pre-LT CAD did not impact post-LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new-onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new-onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre-LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre-LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.