Association Between Bariatric Surgery and Alcohol Use-Related Hospitalization and All-Cause Mortality in a Veterans Affairs Cohort.

Importance: Bariatric surgery procedures, in particular Roux-en-Y gastric bypass (RYGB), have been associated with subsequent alcohol-related complications. However, previous studies lack data to account for changes in body mass index (BMI) or alcohol use over time, which are key potential confounders. Objective: To evaluate the association between RYGB, sleeve gastrectomy, or gastric banding on subsequent alcohol use disorder (AUD)-related hospitalization and all-cause mortality as compared with referral to a weight management program alone. Design, Setting, and Participants: This cohort study included 127 Veterans Health Administration health centers in the US. Patients who underwent RYGB, sleeve gastrectomy, or gastric banding or who were referred to MOVE!, a weight management program, and had a BMI (calculated as weight in kilograms divided by height in meters squared) of 30 or greater between January 1, 2008, and December 31, 2021, were included in the study. Exposures: RYGB, sleeve gastrectomy, or gastric banding or referral to the MOVE! program. Main Outcomes and Measures: The primary outcome was time to AUD-related hospitalization from the time of bariatric surgery or MOVE! referral. The secondary outcome was time to all-cause mortality. Separate propensity scores were created for each pairwise comparison (RYGB vs MOVE! program, RYGB vs sleeve gastrectomy, sleeve gastrectomy vs MOVE!). Sequential Cox regression approaches were used for each pairwise comparison to estimate the relative hazard of the primary outcome in unadjusted, inverse probability treatment weighting (IPTW)-adjusted (generated from the pairwise logistic regression models), and IPTW-adjusted approaches with additional adjustment for time-updating BMI and categorical Alcohol Use Disorders Identification Test-Concise scores. Results: A total of 1854 patients received RYGB (median [IQR] age, 53 [45-60] years; 1294 men [69.8%]), 4211 received sleeve gastrectomy (median [IQR] age, 52 [44-59] years; 2817 men [66.9%]), 265 received gastric banding (median [IQR] age, 55 [46-61] years; 199 men [75.1%]), and 1364 were referred to MOVE! (median [IQR] age, 59 [49-66] years; 1175 men [86.1%]). In IPTW Cox regression analyses accounting for time-updating alcohol use and BMI, RYGB was associated with an increased hazard of AUD-related hospitalization vs MOVE! (hazard ratio [HR], 1.70; 95% CI, 1.20-2.41; P = .003) and vs sleeve gastrectomy (HR, 1.98; 95% CI, 1.55-2.53; P < .001). There was no significant difference between sleeve gastrectomy and MOVE! (HR, 0.76; 95% CI, 0.56-1.03; P = .08). While RYGB was associated with a reduced mortality risk vs MOVE! (HR, 0.63; 95% CI, 0.49-0.81; P < .001), this association was mitigated by increasing alcohol use over time. Conclusions and Relevance: This cohort study found that RYGB was associated with an increased risk of AUD-related hospitalizations vs both sleeve gastrectomy and the MOVE! program. The mortality benefit associated with RYGB was diminished by increased alcohol use, highlighting the importance of careful patient selection and alcohol-related counseling for patients undergoing this procedure.

Performance of risk prediction models for post-operative mortality in patients undergoing liver resection.

BACKGROUND: Liver resection is commonly performed for hepatic tumors, however preoperative risk stratification remains challenging. We evaluated the performance of contemporary prediction models for short-term mortality after liver resection in patients with and without cirrhosis. METHODS: This retrospective cohort study examined National Surgical Quality Improvement Program data. We included patients who underwent liver resections from 2014 to 2019. VOCAL-Penn, MELD, MELD-Na, ALBI, and Mayo risk scores were evaluated in terms of model discrimination and calibration for 30-day post-operative mortality. RESULTS: A total 15,198 patients underwent liver resection, of whom 249 (1.6%) experienced 30-day post-operative mortality. The VOCAL-Penn score had the highest discrimination (area under the ROC curve [AUC] 0.74) compared to all other models. The VOCAL-Penn score similarly outperformed other models in patients with (AUC 0.70) and without (AUC 0.74) cirrhosis. CONCLUSION: The VOCAL-Penn score demonstrated superior predictive performance for 30-day post-operative mortality after liver resection as compared to existing clinical standards.

Algorithms to Identify Alcoholic Hepatitis Hospitalizations in Patients with Cirrhosis.

BACKGROUND: Alcoholic hepatitis (AH) is a clinically diagnosed syndrome with high short-term mortality for which liver transplantation may be curative. A lack of validated algorithms to identify AH hospitalizations has hindered clinical epidemiology research. METHODS: This was a retrospective cohort study of patients with cirrhosis using Veterans Health Administration (VHA) data from 2008 to 2015. We randomly sampled hospitalizations based upon abnormal liver tests and administrative codes for acute hepatitis or alcohol-associated liver disease (ALD). Hospitalizations were manually adjudicated for AH per society guidelines. A priori algorithms were evaluated to compute positive predicted value (PPV) and positive likelihood ratio (LR+), and were tested in an external University of Pennsylvania Health System (UPHS) cohort. RESULTS: Of 368 hospitalizations, 142 (38.6%) were adjudicated as AH. AH patients were younger (55 vs. 58 years, p < 0.001), less likely to have prior cirrhosis decompensation (57% vs. 73.9%, p < 0.001), and had higher AST-to-ALT ratios (median 2.9 vs. 1.9 mg/dL, p < 0.001) and higher bilirubin levels (median 2.9 vs. 1.9 mg/dL, p < 0.001). Algorithms combining clinical laboratory criteria (AST > 85 U/L but < 450 U/L, AST-to-ALT ratio > 2, total bilirubin > 5 mg/dL) and administrative coding criteria yielded the highest PPV (96.4%, 95% CI 87.7-99.6) and the highest LR+ (43.0, 95% CI 10.6-173.5). Several algorithms demonstrated 100% PPV for definite AH in the UPHS external cohort. CONCLUSION: We have identified algorithms for AH hospitalizations with excellent PPV and LR+. These high-specificity algorithms may be used in VHA datasets to identify patients with high likelihood of AH, but should not be used to study AH incidence.

Discordance in categorization of acute-on-chronic liver failure in the United Network for Organ Sharing database.

BACKGROUND & AIMS: Studies regarding acute-on-chronic liver failure (ACLF) among liver transplant (LT) candidates from the United Network for Organ Sharing (UNOS) database are being used to inform LT policy changes worldwide. We assessed the validity of identifying ACLF in UNOS. METHODS: We performed stratified random sampling among 3 US LT centers between 2013-2019 to obtain a representative patient sample across ACLF grades. We compared the concordance of ACLF classification by UNOS vs. blinded manual chart review, according to EASL-CLIF. RESULTS: Among 481 sampled LT registrants, 250 (52%) had no ACLF, 75 (16%) had ACLF grade 1, 79 (16%) had ACLF grade 2, and 77 (16%) had ACLF grade 3 per UNOS categorization. Concordance of ACLF grade by UNOS vs. chart review was: 72%, 64%, 56%, and 64% for no ACLF, grade 1, grade 2, and grade 3, respectively, with an overall Cohen's kappa coefficient of 0.48 (95% CI 0.42-0.54). Absence of acute decompensation was the most common reason for overestimation, and discordant brain and respiratory failure categorization were the most common reasons for underestimation of ACLF by UNOS. CONCLUSIONS: In this retrospective multi-center study, ACLF categorization by UNOS showed weak agreement with manual chart review. These findings are informative for ongoing allocation policy discussions, highlight the importance of prospective studies regarding ACLF in LT, and should encourage UNOS reform. LAY SUMMARY: Acute-on-chronic-liver-failure (ACLF) is a specific and common form of liver failure associated with high death rates. Studies have been published using the United States transplant registry (UNOS) to identify and describe outcomes of transplant candidates and recipients with ACLF, and these data are driving policy changes for transplant allocation around the world, but nobody has shown whether these data are reliable. We found that UNOS was not categorizing ACLF in concordance or accurately when compared to chart review, which shows the need for UNOS reform and non-UNOS studies to appropriately inform policies regarding the transplantation of patients with ACLF.

Impact of Race-Adjusted Glomerular Filtration Rate Estimation on Eligibility for Simultaneous Liver-Kidney Transplantation.

Estimated glomerular filtration rate (eGFR) is adjusted for Black race in commonly used formulas. This has potential implications for access to simultaneous liver-kidney transplantation (SLKT) as qualifying criteria rely on eGFR. We performed a retrospective study of United Network for Organ Sharing national transplant registry data between February 28, 2002, and March 31, 2019, to evaluate the proportion of Black patients who would be reclassified as meeting SLKT criteria (as defined per current policies) if race adjustment were removed from 2 prominent eGFR equations (Modification of Diet in Renal Disease-4 [MDRD-4] and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Of the 7937 Black patients listed for transplant during the study period, we found that 3.6% would have been reclassified as qualifying for chronic kidney disease (CKD)-related SLKT with removal of race adjustment for MDRD-4, and 3.0% would have been reclassified with CKD-EPI; this represented 23.7% and 18.7% increases in SLKT candidacy, respectively. Reclassification impacted women more than men (eg, 4.5% versus 3.0% by MDRD-4; P < 0.05). In an exploratory analysis, patients meeting SLKT criteria by race-unadjusted eGFR equations were significantly more likely to receive liver transplantation alone (LTA) compared with SLKT. Approximately 2.0% of reclassified patients required kidney transplantation within 1 year of LTA versus 0.3% of nonreclassified patients. In conclusion, race adjustment in eGFR equations may impact SLKT candidacy for 3.0% to 4.0% of Black patients listed for LTA overall. Approximately 2.0% of patients reclassified as meeting SLKT criteria require short-term post-LTA kidney transplantation. These data argue for developing novel algorithms for glomerular filtration rate estimation free of race to promote equity.

External Validation of the VOCAL-Penn Cirrhosis Surgical Risk Score in 2 Large, Independent Health Systems.

Cirrhosis poses an increased risk of postoperative mortality, yet it remains challenging to accurately risk stratify patients in clinical practice. The VOCAL-Penn cirrhosis surgical risk score was recently developed and internally validated in the national Veterans Affairs health system; however, to date this score has not been evaluated in independent cohorts. The goal of this study was to compare the predictive performance of the VOCAL-Penn to the Mayo risk, Model for End-Stage Liver Disease (MELD), and MELD-sodium (MELD-Na) scores in 2 large health systems. We performed a retrospective cohort study of patients with cirrhosis undergoing surgical procedures of interest at the Beth Israel Deaconess Medical Center or University of Pennsylvania Health System from January 1, 2008, to October 1, 2015. The outcomes of interest were 30-day and 90-day postoperative mortality. Concordance statistics (C-statistics), calibration curves, Brier scores, and the index of prediction accuracy (IPA) were compared for each predictive model. A total of 855 surgical procedures were identified. The VOCAL-Penn score had the numerically highest C-statistic for 90-day postoperative mortality (eg, 0.82 versus 0.79 Mayo versus 0.78 MELD-Na versus 0.79 MELD), although differences were not statistically significant. Calibrations were excellent for the VOCAL-Penn, MELD, and MELD-Na; however, the Mayo score consistently overestimated risk. The VOCAL-Penn had the lowest Brier score and highest IPA at both time points, suggesting superior overall predictive model performance. In subgroup analyses of patients with higher MELD scores, the VOCAL-Penn had significantly higher C-statistics compared with the MELD and MELD-Na. The VOCAL-Penn score (www.vocalpennscore.com) has excellent discrimination and calibration for postoperative mortality among diverse patients with cirrhosis. Overall performance is superior to the Mayo, MELD, and MELD-Na scores. In contrast to the MELD/MELD-Na, the VOCAL-Penn retains excellent discrimination among patients with higher MELD scores.

The efficacy and safety of endoscopic ultrasound-guided liver biopsy versus percutaneous liver biopsy in patients with chronic liver disease: a retrospective single-center study.

BACKGROUND AND AIMS: There is limited literature on endoscopic ultrasound-guided liver biopsy (EUS-LB), a new method of obtaining liver biopsy (LB). METHODS: We conducted a retrospective study of the efficacy and safety of EUS-LB compared to percutaneous liver biopsy (PC-LB) in patients with chronic liver disease at our center between January 2018 and August 2019. RESULTS: Thirty patients underwent EUS-LB and 60 patients underwent PC-LB were identified (median follow-up post-LB was 8 days; interquartile range (IQR), 3-5 days). The median number of portal tracts was significantly higher in the PC-LB group (13 vs. 5; P < 0.0001). A histologic diagnosis was established in 93% of the EUS-LB group, compared to 100% in the PC-LB group (P = 0.841). Patients in EUS-LB group had significantly shorter hospital stay (median time of hospital stay was 3 vs. 4.2 h in the EUS-LB vs. PC-LB group, respectively; P = 0.004) and reported less pain compared to PC-LB group (median pain score was 0 vs. 3.5; P = 0.0009). EUS-LB were performed using a 19-gauge (n = 27) or 22-gauge (n = 3); there was a tendency towards higher number of portal tracts in the 22- vs. the 19-gauge needle group (6 vs. 5; P = 0.501). No patient in either group had significant adverse events such as bleeding or death. CONCLUSION: EUS-LB is safe and is associated with less pain, shorter hospital stay, and high diagnostic yield (93%) compared to PC-LB. Randomized trials are needed to standardize the utility of EUS-LB.