Sumeet K. Asrani M.D.

Mahmud, N., Asrani, S.K., Kaplan, D.E., Ogola, G.O., Taddei, T.H., Kamath, P.S. and Serper, M. (2020). “The Predictive Role of MELD-Lactate and Lactate Clearance for In-Hospital Mortality among a National Cirrhosis Cohort.” Liver Transpl Oct 6. [ Epub ahead of print].

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BACKGROUND: The burden of cirrhosis hospitalizations is increasing. Admission MELD-lactate was recently demonstrated to be a superior predictor of in-hospital mortality as compared to MELD in limited cohorts. We aimed to identify specific classes of hospitalizations where MELD-lactate may be especially useful, and to evaluate the predictive role of lactate clearance. METHODS: This was a retrospective cohort study of 1,036 cirrhosis hospitalizations for gastrointestinal bleeding, infection, or other portal hypertension-related indications in the Veterans Health Administration where MELD-lactate was measured upon admission. Performance characteristics for in-hospital mortality were compared between MELD-lactate and MELD/MELD-Na, with stratified analyses of MELD categories (≤15, 15-25, ≥25) and reason for admission. We also incorporated day 3 lactate levels into modeling, and tested for an interaction between day 1 MELD-lactate and day 3 lactate clearance. RESULTS: MELD-lactate had superior discrimination for in-hospital mortality as compared to MELD or MELD-Na (area under the curve [AUC] 0.789 vs. 0.776 vs. 0.760, p<0.001), and superior calibration. MELD-lactate had higher discrimination among hospitalizations with MELD ≤15 (AUC 0.763 vs. 0.608 for MELD, global p=0.01) and hospitalizations for infection (AUC 0.791 vs. 0.674 for MELD, global p<0.001). We found a significant interaction between day 1 MELD-lactate and day 3 lactate clearance; heat maps were created as clinical tools to risk stratify patients based on these clinical data. CONCLUSION: In comparison to MELD or MELD-Na, MELD-lactate has significantly superior performance in predicting in-hospital mortality among patients hospitalized for infection and/or with MELD ≤15. Incorporating day 3 lactate clearance may further improve prognostication.

Asrani, S.K., Mellinger, J., Arab, J.P. and Shah, V.H. (2020). “Reducing the Global Burden of Alcohol-Associated Liver Disease: A Blueprint for Action.” Hepatology Sep 28. [Epub ahead of print.].

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Alcohol-associated liver disease (ALD) is a major driver of global liver related morbidity and mortality. There are 2.4 billion drinkers (950 million heavy drinkers) and the lifetime prevalence of any alcohol use disorder (AUD) is 5.1%-8.6%. In 2017, global prevalence of alcohol-associated compensated and decompensated cirrhosis was 23.6 million and 2.5 million, respectively. Combined, alcohol-associated cirrhosis and liver cancer account for 1% of all deaths worldwide with this burden expected to increase. Solutions for this growing epidemic must be multi-faceted and focused on both population and patient-level interventions. Reductions in ALD-related morbidity and mortality require solutions that focus on early identification and intervention, reducing alcohol consumption at the population level (taxation, reduced availability and restricted promotion), and solutions tailored to local socioeconomic realities (unrecorded alcohol consumption, focused youth education). Simple screening tools and algorithms can be applied at the population level to identify alcohol misuse, diagnose ALD using non-invasive serum and imaging markers, and risk-stratify higher-risk ALD/AUD patients. Novel methods of healthcare delivery and platforms are needed (telehealth, outreach, use of non-healthcare providers, partnerships between primary and specialty care/tertiary hospitals) to proactively mitigate the global burden of ALD. An integrated approach that combines medical and AUD treatment is needed at the individual level to have the highest impact. Future needs include (1) improving quality of ALD data and standardizing care, (2) supporting innovative healthcare delivery platforms that can treat both ALD and AUD, (3) stronger and concerted advocacy by professional hepatology organizations, and (4) advancing implementation of digital interventions.

Maddur, H. and Asrani, S.K. (2020). “Alcohol-associated hepatitis and liver transplantation: Mind the (racial, sex, economic, geographic, center, waitlist, and posttransplant outcomes) gap.” Am J Transplant Aug 9. [Epub ahead of print.].

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Over the last decade, liver transplantation (LT) for alcohol‐associated hepatitis (AH) has increased. In addition, the true number of patients undergoing LT for AH is likely underestimated. Changes in public perception may also be contributing. Given the rapidly evolving landscape of transplantation for AH, continuous examination of the US experience and relevant outcomes is needed. In this issue of the American Journal of Transplantation, Cotter and colleagues describe recent trends in LT for AH. First, the overall rates of transplantation for AH increased 5‐fold during the study period, albeit stabilizing during the last 2 years of the study period. LT rates had an 8‐fold variation between regions in addition to significant center variation within regions. Moreover, as compared to other indications, there were notable differences by demographics beyond younger age. LT recipients were disproportionately white (93% in some regions), male, more educated, and the majority had private insurance. Finally, outcomes after LT for AH were lower for select patient groups: lower survival was seen among women and nonwhite LT recipients. [No abstract; excerpt from article.].

Bendel, E. C., K. Sniderman, C. Shaw, R. T. Frederick, F. Wong, A. Sanyal, S. K. Asrani, P. S. Kamath, J. Capel and Z. J. Haskal (2020). “Feasibility and Procedural Safety of alfapump System Implantation by IR: Experience from the MOSAIC Study, a Multicenter, Open-Label Prospective Study in Cirrhotic Patients with Refractory Ascites.” J Vasc Interv Radiol 31(8): 1256-1262.e1253.

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PURPOSE: To evaluate feasibility, procedural outcomes, and safety aspects of implantation of the alfapump system for management of refractory ascites by interventional radiology (IR) methods. MATERIALS AND METHODS: The multicenter open-label prospective MOSAIC study included 29 patients (mean age 60.0 y ± 9.9; range, 32-72 y, 17 [56.7%] male) with cirrhotic refractory ascites who received an alfapump system implanted by IR. The fully subcutaneous alfapump system consists of a pump and 2 silicone catheters, whose distal ends are inserted in the peritoneum and the bladder, respectively. The device moves ascites from the peritoneum to the bladder, reducing the requirement of paracentesis. Pumped volume and speed can be customized as required. The implant procedure was performed under general or local anesthesia. Both catheters were placed under ultrasound guidance. The pump was inserted in a subcutaneous pocket on the upper abdomen. Incidence and severity of procedure-related serious adverse events up to 3 months after implantation were recorded. RESULTS: Technical success was achieved in 29 (100%) IR implant procedures. The pump was usually implanted on the right abdomen (76.7%). In 5 patients, deviation from the Instructions for Use was required. Adverse events (requirement of additional incisions, postoperative bleed) occurred in 3 patients. At 3 months after implantation, 3 possibly procedure-related serious adverse events (ascites leakage, bacterial peritonitis, postoperative bleeding) had occurred. Two explantations (2/29; 6.8%) (cellulitis, pump pocket infection) and 4 reinterventions (pump or catheter replacement) were required, corresponding to an adverse event incidence rate of 9/29 (31.0%). CONCLUSIONS: Placement of the alfapump using IR methods is both feasible and technically successful.

Sundaram, V., P. Shah, N. Mahmud, C. C. Lindenmeyer, A. S. Klein, R. J. Wong, C. J. Karvellas, S. K. Asrani and R. Jalan (2020). “Patients with severe acute-on-chronic liver failure are disadvantaged by model for end-stage liver disease-based organ allocation policy.” Aliment Pharmacol Ther Jul 29. [Epub ahead of print.].

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BACKGROUND: Mortality for patients with acute-on-chronic liver failure (ACLF) may be underestimated by the model for end-stage liver disease-sodium (MELD-Na) score. AIM: To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD-Na score ≥35, and therefore having similar priority for liver transplantation. METHODS: We analysed the United Network for Organ Sharing (UNOS) database, years 2010-2017. Waitlist outcomes were evaluated using Fine and Gray’s competing risks regression. RESULTS: We identified 6342 candidates at listing with a MELD-Na score ≥35, of whom 3122 had ACLF-3. Extra-hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF-3 had a significantly higher risk for 90-day waitlist mortality (Sub-hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12-1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF-3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20-1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54-3.58) was associated with increased waitlist death. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54-0.68). The Share 35 rule was associated with reduced 90-day waitlist mortality among the full cohort of patients listed with ACLF-3 and MELD-Na score ≥35 (SHR = 0.59; 95% CI 0.49-0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58-1.02). CONCLUSION: The MELD-Na score disadvantages patients with ACLF-3, both with and without extra-hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration.