Sumeet K. Asrani M.D.

Griffin, C., U. Agbim, A. Ramani, N. Shankar, F. Kanwal and S. K. Asrani (2021). “Underestimation of cirrhosis related mortality in the Medicare eligible population, 1999-2018.” Clin Gastroenterol Hepatol Oct 30;S1542-3565(21)01149-6. [Epub ahead of print].

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The burden of cirrhosis may be increasing, especially among the elderly. A recent updated definition of cirrhosis has a >90% positive predictive value (PPV) for identifying cirrhosis and cirrhosis related complications. We hypothesized that cirrhosis-related mortality is underestimated, and that the elderly are disproportionally impacted. In this study, we aimed to 1) examine trends in liver related mortality using this updated definition among the elderly and 2) identify changes by relevant subsets of gender, race and rurality. [No abstract; excerpt from article].

Asrani, S. K., N. Shankar, B. da Graca, M. K. Nadim and A. Cardenas (2021). “Role of novel kidney biomarkers in patients with cirrhosis and after liver transplantation.” Liver Transpl Oct 29. [Epub ahead of print].

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Acute kidney injury (AKI) and chronic kidney disease (CKD) are important drivers of morbidity and mortality in patients with cirrhosis before and after liver transplantation (LT). In this review, we examine the role of novel kidney biomarkers for early recognition of kidney injury. Studies are limited by lack of reference standards, heterogeneous definitions of outcomes and biomarker cutoffs, and inconsistent diagnostic performance. Overall, a change in biomarker is more relevant than an absolute cutoff. CIRRHOSIS: Cystatin C and urinary neutrophil gelatinase-associated lipocalin (NGAL) are the most studied candidate biomarkers and identify AKI or progression of AKI earlier than serum creatinine (sCr). Kidney injury molecule 1 and liver-type fatty acid binding protein (L-FABP) also show potential. NGAL and IL-18 may play a role in differentiating acute tubular necrosis from other forms of AKI. Combining novel biomarkers with the Model for End-Stage Liver Disease (MELD) score may assist prognosis. Persistent elevations in select markers (e.g., NGAL) can portend irreversible injury. TRANSPLANT: Several pretransplant markers (including sCr) predict posttransplant kidney dysfunction. Pretransplant assessment of clinical factors (e.g., age, diabetes) and novel markers (osteopontin and TIMP1) may predict renal kidney recovery after LT. Intraoperative changes in biomarkers predict early post-LT AKI. Prediction of CKD remains difficult, although a combination of biomarkers (e.g., beta 2 microglobulin, CD40) are promising. Novel biomarkers have yet to replace sCr in guideline-based evaluation and management of kidney dysfunction in patients with cirrhosis. We propose a theoretical framework for practical incorporation of these biomarkers that considers patient characteristics (risk for irreversible injury), markers of functional and structural change, and assessment of the AKI-CKD continuum to identify patients at highest risk for progressive kidney disease before and after LT.

Asrani, S. K. and J. Levitsky (2021). “Mission accomplished? Early data from the simultaneous liver-kidney transplantation allocation policy.” Am J Transplant 21(11): 3513-3515.

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This editorial reviews Wilk et al.’s article (page 3593-3607) that reports the initial data following implementation of the 2017 OPTN simultaneous liver-kidney transplantation policy, citing both accomplishments to date and remaining gaps need related to policy success, organ allocation, and transplant patient outcomes.

Singal, A. K., R. J. Wong, R. Jalan, S. Asrani and Y. F. Kuo (2021). “Primary biliary cholangitis has the highest waitlist mortality in patients with cirrhosis and acute on chronic liver failure awaiting liver transplant.” Clin Transplant: e14479.

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BACKGROUND: Data are sparse on etiology specific outcomes on waitlist (WL) and post-transplant outcomes among patients with acute on chronic liver failure (ACLF). METHODS AND RESULTS: In a retrospective cohort of 14,774 adults from United network for organ sharing (UNOS) database listed for Liver transplantation (LT) with cirrhosis and ACLF (January 2013-June 2019), 40% were due to alcohol-associated liver disease (ALD), followed by hepatitis C virus (HCV) at 20%, non-alcoholic steatohepatitis (19%), cryptogenic cirrhosis (7%), autoimmune hepatitis (5%), primary sclerosing cholangitis (PSC) at 3%, and 2% each for hepatitis B, primary biliary cholangitis (PBC), and metabolic etiology. Using competing risk analysis, cumulative risk of WL mortality was highest for PBC at 20.5% and lowest for PSC at 13.3%, P < .001. Compared with ALD as reference, WL mortality was higher for PBC (1.45 [1.16-1.82]), and similar for other etiologies, P < .001. Of this cohort, 9650 (65.3%) patients received LT, with 1-year. patient survival of 91.6% for PBC, worst for cryptogenic cirrhosis (89.5%) and best for PSC and ALD (93.4%), P < .001. CONCLUSION: Among listed candidates with ACLF, those with PBC have highest WL mortality 1-year. post-transplant survival was excellent among recipients for PBC. If these findings are validated in prospective studies, liver disease etiology should be considered for LT selection among patients in ACLF.

Serper, M., S. Asrani, L. VanWagner, P. P. Reese, M. Kim and M. S. Wolf (2021). “”Redefining Success After Liver Transplantation: From Mortality Toward Function and Fulfillment”.” Liver Transpl. [Epub ahead of print].

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Liver transplantation (LT), the only cure for end-stage liver disease, is a lifesaving, costly and limited resource. LT recipients (LTRs) are aging with an increasing burden of medical comorbidities. Patient and graft survival exceed 70% at 5 years, however, patient-centered health outcomes beyond survival have received relatively little attention. LTRs must have strong self-management skills to navigate health systems, adhere to clinical monitoring, and take complex, multi-drug regimens. All of these tasks require formidable cognitive abilities for active learning and problem solving. Yet, LTRs are at higher risk for impaired cognition due to high prevalence of pre-transplant hepatic encephalopathy, multiple chronic conditions, alcohol use, physical frailty, sarcopenia, and older age. Cognitive impairment post-transplant may persist and has been causally linked to poor self-management skills, worse physical function, and inferior health outcomes in other healthcare settings, yet its impact after LT is largely unknown. There is a need to study potentially modifiable, post-transplant targets including caregiver support, physical activity, sleep, and treatment adherence to inform future health system responses to promote the long-term health and well-being of LTRs. Prospective, longitudinal data collection that encompasses key socio-demographic, cognitive-behavioral, psychosocial, and medical factors is needed to improve risk prediction and better inform patients and caregiver expectations. Interventions with proactive monitoring, reducing medical complexity, and improved care coordination can be tailored to optimize posttransplant care. CONCLUSIONS: We propose a research agenda focused on understudied, potentially modifiable risk factors to improve the long-term health of LTRs. Our conceptual model accounts for cognitive function, caregiver and patient self-management skills, health behaviors, and patient-centered outcomes beyond mortality. We propose actionable health-system, patient, and caregiver-directed interventions to fill knowledge gaps and improve outcomes.