Browsing by Author "Kubal, Chandrashekhar"
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Item Association of State Medicaid Expansion With Racial/Ethnic Disparities in Liver Transplant Wait-listing in the United States(JAMA, 2020-10-08) Nephew, Lauren D.; Mosesso, Kelly; Desai, Archita; Ghabril, Marwan; Orman, Eric S.; Patidar, Kavish R.; Kubal, Chandrashekhar; Noureddin, Mazen; Chalasani, Naga; Medicine, School of MedicineImportance Millions of Americans gained insurance through the state expansion of Medicaid, but several states with large populations of racial/ethnic minorities did not expand their programs. Objective To investigate the implications of Medicaid expansion for liver transplant (LT) wait-listing trends for racial/ethnic minorities. Design, Setting, and Participants A cohort study was performed of adults wait-listed for LT using the United Network of Organ Sharing database between January 1, 2010, and December 31, 2017. Poisson regression and a controlled, interrupted time series analysis were used to model trends in wait-listing rates by race/ethnicity. The setting was LT centers in the United States. Main Outcomes and Measures (1) Wait-listing rates by race/ethnicity in states that expanded Medicaid (expansion states) compared with those that did not (nonexpansion states) and (2) actual vs predicted rates of LT wait-listing by race/ethnicity after Medicaid expansion. Results There were 75 748 patients (median age, 57.0 [interquartile range, 50.0-62.0] years; 48 566 [64.1%] male) wait-listed for LT during the study period. The cohort was 8.9% Black and 16.4% Hispanic. Black patients and Hispanic patients were statistically significantly more likely to be wait-listed in expansion states than in nonexpansion states (incidence rate ratio [IRR], 1.54 [95% CI, 1.44-1.64] for Black patients and 1.21 [95% CI, 1.15-1.28] for Hispanic patients). After Medicaid expansion, there was a decrease in the wait-listing rate of Black patients in expansion states (annual percentage change [APC], −4.4%; 95% CI, −8.2% to −0.6%) but not in nonexpansion states (APC, 0.5%; 95% CI, −4.0% to 5.2%). This decrease was not seen when Black patients with hepatitis C virus (HCV) were excluded from the analysis (APC, 3.1%; 95% CI, −2.4% to 8.9%), suggesting that they may be responsible for this expansion state trend. Hispanic Medicaid patients without HCV were statistically significantly more likely to be wait-listed in the post–Medicaid expansion era than would have been predicted without Medicaid expansion (APC, 13.2%; 95% CI, 4.0%-23.2%). Conclusions and Relevance This cohort study found that LT wait-listing rates have decreased for Black patients with HCV in states that expanded Medicaid. Conversely, wait-listing rates have increased for Hispanic patients without HCV. Black patients and Hispanic patients may have benefited differently from Medicaid expansion.Item Deceased Donor Liver Transplantation from a SARS‐CoV‐2–Positive Donor to a SARS‐CoV‐2–Positive Recipient(Wiley, 2021-12) Barros, Nicolas; Ermel, Aaron; Mihaylov, Plamen; Lacerda, Marco; Fridell, Jonathan; Kubal, Chandrashekhar; Medicine, School of MedicineItem Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease(BMC, 2020-09-16) Coppel, Scott; Mathur, Karan; Ekser, Burcin; Patidar, Kavish R.; Orman, Eric; Desai, Archita P.; Vilar-Gomez, Eduardo; Kubal, Chandrashekhar; Chalasani, Naga; Nephew, Lauren; Ghabril, Marwan; Medicine, School of MedicineBackground We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT). Methods Adults with cirrhosis evaluated for their first LT in 2012 were followed through their clinical course with last follow up in 2019. Extra-hepatic comorbidity burden was measured using the Charlson Comorbidity Index (CCI). The endpoints were 90-day transplant free survival (Cox-Proportional Hazard regression), and overall mortality (competing risk analysis). Results The study included 340 patients, mean age 56 ± 11, 63% male and MELD-Na 17.2 ± 6.6. The CCI was 0 (no comorbidities) in 44%, 1–2 in 44% and > 2 (highest decile) in 12%, with no differences based on gender but higher CCI in patients with fatty and cryptogenic liver disease. Thirty-three (10%) of 332 patients not receiving LT within 90 days died. Beyond MELD-Na, the CCI was independently associated with 90-day mortality (hazard ratio (HR), 1.32 (95% confidence interval (CI) 1.02–1.72). Ninety-day mortality was specifically increased with higher CCI category and MELD ≥18 (12% (CCI = 0), 22% (CCI = 1–2) and 33% (CCI > 2), (p = 0.002)) but not MELD-Na ≤17. At last follow-up, 69 patients were alive, 100 underwent LT and 171 died without LT. CCI was associated with increased overall mortality in the competing risk analysis (Sub-HR 1.24, 95%CI 1.1–1.4). Conclusions Extra-hepatic comorbidity burden significantly impacts short-term mortality in patients with cirrhosis and high MELD-Na. This has implications in determining urgency of LT and mortality models in cirrhosis and LT waitlisting, especially with an ageing population with increasing prevalence of fatty liver disease.Item Hepatic Ischemia/Reperfusion Injury After Liver Transplantation Is Not Associated with Early Impairment of Left Ventricular Ejection Fraction(International Scientific Information, 2022-12-13) Rokop, Zachary P.; Frick, Kyle; Zenisek, Joseph; Kroepfl, Elizabeth; Mihaylov, Plamen; Patidar, Kavish R.; Nephew, Lauren; Mangus, Richard S.; Kubal, Chandrashekhar; Surgery, School of MedicineBackground: Early myocardial dysfunction is a known complication following liver transplant. Although hepatic ischemia/reperfusion injury (hIRI) has been shown to cause myocardial injury in rat and porcine models, the clinical association between hIRI and early myocardial dysfunction in humans has not yet been established. We sought to define this relationship through cardiac evaluation via transthoracic echocardiography (TTE) on postoperative day (POD) 1 in adult liver transplant recipients. Material/Methods: TTE was performed on POD1 in all liver transplant patients transplanted between January 2020 and April 2021. Hepatic IRI was stratified by serum AST levels on POD1 (none: <200; mild: 200–2000; moderate: 2000–5000; severe: >5000). All patients had pre-transplant TTE as part of the transplant evaluation. Results: A total of 173 patients underwent liver transplant (LT) between 2020 and 2021 and had a TTE on POD 1 (median time to echo: 1 day). hIRI was present in 142 (82%) patients (69% mild, 8.6% moderate, 4% severe). Paired analysis between pre-LT and post-LT left ventricular ejection fraction (LVEF) of the entire study population demonstrated no significant decrease following LT (mean difference: −1.376%, P=0.08). There were no significant differences in post-LT LVEF when patients were stratified by severity of hIRI. Three patients (1.7%) had significant post-transplant impairment of LVEF (<35%). None of these patients had significant hIRI. Conclusions: hIRI after liver transplantation is not associated with immediate reduction in LVEF. The pathophysiology of post-LT cardiomyopathy may be driven by extra-hepatic triggers.Item Heterogeneity of Hepatic Stellate Cells in Fibrogenesis of the Liver: Insights from Single-Cell Transcriptomic Analysis in Liver Injury(MDPI, 2021-08-19) Zhang, Wenjun; Conway, Simon J.; Liu, Ying; Snider, Paige; Chen, Hanying; Gao, Hongyu; Liu, Yunlong; Isidan, Kadir; Lopez, Kevin J.; Campana, Gonzalo; Li, Ping; Ekser, Burcin; Francis, Heather; Shou, Weinian; Kubal, Chandrashekhar; Pediatrics, School of MedicineBackground & Aims: Liver fibrosis is a pathological healing process resulting from hepatic stellate cell (HSC) activation and the generation of myofibroblasts from activated HSCs. The precise underlying mechanisms of liver fibrogenesis are still largely vague due to lack of understanding the functional heterogeneity of activated HSCs during liver injury. Approach and Results: In this study, to define the mechanism of HSC activation, we performed the transcriptomic analysis at single-cell resolution (scRNA-seq) on HSCs in mice treated with carbon tetrachloride (CCl4). By employing LRAT-Cre:Rosa26mT/mG mice, we were able to isolate an activated GFP-positive HSC lineage derived cell population by fluorescence-activated cell sorter (FACS). A total of 8 HSC subpopulations were identified based on an unsupervised analysis. Each HSC cluster displayed a unique transcriptomic profile, despite all clusters expressing common mouse HSC marker genes. We demonstrated that one of the HSC subpopulations expressed high levels of mitosis regulatory genes, velocity, and monocle analysis indicated that these HSCs are at transitioning and proliferating phases at the beginning of HSCs activation and will eventually give rise to several other HSC subtypes. We also demonstrated cell clusters representing HSC-derived mature myofibroblast populations that express myofibroblasts hallmark genes with unique contractile properties. Most importantly, we found a novel HSC cluster that is likely to be critical in liver regeneration, immune reaction, and vascular remodeling, in which the unique profiles of genes such as Rgs5, Angptl6, and Meg3 are highly expressed. Lastly, we demonstrated that the heterogeneity of HSCs in the injured mouse livers is closely similar to that of cirrhotic human livers. Conclusions: Collectively, our scRNA-seq data provided insight into the landscape of activated HSC populations and the dynamic transitional pathway from HSC to myofibroblasts in response to liver injury.Item HLA-DR Mismatch and Black Race Are Associated With Recurrent Autoimmune Hepatitis After Liver Transplantation(Wolters Kluwer, 2021-06-10) McCabe, Marshall; Rush, Natalia; Lammert, Craig; Patidar, Kavish R.; Nephew, Lauren; Saxena, Romil; Ekser, Burcin; Salven, James; Kubal, Chandrashekhar; Ghabril, Marwan; Medicine, School of MedicineThe predictors of recurrent autoimmune hepatitis (R-AIH) after liver transplantation (LT) are heterogeneous with limited data to guide immunosuppression, with little data on impact of race. Aims: To describe the incidence, predictors, and outcomes of R-AIH. Methods: We studied patients undergoing LT for AIH during 2000-2017 at our center. Liver biopsies were performed for clinical indications. R-AIH was defined using clinical and histologic criteria. Results: Among 75 patients undergoing LT for AIH (mean age 45 ± 16, 65% female individuals, 19% Black), 71 (95%) received antithymocyte globulin induction with tacrolimus-based immunosuppression. R-AIH developed in 20 (27%) patients at a median interval of 313 d (interquartile range, 155-1205). R-AIH was associated with level 2 HLA-DR mismatch (hazard ratio, 3.6; (95% confidence interval, 1.3-9.9; P = 0.01) and Black race (hazard ratio, 4.5; 95% confidence interval, 1.8-11.8; P = 0.002)] in the multivariable analysis. R-AIH developed in 62% of patients with level 2 HLA-DR mismatch on single-agent immunosuppression but in <20% of patients with no or 1 HLA-DR mismatch regardless of maintenance immunosuppression. R-AIH developed in 8 (57%) of 14 Black patients (71% on single-agent and 43% on dual-agent maintenance immunosuppression). Patient and graft survival were not impacted by R-AIH over a median follow-up of 8.3 y (interquartile range, 3-12). Conclusions: High-level HLA-DR mismatch and Black recipient race are associated with an increased risk of R-AIH. Immunosuppression did not predict R-AIH, but higher rates of disease recurrence with single-agent maintenance immunosuppression with these risk factors were observed and may guide maintenance immunosuppression in LT for AIH.Item Karnofsky performance status predicts outcomes in candidates for simultaneous liver-kidney transplant(Wiley, 2021-02) Shamseddeen, Hani; Pike, Francis; Ghabril, Marwan; Patidar, Kavish R.; Desai, Archita P.; Nephew, Lauren; Anderson, Melissa; Kubal, Chandrashekhar; Chalasani, Naga; Orman, Eric S.; Medicine, School of MedicineKarnofsky performance status (KPS), a measure of physical frailty, predicts pre-transplant and post-transplant outcomes in liver transplantation, but has not been assessed in simultaneous liver–kidney transplantation (SLKT). We examined the association between KPS and outcomes in SLKT waitlist registrants and recipients (2005-2018) in the UNOS database. KPS was categorized into A (able to work), B (able to provide self-care), and C (unable to provide self-care). Cox regression and competing risk analysis were used to assess the association between KPS groups and outcomes. A total of 10,785 patients were waitlisted (KPS: 19% A, 46% B, 35% C), and 5,516 underwent SLKT (12% A, 36% B, 52% C). One-year waitlist mortality was 17%, 22%, and 32% for KPS A, B, and C, respectively. In adjusted competing risk regression, KPS C was associated with increased waitlist mortality (SHR 1.15, 95%CI 1.04-1.28). One-year post-transplant survival was 92%, 91%, and 87% for KPS A, B, and C, respectively. In adjusted Cox regression, KPS C was associated with increased post-transplant mortality (HR 1.32, 95%CI 1.08-1.61). It was also associated with increased liver and kidney graft losses and with hospital length of stay. Frailty, as assessed by KPS, is associated with poor outcomes in SLKT pre- and post-transplant.Item Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation(BMC, 2020-01-06) Ngwa, Taiwo; Orman, Eric; Gomez, Eduardo Vilar; Vuppalanchi, Raj; Kubal, Chandrashekhar; Chalasani, Naga; Ghabril, Marwan; Medicine, School of MedicineBackground Recent evidence cautions against the use of non-selective beta-blockers (NSBB) in patients with refractory ascites or spontaneous bacterial peritonitis while other data suggests a survival benefit in patients with advanced liver disease. The aim of this study was to describe the use and impact of NSBB in patients with cirrhosis referred for liver transplantation. Methods A single-center cohort of patients with cirrhosis, who were referred and evaluated for liver transplantation between January and June 2012 were studied for baseline characteristics and clinical outcomes. Patients were grouped according to the use of NSBB at initial evaluation, with the endpoint of 90-day mortality. Results Sixty-five (38%) of 170 consecutive patients evaluated for liver transplantation were taking NSBB. Patients taking NSBB had higher MELD and Child Pugh score. NSBB use was associated with lower 90-day mortality (6% vs. 15%) with a risk adjusted hazard ratio of 0.27 (95%CI .09–0.88, p = .03). Patients taking NSBB developed acute kidney injury (AKI) within 90 days more frequently than patients not taking NSBB (22% vs 11%), p = 0.048). However, this was related to increased stage 1 AKI episodes, all of which resolved. Twelve (27%) of 45 patients with > 90 day follow up discontinued NSBB, most commonly for hypotension and AKI, had increased subsequent MELD and mortality. Conclusions NSBB use in patients with cirrhosis undergoing liver transplant evaluation is associated with better short-term survival. Nevertheless, ongoing tolerance of NSBB in this population is dynamic and may select a subset of patients with better hemodynamic reserve.Item Prognostic Impact of Peritransplant Serum Sodium Concentrations in Liver Transplantation(International Scientific Information, 2019-07-16) Mihaylov, Plamen; Nagai, Shunji; Ekser, Burcin; Mangus, Richard; Fridell, Jonathan; Kubal, Chandrashekhar; Surgery, School of MedicineBACKGROUND Serum sodium (Na) is considered to reflect the severity of liver cirrhosis. In the last few years, much effort has been made to integrate this association into prognostic models after liver transplantation. The aim of this study was to investigate the associations between peritransplant Na and neurological complications, as well as short-term survival, after liver transplantation. MATERIAL AND METHODS A total of 306 liver transplantations between 2012 and 2015 were evaluated. Pre- and posttransplant sodium concentrations were investigated with regard to 3-month survival and incidence of posttransplant neurological complications, along with other factors present in the operative side of the recipient and donor. RESULTS The 3-month survival rate was 94%. Neither hyponatremia (<130 mEq/L) nor hypernatremia (>145 mEq/L) at pretransplantion predicted 3-month survival. A large amount of intraoperative blood transfusion and a large delta Na showed a significant association with poor outcomes at 3 months. On multivariate analysis, the requirement of blood transfusion and warm ischemia time remained independent prognostic factors for 3-month mortality. Hyponatremia and a large delta Na tended to lead to the frequent development of neurological complications. These complications, secondary to rapid Na correction, were concerning and potentially led to a prolonged hospital stay and early mortality. CONCLUSIONS Rapid change in the sodium level might be caused by large amounts of blood transfusion products. This leads to a diminished short-term survival, as well as a higher rate of neurological complications.Item Sex disparities in waitlisting and liver transplant for acute liver failure(Elsevier, 2020-11-01) Nephew, Lauren D.; Zia, Zahra; Ghabril, Marwan; Orman, Eric; Lammert, Craig; Kubal, Chandrashekhar; Chalasani, Naga; Medicine, School of MedicineBackground & aims: Sex disparities in liver transplantation (LT) for chronic liver disease have been described. It is unclear if similar disparities exist for acute liver failure (ALF). Methods: Adults waitlisted for LT from 2002 to 2016 with ALF were investigated using the United Network of Organ Sharing database. Clinical characteristics and causative aetiologies were compared between men and women who were waitlisted Status-1. Differences in LT, waitlist removal, and 1-year post-transplant survival were explored. Results: Of 8,408 patients waitlisted for LT with ALF, 41.3% of men and 63.9% of women were waitlisted Status-1 (p <0.001). Women had significantly higher international normalised ratio, higher frequency of grade 3-4 hepatic encephalopathy, and different aetiologies of ALF than men. On univariable analysis, women were less likely to undergo LT (subdistribution hazard ratio [SHR] 0.90; 95% CI 0.84-0.97) and were more likely to die or be removed from the waitlist as a result of clinical deterioration (SHR 1.14; 95% CI 1.002-1.30) than men. The disparities in LT (HR 0.95; 95% CI 0.87-1.03) and death/clinical deterioration (SHR 1.13; 95% CI 0.99-1.29) were no longer significant on multivariable analysis. On multivariable analysis, there was no difference in 1-year post-transplant survival between men and women. Conclusions: Women with ALF are more likely to be waitlisted Status-1 than men. There were no clear disparities in LT or waitlist removal. Sex differences in LT and waitlist removal were attenuated on fully adjusted models, suggesting that these disparities may in part be mitigated by Status-1 listing. Lay summary: Women with acute liver failure appear to be sicker than men and more often require urgent Status-1 waitlisting. There were no sex disparities in waitlist removal because of clinical deterioration or liver transplantation. This is in contrast to chronic liver disease, where sex disparities exist. The Status-1 waitlisting that women with acute liver failure receive may in part mitigate sex disparities in liver transplantation.