Browsing by Author "Nephew, Lauren"

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    Black Adult Patients With Acute Liver Failure Are Sicker and More Likely to Undergo Liver Transplantation Than White Patients
    (Wiley, 2019) Nephew, Lauren; Zia, Zahra; Ghabril, Marwan; Orman, Eric; Lammert, Craig; Chalasani, Naga; Medicine, School of Medicine
    Racial and ethnic differences in the presentation and outcomes of patients wait‐listed with acute liver failure (ALF) have not been explored. Adult patients with ALF wait‐listed for liver transplantation (LT) from 2002 to 2016 were investigated using the United Network for Organ Sharing database. Clinical characteristics and causative etiologies were compared between white, black, Hispanic, and Asian patients with ALF who were wait‐listed as status 1. A competing risk analysis was used to explore differences in LT and wait‐list removal rates. Kaplan‐Meier survival curves were used to explore differences in 1‐year posttransplant survival. There were 8208 patients wait‐listed with a primary diagnosis of ALF; 4501 were wait‐listed as status 1 (55.3% of whites, 64.4% of blacks, 51.6% of Hispanics, 40.7% of Asians; P < 0.001). Black patients had higher bilirubin and Model for End‐Stage Liver Disease at wait‐listing than other groups. White patients were the most likely to have acetaminophen toxicity as a causative etiology, whereas black patients were the most likely to have autoimmune liver disease. Black patients were significantly more likely to undergo LT than white patients (hazard ratio, 1.20; 95% confidence interval, 1.08‐1.30). There was no difference in wait‐list removal because of death or clinical deterioration among racial/ethnic groups. The 1‐year posttransplant survival was lowest in black patients (79.6%) versus white (82.8%), Hispanic (83.9%), and Asian (89.3%) patients (P = 0.02). In conclusion, etiologies of ALF vary by race and ethnicity. Black patients with ALF were more likely to be wait‐listed as status 1 and undergo LT than white patients, but they were sicker at presentation. The 1‐year posttransplant survival rate was lowest among black patients.
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    Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents
    (Wolters Kluwer, 2021-11-03) Mathur, Karan; Mazhar, Areej; Patel, Milin; Dakhoul, Lara; Burney, Heather; Liu, Hao; Nephew, Lauren; Chalasani, Naga; deLemos, Andrew; Gawrieh, Samer; Medicine, School of Medicine
    Introduction: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. Methods: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. Results: In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. Discussion: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.
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    Confusion assessment method accurately screens for hepatic encephalopathy and predicts short‑term mortality in hospitalized patients with cirrhosis
    (Springer, 2023) Desai, Archita P.; Gandhi, Devika; Xu, Chenjia; Ghabril, Marwan; Nephew, Lauren; Patidar, Kavish R.; Campbell, Noll L.; Chalasani, Naga; Orman, Eric S.; Medicine, School of Medicine
    Hepatic encephalopathy (HE), a subtype of delirium, is common in cirrhosis and associated with poor outcomes. Yet, objective bedside screening tools for HE are lacking. We examined the relationship between an established screening tool for delirium, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and short-term outcomes while comparing its performance with previously established measures of cognitive function such as West Haven criteria (WHC). Prospectively enrolled adults with cirrhosis who completed the CAM-ICU from 6/2014-6/2018 were followed for 90 days. Blinded provider-assigned West Haven Criteria (WHC) and other measures of cognitive function were collected. Logistic regression was used to test associations between CAM-ICU status and outcomes. Mortality prediction by CAM-ICU status was assessed using Area under the Receiver Operating Characteristics curves (AUROC). Of 469 participants, 11% were CAM-ICU( +), 55% were male and 94% were White. Most patients were Childs-Pugh class C (59%). CAM-ICU had excellent agreement with WHC (Kappa = 0.79). CAM-ICU( +) participants had similar demographic features to those CAM-ICU(-), but had higher MELD (25 vs. 19, p < 0.0001), were more often admitted to the ICU (28% vs. 7%, p < 0.0001), and were more likely to be admitted for HE and infection. CAM-ICU( +) participants had higher mortality (inpatient:37% vs. 3%, 30-day:51% vs. 11%, 90-day:63% vs. 23%, p < 0.001). CAM-ICU status predicted mortality with AUROC of 0.85, 0.82 and 0.77 for inpatient, 30-day and 90-day mortality, respectively. CAM-ICU easily screens for delirium/HE, has excellent agreement with WHC, and identifies a hospitalized cirrhosis cohort with high short-term mortality.
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    Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia
    (American Association for Cancer Research, 2024) Ross-Driscoll, Katherine; Ayuk-Arrey, Arrey-Takor; Lynch, Raymond; McCullough, Lauren E.; Roccaro, Giorgio; Nephew, Lauren; Hundley, Jonathan; Rubin, Raymond A.; Patzer, Rachel; Surgery, School of Medicine
    Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42-0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32-0.89).Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step. Significance: Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.
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    Eight‐Fold Increase in Dietary Supplement–Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States
    (Wiley, 2022-02) Ghabril, Marwan; Ma, Jiayi; Patidar, Kavish R.; Nephew, Lauren; Desai, Archita P.; Orman, Eric S.; Vuppalanchi, Raj; Kubal, Shekhar; Chalasani, Naga; Medicine, School of Medicine
    We investigated the trends in listing and outcomes of drug-induced acute liver failure (DIALF) over the last quarter century in the United States using the United Network for Organ Sharing (UNOS) database. We examined waitlisted patients in the UNOS database between 1995 and 2020 with a diagnosis of DIALF and assessed trends in etiologies, demographic and clinical characteristics, and outcomes over 3 periods: 1995-2003, 2004-2012, and 2013-2020. Patients with DIALF and cirrhosis were classified as drug-induced acute-on-chronic liver failure. Implicated agents including acetaminophen (APAP) and herbal or dietary supplements (HDSs) were ascertained. There were 2146 individuals with DIALF during the study period. The observed demographic trends between the earliest and latest period included fewer pediatric patients (18.8% to 13.5%) but with an increasing number of males in non-APAP DIALF (31.8% to 41.4%) and increased racial diversity in APAP DIALF. Antimicrobials remained the most common non-APAP agents across all periods, but antiepileptics, propylthiouracil, and mushroom poisoning decreased, while HDSs markedly increased from 2.9% to 24.1% of all non-APAP DIALF patients. The overall 5-year post-liver transplantation (LT) patient survival improved significantly over the 3 periods (69.9% to 77.4% to 83.3%) and was evident for both APAP and non-APAP DIALF. Over the last quarter century, there has been an 8-fold increase in HDS-related liver failure necessitating waitlisting for liver transplantation in the United States. There are other important temporal trends during the study period, including improved survival following LT among both APAP and non-APAP DIALF patients.
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    Expanding the Donor Pool with Utilization of Extended Criteria DCD Livers
    (AASLD, 2019) Mihaylov, Plamen; Mangus, Richard; Ekser, Burcin; Cabrales, Arianna; Timsina, Lava; Fridell, Jonathan; Lacerda, Marco; Ghabril, Marwan; Nephew, Lauren; Chalasani, Naga; Kubal, Chandrashekhar A.; Pediatrics, School of Medicine
    Utilization of donation after circulatory death donor (DCD) livers for transplantation has remained cautious in the U.S. The aim of this study was to demonstrate the expansion of DCD liver transplant (LT) program with the use of extended criteria DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with one of the followings: 1) donor age >50 years, 2) donor BMI >35 kg/m2, 3) donor functional warm ischemia time (fWIT) >30 minutes, and 4) donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush, and efforts to minimize ischemic times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC) and change in DCD LT volume. Of 135 consecutive DCD LT, 62 were ECD DCDs. 24 ECD DCD LT were performed before (Era I) and 38 after the institution of optimization protocol (Era II), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in Era II, with a significantly lower incidence of IC (5% vs. 17% in Era I; P = 0.03) and better 1‐year graft survival (93% vs. 75% in Era I, P = 0.07). Survival outcomes for ECD DCD LT in Era II were comparable to matched deceased donor (DBD) LT. With the expansion of the DCD donor pool, the number of DCD LT performed at our center gradually increased in Era II to account for > 20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.
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    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 Medicine
    Background 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.
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    Features of Blood Clotting on Thromboelastography in Hospitalized Patients With Cirrhosis
    (Elsevier, 2020-12) Shamseddeen, Hani; Patidar, Kavish R.; Ghabril, Marwan; Desai, Archita P.; Nephew, Lauren; Kuehl, Sandra; Chalasani, Naga; Orman, Eric S.; Medicine, School of Medicine
    Introduction: Thromboelastography (TEG) provides a global assessment of hemostasis and may have value for patients with cirrhosis who have multiple hemostatic defects. We sought to examine the characteristics of TEG in hospitalized patients with cirrhosis and its relationship with outcomes. Methods: We performed a cohort study of all adults with cirrhosis hospitalized at Indiana University Hospital between November 2015 and October 2018 with a TEG. We examined the relationships among TEG, traditional measures of hemostasis, liver disease severity, and outcomes, including mortality, discharge to hospice, length of stay, and 30-day readmission. Results: A total of 344 patients met inclusion and exclusion criteria. R-value was elevated (≥10 min) in 4.5%, alpha angle was low (<45°) in 9.3%, and maximum amplitude (maximum amplitude) was low (<55 mm) in 72.1%. K-value, alpha angle, and maximum amplitude were all correlated with both platelet count and fibrinogen (absolute rho range 0.52-0.67); R-value and international normalized ratio (INR) were not strongly correlated with traditional measures or TEG, respectively. Patients with bleeding had hypercoagulable profiles, and patients with infection had increased R-value and decreased alpha angle. A total of 35.8% died or were discharged to hospice, and these patients had a greater R-value and smaller alpha angle. However, after adjustment for model for end-stage liver disease (MELD), neither R-value nor alpha angle were associated with discharge outcomes. Conclusions: TEG provides insight into the hemostatic state of patients with cirrhosis beyond that of standard measures of hemostasis. It is associated with liver disease severity and outcomes and may play a role complementary to standard measures of hemostasis in this population.
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    Health care–related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease
    (Wolters Kluwer, 2024-01-11) Ufere, Nneka N.; Lago-Hernandez, Carlos; Alejandro-Soto, Alysa; Walker, Tiana; Li, Lucinda; Schoener, Kimberly; Keegan, Eileen; Gonzalez, Carolina; Bethea, Emily; Singh, Siddharth; El-Jawahri, Areej; Nephew, Lauren; Jones, Patricia; Serper, Marina; Medicine, School of Medicine
    Background: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). Methods: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. Results: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. Conclusions: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.
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    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 Medicine
    Background: 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.