Lauren D. Nephew

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AASLD Deepens Commitment to Diversity, Equity, and Inclusion
(Wiley, 2021-10) Malespin, Miguel; May, Elizabeth J.; Nephew, Lauren D.; Paul, Sonali; McCary, Alexis; Kilaru, Saikiran; Mukhtar, Nizar A.; Hassan, Mohamed A.; Brady, Carla W.; Medicine, School of Medicine
On June 2, 2020, the American Association for the Study of Liver Disease (AASLD) joined colleagues in gastroenterology in a joint statement condemning racism and injustice and pledging to lead change. This pledge offers a commitment to “continue to advocate for diversity in our staff and governance, grant awards to research health care disparities, ensure quality care for all, and work tirelessly to reduce inequalities in health care delivery and access.”
Accountability in clinical trial diversity: The buck stops where?
(Elsevier, 2021-06-01) Nephew, Lauren D.; Medicine, School of Medicine
If the Pfizer and Moderna Coronavirus Disease (COVID-19) studies taught us one thing, it is that clinical trials can better reflect the diverse demographics of the population. Why then, do not most other Phase 3 clinical trials account for the diversity of the population who will most likely use the drug? Most do not, because there is no accountability. In developing the COVID-19 vaccine, industry and its partners were well aware of their mandate: develop a vaccine quickly that would be acceptable and legitimate to the public.
Admission plasma uromodulin and the risk of acute kidney injury in hospitalized patients with cirrhosis: a pilot study
(American Physiological Society, 2019-10-01) Patidar, Kavish R.; Garimella, Pranav S.; Macedo, Etienne; Slaven, James E.; Ghabril, Marwan S.; Weber, Regina E.; Anderson, Melissa; Orman, Eric S.; Nephew, Lauren D.; Desai, Archita P.; Chalasani, Naga; El-Achkar, Tarek M.; Medicine, School of Medicine
Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis. Uromodulin, a protein uniquely produced by the kidney and released both in the urine and circulation, has been shown to regulate AKI and is linked to tubular reserve. Although low levels of urine uromodulin are associated with AKI after cardiac surgery, it is unclear whether circulating uromodulin can stratify the risk of AKI, particularly in a susceptible population such as hospitalized patients with cirrhosis. Thus, we investigated whether plasma uromodulin measured at the time of admission is associated with subsequent hospital-acquired AKI (defined by a rise in serum creatinine >0.3mg/dL within 48 h or ≥ 1.5 times baseline) in patients with cirrhosis. A total of 98 patients [mean age 54 yr, Model for Endstage Liver Disease Sodium (MELD-Na) score 19, and baseline creatinine of 0.95 mg/dL] were included, of which 13% (n = 13) developed AKI. Median uromodulin levels were significantly lower in patients who developed AKI compared with patients who did not (9.30 vs. 13.35 ng/mL, P = 0.02). After adjusting for age, sex, diabetes, hypertension, albumin, and MELD-Na score as covariates on multivariable logistic regression, uromodulin was independently associated with AKI [odd ratios of 1.19 (95% confidence interval 1.02, 1.37; P = 0.02)]. Lower uromodulin levels on admission are associated with increased odds of subsequent AKI in hospitalized patients with cirrhosis. Further studies are needed to better understand the role of uromodulin in the pathogenesis and as a predictive biomarker of AKI in this population. NEW & NOTEWORTHY In this study, we found that admission plasma uromodulin levels are significantly lower in patients who developed subsequent acute kidney injury (AKI) during their hospital stay compared with patients who did not. Additionally, uromodulin is independently associated with AKI development after adjusting for clinically relevant parameters such as age, sex, diabetes, hypertension, severity of cirrhosis, and kidney function. To our knowledge, this is the first study linking plasma uromodulin with AKI development in patients with cirrhosis.
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 Medicine
Importance 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.
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.
Changing epidemiology and outcomes of acute kidney injury in hospitalized patients with cirrhosis - a US population-based study
(Elsevier, 2020-11) Desai, Archita P.; Knapp, Shannon M.; Orman, Eric S.; Ghabril, Marwan S.; Nephew, Lauren D.; Anderson, Melissa; Ginès, Pere; Chalasani, Naga P.; Patidar, Kavish R.; Medicine, School of Medicine
Background & aims: Acute kidney injury (AKI) is a significant clinical event in cirrhosis yet contemporary population-based studies on the impact of AKI on hospitalized cirrhotics are lacking. We aimed to characterize longitudinal trends in incidence, healthcare burden and outcomes of hospitalized cirrhotics with and without AKI using a nationally representative dataset. Methods: Using the 2004-2016 National Inpatient Sample (NIS), admissions for cirrhosis with and without AKI were identified using ICD-9 and ICD-10 codes. Regression analysis was used to analyze the trends in hospitalizations, costs, length of stay and inpatient mortality. Descriptive statistics, simple and multivariable logistic regression were used to assess associations between individual characteristics, comorbidities, and cirrhosis complications with AKI and death. Results: In over 3.6 million admissions for cirrhosis, 22% had AKI. AKI admissions were more costly (median $13,127 [IQR $7,367-$24,891] vs. $8,079 [IQR $4,956-$13,693]) and longer (median 6 [IQR 3-11] days vs. 4 [IQR 2-7] days). Over time, AKI prevalence doubled from 15% in 2004 to 30% in 2016. CKD was independently and strongly associated with AKI (adjusted odds ratio 3.75; 95% CI 3.72-3.77). Importantly, AKI admissions were 3.75 times more likely to result in death (adjusted odds ratio 3.75; 95% CI 3.71-3.79) and presence of AKI increased risk of mortality in key subgroups of cirrhosis, such as those with infections and portal hypertension-related complications. Conclusions: The prevalence of AKI is significantly increased among hospitalized cirrhotics. AKI substantially increases the healthcare burden associated with cirrhosis. Despite advances in cirrhosis care, a significant gap remains in outcomes between cirrhotics with and without AKI, suggesting that AKI continues to represent a major clinical challenge.
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.
Clinical features of ileal pouch-anal anastomosis in African American patients with underlying ulcerative colitis
(Blackwell Publishing Ltd, 2009-07-20) Moore, L; Tang, L; Lopez, R; Shen, B
Background: The prevalence of inflammatory bowel disease in African Americans appears to be increasing. The data on differences in disease behavior and severity between the races have been conflicting. Aim: To evaluate the effect of race on outcome and natural history of patients with ileal pouch-anal anastomosis. Methods: All African American patients with underlying ulcerative colitis and ileal pouch-anal anastomosis who were seen in our subspecialty Pouchitis Clinic from 2002 to 2008 were included. The control group consisted of Caucasian patients with ulcerative colitis and ileal pouch-anal anastomosis who were randomly selected from the same Pouch Registry at a ratio of 4:1. We compared pouch failure, Crohn’s disease of the pouch, and chronic pouchitis rates, as well as other 23 demographic and clinical variables between African American and Caucasian patients. Results: A total of 12 African American patients and 48 Caucasian patients were evaluated in this case-control study. There were no significant differences in the frequency of pouch failure, Crohn’s disease of the pouch, or chronic pouchitis between the African American and Caucasian groups. However, African American patients were found to have a significantly shorter duration of inflammatory bowel disease (11.5 years vs. 17.0 years, P = 0.024) as well as significantly shorter duration of pouch (1.5 years vs. 4 years, P = 0.02). African Americans were also less likely to have pancolitis at the time of colectomy (83% vs. 100%, P = 0.037). Conclusions: While there were no significant differences in pouch outcomes between the races, African American patients appeared to have more left-sided colitis at the time of colectomy, with a shorter duration of inflammatory bowel and ileal pouch. This finding suggests that the natural history of ulcerative colitis and disease course before and after restorative proctocolectomy may be different between these racial groups.
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.
Contemporary Trends in Hospitalizations for Comorbid Chronic Liver Disease and Substance Use Disorders
(Wolters Kluwer, 2021-06-18) Desai, Archita P.; Greene, Marion; Nephew, Lauren D.; Orman, Eric S.; Ghabril, Marwan; Chalasani, Naga; Menachemi, Nir; Medicine, School of Medicine
Introduction: Chronic liver diseases (CLDs) and substance use disorders (SUDs) are increasingly prevalent and often coexist. Contemporary studies describing the characteristics and hospitalization trends of those with comorbid CLD-SUD are lacking. We aimed to characterize a population-based cohort with comorbid CLD-SUD and describe trends in these hospitalizations over time by individual-level characteristics. Methods: We performed a cross-sectional analysis of the National Inpatient Sample from 2005 through 2017. Diagnosis codes were used to identify adult hospitalizations with CLD, SUD, or both. Bivariate and multivariate analyses were used to make comparisons between diagnosis categories. Unadjusted and age-adjusted trends in these hospitalizations were described over time. Results: Of 401,867,749 adult hospital discharges, 3.2% had CLD-only and 1.7% had comorbid CLD-SUD. Compared with CLD-only, comorbid CLD-SUD hospitalizations resulted in higher inpatient mortality (3.1% vs 2.4%, P < 0.001) and were associated with younger age, male sex, Native American race, and urban and Western US location. Over time, comorbid hospitalizations grew 34%, and the demographics shifted with larger increases in hospitalization rates seen in younger individuals, women, Native Americans, and those publicly insured. In comorbid hospitalizations, alcoholic SUD and CLD decreased, but drug SUDs and nonalcoholic fatty liver diseases are fast-growing contributors. Discussion: In this comprehensive analysis of US hospitalizations, comorbid CLD-SUD hospitalizations are increasing over time and lead to higher inpatient mortality than CLD alone. We further characterize the changing demographics of these hospitalizations, providing a contemporary yet inclusive look at comorbid CLD-SUD hospitalizations. These data can guide interventions needed to improve the poor outcomes suffered by this growing population.

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