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Browsing by Author "Vilar-Gomez, Eduardo"
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Item ADH1B*2 is Associated With Reduced Severity of Nonalcoholic Fatty Liver Disease in Adults, Independent of Alcohol Consumption(Elsevier, 2020) Vilar-Gomez, Eduardo; Sookoian, Silvia; Pirola, Carlos Jose; Liang, Tiebing; Gawrieh, Samer; Cummings, Oscar; Liu, Wanqing; Chalasani, Naga; Medicine, School of MedicineBackground & Aims Alcohol dehydrogenase 1B (ADH1B) is involved in alcohol metabolism. The allele A ( ADH1B*2) of rs1229984: A>G variant in ADH1B is associated a higher alcohol metabolizing activity, compared to the ancestral allele G ( ADH1B*1). Moderate alcohol consumption is associated with reduced severity of nonalcoholic fatty liver disease (NAFLD), based on histologic analysis, compared with no alcohol consumption. However, it is unclear whether ADH1B*2 modifies the relationship between moderate alcohol consumption and severity of NAFLD. We examined the association between ADH1B*2 and moderate alcohol consumption and histologic severity of NAFLD. Methods We collected data from 1557 multi-ethnic adult patients with biopsy-proven NAFLD enrolled into 4 different studies conducted by the NASH Clinical Research Network. Histories of alcohol consumption were obtained from answers to standardized questionnaires. Liver biopsies were analyzed by histology and scored centrally according to the NASH CRN criteria. We performed covariate adjusted logistic regressions to identify associations between histologic features of NAFLD severity and moderate alcohol consumption and/or ADH1B*2. Results A higher proportion of Asians/Pacific Islanders/Hawaiians carried the ADH1B*2 allele (86%) than other racial groups (4%–13%). However, the study population comprised mostly non-Hispanic whites (1153 patients, 74%), so the primary analysis focused on this group. Among them, 433 were moderate drinkers and 90 were ADH1B*2 carriers. After we adjusted for confounders, including alcohol consumption status, ADH1B*2 was associated with lower frequency of steatohepatitis (odds ratio [OR], 0.52; P<.01) or fibrosis (odds ratio, 0.69; P=.050) compared with ADH1B*1. Moderate alcohol consumption (g/day) reduced the severity of NAFLD in patients with ADH1B*1 or ADH1B*2. However, ADH1B*2, compared to ADH1B*1, was associated with a reduced risk of definite NASH ( ADH1B*2 OR, 0.80; P<.01 vs ADH1B*1 OR, 0.96; P=.036) and a reduced risk of an NAFLD activity score of 4 or higher ( ADH1B*2 OR, 0.83; P=.012 vs ADH1B*1 OR, 0.96; P=.048) ( P<.01 for the difference in the effect of moderate alcohol consumption between alleles). The relationship between body mass index and NAFLD severity was significantly modified by ADH1B*2, even after we controlled for alcohol consumption. Conclusions ADH1B*2 reduces the risk of NASH and fibrosis in adults with NAFLD regardless of alcohol consumption status. ADH1B*2 might modify the association between high body mass index and NAFLD severity.Item American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable report on physical activity and nonalcoholic fatty liver disease(Wolters Kluwer, 2023-03-30) Stine, Jonathan G.; Long, Michelle T.; Corey, Kathleen E.; Sallis, Robert E.; Allen, Alina M.; Armstrong, Matthew J.; Conroy, David E.; Cuthbertson, Daniel J.; Duarte-Rojo, Andres; Hallsworth, Kate; Hickman, Ingrid J.; Kappus, Matthew R.; Keating, Shelley E.; Pugh, Christopher J. A.; Rotman, Yaron; Simon, Tracey G.; Vilar-Gomez, Eduardo; Wong, Vincent Wai-Sun; Schmitz, Kathryn H.; Medicine, School of MedicineBackground and aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD. Approach and results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.Item Circulating high density lipoprotein distinguishes alcoholic hepatitis from heavy drinkers and predicts 90-day outcome: lipoproteins in alcoholic hepatitis(Elsevier, 2021) Mathur, Karan; Vilar-Gomez, Eduardo; Connelly, Margery A.; He, Hanchang; Sanyal, Arun J.; Chalasani, Naga; Jiang, Z. Gordon; Medicine, School of MedicineBackground: Alcohol-associated liver disease (ALD) and alcoholic hepatitis (AH) significantly impact the liver, an organ central to the lipid and lipoprotein metabolism. Objective: To define changes in the lipid and lipoprotein profiles in subjects with alcoholic hepatitis (AH) versus heavy drinkers with normal liver function and to determine the association of the AH-mediated lipoprotein phenotype with AH severity and outcomes. Methods: AH cases (n=196) and a heavy drinker control group (n=169) were identified in a multicenter, prospective cohort. The relationships between lipid panels and lipoprotein profiles among AH and heavy drinkers were interrogated using three common measurements: the conventional lipid panel, extended lipid panel by NMR, and NMR-based direct lipoprotein profiling. Predictive values for AH severity and mortality were determined using Harrell's C-Index. Results: Lipid and lipoprotein profiles were significantly different in AH compared to heavy drinkers. Among them, high density lipoprotein (HDL) particle concentration exhibited the most significant reduction in AH compared to heavy drinkers (5.3 ± 3.4 vs 22.3 ± 5.4 μmol/L, p < 0.001). Within AH patients, HDL particle concentration was inversely associated with Maddrey's Discriminant Function (DF) (p < 0.001), and independently associated with mortality at both 90 and 365 days even after adjustment for DF (p = 0.02, p = 0.05 respectively). HDL particle concentration less than 3.5 μmol/L and total cholesterol ≤ 96 mg/dL identified AH patients with higher 90-day mortality. Conclusion: Lipid and lipoprotein profiles are profoundly altered in AH and can help in prognosticating disease severity and mortality.Item Clinical characteristics and prognosis of hospitalized patients with moderate alcohol-associated hepatitis(Wiley Online Library, 2024) Gaurnizo-Ortiz, Maria; Nephew, Lauren D.; Vilar-Gomez, Eduardo; Kettler, Carla D.; Slaven, James E.; Ghabril, Marwan S.; Desai, Archita P.; Orman, Eric S.; Chalasani, Naga; Gawrieh, Samer; Patidar, Kavish R.Background and Aims Little is known about the clinical characteristics and prognosis of hospitalized patients with moderate alcohol-associated hepatitis (mAH) as compared to severe alcohol-associated hepatitis (sAH). Therefore, we aimed to describe the clinical characteristics and risk factors associated with mortality in hospitalized mAH patients. Methods Patients hospitalized with alcohol-associated hepatitis (AH) from 1 January 2010 to 31 December 2020 at a large US healthcare system [11 hospitals, one liver transplant centre] were retrospectively analysed for outcomes. Primary outcome was 90-day mortality. AH and mAH were defined according to NIAAA Alcoholic Hepatitis Consortia and Model for End-stage Liver Disease Score ≤ 20 respectively. Multivariable Cox regression analysis was performed to identify independent risk factors associated with 90-day mortality. Results 1504 AH patients were hospitalized during the study period, of whom 39% (n = 590) had mAH. Compared to sAH patients, mAH patients were older (50 vs. 48 years, p < 0.001) and less likely to have underlying cirrhosis (74% vs. 83%, p < 0.001). There were no differences between the two groups for median alcohol intake g/day (mAH 140.0 vs. sAH 112.0, p = 0.071). The cumulative proportion surviving at 90 days was 88% in mAH versus 62% in sAH (p < 0.001). On multivariable analysis, older age [HR 1.03 (95% CI 1.00–1.06), p = 0.020], corticosteroid use [HR 1.80 (95% CI 1.06–3.06), p = 0.030] and acute kidney injury (AKI) [HR 2.43 (95% CI 1.33–4.47), p = 0.004] were independently associated with 90-day mortality. Conclusions mAH carries a 12% mortality rate at 90 days. Age, AKI and corticosteroid use were associated with an increased risk for 90-day mortality. Avoidance of corticosteroids and strategies to reduce the risk of AKI could improve outcomes in mAH patients.Item Comorbidity burden may be associated with increased mortality in patients with severe acute liver injury referred for liver transplantation(International Scientific Information, Inc., 2020-11-03) Steiner-Temnykh, Lindsey; Dakhoul, Lara; Slaven, James; Nephew, Lauren; Patidar, Kavish R.; Orman, Eric; Desai, Archita P.; Vilar-Gomez, Eduardo; Kubal, Chandrashekhar; Ekser, Burcin; Chalasani, Naga; Chabril, MarwanSevere acute liver injury (S-ALI) can lead to acute liver and multisystem failure, with high mortality and need for liver transplantation (LT); however, the burden and impact of liver disease and comorbid conditions are unknown.Item Cost Effectiveness of Different Strategies for Detecting Cirrhosis in Patients With Non-alcoholic Fatty Liver Disease Based on United States Health Care System(Elsevier, 2020) Vilar-Gomez, Eduardo; Lou, Zhouyang; Kong, Nan; Vuppalanchi, Raj; Imperiale, Thomas F.; Chalasani, Naga; Medicine, School of MedicineBackground & Aims Several strategies are available for detecting cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD), but their cost effectiveness is not clear. We developed a decision model to quantify the accuracy and costs of 9 single or combination strategies, including 3 noninvasive tests (fibrosis-4 [FIB-4], vibration controlled transient elastography [VCTE], and magnetic resonance elastography [MRE]) and liver biopsy, for detection of cirrhosis in patients with NAFLD. Methods Data on diagnostic accuracy, costs, adverse events, and cirrhosis outcomes over a 5-y period were obtained from publications. The diagnostic accuracy, per-patient cost per correct diagnosis of cirrhosis, and incremental cost-effectiveness ratios (ICER) were calculated for each strategy for base cirrhosis prevalence values of 0.27%, 2%, and 4%. Results The combination of the FIB-4 and VCTE identified patients with cirrhosis in NAFLD populations with a 0.27%, 2%, and 4% prevalence of cirrhosis with the lowest cost per person ($401, $690, and $1024, respectively) and highest diagnostic accuracy (89.3%, 88.5%, and 87.5% respectively). The combination of FIB-4 and MRE ranked second in cost per person ($491, $781, and $1114, respectively) and diagnostic accuracy (92.4%, 91.6%, 90.6%, respectively). Compared to the combination of FIB-4 and VCTE (least costly), the ICERs were lower for the combination of FIB-4 and MRE ($2864, $2918, and $2921) than the combination of FIB-4 and liver biopsy ($4454, $5156, and $5956) at the cirrhosis prevalence values tested. When goal was to avoid liver biopsy, FIB-4+VCTE and FIB-4+MRE had similar diagnostic accuracies, ranging from 87.5% to 89.3% and 90.6% to 92.4% for cirrhosis diagnosis, although FIB-4+MRE had a slightly higher cost. Conclusions In our cost effectiveness analysis based on United States health care system, we found that results from FIB-4, followed by either VCTE, MRE, or liver biopsy, detect cirrhosis in patients with NAFLD with a high level of accuracy and low cost. Compared to FIB-4 + VCTE which was the least costly strategy, FIB-4+MRE had lower ICER than FIB-4+LB.Item Daily Aspirin Use Reduces Risk of Fibrosis Progression in Patients With Nonalcoholic Fatty Liver Disease, Providing New Uses for an Old Drug(Elsevier, 2019) Vilar-Gomez, Eduardo; Chalasani, Naga; Medicine, School of MedicineItem Early predictors of outcomes of hospitalization for cirrhosis and assessment of the impact of race and ethinicity at safety-net hospitals(PLOS ONE, 2019-03-06) Mukthinuthalapati, V. V. Pavan Kedar; Akinyeye, Samuel; Fricker, Zachary P.; Syed, Moinuddin; Orman, Eric S.; Nephew, Lauren; Vilar-Gomez, Eduardo; Slaven, James; Chalasani, Naga; Balakrishnan, Maya; Long, Michelle T.; Attar, Bashar M.; Ghabril, MarwanBackground Safety-net hospitals provide care for racially/ethnically diverse and disadvantaged urban populations. Their hospitalized patients with cirrhosis are relatively understudied and may be vulnerable to poor outcomes and racial/ethnic disparities. Aims To examine the outcomes of patients with cirrhosis hospitalized at regionally diverse safety-net hospitals and the impact of race/ethnicity. Methods A study of patients with cirrhosis hospitalized at 4 safety-net hospitals in 2012 was conducted. Demographic, clinical factors, and outcomes were compared between centers and racial/ethnic groups. Study endpoints included mortality and 30-day readmission. Results In 2012, 733 of 1,212 patients with cirrhosis were hospitalized for liver-related indications (median age 55 years, 65% male). The cohort was racially diverse (43% White, 25% black, 22% Hispanic, 3% Asian) with cirrhosis related to alcohol and viral hepatitis in 635 (87%) patients. Patients were hospitalized mainly for ascites (35%), hepatic encephalopathy (20%) and gastrointestinal bleeding (GIB) (17%). Fifty-four (7%) patients died during hospitalization and 145 (21%) survivors were readmitted within 30 days. Mortality rates ranged from 4 to 15% by center (p = .007) and from 3 to 10% by race/ethnicity (p = .03), but 30-day readmission rates were similar. Mortality was associated with Model for End-stage Liver Disease (MELD), acute-on-chronic liver failure, hepatocellular carcinoma, sodium and white blood cell count. Thirty-day readmission was associated with MELD and Charlson Comorbidity Index >4, with lower risk for GIB. We did not observe geographic or racial/ethnic differences in hospital outcomes in the risk-adjusted analysis. Conclusions Hospital mortality and 30-day readmission in patients with cirrhosis at safety-net hospitals are associated with disease severity and comorbidities, with lower readmissions in patients admitted for GIB. Despite geographic and racial/ethnic differences in hospital mortality, these factors were not independently associated with mortality.Item Enhanced Liver Fibrosis Score Can Be Used to Predict Liver-Related Events in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis(Elsevier, 2020) Are, Vijay S.; Vuppalanchi, Raj; Vilar-Gomez, Eduardo; Chalasani, Naga; 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.
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