IU Indianapolis ScholarWorks :: Browsing by Author "Vilar-Gomez, Eduardo"

Browsing by Author "Vilar-Gomez, Eduardo"

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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 Medicine
Background & 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.
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 Medicine
Background 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.
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 Medicine
Background: 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.
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 Medicine
Background & 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.
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 Medicine
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 Medicine
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.
Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study
(Elsevier, 2018-08) Vilar-Gomez, Eduardo; Calzadilla-Bertot, Luis; Wong, Vincent Wai-Sun; Castellanos, Marlen; Aller-de la Fuente, Rocio; Metwally, Mayada; Eslam, Mohammed; Gonzalez-Fabian, Licet; Alvarez-Quiñones Sanz, María; Conde-Martin, Antonio Felix; De Boer, Bastiaan; McLeod, Duncan; Chan, Anthony Wing Hung; Chalasani, Naga; George, Jacob; Adams, Leon A.; Romero-Gomez, Manuel; Medicine, School of Medicine
Background & Aims Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced NAFLD. Methods We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n = 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes. Results During a mean follow-up time of 5.5 years (range, 2.7–8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval [CI], 86%–99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%–89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%–29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%–60% vs 6%, 95% CI, 2%–13%) or hepatocellular carcinoma (17%; 95% CI, 8%–31% vs 2.3%, 95% CI, 1%–12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%–18%) than cirrhosis (2%; 95% CI, 0%–6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%–23%) than cirrhosis (6%; 95% CI, 2%–15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild (<33%) steatosis, whereas moderate alcohol consumption was associated with these outcomes only in patients with cirrhosis. Conclusions Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.
Impact of low alcohol consumption in the natural history of cirrhosis
(AME, 2024) Marti-Aguado, David; Vilar-Gomez, Eduardo; Medicine, School of Medicine
Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD
(Wolters Kluwer, 2021) Vilar-Gomez, Eduardo; Pirola, Carlos Jose; Sookoian, Silvia; Wilson, Laura A.; Belt, Patricia; Liang, Tiebing; Liu, Wanqing; Chalasani, Naga; Medicine, School of Medicine
Introduction: This study explored the relationship between patatin-like phospholipase domain-containing 3 gene (PNPLA3 rs738409), nutrient intake, and liver histology severity in patients with nonalcoholic fatty liver disease (NAFLD). Methods: PNPLA3-rs738409 variant was genotyped in 452 non-Hispanic whites with histologically confirmed NAFLD who completed Food Frequency Questionnaire within 6 months of their liver biopsy. The fibrosis severity on liver histology was the outcome of interest. Results: The distribution of PNPLA3 genotypes was CC: 28%, CG: 46%, and GG: 25%. High-carbohydrate (% of energy/d) intake was positively associated (adjusted [Adj] odds ratio [OR]: 1.03, P < 0.01), whereas higher n-3 polyunsaturated fatty acids (n-3 PUFAs) (g/d) (Adj. OR: 0.17, P < 0.01), isoflavones (mg/d) (Adj. OR: 0.74, P = 0.049), methionine (mg/d) (Adj. OR: 0.32, P < 0.01), and choline (mg/d) (Adj. OR: 0.32, P < 0.01) intakes were inversely associated with increased risk of significant fibrosis (stage of fibrosis ≥2). By using an additive model of inheritance, our moderation analysis showed that PNPLA3 rs738409 significantly modulates the relationship between carbohydrate (%), n-3 PUFAs, total isoflavones, methionine, and choline intakes and fibrosis severity in a dose-dependent, genotype manner. These dietary factors tended to have a larger and significant effect on fibrosis severity among rs738409 G-allele carriers. Associations between significant fibrosis and carbohydrates (Adj. OR: 1.04, P = 0.019), n-3 PUFAs (Adj. OR: 0.16, P < 0.01), isoflavones (Adj. OR: 0.65, P = 0.025), methionine (Adj. OR: 0.30, P < 0.01), and total choline (Adj. OR: 0.29, P < 0.01) intakes remained significant only among rs738409 G-allele carriers. Discussion: This gene-diet interaction study suggests that PNPLA3 rs738409 G-allele might modulate the effect of specific dietary nutrients on risk of fibrosis in patients with NAFLD.

Browsing by Author "Vilar-Gomez, Eduardo"

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