Browsing by Author "Noureddin, Mazen"

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    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.
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    Attribution of Nonalcoholic Steatohepatitis as an Etiology of Cirrhosis for Clinical Trials Eligibility: Recommendations from the Multi-stakeholder Liver Forum
    (Elsevier, 2020) Noureddin, Mazen; Chan, Jean L.; Barradas, Katherine; Dimick-Santos, Lara; Schabel, Elmer; Omokaro, Stephanie O.; Anania, Frank A.; Myers, Robert P.; Miller, Veronica; Sanyal, Arun J.; Chalasani, Naga; Medicine, School of Medicine
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    Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension
    (Elsevier, 2020-04) Chalasani, Naga; Abdelmalek, Manal F.; Garcia-Tsao, Guadalupe; Vuppalanchi, Raj; Alkhouri, Naim; Rinella, Mary; Noureddin, Mazen; Pyko, Maxmillan; Shiffman, Mitchell; Sanyal, Arun; Allgood, Adam; Shlevin, Harold; Horton, Rex; Zomer, Eliezer; Irish, William; Goodman, Zachary; Harrison, Stephen A.; Traber, Peter G.; Medicine, School of Medicine
    Background & Aims Increased levels of galectin 3 have been associated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in mice. GR-MD-02 (belapectin) is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies. We performed a phase 2b, randomized trial of the safety and efficacy of GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension. Methods Patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) from 36 centers were randomly assigned, in a double-blind manner, to groups that received biweekly infusions of belapectin 2 mg/kg (n = 54), 8 mg/kg (n = 54), or placebo (n = 54) for 52 weeks. The primary endpoint was change in HVPG (Δ HVPG) at the end of the 52-week period compared with baseline. Secondary endpoints included changes in liver histology and development of liver-related outcomes. Results We found no significant difference in ΔHVPG between the 2 mg/kg belapectin group and placebo group (–0.28 mm HG vs 0.10 mm HG, P = 1.0) or between the 8 mg/kg belapectin and placebo group (–0.25 mm HG vs 0.10 mm HG, P = 1.0). Belapectin had no significant effect on fibrosis or nonalcoholic fatty liver disease activity score, and liver-related outcomes did not differ significantly among groups. In an analysis of a subgroup of patients without esophageal varices at baseline (n = 81), 2 mg/kg belapectin was associated with a reduction in HVPG at 52 weeks compared with baseline (P = .02) and reduced development of new varices (P = .03). Belapectin (2 mg/kg) was well tolerated and produced no safety signals. Conclusions In a phase 2b study of 162 patients with NASH, cirrhosis, and portal hypertension, 1 year of biweekly infusion of belapectin was safe but not associated with significant reduction in HVPG or fibrosis compared with placebo. However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce HVPG and development of varices.
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    Increased mortality from alcohol use disorder, alcohol-associated liver disease, and liver cancer from alcohol among older adults in the United States: 2000 to 2021
    (Wiley, 2025) Danpanichkul, Pojsakorn; Duangsonk, Kwanjit; Tham, Ethan Kai Jun; Tothanarungroj, Primrose; Auttapracha, Thanida; Prasitsumrit, Vitchapong; Sim, Benedix; Tung, Daniel; Barba, Romelia; Wong, Robert J.; Leggio, Lorenzo; Yang, Ju Dong; Chen, Vincent L.; Noureddin, Mazen; Díaz, Luis Antonio; Arab, Juan Pablo; Wijarnpreecha, Karn; Liangpunsakul, Suthat; Medicine, School of Medicine
    Background: To investigate the trends in alcohol-associated liver disease (ALD), liver cancer from alcohol, and alcohol use disorder (AUD) burden among older adults in the United States (US). Methods: We gathered the ALD, liver cancer from alcohol, and AUD prevalence, mortality, and age-standardized rates (ASRs) from the Global Burden of Disease (GBD) Study 2021 between 2010 and 2021. We estimated the annual percent change (APC) with confidence intervals (CIs) for the burden of ALD, liver cancer from alcohol, and AUD in older adults (>70 years) in the United States. The findings were contrasted with global estimates and categorized by sex and state. Results: In 2021, there were approximately 512,340 cases of AUD, 56,990 cases of ALD, and 4490 cases of primary liver cancer from alcohol among older adults in the United States. In contrast to declining ASRs of prevalence and mortality in the global burden, these parameters were increased in older adults in the United States. From 2000 to 2021, prevalence from AUD (APC: 0.54%, 95% CI 0.43% to 0.65%), ALD (APC + 0.54%, 95% CI 0.22% to 0.86%), and primary liver cancer from alcohol (APC 2.93%, 95% CI 2.76% to 3.11%) increased. Forty states in the United States exhibited a rise in the prevalence rates of ALD in older adults. Conclusion: Our findings highlighted the increased prevalence and mortality of AUD, ALD, and primary liver cancer from alcohol among older adults in the United Sates, contrasting with the decline in global trends. Public health strategies on ALD, AUD, and primary liver cancer from alcohol, which targets older adults, are urgently needed.
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    Machine learning liver histology scores correlate with portal hypertension assessments in nonalcoholic steatohepatitis cirrhosi
    (Wiley, 2023) Noureddin, Mazen; Goodman, Zachary; Tai, Dean; Chng, Elaine L. K.; Ren, Yayun; Boudes, Pol; Shlevin, Harold; Garcia-Tsao, Guadalupe; Harrison, Stephen A.; Chalasani, Naga P.; Medicine, School of Medicine
    Background and aims: In cirrhotic nonalcoholic steatohepatitis (NASH) clinical trials, primary efficacy endpoints have been hepatic venous pressure gradient (HVPG), liver histology and clinical liver outcomes. Important histologic features, such as septa thickness, nodules features and fibrosis area have not been included in the histologic assessment and may have important clinical relevance. We assessed these features with a machine learning (ML) model. Methods: NASH patients with compensated cirrhosis and HVPG ≥6 mm Hg (n = 143) from the Belapectin phase 2b trial were studied. Liver biopsies, HVPG measurements and upper endoscopies were performed at baseline and at end of treatment (EOT). A second harmonic generation/two-photon excitation fluorescence provided an automated quantitative assessment of septa, nodules and fibrosis (SNOF). We created ML scores and tested their association with HVPG, clinically significant HVPG (≥10 mm Hg) and the presence of varices (SNOF-V). Results: We derived 448 histologic variables (243 related to septa, 21 related to nodules and 184 related to fibrosis). The SNOF score (≥11.78) reliably distinguished CSPH at baseline and in the validation cohort (baseline + EOT) [AUC = 0.85 and 0.74, respectively]. The SNOF-V score (≥0.57) distinguished the presence of varices at baseline and in the same validation cohort [AUC = 0.86 and 0.73, respectively]. Finally, the SNOF-C score differentiated those who had >20% change in HVPG against those who did not, with an AUROC of 0.89. Conclusion: The ML algorithm accurately predicted HVPG, CSPH, the development of varices and HVPG changes in patients with NASH cirrhosis. The use of ML histology model in NASH cirrhosis trials may improve the assessment of key outcome changes.
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    Saroglitazar, a PPAR-α/γ Agonist, for Treatment of Nonalcoholic Fatty Liver Disease: A Randomized Controlled Double-Blind Phase 2 Trial
    (Wiley, 2021-10) Gawrieh, Samer; Noureddin, Mazen; Loo, Nicole; Mohseni, Rizwana; Awasty, Vivek; Cusi, Kenneth; Kowdley, Kris V.; Lai, Michelle; Schiff, Eugene; Parmar, Deven; Patel, Pankaj; Chalasani, Naga; Medicine, School of Medicine
    Background and Aims Non-alcoholic fatty liver disease (NAFLD) is characterized by insulin resistance and dysregulated lipid and glucose metabolism. Saroglitazar, a novel dual peroxisome proliferator activated receptor-α/γ agonist, improves insulin sensitivity, and lipid and glycemic parameters. Saroglitazar improved nonalcoholic steatohepatitis (NASH) histology in animal studies. In this randomized controlled clinical trial, we evaluated the efficacy and safety of saroglitazar in patients with NAFLD/NASH. Approach & Results A total of 106 patients with NAFLD/NASH with ALT ≥50 U/L at baseline and body mass index ≥25 kg/m2 were randomized in a 1:1:1:1 ratio to receive placebo or saroglitazar 1 mg, 2 mg, or 4 mg for 16 weeks. The primary efficacy endpoint was percentage change from baseline in ALT levels at Week 16. Liver fat content (LFC) was assessed by magnetic resonance imaging-proton density fat fraction. The least squares (LS) mean (SE) percent change from baseline in ALT at Week 16 was -25.5% (5.8), -27.7% (5.9) and -45.8% (5.7) with saroglitazar 1 mg, 2 mg, and 4 mg, respectively versus 3.4% (5.6) in placebo (p<0.001 for all). Compared to placebo, saroglitazar 4 mg improved LFC [4.1%, (5.9) versus -19.7% (5.6)], adiponectin [-0.3 ug/mL (0.3) versus 1.3 ug/mL (0.3)], homeostatic model assessment-insulin resistance [-1.3 (1.8) versus -6.3 (1.7)], and triglycerides [-5.3 mg/dL (10.7) versus -68.7 mg/dL (10.3)] (p<0.05 for all). Saroglitazar 4 mg also improved lipoprotein particle composition and size and reduced lipotoxic lipid species. Saroglitazar was well-tolerated. A mean weight gain of 1.5kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (p>0.05). Conclusions Saroglitazar 4 mg significantly improved ALT, LFC, insulin resistance and atherogenic dyslipidemia in participants with NAFLD/NASH.