Grant Number:	5R01CA256977-04 Interpret this number
Primary Investigator:	Kanwal, Fasiha
Organization:	Baylor College Of Medicine
Project Title:	Multi-Level Evaluation of Racial/Ethnic Disparities in Liver Disease Outcomes
Fiscal Year:	2024

ABSTRACT Cirrhosis – the end-stage result of chronic liver disease – is a condition with high morbidity and mortality that is becoming increasingly common. Nearly half of all patients with cirrhosis develop hepatic decompensation including hepatocellular cancer (HCC), with frequent hospitalization within 5 years of cirrhosis diagnosis. Several studies show that these cirrhosis complications disproportionately affect racial/ethnic minorities and persons of low socioeconomic status (SES). But fundamental questions remain unanswered given that only few studies investigated the mechanisms that underlie these disparities. The research proposed here aims to provide actionable information on what to target to reduce cirrhosis prognosis disparities. We will conduct a comprehensive evaluation of multilevel factors hypothesized to play important roles in causing racial/ethnic and SES disparities in three key measures of cirrhosis prognosis: a) hepatic decompensation, including HCC, b) liver-related hospitalization, and c) overall survival. We propose a large, multicenter, racially and socio-economically diverse cohort study of cirrhosis patients enrolled from four healthcare systems; the project will combine information from existing clinical databases, genomic data, and geospatial analyses with patient- and clinician- surveys to provide unparalleled information about the role of individual, interpersonal, and community-level factors in the racial/ethnic and SES disparities in cirrhosis prognosis. The proposed cohort includes representative groups from all racial/ethnic (blacks, Hispanics, Asian-Pacific Islanders) and SES groups. It also spans the full spectrum of disease severity (from compensated to advanced decompensated disease), rather than focusing on a few groups. We will uncover the relative contributions of established (hepatitis C virus, hepatitis B virus) and emerging (obesity, diabetes) etiological risk factors as well as risk behaviors (alcohol use) to cirrhosis prognosis disparities. We will also characterize pathways that contribute to cirrhosis disparities among the high order determinants at the individual (e.g., medical mistrust), interpersonal (e.g., bias), and community (e.g., access to transportation) levels either directly or by affecting etiological or behavioral risk factors. Identification of these root cause mechanisms will identify actionable targets for intervention and policy change. We will also examine a set of genetic single nucleotide polymorphisms using stored sera in a subset of the cohort to understand the role of genetic differences, if any, in explaining racial/ethnic disparities.




Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Liver Disease, Emerges as the Fastest-Growing Aetiologies for Primary Liver Cancer in the United States.
Authors: Danpanichkul P. , Duangsonk K. , Kalligeros M. , Fallon M.B. , Vuthithammee C. , Pan C.W. , Saokhieo P. , Derrick W. , Pang Y. , Chen V.L. , et al. .
Source: Alimentary Pharmacology & Therapeutics, 2025-01-05 00:00:00.0; , .
EPub date: 2025-01-05 00:00:00.0.
PMID: 39757456
Related Citations

Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified delphi panel.
Authors: Singal A.G. , Quirk L. , Boike J. , Chernyak V. , Feng Z. , Giamarqo G. , Kanwal F. , Ioannou G.N. , Manes S. , Marrero J.A. , et al. .
Source: Hepatology (baltimore, Md.), 2024-12-18 00:00:00.0; , .
EPub date: 2024-12-18 00:00:00.0.
PMID: 39699563
Related Citations

Significant Disparities in Hepatocellular Carcinoma Outcomes by Race/Ethnicity and Sociodemographic Factors.
Authors: Patel S. , Khalili M. , Singal A.G. , Pinheiro P.S. , Jones P.D. , Kim R.G. , Kode V. , Thiemann A. , Zhang W. , Cheung R. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2024-12-05 00:00:00.0; , .
EPub date: 2024-12-05 00:00:00.0.
PMID: 39636161
Related Citations

The Prognostic Significance of Nativity, Enclave Residence, and Socioeconomic Status Among Hispanic Patients with Hepatocellular Carcinoma.
Authors: Whitham Z.A. , Nevarez N.M. , Rong R. , Chang G. , Ethun C.G. , Porembka M.R. , Mansour J.C. , Wang S.C. , Polanco P.M. , Zeh H.J. , et al. .
Source: Annals Of Surgical Oncology, 2024-09-21 00:00:00.0; , .
EPub date: 2024-09-21 00:00:00.0.
PMID: 39306623
Related Citations

PNPLA3, Obesity, and Heavy Alcohol Use in Cirrhosis Patients May Exert a Synergistic Increase Hepatocellular Carcinoma Risk.
Authors: Thrift A.P. , Kanwal F. , Lim H. , Duong H. , Liu Y. , Singal A.G. , Khaderi S. , Asrani S.K. , Amos C.I. , El-Serag H.B. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2024 Sep; 22(9), p. 1858-1866.e4.
EPub date: 2024-05-09 00:00:00.0.
PMID: 38729396
Related Citations

In utero exposure to antihistamines and risk of hepatocellular carcinoma in a multigenerational cohort.
Authors: Murphy C.C. , Seif El Dahan K. , Singal A.G. , Cirillo P.M. , Krigbaum N.Y. , Cohn B.A. .
Source: Hepatology Communications, 2024-08-01 00:00:00.0; 8(8), .
EPub date: 2024-07-22 00:00:00.0.
PMID: 39037384
Related Citations

Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease.
Authors: Kanwal F. , Neuschwander-Tetri B.A. , Loomba R. , Rinella M.E. .
Source: Hepatology (baltimore, Md.), 2024-05-01 00:00:00.0; 79(5), p. 1212-1219.
EPub date: 2023-11-09 00:00:00.0.
PMID: 38445559
Related Citations

Racial and ethnic disparities in alcohol-associated liver disease in the United States: A systematic review and meta-analysis.
Authors: Anouti A. , Seif El Dahan K. , Rich N.E. , Louissaint J. , Lee W.M. , Lieber S.R. , Arab J.P. , Zhang B.Y. , Patel M.J. , Thimphittaya C. , et al. .
Source: Hepatology Communications, 2024-04-01 00:00:00.0; 8(4), .
EPub date: 2024-03-18 00:00:00.0.
PMID: 38497931
Related Citations

Brief alcohol interventions are underutilized in persons with nonalcohol-associated chronic liver diseases.
Authors: Louissaint J. , Melendez-Torres J. , Zhang W. , Kozlitina J. , Anouti A. , Patel M.J. , Zhang B.Y. , Singal A.G. , Mitchell M.C. , Cotter T.G. .
Source: Hepatology Communications, 2024-04-01 00:00:00.0; 8(4), .
EPub date: 2024-04-03 00:00:00.0.
PMID: 38563583
Related Citations

Racial and Ethnic Disparities in Hepatocellular Carcinoma Treatment Receipt in the United States: A Systematic Review and Meta-Analysis.
Authors: Wagle N.S. , Park S. , Washburn D. , Ohsfeldt R. , Kum H.C. , Singal A.G. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2024-01-22 00:00:00.0; , .
EPub date: 2024-01-22 00:00:00.0.
PMID: 38252039
Related Citations

Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA.
Authors: Anouti A. , Patel M.S. , VanWagner L.B. , Lee W.M. , Asrani S.K. , Mufti A.R. , Rich N.E. , Vagefi P.A. , Shah J.A. , Kerr T.A. , et al. .
Source: Liver Transplantation : Official Publication Of The American Association For The Study Of Liver Diseases And The International Liver Transplantation Society, 2024-01-01 00:00:00.0; 30(1), p. 72-82.
EPub date: 2023-07-26 00:00:00.0.
PMID: 37490432
Related Citations

Evaluating dynamic and predictive discrimination for recurrent event models: use of a time-dependent C-index.
Authors: Wang J. , Jiang X. , Ning J. .
Source: Biostatistics (oxford, England), 2023-11-10 00:00:00.0; , .
EPub date: 2023-11-10 00:00:00.0.
PMID: 37952117
Related Citations

Efficacy and safety of atezolizumab/bevacizumab in patients with HCC after prior systemic therapy: A global, observational study.
Authors: Joerg V. , Scheiner B. , D Alessio A. , Fulgenzi C.A.M. , Schönlein M. , Kocheise L. , Lohse A.W. , Huber S. , Wege H. , Kaseb A. , et al. .
Source: Hepatology Communications, 2023-11-01 00:00:00.0; 7(11), .
EPub date: 2023-10-27 00:00:00.0.
PMID: 37889520
Related Citations

Pandemic-related changes in incidence and mortality rates of gastrointestinal cancers during 2020.
Authors: Murphy C.C. , Tavakkoli A. , Wani S. , Singal A.G. .
Source: The American Journal Of Gastroenterology, 2023-10-04 00:00:00.0; , .
EPub date: 2023-10-04 00:00:00.0.
PMID: 37791616
Related Citations

Survival following liver transplantation for hepatocellular carcinoma after implementation of MMaT-3 policy.
Authors: Shaikh A. , Lee T.H. , Rich N.E. , Benhammou J.N. , Lymberopoulos P. , Agopian V.G. , Kim D. , Ahmed A. , Hernaez R. , Berg C.L. , et al. .
Source: Liver Transplantation : Official Publication Of The American Association For The Study Of Liver Diseases And The International Liver Transplantation Society, 2023-10-01 00:00:00.0; 29(10), p. 1138-1142.
EPub date: 2023-05-03 00:00:00.0.
PMID: 37129867
Related Citations

Biliary atresia and liver transplantation in the United States: A contemporary analysis.
Authors: Anouti A. , Patel M.S. , VanWagner L.B. , Lee W.M. , Fung J.J. , Cholankeril G. , Hwang C.S. , Mufti A.R. , Tujios S. , Kerr T. , et al. .
Source: Liver International : Official Journal Of The International Association For The Study Of The Liver, 2023 Oct; 43(10), p. 2198-2209.
EPub date: 2023-08-07 00:00:00.0.
PMID: 37548078
Related Citations

Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era.
Authors: Shaikh A. , Goli K. , Lee T.H. , Rich N.E. , Benhammou J.N. , Keeling S. , Kim D. , Ahmed A. , Goss J. , Rana A. , et al. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2023 Aug; 21(9), p. 2288-2297.e4.
EPub date: 2022-12-12 00:00:00.0.
PMID: 36521738
Related Citations

Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities.
Authors: Bhatnagar A. , Prakash S. , Lymberopoulos P. , Goff C. , Shaikh A. , Kim D. , Ahmed A. , Berg C. , Naggie S. , Kanwal F. , et al. .
Source: American Journal Of Transplantation : Official Journal Of The American Society Of Transplantation And The American Society Of Transplant Surgeons, 2023 Aug; 23(8), p. 1221-1226.
EPub date: 2023-04-26 00:00:00.0.
PMID: 37116583
Related Citations

Actionable Solutions to Achieve Health Equity in Chronic Liver Disease.
Authors: Jones P.D. , Lai J.C. , Bajaj J.S. , Kanwal F. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2023 Jul; 21(8), p. 1992-2000.
EPub date: 2023-04-13 00:00:00.0.
PMID: 37061105
Related Citations

Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma.
Authors: Alden S.L. , Lim M. , Kao C. , Shu D. , Singal A.G. , Noonan A. , Griffith P. , Baretti M. , Ho W.J. , Kamel I. , et al. .
Source: Cancer Research Communications, 2023 Jul; 3(7), p. 1312-1317.
EPub date: 2023-07-20 00:00:00.0.
PMID: 37484200
Related Citations

Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus.
Authors: Patel A.A. , Tapper E.B. , Kanwal F. , Woodrell C.D. , Hansen L. , Lai J.C. , Rogal S. , McDermott C. , Rakoski M. , Ufere N.N. .
Source: Hepatology Communications, 2023-06-01 00:00:00.0; 7(6), .
EPub date: 2023-06-02 00:00:00.0.
PMID: 37267219
Related Citations

Multidisciplinary care for patients with HCC: a systematic review and meta-analysis.
Authors: Seif El Dahan K. , Reczek A. , Daher D. , Rich N.E. , Yang J.D. , Hsiehchen D. , Zhu H. , Patel M.S. , Bayona Molano M.D.P. , Sanford N. , et al. .
Source: Hepatology Communications, 2023-05-01 00:00:00.0; 7(5), .
EPub date: 2023-04-26 00:00:00.0.
PMID: 37102768
Related Citations

Patient Knowledge, Risk Perception, and Barriers to Barrett's Esophagus Screening.
Authors: Kolb J.M. , Chen M. , Tavakkoli A. , Gallegos J. , O'Hara J. , Tarter W. , Hochheimer C.J. , Golubski B. , Kopplin N. , Hennessey L. , et al. .
Source: The American Journal Of Gastroenterology, 2023-04-01 00:00:00.0; 118(4), p. 615-626.
EPub date: 2022-10-11 00:00:00.0.
PMID: 36219171
Related Citations

Stage migration as a surrogate of survival in hepatocellular carcinoma treated with transarterial chemoembolization.
Authors: Kassab I. , Singal A.G. , Ali A. , Narasimman M. , Arvind A. , Ahmed M. , Joshi S. , Manzoor K. , Rich N. , Chen V.L. , et al. .
Source: Hepatology Communications, 2023-04-01 00:00:00.0; 7(4), .
EPub date: 2023-03-24 00:00:00.0.
PMID: 36972387
Related Citations

Longitudinal changes in fibrosis markers are associated with risk of cirrhosis and hepatocellular carcinoma in non-alcoholic fatty liver disease.
Authors: Cholankeril G. , Kramer J.R. , Chu J. , Yu X. , Balakrishnan M. , Li L. , El-Serag H.B. , Kanwal F. .
Source: Journal Of Hepatology, 2023 Mar; 78(3), p. 493-500.
EPub date: 2022-11-17 00:00:00.0.
PMID: 36402450
Related Citations

Non-alcoholic fatty liver disease-related hepatocellular carcinoma.
Authors: Daher D. , Dahan K.S.E. , Singal A.G. .
Source: Journal Of Liver Cancer, 2023 Mar; 23(1), p. 127-142.
EPub date: 2023-02-09 00:00:00.0.
PMID: 37384032
Related Citations

Breakthroughs in hepatocellular carcinoma therapies.
Authors: Singal A.G. , Kudo M. , Bruix J. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2023-02-20 00:00:00.0; , .
EPub date: 2023-02-20 00:00:00.0.
PMID: 36813012
Related Citations

Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection.
Authors: Kramer J.R. , Cao Y. , Li L. , Smith D. , Chhatwal J. , El-Serag H.B. , Kanwal F. .
Source: The American Journal Of Gastroenterology, 2022-11-01 00:00:00.0; 117(11), p. 1834-1844.
EPub date: 2022-08-23 00:00:00.0.
PMID: 36327437
Related Citations

Synergistic Associations of PNPLA3 I148M Variant, Alcohol Intake, and Obesity With Risk of Cirrhosis, Hepatocellular Carcinoma, and Mortality.
Authors: Kim H.S. , Xiao X. , Byun J. , Jun G. , DeSantis S.M. , Chen H. , Thrift A.P. , El-Serag H.B. , Kanwal F. , Amos C.I. .
Source: Jama Network Open, 2022-10-03 00:00:00.0; 5(10), p. e2234221.
EPub date: 2022-10-03 00:00:00.0.
PMID: 36190732
Related Citations

Racial, Ethnic, and Socioeconomic Disparities in Treatment Delay Among Patients With Hepatocellular Carcinoma in the United States.
Authors: Wagle N.S. , Park S. , Washburn D. , Ohsfeldt R.L. , Rich N.E. , Singal A.G. , Kum H.C. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2022-08-04 00:00:00.0; , .
EPub date: 2022-08-04 00:00:00.0.
PMID: 35933076
Related Citations

Contemporary Changes in Etiology for Hepatocellular Carcinoma in Liver Transplantation.
Authors: Goff C. , Shaikh A. , Goli K. , El-Serag H.B. , Kanwal F. , Cholankeril G. , Collaborators from Liver Cancer Investigator Working Group .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2022-07-20 00:00:00.0; , .
EPub date: 2022-07-20 00:00:00.0.
PMID: 35870770
Related Citations

Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort.
Authors: Parikh N.D. , Tayob N. , Al-Jarrah T. , Kramer J. , Melcher J. , Smith D. , Marquardt P. , Liu P.H. , Tang R. , Kanwal F. , et al. .
Source: Jama Network Open, 2022-07-01 00:00:00.0; 5(7), p. e2223504.
EPub date: 2022-07-01 00:00:00.0.
PMID: 35867057
Related Citations

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.
Authors: Lymberopoulos P. , Prakash S. , Shaikh A. , Bhatnagar A. , Allam A.K. , Goli K. , Goss J.A. , Kanwal F. , Rana A. , Kowdley K. , et al. .
Source: Liver Transplantation : Official Publication Of The American Association For The Study Of Liver Diseases And The International Liver Transplantation Society, 2022-06-30 00:00:00.0; , .
EPub date: 2022-06-30 00:00:00.0.
PMID: 35770428
Related Citations

Systematic review and meta-analysis: incidence of variceal hemorrhage in patients with cirrhosis undergoing transesophageal echocardiography.
Authors: Odewole M. , Sen A. , Okoruwa E. , Lieber S.R. , Cotter T.G. , Nguyen A.D. , Mufti A. , Singal A.G. , Rich N.E. .
Source: Alimentary Pharmacology & Therapeutics, 2022-03-28 00:00:00.0; , .
EPub date: 2022-03-28 00:00:00.0.
PMID: 35343613
Related Citations

Comparable Survival for Hepatitis C-Related Hepatocellular Carcinoma After Liver Transplantation Irrespective of Viremic Status.
Authors: Lymberopoulos P. , Shaikh A. , Rich N.E. , Benhammou J.N. , Kanwal F. , Cholankeril G. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2022-03-26 00:00:00.0; , .
EPub date: 2022-03-26 00:00:00.0.
PMID: 35346850
Related Citations

Significant improvements, but consistent disparities in survival for African Americans after liver transplantation.
Authors: Keeling S.S. , McDonald M.F. , Anand A. , Handing G.E. , Prather L.L. , Christmann C.R. , Jalal P.K. , Kanwal F. , Cholankeril G. , Goss J.A. , et al. .
Source: Clinical Transplantation, 2022-03-18 00:00:00.0; , p. e14646.
EPub date: 2022-03-18 00:00:00.0.
PMID: 35304775
Related Citations

Clinical Characteristics and Outcomes of Nonalcoholic Fatty Liver Disease- Associated Hepatocellular Carcinoma In the United States.
Authors: Karim M.A. , Singal A.G. , Kum H.C. , Lee Y.T. , Park S. , Rich N.E. , Noureddin M. , Yang J.D. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2022-03-17 00:00:00.0; , .
EPub date: 2022-03-17 00:00:00.0.
PMID: 35307595
Related Citations

Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease.
Authors: Kramer J.R. , Natarajan Y. , Dai J. , Yu X. , Li L. , El-Serag H.B. , Kanwal F. .
Source: Hepatology (baltimore, Md.), 2021-11-15 00:00:00.0; , .
EPub date: 2021-11-15 00:00:00.0.
PMID: 34779535
Related Citations

NAFLD and HCC: Time to Bridge the Gap.
Authors: Cholankeril G. , Kanwal F. .
Source: Hepatology (baltimore, Md.), 2021 11; 74(5), p. 2336-2338.
EPub date: 2021-08-30 00:00:00.0.
PMID: 34164841
Related Citations

Mediation model with a categorical exposure and a censored mediator with application to a genetic study.
Authors: Wang J. , Ning J. , Shete S. .
Source: Plos One, 2021; 16(10), p. e0257628.
EPub date: 2021-10-12 00:00:00.0.
PMID: 34637449
Related Citations