Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US Minority Populations

Sherif, Zaki A.; Saeed, Armana; Ghavimi, Shima; Nouraie, Mehdi; Laiyemo, Adeyinka O.; Brim, Hassan; Ashktorab, Hassan

doi:10.1007/s10620-016-4143-0

Cited by 140 publications

(123 citation statements)

References 117 publications

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“…alpha-1 antitrypsin, Wilson’s, hemachromatosis, glycogen storage diseases, autoimmune chronic active hepatitis, primary biliary cirrhosis) in addition to HBV) can cause HCC [107]. New nucleotide/nucleoside and protease inhibitors that clear HCV viral loads theoretically should reduce HCC over time for those who can obtain the expensive treatment [108,109], but other conditions such as NAFLD will likely become the dominant etiology among populations in the U.S. Rates of NAFLD are highest among Hispanic patients compared to NHWs and Blacks [110,111], and without a clear definitive treatment path for NAFLD to date, a relative increased disparity could develop for HCC in Hispanics in the future. Variants for NAFLD risk exist in single nucleotide polymorphisms in or near PNPLA3 and PPP1R3B genes in Hispanic Americans and PNPLA3 , NCAN , GCKR , and PPP1R3B genes in Blacks [112].…”

Section: Introductionmentioning

confidence: 99%

Racial Disparity in Gastrointestinal Cancer Risk

et al. 2017

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Cancer from the gastrointestinal tract and its associated excretory organs will occur in over 300,000 Americans in 2017, with colorectal cancer responsible for over forty percent of that burden; there will be over 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to these cancers’ incidence and mortality exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in Non-Hispanic Whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among Blacks. Liver cancer has been most frequent among Asian/Pacific Islanders chiefly due to hepatitis B vertical transmission, but other racial groups show increasing rates due to hepatitis C and emergence of cirrhosis from non-alcoholic fatty liver disease. Gastric cancer incidence remains highest among Asian/Pacific Islanders likely due to gene-environment interaction. In addition to esophageal squamous cell carcinoma, cancers of the small bowel, pancreas and colorectum show the highest rates among Blacks, where the explanations for the disparity are not as obvious and are likely multifactorial, including socio-economic and health care access, treatment and prevention (vaccination and screening) differences, dietary and composition of the gut microbiome, as well as biological and genetic influences. Cognizance of these disparities in gastrointestinal cancer risk, as well as approaches that apply precision medicine methods to populations with the increased risk, may reduce the observed disparities for digestive cancers.

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Section: Introductionmentioning

confidence: 99%

Racial Disparity in Gastrointestinal Cancer Risk

et al. 2017

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“…1). In the last few decades, NAFLD has emerged as the major cause of chronic liver disease in most parts of the western world (2), and approximately 1.0 billion individuals are affected worldwide, ranging from 10% to 36% of the general population (1,3). As a liver-associated complication of diabetes, metabolic syndrome, and obesity, NASH requires medical attention, progresses to end-stage liver disease (ESLD or cirrhosis), and is currently the second leading etiology of liver disease in patients awaiting liver transplantation in the United States (4).…”

Section: Introductionmentioning

confidence: 99%

JCAD Promotes Progression of Nonalcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity

et al. 2017

Cancer Research

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Nonalcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is a malignancy whose incidents are rapidly increasing. However, the mechanisms that drive development of HCC in a steatotic microenvironment remain unknown. Here we report that the obesity-associated protein JCAD is expressed at significantly higher levels in human NASH-HCC specimens compared with pericarcinoma specimens. High JCAD expression was verified in multiple hepatoma cell lines. Forced overexpression of JCAD in hepatoma cells promoted tumor growth and proliferation, whereas JCAD silencing yielded opposite effects. JCAD interacted with the kinase domain of the tumor suppressor kinase LATS2, a core component of the Hippo signaling pathway. JCAD overexpression inhibited the ability of LATS2 to phosphorylate YAP in this pathway, in turn upregulating CCND1 and GLI2 to promote hepatoma cell proliferation. JCAD was induced by fatty acid overload in hepatic cells and was highly expressed in a mouse model of NASH-precarcinoma lesions, where the ratio of phospho-YAP to YAP was decreased. In human NASH-HCC specimens, JCAD expression and YAP phosphorylation patterns paralleled with the mouse model. Our findings illuminate a new role for JCAD and its critical interplay in the Hippo signaling cascade during the transition of NASH to HCC, with potential implications for therapeutic development in this setting.

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“…Populations with higher prevalence of NAFLD include those with obesity, the metabolic syndrome (central obesity, insulin resistance, dyslipidemia, hypertension) and diabetes mellitus. In addition, NAFLD prevalence varies by ethnicity with the highest rates seen in Hispanics [3]. In contrast to other causes of chronic liver disease such as viral hepatitis infections and alcoholic liver disease, which have remained stable in the last decades, the prevalence of NAFLD has steadily increased [4].…”

Section: Epidemiologymentioning

confidence: 99%

Managing the Burden of Non-NASH NAFLD

Danford

Sánchez

Corey

2017

Curr Hepatology Rep

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Purpose of Review The purpose of this review article is to raise awareness of the significance of steatosis that exist within the spectrum of nonalcoholic fatty liver disease (NAFLD). While the impact of nonalcoholic steatohepatitis (NASH), and its potential for histologic progression to cirrhosis and hepatocellular carcinoma is widely appreciated, the impact of non-NASH NAFLD (steatosis) on morbidity and mortality is less well recognized. Recent Findings NAFLD is a spectrum of hepatic pathology with a rising prevalence worldwide. Steatosis without fibrosis carries a low risk of progression to cirrhosis but likely confers an increased risk of diabetes mellitus and cardiovascular disease. Summary About a quarter of the world population is affected by NAFLD. NAFLD represents a burden to affected individuals, economics of the health care system and contributes significantly to morbidity and mortality worldwide. An increased level of awareness and knowledge about risk factors and diagnostic strategies is needed to identify patients affected with disease.

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Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US Minority Populations

Cited by 140 publications

References 117 publications

Racial Disparity in Gastrointestinal Cancer Risk

Racial Disparity in Gastrointestinal Cancer Risk

JCAD Promotes Progression of Nonalcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity

Managing the Burden of Non-NASH NAFLD

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