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      Environmental exposures are important risk factors for advanced liver fibrosis in African American adults

      research-article
      1 , 2 , 2 , 1 , 3 , 4 , 2 , 1 , 5 , 1 , 1 , 1 , 2 , 2 , 1 ,
      JHEP Reports
      Elsevier
      Environmental toxins, Racial disparities, Aetiology, Non-invasive scores, Screening, ALD, alcohol-associated liver disease, ALT, alanine aminotransferase, APC, annual percent change, BMI, body mass index, CI, confidence interval, FIB-4, Fibrosis-4, HBV, hepatitis B virus, HCV, hepatitis C virus, HR, hazard ratio, KI, kidney insufficiency, LF, liver fibrosis, MA, Mexican American, NAFLD, non-alcoholic fatty liver disease, NEI, no exposure identified, NHANES, National Health and Nutrition Evaluation Survey, NHB, non-Hispanic Black, NHW, non-Hispanic White, O, other race, PCB, polychlorinated biphenyl, Q1–Q4, quartiles 1–4, ULN, upper limit of normal, USFLI, US Fatty Liver Index, VH, viral hepatitis, WC, waist circumference

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          Abstract

          Background & Aims

          The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States.

          Methods

          Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999–2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase.

          Results

          The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8–1.9) to 3.5 million (95% CI 2.8–4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44–3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95–5.43) but did not include diabetes (OR 0.88; 95% CI 0.61–1.27; p =0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons.

          Conclusions

          The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed.

          Impact and Implications

          Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.

          Graphical abstract

          Highlights

          • The prevalence of advanced liver fibrosis doubled in the past 20 years in the United States.

          • Prevalence was higher in non-Hispanic Black persons than in non-Hispanic White persons.

          • Risk factors in non-Hispanic Black persons included lead exposure, but not diabetes.

          • Cadmium was a risk factor in all racial/ethnic groups examined.

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          Most cited references45

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          Burden of liver diseases in the world

          Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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            Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.

            Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of 3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients.
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              New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race

              Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.
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                Author and article information

                Contributors
                Journal
                JHEP Rep
                JHEP Rep
                JHEP Reports
                Elsevier
                2589-5559
                06 February 2023
                April 2023
                06 February 2023
                : 5
                : 4
                : 100696
                Affiliations
                [1 ]Division of Liver Diseases, Icahn School of Medicine Mount Sinai, New York, NY, USA
                [2 ]Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [3 ]Department of Medicine, Division of Nephrology, Duke University School of Medicine, Durham, NC, USA
                [4 ]Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [5 ]Department of Medicine, Rush University Medical Center, Chicago, IL, USA
                Author notes
                []Corresponding author. Address: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1123, New York, NY 10029, USA. Tel.: +1-212-659-8371; Fax: +1-212-849-2574. andrea.branch@ 123456mssm.edu
                Article
                S2589-5559(23)00027-7 100696
                10.1016/j.jhepr.2023.100696
                10017423
                36937989
                839633b6-e93d-4729-bb8c-a98a43265ef0
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 October 2022
                : 10 January 2023
                : 21 January 2023
                Categories
                Research Article

                environmental toxins,racial disparities,aetiology,non-invasive scores,screening,ald, alcohol-associated liver disease,alt, alanine aminotransferase,apc, annual percent change,bmi, body mass index,ci, confidence interval,fib-4, fibrosis-4,hbv, hepatitis b virus,hcv, hepatitis c virus,hr, hazard ratio,ki, kidney insufficiency,lf, liver fibrosis,ma, mexican american,nafld, non-alcoholic fatty liver disease,nei, no exposure identified,nhanes, national health and nutrition evaluation survey,nhb, non-hispanic black,nhw, non-hispanic white,o, other race,pcb, polychlorinated biphenyl,q1–q4, quartiles 1–4,uln, upper limit of normal,usfli, us fatty liver index,vh, viral hepatitis,wc, waist circumference

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