Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.


Journal

Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946

Informations de publication

Date de publication:
01 08 2023
Historique:
received: 25 08 2022
accepted: 02 01 2023
pmc-release: 01 08 2024
medline: 19 7 2023
pubmed: 23 2 2023
entrez: 22 2 2023
Statut: ppublish

Résumé

The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH. Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD. Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.

Sections du résumé

BACKGROUND AIMS
The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH.
APPROACH RESULTS
Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD.
CONCLUSIONS
Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.

Identifiants

pubmed: 36805976
doi: 10.1097/HEP.0000000000000313
pii: 01515467-202308000-00021
pmc: PMC10496090
mid: NIHMS1927119
doi:

Types de publication

Multicenter Study Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

578-591

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK112293
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126042
Pays : United States

Informations de copyright

Copyright © 2023 American Association for the Study of Liver Diseases.

Références

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of NAFLD-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.
Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the US. Gastroenterology. 2015;148:547–555.
Frank TD, Carter A, Jahagirdar D, Biehl MH, Douwes-Schultz D, Larson SL, et al. Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Lancet HIV. 2019;6:e831–e859.
Saag MS, Gandhi RT, Hoy JF, Landovitz RJ, Thompson MA, Sax PE, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2020 Recommendations of the International Antiviral Society–USA Panel. JAMA. 2020;324:1651–1669.
Ghosn J, Taiwo B, Seedat S, Autran B, Katlama C. HIV. Lancet. 2018;392:685–697.
Sapuła M, Suchacz M, Załęski A, Wiercińska-Drapało A. Impact of Combined antiretroviral therapy on metabolic syndrome components in adult people living with HIV: a literature review. Viruses. 2022;14:122.
Joshi D, O'Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet. 2011;377:1198–1209.
Acharya C, Dharel N, Sterling RK. Chronic liver disease in the HIV patient. Clin Liver Dis. 2015;19:1–22.
Crum-Cianflone NF. Editorial commentary: elevated aminotransferase levels among HIV-infected persons: what’s lurking under the surface? Clin Infect Dis. 2015;60:1579–1581.
Maurice JB, Patel A, Scott AJ, Patel K, Thursz M, Lemoine M. Prevalence and risk factors of NAFLD in HIV-monoinfection. AIDS. 2017;31:1621–1632.
Verna EC. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in patients with HIV. Lancet Gastroenterol Hepatol. 2017;2:211–223.
Lake JE, Overton T, Naggie S, Sulkowski M, Loomba R, Kleiner DE, et al. Expert panel review on NAFLD in persons with HIV. Clin Gastroenterol Hepatol. 2022;20:256–268.
Crum-Cianflone N, Dilay A, Collins G, Asher D, Campin R, Medina S, et al. NAFLD among HIV-infected persons. J Acquir Immune Defic Syndr. 2009;50:464–473.
Price JC, Seaberg EC, Latanich R, Budoff MJ, Kingsley LA, Palella FJ Jr, et al. Risk factors for fatty liver in the Multicenter AIDS Cohort Study. Am J Gastroenterol. 2014;109:695–704.
Li Vecchi V, Soresi M, Giannitrapani L, Di Carlo P, Mazzola G, Colletti P, et al. Prospective evaluation of hepatic steatosis in HIV-infected patients with or without HCV co-infection. Int J Infect Dis. 2012;16:e397–e402.
Pembroke T, Deschenes M, Lebouche B, Benmassaoud A, Sewitch M, Ghali P, et al. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis. J Hepatol. 2017;67:801–808.
Morse CG, McLaughlin M, Matthews L, Proschan M, Thomas F, Gharib AM, et al. Nonalcoholic steatohepatitis and hepatic fibrosis in HIV-1-monoinfected adults with elevated aminotransferase levels on antiretroviral therapy. Clin Infect Dis. 2015;60:1569–1578.
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the US: impact of ethnicity. Hepatology. 2004;40:1387–1395.
Harrison SA, Gawrieh S, Roberts K, Lisanti CJ, Schwope RB, Cebe KM, et al. Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort. J Hepatol. 2021;75:284–291.
Gaslightwala I, Bini EJ. Impact of HIV infection on the prevalence and severity of steatosis in patients with chronic HCV infection. J Hepatol. 2006;44:1026–1032.
Benmassaoud A, Ghali P, Cox J, Wong P, Szabo J, Deschenes M, et al. Screening for NASH by using cytokeratin 18 and transient elastography in HIV mono-infection. PLoS One. 2018;13:e0191985.
Macias J, Gonzalez J, Tural C, Ortega-Gonzalez E, Pulido F, Rubio R, et al. Prevalence and factors associated with liver steatosis as measured by transient elastography with controlled attenuation parameter in HIV-infected patients. AIDS. 2014;28:1279–1287.
Lemoine M, Assoumou L, De Wit S, Girard PM, Valantin MA, Katlama C, et al. Diagnostic Accuracy of noninvasive markers of steatosis, NASH, and liver fibrosis in HIV-monoinfected individuals at risk of NAFLD: results From the ECHAM Study. J Acquir Immune Defic Syndr. 2019;80:e86–e94.
Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with NAFLD. Gastroenterology. 2015;149:389–397 e310.
Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, Castellanos M. Aller-de la Fuente R, Metwally M, Eslam M, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced NAFLD: a multi-national cohort study. Gastroenterology. 2018;155:443–457 e417.
Sanyal AJ, Van Natta ML, Clark J, Neuschwander-Tetri BA, Diehl A, Dasarathy S, et al. Prospective study of outcomes in adults with NAFLD. N Engl J Med. 2021;385:1559–1569.
Guaraldi G, Squillace N, Stentarelli C, Orlando G, D'Amico R, Ligabue G, et al. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47:250–257.
Mohammed SS, Aghdassi E, Salit IE, Avand G, Sherman M, Guindi M, et al. HIV-positive patients with NAFLD have a lower body mass index and are more physically active than HIV-negative patients. J Acquir Immune Defic Syndr. 2007;45:432–438.
Riddle TM, Kuhel DG, Woollett LA, Fichtenbaum CJ, Hui DY. HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. J Biol Chem. 2001;276:37514–37519.
Price JC, Thio CL. Liver disease in the HIV-infected individual. Clin Gastroenterol Hepatol. 2010;8:1002–1012.
Stankov MV, Panayotova-Dimitrova D, Leverkus M, Vondran FW, Bauerfeind R, Binz A, et al. Autophagy inhibition due to thymidine analogues as novel mechanism leading to hepatocyte dysfunction and lipid accumulation. AIDS. 2012;26:1995–2006.
Mohr R, Boesecke C, Dold L, Schierwagen R, Schwarze-Zander C, Wasmuth JC, et al. Return-to-health effect of modern combined antiretroviral therapy potentially predisposes HIV patients to hepatic steatosis. Medicine (Baltimore). 2018;97:e0462.
Machado MV, Oliveira AG, Cortez-Pinto H. Hepatic steatosis in patients coinfected with HIV/HCV: a meta-analysis of the risk factors. Hepatology. 2010;52:71–78.
Knight JR, Sherritt L, Harris SK, Gates EC, Chang G. Validity of brief alcohol screening tests among adolescents: a comparison of the AUDIT, POSIT, CAGE, and CRAFFT. Alcohol Clin Exp Res. 2003;27:67–73.
Frank D, DeBenedetti AF, Volk RJ, Williams EC, Kivlahan DR, Bradley KA. Effectiveness of the AUDIT-C as a screening test for alcohol misuse in three race/ethnic groups. J Gen Intern Med. 2008;23:781–787.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of NAFLD: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–357.
Siddiqui MS, Vuppalanchi R, Van Natta ML, Hallinan E, Kowdley KV, Abdelmalek M, et al. Vibration-controlled transient elastography to assess fibrosis and steatosis in patients with NAFLD. Clin Gastroenterol Hepatol. 2019;17:156–163 e152.
Ajmera VH, Cachay ER, Ramers CB, Bassirian S, Singh S, Bettencourt R, et al. Optimal threshold of controlled attenuation parameter for detection of HIV-associated NAFLD with MRI as the reference standard. Clin Infect Dis. 2021;72:2124–2131.
Price JC, Dodge JL, Ma Y, Scherzer R, Korn N, Tillinghast K, et al. Controlled attenuation parameter and magnetic resonance spectroscopy-measured liver steatosis are discordant in obese HIV-infected adults. AIDS. 2017;31:2119–2125.
Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty Liver Disease. Gastroenterology. 2017;152:598–607 e592.
Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–526.
Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–1325.
Kanwal F, Shubrook JH, Adams LA, Pfotenhauer K, Wai-Sun Wong V, Wright E, et al. Clinical care pathway for the risk stratification and management of patients with NAFLD. Gastroenterology. 2021;161:1657–1669.
Gawrieh S, Wilson LA, Cummings OW, Clark JM, Loomba R, Hameed B, et al. Histologic findings of advanced fibrosis and cirrhosis in patients with NAFLD who have normal aminotransferase levels. Am J Gastroenterol. 2019;114:1626–1635.
Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137:1–10.
Sterling RK, Smith PG, Brunt EM. Hepatic steatosis in HIV: a prospective study in patients without viral hepatitis, diabetes, or alcohol abuse. J Clin Gastroenterol. 2013;47:182–187.
Sterling RK, Contos MJ, Smith PG, Stravitz RT, Luketic VA, Fuchs M, et al. Steatohepatitis: risk factors and impact on disease severity in HIV/HCV coinfection. Hepatology. 2008;47:1118–1127.
Hadigan C, Liebau J, Andersen R, Holalkere NS, Sahani DV. Magnetic resonance spectroscopy of hepatic lipid content and associated risk factors in HIV infection. J Acquir Immune Defic Syndr. 2007;46:312–317.
McGovern BH, Ditelberg JS, Taylor LE, Gandhi RT, Christopoulos KA, Chapman S, et al. Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients. Clin Infect Dis. 2006;43:365–372.
Ryom L, De Miguel R, Cotter AG, Podlekareva D, Beguelin C, Waalewijn H, et al. Major revision version 11.0 of the European AIDS Clinical Society Guidelines 2021. HIV Med. 2022;23:849–858.
Vuille-Lessard E, Lebouche B, Lennox L, Routy JP, Costiniuk CT, Pexos C, et al. Nonalcoholic fatty liver disease diagnosed by transient elastography with controlled attenuation parameter in unselected HIV monoinfected patients. AIDS. 2016;30:2635–2643.
Bischoff J, Gu W, Schwarze-Zander C, Boesecke C, Wasmuth JC, van Bremen K, et al. Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART). EClinicalMedicine. 2021;40:101116.
Lemoine M, Lacombe K, Bastard JP, Sebire M, Fonquernie L, Valin N, et al. Metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV-monoinfected patients. AIDS. 2017;31:1955–1964.
Kardashian A, Ma Y, Scherzer R, Price JC, Sarkar M, Korn N, et al. Sex differences in the association of HIV infection with hepatic steatosis. AIDS. 2017;31:365–373.
Younossi ZM, Stepanova M, Negro F, Hallaji S, Younossi Y, Lam B, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore). 2012;91:319–327.
Ye Q, Zou B, Yeo YH, Li J, Huang DQ, Wu Y, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5:739–752.
Lean ME, Han TS, Morrison CE. Waist circumference as a measure for indicating need for weight management. BMJ. 1995;311:158–161.
Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol. 2007;189:W320–W323.
Cengiz M, Sentürk S, Cetin B, Bayrak AH, Bilek SU. Sonographic assessment of fatty liver: intraobserver and interobserver variability. Int J Clin Exp Med. 2014;7:5453–5460.
Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Ledinghen V, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66:1022–1030.
Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010;28:155–161.

Auteurs

Samer Gawrieh (S)

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Jordan E Lake (JE)

Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Paula Debroy (P)

Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Julia A Sjoquist (JA)

Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Montreca Robison (M)

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Mark Tann (M)

Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Fatih Akisik (F)

Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Surya S Bhamidipalli (SS)

Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Chandan K Saha (CK)

Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Kimon Zachary (K)

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Gregory K Robbins (GK)

Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Samir K Gupta (SK)

Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Raymond T Chung (RT)

Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Naga Chalasani (N)

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Kathleen E Corey (KE)

Division of Gastroenterology, Department of Medicine, Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

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