Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV–HIV Co-infected Adults

Digestive Diseases and Sciences - Tập 67 - Trang 676-688 - 2021
Richard K. Sterling1, Wendy C. King2, Mandana Khalili3, David E. Kleiner4, Amanda S. Hinerman2, Mark Sulkowski5, Raymond T. Chung6, Mamta K. Jain7, M auricio Lisker-Melman8, David K. Wong9, Marc G. Ghany4
1Section of Hepatology, Virginia Commonwealth University, Richmond, USA
2Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA
3University of California San Francisco, San Francisco, USA
4National Institutes of Health, Bethesda, USA
5Johns Hopkins University, Baltimore, USA
6Massachusetts General Hospital, Boston, USA
7UT Southwestern Medical Center, Dallas, USA
8Washington University School of Medicine, St. Louis, USA.
9University Health Network, Toronto, Canada

Tóm tắt

There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation. Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV–HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated. HBV–HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV–HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV–HIV. Negative predictive values were higher than positive predictive values for all scores in both groups. The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.

Tài liệu tham khảo

Younossi ZM, Stepanova M, Younossi Yet al Epidemiology of chronic liver diseases in the USA in the past three decades. Gut 2020;69:564–568. https://doi.org/10.1136/gutjnl-2019-318813. Epub 2019 Jul 31 Younossi Z, Anstee QM, Marietti M et al. Global burden of NAHEPATIC STEATOSIS and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20 Unalp-Arida A, Ruhl CE. Noninvasive fatty liver markers predict liver disease mortality in the U.S. population. Hepatology. 2016;63:1170–83. Lee YB, Ha Y, Chon YE et al. Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B. Clin Mol Hepatol. 2019;25:52–64 Chan AW, Wong GL, Chan HY et al. Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B. J Gastroenterol Hepatol. 2017;32:667–676 Suliman I, Abdelgelil N, Kassamali F, Hassanein TI. The effects of hepatic steatosis on the natural history of HBV infection. Clin Liver Dis. 2019;23:433–450 Khalili M, King W, Kleiner D, et al HBV-HIV Cohort Study of the Hepatitis B Research Network. Fatty Liver Disease in a Prospective North American Cohort of Adults with HIV and Hepatitis B Coinfection. Clin Infect Dis. 2020 Sep 1:ciaa1303. https://doi.org/10.1093/cid/ciaa1303. Online ahead of print. Khalili M, King W, Kleiner D. Nonalcoholic Fatty Liver Disease (NAFLD) and its Clinical and Metabolic Correlates in a Prospective North American Cohort with HIV-HBV Coinfection on Combined Anti-Retroviral Therapy (cART). Hepatology. 2019;70:1362A–1363A Shi FY, Jing L, Wenjun C et al. Fatty liver disease index: a simple screening tool to facilitate diagnosis of nonalcoholic fatty liver disease in the Chinese population. Dig Dis Sci. 2013;58:3326–3334. https://doi.org/10.1007/s10620-013-2774-y. Demir K, Akyuz F, Ozdil S et al. What is the reason of elevated alanine aminotransferase level in HBeAg negative patients with low viremia: NAFLD or chronic hepatitis? Ann Hepatol. 2007;6:92–96 Fricker ZP, Pedley A, Massaro JM. Liver fat is associated with markers of inflammation and oxidative stress in analysis of data from the Framingham heart study. Clin Gastroenterol Hepatol. 2019;17:1157–1164 Li Y, Liu L, Wang B, Wang J, Chen D. Simple steatosis is a more relevant source of serum inflammatory markers than omental adipose tissue. Clin Res Hepatol Gastroenterol. 2014;38:46–54 Otgonsuren M, Estep MJ, Hossain N et al. Single non-invasive model to diagnose non-alcoholic fatty liver disease (NAHEPATIC STEATOSIS) and non-alcoholic steatohepatitis (NASH). J Gastroenterol Hepatol. 2014;29:2006–13 Sviklāne L, Olmane E, Dzērve Z et al. Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes. J Gastroenterol Hepatol. 2018;33:270–276 Gastaldelli A, Kozakova M, Højlund K et al RISC Investigators. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology. 2009;49:1537–44. Paris R, Giral P, Khan JF et al LIDO Study Group. Fatty liver is an independent predictor of early carotid atherosclerosis. J Hepatol. 2016;65:95–102. Kozakova M, Palombo C, Eng MP, et al RISC Investigators. Fatty liver index, gamma-glutamyltransferase, and early carotid plaques. Hepatology. 2012;55:1406–15. Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56:422–433 World Health Organization Hepatitis B Fact Sheet. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b. Accessed November, 2020. Schwenzer NF, Springer F, Schraml C et al. Noninvasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol. 2009;51:433–445 Bril F, Ortiz-Lopez C, Lomonaco R et al Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Int. 2015;35:2139–46. Paige JS, Bernstein GS, Heba E, et al A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease. AJR Am J Roentgenol. 2017;208:W168-W177. Siddiqui MS, Vuppalanchi R, Van Natta ML et al NASH Clinical Research Network. Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2019;17:156–163. Karlas T, Petroff D, Garnov N et al. Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and 1H-MR spectroscopy. PLoS One. 2014;9:e91987 Bedogni G, Bellentani S, Miglioli L et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;2:33 Calori G, Lattuada G, Ragogna F et al. Fatty liver index and mortality: the Cremona study in the 15th year of follow-up. Hepatology. 2011;54:145–152 Lee JH, Kim D, Kim HJ. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010;42:503–508 Bedogni G, Kahn, Bellentani S, Tiribelli C, A simple index of lipid over accumulation is a good marker of liver steatosis. BMC Gastroenterol. 2010;25;10:98. Cuthbertson DJ, Weickert MO, Lythgoe D et al. External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals. Eur J Endocrinol. 2014;171:561–569 Stern C, Castera L. Non-invasive diagnosis of hepatic steatosis. Hepatol Int. 2017;11:70–78 Festi D, Schiumerini R, Marzi L et al. Review article: the diagnosis of non-alcoholic fatty liver disease—availability and accuracy of non-invasive methods. Aliment Pharmacol Ther. 2013;37:392–400 Zhang Z, Wang G, Kang K, Wu G, Wang P. Diagnostic accuracy and clinical utility of a new noninvasive index for hepatic steatosis in patients with hepatitis B virus infection. Sci Rep. 2016;6:32875 Ooi GJ, Earnest A, Kemp WW, Burton PR, Laurie C, Majeed A, Johnson N, McLean C, Roberts SK, Brown WA. Evaluating feasibility and accuracy of non-invasive tests for nonalcoholic fatty liver disease in severe and morbid obesity. Int J Obes (Lond). 2018;42:1900–1911 Fedchuk L, Nascimbeni F, Pais R et al. LIDO Study Group. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2014;40:1209–22. Kotronen A, Peltonen M, Hakkarainen A et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009;137:865–872 Wlazlo N, van Greevenbroek MM, Ferreira I, Bravenboer B, Stehouwer CD. The diagnosis of non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2012;35:204–5; author reply205–6.) Simental-Mendía LE, Simental-Mendía E, Rodríguez-Hernández H et al. The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women. Ann Hepatol. 2016;15:715–20. Petta S, Amato M, Cabibi D et al. Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1. Hepatology. 2010;52:1543–1552 Musso G, Cassader M, Gambino R. Diagnostic accuracy of adipose insulin resistance index and visceral adiposity index for progressive liver histology and cardiovascular risk in nonalcoholic fatty liver disease. Hepatology. 2012;56:788–789 Amato MC, Giordano C, Galia M et al.; for the AlkaMeSy Study Group. Visceral adiposity index (VAI): a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33:920–922 Guerrero-Romero F, Simental-Mendia LE, Gonzalez-Ortiz M, et al. The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95:3347–51. Sterling RK, Wahed AS, King WC, et al. and the HBV-HIV Cohort Study of the Hepatitis B Research Network. Spectrum of Liver Disease in Hepatitis B Virus (HBV) Patients Co-infected with Human Immunodeficiency Virus (HIV): Results of the HBV-HIV Cohort Study. Am J Gastroenterol. 2019;114:746–757. Ghany MG, Perrillo R, Li R et al. Hepatitis B Research Network; Hepatitis B Research Network. Characteristics of adults in the hepatitis B research network in North America reflect their country of origin and hepatitis B virus genotype. Clin Gastroenterol Hepatol. 2015;13:183–92. Di Bisceglie AM, Lombardero M, Teckman et al. Research Network HBRN. Determination of hepatitis B phenotype using biochemical and serological markers. J Viral Hepat. 2017;24:320–329. NIAAA. What is "low-risk" drinking? National Institute on Alcohol Abuse and Alcoholism. http://rethinkingdrinking.niaaa.nih.gov/IsYourDrinkingPatternRisky/WhatsLowRiskDrinking.asp, Accessed July 15, 2016 Kleiner DE, Brunt EM. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32:3–13 Chon YE, Jung KS, Kim SU, Park JY, Park YN, Kim DY, Ahn SH, Chon CY, Lee HW, Park Y, Han KH. Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population. Liver Int. 2014;34:102–109 Xu L, Lu W, Li P et al. A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B. Dig Liver Dis. 2017;49:910–917 Borman MA, Ladak F, Crotty P et al. The Fatty Liver Index has limited utility for the detection and quantification of hepatic steatosis in obese patients. Hepatol Int. 2013;7:592–599 Prati D, Taioli E, Zanella A et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137:1–10