Nonalcoholic fatty liver disease and hepatic fibrosis among perinatally HIV-monoinfected Asian adolescents receiving antiretroviral therapy


Autoři: Tavitiya Sudjaritruk aff001;  Torsak Bunupuradah aff003;  Linda Aurpibul aff002;  Pope Kosalaraksa aff004;  Nia Kurniati aff005;  Jiratchaya Sophonphan aff003;  Panruethai Trinavarat aff006;  Pannee Visrutaratna aff007;  Jiraporn Srinakarin aff008;  Nataruks Chaijitraruch aff009;  Thanyawee Puthanakit aff003
Působiště autorů: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand aff001;  Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand aff002;  HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand aff003;  Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aff004;  Department of Child Health, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia aff005;  Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand aff006;  Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand aff007;  Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aff008;  Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand aff009;  Center of Excellence in Pediatric Infectious Diseases and Vaccine, Chulalongkorn University, Bangkok, Thailand aff010
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226375

Souhrn

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10–25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6–19.2) years and 10.5 (7.1–12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8–18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7–511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1–289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.

Klíčová slova:

Aminotransferases – Fatty liver – Fibrosis – Liver fibrosis – Obesity – Steatosis – Ultrasound imaging


Zdroje

1. Brady MT, Oleske JM, Williams PL, Elgie C, Mofenson LM, Dankner WM, et al. Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era. J Acquir Immune Defic Syndr. 2010; 53(1):86–94. doi: 10.1097/QAI.0b013e3181b9869f 20035164

2. Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006; 43(1):27–34. doi: 10.1097/01.qai.0000233310.90484.16 16878047

3. World Health Organization. Prevalence of obesity among children and adolescents, BMI>+2 standard deviation above the median (crude estimates) by WHO region. 2017 [cited 2019 July 19]. Available from: http://apps.who.int/gho/data/view.main.BMIPLUS2REGv?lang=en

4. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006; 118(4):1388–93. doi: 10.1542/peds.2006-1212 17015527

5. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002; 346(16):1221–31. doi: 10.1056/NEJMra011775 11961152

6. Crum-Cianflone N, Dilay A, Collins G, Asher D, Campin R, Medina S, et al. Nonalcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr. 2009; 50(5):464–73. doi: 10.1097/QAI.0b013e318198a88a 19225402

7. 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(2):250–7. doi: 10.1086/589294 18532884

8. Vuille-Lessard E, Lebouché 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(17):2635–2643. doi: 10.1097/QAD.0000000000001241 27603289

9. Sterling RK, Smith PG, Brunt EM. Hepatic steatosis in human immunodeficiency virus: a prospective study in patients without viral hepatitis, diabetes, or alcohol abuse. J Clin Gastroenterol. 2013; 47(2):182–7. doi: 10.1097/MCG.0b013e318264181d 23059409

10. McCullough AJ. Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol. 2006; 40 Suppl 1:S17–29.

11. Han SH, Kim SU, Kim CO, Jeong SJ, Park JY, Choi JY, et al. Abnormal liver stiffness assessed using transient elastography (Fibroscan®) in HIV-infected patients without HBV/HCV coinfection receiving combined antiretroviral treatment. PLoS One. 2013; 8(1):e52720. doi: 10.1371/journal.pone.0052720 23300987

12. Festi D, Schiumerini R, Marzi L, Di Biase AR, Mandolesi D, Montrone 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(4):392–400. doi: 10.1111/apt.12186 23278163

13. Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan®) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease—Where do we stand? World J Gastroenterol. 2016; 22(32):7236–51. doi: 10.3748/wjg.v22.i32.7236 27621571

14. Nobili V, Vizzutti F, Arena U, Abraldes JG, Marra F, Pietrobattista A, et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology. 2008; 48(2):442–8. doi: 10.1002/hep.22376 18563842

15. Kwok R, Tse YK, Wong GL, Ha Y, Lee AU, Ngu MC, et al. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease—the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther. 2014; 39(3):254–69. doi: 10.1111/apt.12569 24308774

16. Kruger FC, Daniels CR, Kidd M, Swart G, Brundyn K, van Rensburg C, et al. APRI: a simple bedside marker for advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH. S Afr Med J. 2011; 101(7):477–80. 21920102

17. Ferraioli G, Calcaterra V, Lissandrin R, Guazzotti M, Maiocchi L, Tinelli C, et al. Noninvasive assessment of liver steatosis in children: the clinical value of controlled attenuation parameter. BMC Gastroenterol. 2017; 17(1):61. doi: 10.1186/s12876-017-0617-6 28472948

18. Hwang JY, Yoon HM, Kim JR, Lee JS, Jung AY, Kim KM, et al. Diagnostic performance of transient elastography for liver fibrosis in children: A systematic review and meta-analysis. AJR Am J Roentgenol. 2018; 211(5):W257–66. doi: 10.2214/AJR.18.19535 30106615

19. Fitzpatrick E, Dhawan A. Noninvasive biomarkers in non-alcoholic fatty liver disease: current status and a glimpse of the future. World J Gastroenterol. 2014; 20(31):10851–63. doi: 10.3748/wjg.v20.i31.10851 25152587

20. Fitzpatrick E, Mitry RR, Quaglia A, Hussain MJ, DeBruyne R, Dhawan A. Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD. J Pediatr Gastroenterol Nutr. 2010; 51(4):500–6. doi: 10.1097/MPG.0b013e3181e376be 20808246

21. Feldstein AE, Alkhouri N, De Vito R, Alisi A, Lopez R, Nobili V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol. 2013; 108(9):1526–31. doi: 10.1038/ajg.2013.168 23752877

22. 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(10):1569–78. doi: 10.1093/cid/civ101 25681381

23. Morse CG, McLaughlin M, Proschan M, Koh C, Kleiner DE, Heller T, et al. Transient elastography for the detection of hepatic fibrosis in HIV-monoinfected adults with elevated aminotransferases on antiretroviral therapy. AIDS. 2015; 29(17):2297–302. doi: 10.1097/QAD.0000000000000841 26544701

24. Kapogiannis BG, Leister E, Siberry GK, Van Dyke RB, Rudy B, Flynn P, et al. Prevalence of and progression to abnormal noninvasive markers of liver disease (aspartate aminotransferase-to-platelet ratio index and Fibrosis-4) among US HIV-infected youth. AIDS. 2016; 30(6):889–98. doi: 10.1097/QAD.0000000000001003 26959353

25. Crum-Cianflone N, Collins G, Medina S, Asher D, Campin R, Bavaro M, et al. Prevalence and factors associated with liver test abnormalities among human immunodeficiency virus-infected persons. Clin Gastroenterol Hepatol. 2010; 8(2):183–91. doi: 10.1016/j.cgh.2009.09.025 19800985

26. Sterling RK, Chiu S, Snider K, Nixon D. The prevalence and risk factors for abdominal liver enzymes in HIV-positive patients without hepatitis B or C coinfections. Dig Dis Sci. 2008; 53(5):1375–82. doi: 10.1007/s10620-007-9999-6 17939038

27. Ingiliz P, Valantin MA, Duvivier C, Medja F, Dominguez S, Charlotte F, et al. Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy. Hepatology. 2009; 49(2):436–42. doi: 10.1002/hep.22665 19085967

28. Pruenglampoo S, Taejaroenkul S, Sirisanthana V. Relationships between waist-to-hip circumference ratio and gender, age and nutritional status in Thai children in Mueang District, Chiang Mai Province. Chiang Mai Med J. 2012; 51(2):29–37.

29. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120(16):1640–5. doi: 10.1161/CIRCULATIONAHA.109.192644 19805654

30. Centers for Disease Control and Prevention. BMI percentile calculator for child and teen English version. 2019 [cited 2019 July 19]. Available from: https://www.cdc.gov/healthyweight/bmi/calculator.html.

31. Barlow SE, Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007; 120 Suppl 4:S164–92.

32. Centers for Disease Control and Prevention. Defining adult overweight and obesity. [cited 2019 July 19]. Available from: https://www.cdc.gov/obesity/adult/defining.html.

33. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005; 115(4):e500–3. doi: 10.1542/peds.2004-1921 15741351

34. Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R, et al. Ultrasonographic quantitative estimation of hepatic steatosis in children with NAFLD. J Pediatr Gastroenterol Nutr. 2011; 53(2):190–5. doi: 10.1097/MPG.0b013e31821b4b61 21788761

35. Sasso M, Beaugrand M, de Ledinghen V, Douvin C, Marcellin P, Poupon R, et al. Controlled attenuation parameter (CAP): a novel VCTETM guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010; 36(11):1825–35. doi: 10.1016/j.ultrasmedbio.2010.07.005 20870345

36. McGoogan KE, Smith PB, Choi SS, Berman W, Jhaveri R. Performance of the AST-to-platelet ratio index as a noninvasive marker of fibrosis in pediatric patients with chronic viral hepatitis. J Pediatr Gastroenterol Nutr. 2010; 50(3):344–6. doi: 10.1097/MPG.0b013e3181aed725 20118806

37. 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(6):1317–25. doi: 10.1002/hep.21178 16729309

38. Doycheva I, Watt KD, Alkhouri N. Nonalcoholic fatty liver disease in adolescents and young adults: The next frontier in the epidemic. Hepatology. 2017; 65(6):2100–9. doi: 10.1002/hep.29068 28103626

39. Lombardi R, Sambatakou H, Mariolis I, Cokkinos D, Papatheodoridis GV, Tsochatzis EA. Prevalence and predictors of liver steatosis and fibrosis in unselected patients with HIV mono-infection. Dig Liver Dis. 2016; 48(12):1471–7. doi: 10.1016/j.dld.2016.08.117 27623186

40. Pembroke T, Deschenes M, Lebouché 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(4):801–8. doi: 10.1016/j.jhep.2017.05.011 28527666

41. Maurice JB, Patel A, Scott AJ, Patel K, Thursz M, Lemoine M. Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-monoinfection. AIDS. 2017; 31(11):1621–32. doi: 10.1097/QAD.0000000000001504 28398960

42. Lombardi R, Lever R, Smith C, Marshall N, Rodger A, Bhagani S, et al. Liver test abnormalities in patients with HIV mono-infection: assessment with simple noninvasive fibrosis markers. Ann Gastroenterol. 2017; 30(3):349–56. doi: 10.20524/aog.2017.0141 28469366

43. Lui G, Wong VW, Wong GL, Chu WC, Wong CK, Yung IM, et al. Liver fibrosis and fatty liver in Asian HIV-infected patients. Aliment Pharmacol Ther. 2016; 44(4):411–21. doi: 10.1111/apt.13702 27301337

44. Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients. 2013; 5(5):1544–60. doi: 10.3390/nu5051544 23666091

45. Merchante N, Pérez-Camacho I, Mira JA, Rivero A, Macías J, Camacho A, et al. Prevalence and risk factors for abnormal liver stiffness in HIV-infected patients without viral hepatitis coinfection: role of didanosine. Antivir Ther. 2010; 15(5):753–63. doi: 10.3851/IMP1612 20710057

46. Debes JD, Bohjanen PR, Boonstra A. Mechanisms of accelerated liver fibrosis progression during HIV infection. J Clin Transl Hepatol. 2016; 4(4):328–35. doi: 10.14218/JCTH.2016.00034 28097102

47. Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012; 56(6):1384–91. doi: 10.1016/j.jhep.2011.10.027 22326465

48. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005; 129(1):113–21. doi: 10.1053/j.gastro.2005.04.014 16012941

49. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012; 142(7):1592–609. doi: 10.1053/j.gastro.2012.04.001 22656328


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2019 Číslo 12