Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Infectious Diseases and Therapy
Published in: Infectious Diseases and Therapy 1/2019

Open Access 01-03-2019 | Insulins | Review

A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?

Authors: Berend J. van Welzen, Tania Mudrikova, Ayman El Idrissi, Andy I. M. Hoepelman, Joop E. Arends

Published in: Infectious Diseases and Therapy | Issue 1/2019

Login to get access

Abstract

The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers. Both HIV-infection itself and combination antiretroviral therapy (cART) can contribute to the development of NAFLD/NASH in various ways. As ongoing HIV-related immune activation is associated with insulin resistance, early initiation of cART is needed to limit its duration. In addition, the use of early-generation nucleoside reverse transcriptase inhibitors and protease inhibitors is also associated with the development of NAFLD/NASH. Patients at risk should therefore receive antiretroviral drugs with a more favorable metabolic profile. Only weight reduction is considered to be an effective therapy for all patients with NAFLD/NASH, although certain drugs are available for specific subgroups. Since patients with NASH are at risk of developing liver cirrhosis and hepatocellular carcinoma, several non-antifibrotic and antifibrotic drugs are under investigation in clinical trials to broaden the therapeutic options. The epidemiology and etiology of NAFLD/NASH in HIV-positive patients is likely to change in the near future. Current guidelines recommend early initiation of cART that is less likely to induce insulin resistance, mitochondrial dysfunction and dyslipidemia. In contrast, as a result of increasing life expectancy in good health, this population will adopt the more traditional risk factors for NAFLD/NASH. HIV-treating physicians should be aware of the etiology, pathogenesis and treatment of NAFLD/NASH in order to identify and treat the patients at risk.
Literature
1.
Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet. 2014;384:258–71.PubMed
2.
3.
Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44:S6–9.PubMed
4.
Galvan FH, Bing EG, Fleishman JA, London AS, Caetano R, Burnam MA, et al. The prevalence of alcohol consumption and heavy drinking among people with HIV in the United States: results from the HIV Cost and Services Utilization Study. J Stud Alcohol. 2002;63:179–86.PubMed
5.
Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol. 2004;40:578–84.PubMed
6.
Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383:1749–61.PubMed
7.
Kleiner DE, Makhlouf HR. Histology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in adults and children. Clin Liver Dis. 2016;20:293–312.PubMed
8.
Aboud M, Elgalib A, Kulasegaram R, Peters B. Insulin resistance and HIV infection: a review. Int J Clin Pract. 2007;61:463–72.PubMed
9.
Araujo S, Banon S, Machuca I, Moreno A, Perez-Elias MJ, Casado JL. Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs. Eur J Endocrinol. 2014;171:545–54.PubMed
10.
Blas-Garcia A, Apostolova N, Esplugues JV. Oxidative stress and mitochondrial impairment after treatment with anti-HIV drugs: clinical implications. Curr Pharm Des. 2011;17:4076–86.PubMed
11.
12.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.PubMed
13.
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;28:1279–87.PubMed
14.
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;50:464–73.PubMedPubMedCentral
15.
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;47:250–7.PubMed
16.
Lui G, Wong VW-S, Wong GL-H, Chu WC-W, Wong C-K, Yung IMH, et al. Liver fibrosis and fatty liver in Asian HIV-infected patients. Aliment Pharmacol Ther. 2016;44:411–21.PubMed
17.
Nishijima T, Gatanaga H, Shimbo T, Komatsu H, Nozaki Y, Nagata N, et al. Traditional but not HIV-related factors are associated with nonalcoholic fatty liver disease in Asian patients with HIV-1 infection. PLoS ONE. 2014;9:e87596.PubMedPubMedCentral
18.
Vuille-Lessard E, Lebouche B, Lennox L, Routy J-P, 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;30:2635–43.PubMed
19.
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;31:1621–32.PubMed
20.
Ingiliz P, Valantin M-A, 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;49:436–42.PubMed
21.
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;60:1569–78.PubMedPubMedCentral
22.
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;47:182–7.PubMedPubMedCentral
23.
Lemoine M, Barbu V, Girard PM, Kim M, Bastard J-P, Wendum D, et al. Altered hepatic expression of SREBP-1 and PPARgamma is associated with liver injury in insulin-resistant lipodystrophic HIV-infected patients. AIDS. 2006;20:387–95.PubMed
24.
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;30:349–56.PubMedPubMedCentral
25.
Price JC, Seaberg EC, Latanich R, Budoff MJ, Kingsley LA, Palella FJJ, et al. Risk factors for fatty liver in the multicenter AIDS cohort study. Am J Gastroenterol. 2014;109:695–704.PubMedPubMedCentral
26.
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;31:365–73.PubMedPubMedCentral
27.
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 Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–23.PubMed
28.
Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495–500.PubMed
29.
Stern C, Castera L. Non-invasive diagnosis of hepatic steatosis. Hepatol Int. 2017;11:70–8.PubMed
30.
Khov N, Sharma A, Riley TR. Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:6821–5.PubMedPubMedCentral
31.
32.
Caussy C, Reeder SB, Sirlin CB, Loomba R. Noninvasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials. Hepatology. 2018;68:763–72.PubMed
33.
Sasso M, Beaugrand M, de Ledinghen V, Douvin C, Marcellin P, Poupon R, et al. Controlled attenuation parameter (CAP): a novel VCTE 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;36:1825–35.PubMed
34.
Wang Y, Fan Q, Wang T, Wen J, Wang H, Zhang T. Controlled attenuation parameter for assessment of hepatic steatosis grades: a diagnostic meta-analysis. Int J Clin Exp Med. 2015;8:17654–63.PubMedPubMedCentral
35.
Ajmera V, Loomba R. Can elastography differentiate isolated fatty liver from nonalcoholic steatohepatitis? Semin Liver Dis. 2018;38:14–20.PubMed
36.
Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11(1–16):vii.
37.
Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43:S99–112.PubMed
38.
Verma S, Jensen D, Hart J, Mohanty SR. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Liver Int. 2013;33:1398–405.PubMed
39.
Sorrentino P, Tarantino G, Conca P, Perrella A, Terracciano ML, Vecchione R, et al. Silent non-alcoholic fatty liver disease-a clinical-histological study. J Hepatol. 2004;41:751–7.PubMed
40.
Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology. 2012;55:447–54.PubMedPubMedCentral
41.
Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.PubMed
42.
Ryom L, Boesecke C, Bracchi M, Ambrosioni J, Pozniak A, Arribas J, et al. Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0. HIV Med. 2018;19:309–15.PubMedPubMedCentral
43.
44.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–57.PubMed
45.
Mellinger JL, Pencina KM, Massaro JM, Hoffmann U, Seshadri S, Fox CS, et al. Hepatic steatosis and cardiovascular disease outcomes: an analysis of the Framingham Heart Study. J Hepatol. 2015;63:470–6.PubMedPubMedCentral
46.
Crum-Cianflone N, Krause D, Wessman D, Medina S, Stepenosky J, Brandt C, et al. Fatty liver disease is associated with underlying cardiovascular disease in HIV-infected persons(*). HIV Med. 2011;12:463–71.PubMedPubMedCentral
47.
Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–48.PubMed
48.
Fruhbeck G, Mendez-Gimenez L, Fernandez-Formoso J-A, Fernandez S, Rodriguez A. Regulation of adipocyte lipolysis. Nutr Res Rev. 2014;27:63–93.PubMed
49.
Xia B, Cai GH, Yang H, Wang SP, Mitchell GA, Wu JW. Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice. PLoS Genet. 2017;13:e1007110.PubMedPubMedCentral
50.
Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115:1343–51.PubMedPubMedCentral
51.
Parks EJ. Dietary carbohydrate’s effects on lipogenesis and the relationship of lipogenesis to blood insulin and glucose concentrations. Br J Nutr. 2002;87(Suppl 2):S247–53.PubMed
52.
53.
Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–5.
54.
Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, et al. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology. 2004;40:185–94.PubMed
55.
56.
Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016;13:412–25.PubMed
57.
Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: Clinical impact. J Hepatol. 2018;68:268–79.PubMed
58.
Macias J, Rivero-Juarez A, Neukam K, Tellez F, Merino D, Frias M, et al. Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals. AIDS. 2015;29:1927–35.PubMed
59.
Vodkin I, Valasek MA, Bettencourt R, Cachay E, Loomba R. Clinical, biochemical and histological differences between HIV-associated NAFLD and primary NAFLD: a case-control study. Aliment Pharmacol Ther. 2015;41:368–78.PubMed
60.
Lebovics E, Thung SN, Schaffner F, Radensky PW. The liver in the acquired immunodeficiency syndrome: a clinical and histologic study. Hepatology. 1985;5:293–8.PubMed
61.
Glasgow BJ, Anders K, Layfield LJ, Steinsapir KD, Gitnick GL, Lewin KJ. Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS). Am J Clin Pathol. 1985;83:582–8.PubMed
62.
Mohammed SS, Aghdassi E, Salit IE, Avand G, Sherman M, Guindi M, et al. HIV-positive patients with nonalcoholic fatty liver disease have a lower body mass index and are more physically active than HIV-negative patients. J Acquir Immune Defic Syndr. 2007;45:432–8.PubMed
63.
Gutierrez AD, Balasubramanyam A. Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms, and management. Endocrine. 2012;41:1–10.PubMed
64.
Limone P, Biglino A, Valle M, Degioanni M, Paola Servato M, Berardi C, et al. Insulin resistance in HIV-infected patients: relationship with pro-inflammatory cytokines released by peripheral leukocytes. J Infect. 2003;47:52–8.PubMed
65.
Nicolau J, Lequerre T, Bacquet H, Vittecoq O. Rheumatoid arthritis, insulin resistance, and diabetes. Joint Bone Spine. 2017;84:411–6.PubMed
66.
Nou E, Lo J, Grinspoon SK. Inflammation, immune activation, and cardiovascular disease in HIV. AIDS. 2016;30:1495–509.PubMedPubMedCentral
67.
El-Sadr WM, Mullin CM, Carr A, Gibert C, Rappoport C, Visnegarwala F, et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med. 2005;6:114–21.PubMed
68.
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7.PubMed
69.
Duncan BB, Schmidt MI, Pankow JS, Ballantyne CM, Couper D, Vigo A, et al. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes. 2003;52:1799–805.PubMed
70.
Armah KA, McGinnis K, Baker J, Gibert C, Butt AA, Bryant KJ, et al. HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation. Clin Infect Dis. 2012;55:126–36.PubMedPubMedCentral
71.
Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74:1045–52.PubMed
72.
Constans J, Pellegrin JL, Peuchant E, Dumon MF, Pellegrin I, Sergeant C, et al. Plasma lipids in HIV-infected patients: a prospective study in 95 patients. Eur J Clin Invest. 1994;24:416–20.PubMed
73.
Zangerle R, Sarcletti M, Gallati H, Reibnegger G, Wachter H, Fuchs D. Decreased plasma concentrations of HDL cholesterol in HIV-infected individuals are associated with immune activation. J Acquir Immune Defic Syndr. 1994;7:1149–56.PubMed
74.
da Cunha J, Maselli LMF, Stern ACB, Spada C, Bydlowski SP. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: old and new drugs. World J Virol. 2015;4:56–77.PubMedPubMedCentral
75.
Dekkers CC, Westerink J, Hoepelman AIM, Arends JE. Overcoming obstacles in lipid-lowering therapy in patients with HIV—a systematic review of current evidence. AIDS Rev. 2018;20:205–19.PubMed
76.
Brown TT, Li X, Cole SR, Kingsley LA, Palella FJ, Riddler SA, et al. Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. AIDS. 2005;19:1375–83.PubMed
77.
Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JMAH, Miller MD, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004;292:191–201.PubMed
78.
Crane HM, Grunfeld C, Willig JH, Mugavero MJ, Van Rompaey S, Moore R, et al. Impact of NRTIs on lipid levels among a large HIV-infected cohort initiating antiretroviral therapy in clinical care. AIDS. 2011;25:185–95.PubMedPubMedCentral
79.
Dalakas MC, Illa I, Pezeshkpour GH, Laukaitis JP, Cohen B, Griffin JL. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med. 1990;322:1098–105.
80.
81.
Brinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet. 1999;354:1112–5.
82.
Gardner K, Hall PA, Chinnery PF, Payne BAI. HIV treatment and associated mitochondrial pathology: review of 25 years of in vitro, animal, and human studies. Toxicol Pathol. 2014;42:811–22.PubMed
83.
Kakuda TN, Brundage RC, Anderson PL, Fletcher CV. Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy. AIDS. 1999;13:2311–2.PubMed
84.
Baril J-G, Junod P, Leblanc R, Dion H, Therrien R, Laplante F, et al. HIV-associated lipodystrophy syndrome: a review of clinical aspects. Can J Infect Dis Med Microbiol. 2005;16:233–43.PubMedPubMedCentral
85.
Wei Y, Rector RS, Thyfault JP, Ibdah JA. Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J Gastroenterol. 2008;14:193–9.PubMedPubMedCentral
86.
Johnson AA, Ray AS, Hanes J, Suo Z, Colacino JM, Anderson KS, et al. Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase. J Biol Chem. 2001;276:40847–57.PubMed
87.
Birkus G, Hitchcock MJM, Cihlar T. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2002;46:716–23.PubMedPubMedCentral
88.
Lee GA, Rao M, Mulligan K, Lo JC, Aweeka F, Schwarz J-M, et al. Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. AIDS. 2007;21:2183–90.PubMedPubMedCentral
89.
Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275:20251–4.
90.
Vyas AK, Koster JC, Tzekov A, Hruz PW. Effects of the HIV protease inhibitor ritonavir on GLUT4 knock-out mice. J Biol Chem. 2010;285:36395–400.PubMedPubMedCentral
91.
Schutt M, Zhou J, Meier M, Klein HH. Long-term effects of HIV-1 protease inhibitors on insulin secretion and insulin signaling in INS-1 beta cells. J Endocrinol. 2004;183:445–54.PubMed
92.
Behrens G, Dejam A, Schmidt H, Balks HJ, Brabant G, Korner T, et al. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS. 1999;13:F63–70.PubMed
93.
Busti AJ, Bedimo R, Margolis DM, Hardin DS. Improvement in insulin sensitivity and dyslipidemia in protease inhibitor-treated adult male patients after switch to atazanavir/ritonavir. J Investig Med. 2008;56:539–44.PubMed
94.
Hui DY. Effects of HIV protease inhibitor therapy on lipid metabolism. Prog Lipid Res. 2003;42:81–92.PubMed
95.
Cahn PE, Gatell JM, Squires K, Percival LD, Piliero PJ, Sanne IA, et al. Atazanavir–a once-daily HIV protease inhibitor that does not cause dyslipidemia in newly treated patients: results from two randomized clinical trials. J Int Assoc Physicians AIDS Care (Chic). 2004;3:92–8.
96.
Ofotokun I, Na LH, Landovitz RJ, Ribaudo HJ, McComsey GA, Godfrey C, et al. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis. 2015;60:1842–51.PubMedPubMedCentral
97.
Overton ET, Arathoon E, Baraldi E, Tomaka F. Effect of darunavir on lipid profile in HIV-infected patients. HIV Clin Trials. 2012;13:256–70.PubMed
98.
Liang JS, Distler O, Cooper DA, Jamil H, Deckelbaum RJ, Ginsberg HN, et al. HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med. 2001;7:1327–31.PubMed
99.
den Boer MAM, Berbee JFP, Reiss P, van der Valk M, Voshol PJ, Kuipers F, et al. Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue. Arterioscler Thromb Vasc Biol. 2006;26:124–9.
100.
Maggi P, Bellacosa C, Carito V, Perilli F, Lillo A, Volpe A, et al. Cardiovascular risk factors in patients on long-term treatment with nevirapine- or efavirenz-based regimens. J Antimicrob Chemother. 2011;66:896–900.PubMed
101.
Tebas P, Sension M, Arribas J, Duiculescu D, Florence E, Hung C-C, et al. Lipid levels and changes in body fat distribution in treatment-naive, HIV-1-Infected adults treated with rilpivirine or Efavirenz for 96 weeks in the ECHO and THRIVE trials. Clin Infect Dis. 2014;59:425–34.PubMed
102.
Lazzarin A, Campbell T, Clotet B, Johnson M, Katlama C, Moll A, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet. 2007;370:39–48.PubMed
103.
Orkin C, Squires KE, Molina J-M, Sax PE, Wong W-W, Sussmann O, et al. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis Published Online First. 2018. https://​doi.​org/​10.​1093/​cid/​ciy540.
104.
Molina J-M, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018;5:e211–20.PubMed
105.
Quercia R, Roberts J, Martin-Carpenter L, Zala C. Comparative changes of lipid levels in treatment-naive, HIV-1-infected adults treated with dolutegravir vs. efavirenz, raltegravir, and ritonavir-boosted darunavir-based regimens over 48 weeks. Clin Drug Investig. 2015;35:211–9.PubMedPubMedCentral
106.
Macias J, Mancebo M, Merino D, Tellez F, Montes-Ramirez ML, Pulido F, et al. Changes in liver steatosis after switching from efavirenz to raltegravir among human immunodeficiency virus-infected patients with nonalcoholic fatty liver disease. Clin Infect Dis. 2017;65:1012–9.PubMed
107.
Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390:2063–72.PubMed
108.
Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink H-J, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiori. Lancet. 2017;390:2073–82.PubMed
109.
MacInnes A, Lazzarin A, Di Perri G, Sierra-Madero JG, Aberg J, Heera J, et al. Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HIV Clin Trials. 2011;12:24–36.PubMed
110.
Cooper DA, Cordery DV, Reiss P, Henry K, Nelson M, O’Hearn M, et al. The effects of enfuvirtide therapy on body composition and metabolic parameters over 48 weeks in the TORO body imaging substudy. HIV Med. 2011;12:31–9.PubMed
111.
Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16:797–808.
112.
Kralj D, Virovic Jukic L, Stojsavljevic S, Duvnjak M, Smolic M, Curcic IB. Hepatitis C virus, insulin resistance, and steatosis. J Clin Transl Hepatol. 2016;4:66–75.PubMedPubMedCentral
113.
Jackel-Cram C, Babiuk LA, Liu Q. Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. J Hepatol. 2007;46:999–1008.PubMed
114.
Abid K, Pazienza V, de Gottardi A, Rubbia-Brandt L, Conne B, Pugnale P, et al. An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation. J Hepatol. 2005;42:744–51.PubMed
115.
Kumar D, Farrell GC, Fung C, George J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology. 2002;36:1266–72.PubMed
116.
Wong VW-S, Wong GL-H, Chu WC-W, Chim AM-L, Ong A, Yeung DK-W, et al. Hepatitis B virus infection and fatty liver in the general population. J Hepatol. 2012;56:533–40.PubMed
117.
Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, et al. Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retroviruses. 2016;32:50–8.PubMedPubMedCentral
118.
Wong C, Gange SJ, Buchacz K, Moore RD, Justice AC, Horberg MA, et al. First occurrence of diabetes, chronic kidney disease, and hypertension among North American HIV-infected Adults, 2000–2013. Clin Infect Dis. 2017;64:459–67.PubMed
119.
Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51:121–9.PubMedPubMedCentral
120.
Dixon JB, Bhathal PS, Hughes NR, O’Brien PE. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology. 2004;39:1647–54.
121.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:365–7.
122.
Ascha MS, Hanouneh IA, Lopez R, Tamimi TA-R, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51:1972–8.PubMed
123.
EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 64:1388–1402.
124.
Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.PubMedPubMedCentral
125.
Aghamohammadzadeh N, Niafar M, Dalir Abdolahinia E, Najafipour F, Mohamadzadeh Gharebaghi S, Adabi K, et al. The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients. Ther Adv Endocrinol Metab. 2015;6:56–60.PubMedPubMedCentral
126.
Li Z, Sun M, Wang F, Shi J, Wang K. Association between pioglitazone use and the risk of bladder cancer among subjects with diabetes mellitus: a dose-response meta-analysis. Int J Clin Pharmacol Ther. 2017;55:210–9.PubMed
127.
Korhonen P, Heintjes EM, Williams R, Hoti F, Christopher S, Majak M, et al. Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries. BMJ. 2016;354:i3903.PubMedPubMedCentral
128.
Shouhed D, Steggerda J, Burch M, Noureddin M. The role of bariatric surgery in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expert Rev Gastroenterol Hepatol. 2017;11:797–811.PubMed
129.
Furuya CKJ, de Oliveira CPMS, de Mello ES, Faintuch J, Raskovski A, Matsuda M, et al. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol. 2007;22:510–4.PubMed
130.
Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795–807.PubMed
131.
Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018;320:379–96.PubMed
132.
French MA, King MS, Tschampa JM, da Silva BA, Landay AL. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4 + T cells. J Infect Dis. 2009;200:1212–5.PubMed
133.
Mendez-Lagares G, Romero-Sanchez MC, Ruiz-Mateos E, Genebat M, Ferrando-Martinez S, Munoz-Fernandez MA, et al. Long-term suppressive combined antiretroviral treatment does not normalize the serum level of soluble CD14. J Infect Dis. 2013;207:1221–5.PubMed
134.
Guihot A, Dentone C, Assoumou L, Parizot C, Calin R, Seang S, et al. Residual immune activation in combined antiretroviral therapy-treated patients with maximally suppressed viremia. AIDS. 2016;30:327–30.PubMed
135.
Crum-Cianflone N, Roediger MP, Eberly L, Headd M, Marconi V, Ganesan A, et al. Increasing rates of obesity among HIV-infected persons during the HIV epidemic. PLoS ONE. 2010;5:e10106.PubMedPubMedCentral
136.
Younossi ZM, Loomba R, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, et al. Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2018;68:361–71.PubMed
137.
Cariou B, Hanf R, Lambert-Porcheron S, Zair Y, Sauvinet V, Noel B, et al. Dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care. 2013;36:2923–30.PubMedPubMedCentral
138.
Ratziu V, Harrison SA, Francque S, Bedossa P, Lehert P, Serfaty L, et al. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-alpha and -delta, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150(1147–1159):e5.
139.
140.
Wang P-X, Ji Y-X, Zhang X-J, Zhao L-P, Yan Z-Z, Zhang P, et al. Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates. Nat Med. 2017;23:439–49.PubMed
141.
Budas G, Karnik S, Jonnson T, Shafizadeh T, Watkins SBD. Reduction of liver steatosis and fibrosis with an ASK1 inhibitor in a murine model of NASH is accomplished by improvements in cholesterol, bile acid and lipid metabolism. J Hepatol. 2016;64(Suppl):170.
142.
Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial. Hepatology. Published Online First. 2017. https://​doi.​org/​10.​1002/​hep.​29514.
143.
Sanyal MF, Abdelmalek AM, Caldwell S, Diehl MLS. Efficacy and safety of simtuzumab for the treatment of nonalcoholic steatohepatitis with bridging fibrosis or cirrhosis: results of two phase 2b, dose-ranging, randomized, placebo-controlled trials. J Hepatol. 2017;66:S54.
144.
145.
Safadi R, Konikoff FM, Mahamid M, Zelber-Sagi S, Halpern M, Gilat T, et al. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12(2085–91):e1.
146.
147.
Fourman LT, Czerwonka N, Feldpausch MN, Weiss J, Mamputu J-C, Falutz J, et al. Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV. AIDS. 2017;31:2253–9.PubMedPubMedCentral
148.
Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312:380–9.PubMedPubMedCentral
149.
Schwarz J-M, Mulligan K, Lee J, Lo JC, Wen M, Noor MA, et al. Effects of recombinant human growth hormone on hepatic lipid and carbohydrate metabolism in HIV-infected patients with fat accumulation. J Clin Endocrinol Metab. 2002;87:942.PubMed
Metadata
Title
A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?
Authors
Berend J. van Welzen
Tania Mudrikova
Ayman El Idrissi
Andy I. M. Hoepelman
Joop E. Arends
Publication date
01-03-2019
Publisher
Springer Healthcare
Published in
Infectious Diseases and Therapy / Issue 1/2019
Print ISSN: 2193-8229
Electronic ISSN: 2193-6382
DOI
https://doi.org/10.1007/s40121-018-0229-7

Other articles of this Issue 1/2019

Infectious Diseases and Therapy 1/2019 Go to the issue

Original Research

Evidence from an In Vitro Study: Is Oxacillin Plus Vancomycin a Better Choice for Heteroresistant Vancomycin-Intermediate Staphylococcus aureus?

Review

Public Health Considerations among People who Inject Drugs with HIV/HCV Co-Infection: A Review

Review

Biologic Markers of Antibiotic-Refractory Lyme Arthritis in Human: A Systematic Review

Original Research

Risk Factors for Bloodstream Infections Among an Urban Population with Skin and Soft Tissue Infections: A Retrospective Unmatched Case-Control Study

Original Research

Clostridium difficile-associated Diarrhea in Developing Countries: A Systematic Review and Meta-Analysis

Original Research

Cost-Effectiveness of the Pneumococcal Conjugate Vaccine (10- or 13-Valent) Versus No Vaccination for a National Immunization Program in Tunisia or Algeria

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits