Highlights
- •Prevalence of NAFLD is high in this cohort of PLWH according to non-invasive methods.
- •PLWH exposed to integrase strand transfer inhibitors showed a lower risk for NAFLD.
- •PLWH with NAFLD exposed to thymidine analogues had a higher risk for significant fibrosis.
- •A lower risk for significant fibrosis was observed in PLWH with NAFLD exposed to NNRTIs.
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities
in people living with HIV (PLWH). Factors that could lead to a higher prevalence of
NAFLD or ease the onset of fibrosis are unclear.
Methods
Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and
more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver
fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively.
Factors associated with both were analysed.
Results
A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36; these patients
had higher risk for significant fibrosis (OR 1.91; 95%CI 1.11–3.28). Factors associated
with NAFLD were body mass index (OR 2.05; 95%CI 1.94–2.16) and diabetes (OR 4.68;
95%CI 2.17–10.08), while exposure to integrase strand transfer inhibitors showed a
lower risk (OR 0.78; 95%CI 0.62–0.97). In patients with HSI>36, being female (OR 7.33;
95%CI 1.34–40), age (OR 1.22; 95%CI 1.11–1.34), body mass index (OR 1.35; 95%CI 1.18–1.54)
and exposure to thymidine analogues (OR 75.4, 95%CI 6.9–823.5) were associated with
a higher risk of significant fibrosis. However, exposure to non-nucleoside reverse
transcriptase inhibitors (OR 0.12, 95%CI 0.02–0.89) and time of exposure to protease
inhibitors (OR 0.97, 95%CI 0.95–1) showed a lower risk.
Conclusion
NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower
risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues
had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this
risk.
Keywords
List of abbreviations:
AIDS (Acquired immunodeficiency syndrome), ALT (Alanine aminotransferase), ART (Antiretroviral treatment), ARV (Antiretroviral), AST (Aspartate aminotransferase), BMI (Body mass index), CoRIS (Cohort of the spanish HIV research network), HBV (Hepatitis B virus), HCV (Hepatitis C virus), HIV (Human immunodeficiency virus), HSI (Hepatic steatosis index), IFG (Impaired fasted glucose), INSTIs (integrase strand transfer inhibitors), MSM (men who have sex with men), NAFLD (non-alcoholic fatty liver disease), NFS (NAFLD fibrosis score), NNRTIs (non-nucleoside reverse transcriptase inhibitors), NRTIs (nucleos(t)ide reverse transcriptase inhibitors), PI (protease inhibitors), PLWH (people living with HIV)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort.Lancet Public Heal. 2017; 2: e35-e46https://doi.org/10.1016/S2468-2667(16)30020-2
- Human immunodeficiency virus/hepatitis C virus coinfection in Spain: prevalence and patient characteristics.Open Forum Infect Dis. 2016; 3https://doi.org/10.1093/ofid/ofw059
- Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology. 2016; 64: 73-84https://doi.org/10.1002/HEP.28431
- Prevalence of and risk factors for hepatic steatosis in northern Italy.Ann Intern Med. 2000; 132: 112-117https://doi.org/10.7326/0003-4819-132-2-200001180-00004
- Health and economic burden of nonalcoholic fatty liver disease in the united states and its impact on veterans.Fed Pract. 2019; 36: 14-19
- Hepatocellular carcinoma in the absence of cirrhosis in united states veterans is associated with nonalcoholic fatty liver disease.Clin Gastroenterol Hepatol. 2016; 14: 124-131.e1https://doi.org/10.1016/j.cgh.2015.07.019
- Nonviral liver disease is the leading indication for liver transplant in the United States in persons living with human immunodeficiency virus.Am J Transplant. 2021; 21: 3148-3156https://doi.org/10.1111/AJT.16569
- Effect of a low free sugar diet vs usual diet on nonalcoholic fatty liver disease in adolescent boys: a randomized clinical trial.JAMA J Am Med Assoc. 2019; 321: 256-265https://doi.org/10.1001/jama.2018.20579
- The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis.J Hepatol. 2019; 71: 793-801https://doi.org/10.1016/j.jhep.2019.06.021
- Mechanisms of liver disease in patients infected with HIV.BMJ Open Gastroenterol. 2017; 4https://doi.org/10.1136/bmjgast-2017-000166
- Impaired lipid profile and insulin resistance in a cohort of Austrian HIV patients.J Infect Chemother. 2016; 22: 248-253https://doi.org/10.1016/j.jiac.2016.01.007
- A review of non-alcoholic fatty liver disease in HIV-infected patients: the next big thing?.Infect Dis Ther. 2019; 8: 33-50https://doi.org/10.1007/S40121-018-0229-7
- Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in patients with HIV.Lancet Gastroenterol Hepatol. 2017; 2: 211-223https://doi.org/10.1016/S2468-1253(16)30120-0
- Risk factors for fatty liver in the multicenter AIDS cohort study.Am J Gastroenterol. 2014; 109: 695-704https://doi.org/10.1038/ajg.2014.32
- Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-monoinfection.AIDS. 2017; 31: 1621-1632https://doi.org/10.1097/QAD.0000000000001504
- Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease.Gastroenterology. 2019; 156: 1264-1281.e4https://doi.org/10.1053/j.gastro.2018.12.036
- Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study.Hepatology. 2014; 60: 1920-1928https://doi.org/10.1002/hep.27362
- Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment.Radiology. 2006; 239: 105-112https://doi.org/10.1148/radiol.2391050361
- Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.J Hepatol. 2017; 66: 1022-1030https://doi.org/10.1016/J.JHEP.2016.12.022
- Incidence and predictors of hepatic steatosis and fibrosis by serum biomarkers in a large cohort of human immunodeficiency virus mono-infected patients.Open Forum Infect Dis. 2015; 2https://doi.org/10.1093/OFID/OFV015
- Diagnostic value of serological biomarkers for detection of non-alcoholic fatty liver disease (NAFLD) and/or advanced liver fibrosis in people living with HIV.HIV Med. 2021; 22: 445-456https://doi.org/10.1111/hiv.13060
- EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update.J Hepatol. 2021; 75: 659-689https://doi.org/10.1016/J.JHEP.2021.05.025
- [Spanish cohort of naïve HIV-infected patients (CoRIS): rationale, organization and initial results].Enferm Infecc Microbiol Clin. 2007; 25: 23-31https://doi.org/10.1157/13096749
- Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease.Dig Liver Dis. 2010; 42: 503-508https://doi.org/10.1016/j.dld.2009.08.002
- The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.Hepatology. 2007; 45: 846-854https://doi.org/10.1002/hep.21496
- Prediction versus aetiology: common pitfalls and how to avoid them.Nephrol Dial Transplant. 2017; 32: ii1-ii5https://doi.org/10.1093/NDT/GFW459
- Epidemiology of nonalcoholic fatty liver disease in Europe: a systematic review and meta-analysis.Ann Gastroenterol. 2021; 34https://doi.org/10.20524/aog.2021.0604
- Traditional but not HIV-related factors are associated with nonalcoholic fatty liver disease in asian patients with HIV-1 infection.PLoS ONE. 2014; 9https://doi.org/10.1371/journal.pone.0087596
- Hepatic steatosis in human immunodeficiency virus: a prospective study in patients without viral hepatitis, diabetes, or alcohol abuse.J Clin Gastroenterol. 2013; 47: 182-187https://doi.org/10.1097/MCG.0b013e318264181d
- The association between adherence to the Mediterranean diet and hepatic steatosis: cross-sectional analysis of two independent studies, the UK Fenland Study and the Swiss CoLaus Study.BMC Med. 2019; 17https://doi.org/10.1186/S12916-019-1251-7
- Mechanistic insights into antiretroviral drug-induced liver injury.Pharmacol Res Perspect. 2020; 8https://doi.org/10.1002/prp2.598
- Weight gain and integrase inhibitors.Curr Opin Infect Dis. 2020; 33: 10-19https://doi.org/10.1097/QCO.0000000000000616
- Hepatic steatosis associated with exposure to elvitegravir and raltegravir.Clin Infect Dis. 2021; https://doi.org/10.1093/cid/ciab057
- 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: 1012-1019https://doi.org/10.1093/cid/cix467
- Women have a lower risk of nonalcoholic fatty liver disease but a higher risk of progression vs men: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2021; 19: 61-71.e15https://doi.org/10.1016/J.CGH.2020.04.067
- Evaluating liver fibrosis by transient elastometry in patients With HIV-HCV coinfection and monoinfection.Hepat Mon. 2014; 14https://doi.org/10.5812/hepatmon.15426
- Liver stiffness change with HCV cure in HIV-infected patients on non-nucleoside analogues.J Antimicrob Chemother. 2021; https://doi.org/10.1093/JAC/DKAB157
- Lipidomics reveals reduced inflammatory lipid species and storage lipids after switching from EFV/FTC/TDF to RPV/FTC/TDF: a randomized Open-label trial.J Clin Med. 2020; 9: 1246https://doi.org/10.3390/jcm9051246
- Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells.Gut. 2020; 69: 920-932https://doi.org/10.1136/gutjnl-2019-318372
- HIV protease inhibitors and insulin resistance: lessons from in-vitro, rodent and healthy human volunteer models.Curr Opin HIV AIDS. 2008; 3: 660-665https://doi.org/10.1097/COH.0b013e3283139134
Article info
Publication history
Published online: February 08, 2023
Accepted:
January 21,
2023
Received in revised form:
January 19,
2023
Received:
October 21,
2022
Identification
Copyright
© 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
