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Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART)
Copyright policy )Elsevier BVStratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART)
Background: De novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD. Methods: This study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates. Findings: 319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m2 (OR: 4·238, 95% CI: 2·078–8·938; p < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362–10·899); p < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370–4·048; p = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315–24·981; p < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12–0·64; p = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101–0·945; p = 0·04). Interpretation: Steatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m2. While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis. Funding: There was no additional funding received for this project. All funders mentioned in the ‘declaration of interests’ section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Goethe University Frankfurt Germany
- University Hospital Bonn Germany
Microsoft Academic Graph classification: Comorbidity medicine.disease medicine Pre-exposure prophylaxis Lower risk Fatty liver business.industry business Internal medicine medicine.medical_specialty Transient elastography Proportional hazards model Body mass index Steatosis
General Medicine, Research Paper, Steatosis, Hiv, Nafld, Cap, cART, AST, aspartate aminotransferase, APRI, AST to platelet ratio index, BMI, body mass index, CAP, controlled attenuation parameter, ART, antiretroviral treatment, DAA, direct-acting antiviral, FAST, FibroScan-AST, FIB4, fibrosis-4, HCV, chronic hepatitis C, INSTI, integrase strand transfer inhibitors, NAFLD, Non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, PrEP, pre-exposure prophylaxis, PLHIV, people living with HIV, TAF, tenofovir-alafenamid, TDF, Tenofovir disoproxilfumarate, TE, transient elastography, Medicine (General), R5-920
General Medicine, Research Paper, Steatosis, Hiv, Nafld, Cap, cART, AST, aspartate aminotransferase, APRI, AST to platelet ratio index, BMI, body mass index, CAP, controlled attenuation parameter, ART, antiretroviral treatment, DAA, direct-acting antiviral, FAST, FibroScan-AST, FIB4, fibrosis-4, HCV, chronic hepatitis C, INSTI, integrase strand transfer inhibitors, NAFLD, Non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, PrEP, pre-exposure prophylaxis, PLHIV, people living with HIV, TAF, tenofovir-alafenamid, TDF, Tenofovir disoproxilfumarate, TE, transient elastography, Medicine (General), R5-920
Microsoft Academic Graph classification: Comorbidity medicine.disease medicine Pre-exposure prophylaxis Lower risk Fatty liver business.industry business Internal medicine medicine.medical_specialty Transient elastography Proportional hazards model Body mass index Steatosis
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- Goethe University Frankfurt Germany
- University Hospital Bonn Germany
Background: De novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD. Methods: This study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates. Findings: 319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m2 (OR: 4·238, 95% CI: 2·078–8·938; p < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362–10·899); p < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370–4·048; p = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315–24·981; p < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12–0·64; p = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101–0·945; p = 0·04). Interpretation: Steatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m2. While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis. Funding: There was no additional funding received for this project. All funders mentioned in the ‘declaration of interests’ section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.