Riassunto analitico
Background
In the era of modern ART, non-alcoholic fatty liver disease (NAFLD) has become a major metabolic concern in PLWH. In general population NAFLD was related to hypothyroidism, hypogonadism, insulin resistance, hypovitaminosis D and gh-igf-1 axis disorders, but this has never been investigated in HIV setting, therefore our objective was to investigate NAFLD and NAFLD with fibrosis (NAFLDWF) in PLWH with single endocrine disorders.
Methods
This was a cross-sectional study of patients attending Modena HIV Metabolic Clinic from 2018 to 2020. Hepatic fibrosis was assessed by measuring liver stiffness using transient elastography (TE), while the presence of hepatic steatosis was measured using integrated CAP. NAFLD was defined as CAP ≥ 248 dB/m, while NAFLDWF was defined as the simultaneous presence of hepatic steatosis (CAP ≥ 248 dB/m) and cirrhosis or significant liver fibrosis (LSM ≥ 7.1kPa). Logistic regressions were conducted to identify independent predictors for NAFLD and NAFLDWF and Bayesian Networks were applied to identify the structure of the relationship network among the different predictors and the outcomes through a Directed Acyclic Graph (DAG).
Results
We enrolled 1434 PLWH (75.52% males). Mean age was 54.15 ( 9.1) years, mean BMI 24.22 (IRQ=22.21-26.4), current median CD4=702/μL (IQR=541.5-900.5). HIV viral load undetectable in 98.33% of cases. NAFLD was diagnosed in 563 patients (39.26% of the total cohort).
In multivariable logistic regression analyses, independent predictors for NAFLD and NAFLDWF were insulin resistance, diabetes, hypovitaminosis D (also IGF-1 for NAFLDWF). Our DAG model regarding NAFLD showed that variables associated with NAFLD were age, insulin resistance and hypovitaminosis D. The association between hypothyroidism and NAFLD was mediated by insulin resistance, while other endocrine disorders studied in our study appeared not to be clearly associated with NAFLD. In our DAG model regarding NAFLDWF both diabetes and insulin resistance were correlated to NAFLDWF, while age was not directly associated with NAFLD with fibrosis, but the association was mediated by diabetes.
Conclusion
We described a dynamic interplay among various endocrine disorders and NAFLD showing that NAFLD in PLWH is driven by insulin resistance, hypovitaminosis D and age. The relationship between diabetes and NAFLD is peculiar in PLWH as we did not observe the direct relationship. However, we may argue that diabetes has potential effect on fibrosis progression in PLWH with NAFLD. Identifying pathways involved in the development of NAFLD can direct therapeutic interventions towards NAFLD. Further studies and larger datasets are needed to investigate this phenomenon.
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Abstract
Background
In the era of modern ART, non-alcoholic fatty liver disease (NAFLD) has become a major metabolic concern in PLWH. In general population NAFLD was related to hypothyroidism, hypogonadism, insulin resistance, hypovitaminosis D and gh-igf-1 axis disorders, but this has never been investigated in HIV setting, therefore our objective was to investigate NAFLD and NAFLD with fibrosis (NAFLDWF) in PLWH with single endocrine disorders.
Methods
This was a cross-sectional study of patients attending Modena HIV Metabolic Clinic from 2018 to 2020. Hepatic fibrosis was assessed by measuring liver stiffness using transient elastography (TE), while the presence of hepatic steatosis was measured using integrated CAP. NAFLD was defined as CAP ≥ 248 dB/m, while NAFLDWF was defined as the simultaneous presence of hepatic steatosis (CAP ≥ 248 dB/m) and cirrhosis or significant liver fibrosis (LSM ≥ 7.1kPa). Logistic regressions were conducted to identify independent predictors for NAFLD and NAFLDWF and Bayesian Networks were applied to identify the structure of the relationship network among the different predictors and the outcomes through a Directed Acyclic Graph (DAG).
Results
We enrolled 1434 PLWH (75.52% males). Mean age was 54.15 ( 9.1) years, mean BMI 24.22 (IRQ=22.21-26.4), current median CD4=702/μL (IQR=541.5-900.5). HIV viral load undetectable in 98.33% of cases. NAFLD was diagnosed in 563 patients (39.26% of the total cohort).
In multivariable logistic regression analyses, independent predictors for NAFLD and NAFLDWF were insulin resistance, diabetes, hypovitaminosis D (also IGF-1 for NAFLDWF). Our DAG model regarding NAFLD showed that variables associated with NAFLD were age, insulin resistance and hypovitaminosis D. The association between hypothyroidism and NAFLD was mediated by insulin resistance, while other endocrine disorders studied in our study appeared not to be clearly associated with NAFLD. In our DAG model regarding NAFLDWF both diabetes and insulin resistance were correlated to NAFLDWF, while age was not directly associated with NAFLD with fibrosis, but the association was mediated by diabetes.
Conclusion
We described a dynamic interplay among various endocrine disorders and NAFLD showing that NAFLD in PLWH is driven by insulin resistance, hypovitaminosis D and age. The relationship between diabetes and NAFLD is peculiar in PLWH as we did not observe the direct relationship. However, we may argue that diabetes has potential effect on fibrosis progression in PLWH with NAFLD. Identifying pathways involved in the development of NAFLD can direct therapeutic interventions towards NAFLD. Further studies and larger datasets are needed to investigate this phenomenon.
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