Riassunto analitico
Background: Metabolic associated fatty liver disease (MAFLD) represents a recently new proposed definition for the Non-Alcoholic Fatty Liver Disease (NAFLD), based on positive and inclusionary criteria rather than negative and exclusionary ones. Very few studies analyzed the HIV infection in the current debate over the change of terminology. Therefore, our primary objective was to characterize MAFLD in comparison to NAFLD, determining prevalence and predictors of both conditions. Our secondary objective was to describe progression of NAFLD and MAFLD towards significant fibrosis in people living with HIV (PLWH).
Methods: Two prospective cohorts comprising PLWH on stable antiretroviral therapy were evaluated. For the longitudinal study, PLWH with at least two visits were included. NAFLD was defined as hepatic steatosis in absence of excessive alcohol intake and/or hepatic viral infections, MAFLD was defined as hepatic steatosis in presence of at least one of the following: overweight/obesity (BMI >25 kg/m2), type 2 diabetes mellitus, or PLWH without diabetes and BMI <25 kg/m2 and at least two metabolic risk factors. Transient elastography was used to diagnose both steatosis (if Controlled Attenuation Parameter, CAP >248 dB/m) and significant fibrosis (liver stiffness > 7,1 kPa). Predictors of NAFLD and MAFLD were explored in logistic regression, while multi-state Markov models were used to describe progression and/or regression of NAFLD/MAFLD and liver fibrosis.
Results: A total of 1947 PLWH were included in the cross-sectional study (mean age 54 years, 74% males, median HIV duration 21 years, median current CD4 703, 98% with undetectable HIV viral load, current ART exposure to InSTI 53%, PI/c 25%, 32% NNRTI). PLWH with BMI >25 kg/m2 were 23,4% and with diabetes 49,5%. NAFLD was diagnosed in 618/1714 (36,1%) PLWH, after excluding excessive alcohol intake (1,8%), HBV (1,2%) and HCV (9,2%) infections. MAFLD was diagnosed in 648 (33,3%) PLWH. Prevalence of significant liver fibrosis differed across the groups: 9,9% in no NAFLD-no MAFLD, 9,3% in NAFLD only, 26,5% in NAFLD/MAFLD overlap, 48% in MAFLD with diabetes and overweight/obesity, and 16,7% in lean MAFLD. Male sex, higher CD4, triglycerides and BMI were associated with NAFLD/MAFLD. Significant liver fibrosis was associated with MAFLD with diabetes and overweight/obesity.
Regarding the secondary objective, a total of 888 PLWH were included in the longitudinal study (mean age 54,4 years, 77% male sex, mean follow-up time of two years). NAFLD was diagnosed in 285 (42,9%) PLWH, after excluding excessive alcohol intake and/or hepatic viral infection, and MAFLD in 305 (34,3%). In particular, MAFLD with BMI >25 kg/m2 was diagnosed in 244 (27,5%), MAFLD with diabetes in 86 (9,7%) and lean MAFLD in 33 (3.7%). Markov models showed that PLWH with BMI >25 kg/m2 had the higher probability of MAFLD and liver fibrosis progression, while PLWH with lean MAFLD had a higher probability of MAFLD regression and PLWH with MAFLD and diabetes had a higher probability of fibrosis regression.
Conclusions: PLWH showed a substantial overlap between NAFLD and MAFLD, but MAFLD with diabetes and/or overweight/obesity presents a higher risk of significant liver fibrosis. HIV-related and metabolic variables were independent predictors of NAFLD/MAFLD. The use of the new MAFLD diagnosis criteria in PLWH is more useful to evaluate PLWH needing an advanced screening and surveillance for their metabolic risk factors and liver fibrosis development.
Markov models represent dynamic developments of liver steatosis and/or fibrosis over a mean period of time of two years. MAFLD main criteria could be used in clinical practice to assess PLWH risk of progression of steatosis/fibrosis and related hepatic adverse outcomes.
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Abstract
Background: Metabolic associated fatty liver disease (MAFLD) represents a recently new proposed definition for the Non-Alcoholic Fatty Liver Disease (NAFLD), based on positive and inclusionary criteria rather than negative and exclusionary ones. Very few studies analyzed the HIV infection in the current debate over the change of terminology. Therefore, our primary objective was to characterize MAFLD in comparison to NAFLD, determining prevalence and predictors of both conditions. Our secondary objective was to describe progression of NAFLD and MAFLD towards significant fibrosis in people living with HIV (PLWH).
Methods: Two prospective cohorts comprising PLWH on stable antiretroviral therapy were evaluated. For the longitudinal study, PLWH with at least two visits were included. NAFLD was defined as hepatic steatosis in absence of excessive alcohol intake and/or hepatic viral infections, MAFLD was defined as hepatic steatosis in presence of at least one of the following: overweight/obesity (BMI >25 kg/m2), type 2 diabetes mellitus, or PLWH without diabetes and BMI <25 kg/m2 and at least two metabolic risk factors. Transient elastography was used to diagnose both steatosis (if Controlled Attenuation Parameter, CAP >248 dB/m) and significant fibrosis (liver stiffness > 7,1 kPa). Predictors of NAFLD and MAFLD were explored in logistic regression, while multi-state Markov models were used to describe progression and/or regression of NAFLD/MAFLD and liver fibrosis.
Results: A total of 1947 PLWH were included in the cross-sectional study (mean age 54 years, 74% males, median HIV duration 21 years, median current CD4 703, 98% with undetectable HIV viral load, current ART exposure to InSTI 53%, PI/c 25%, 32% NNRTI). PLWH with BMI >25 kg/m2 were 23,4% and with diabetes 49,5%. NAFLD was diagnosed in 618/1714 (36,1%) PLWH, after excluding excessive alcohol intake (1,8%), HBV (1,2%) and HCV (9,2%) infections. MAFLD was diagnosed in 648 (33,3%) PLWH. Prevalence of significant liver fibrosis differed across the groups: 9,9% in no NAFLD-no MAFLD, 9,3% in NAFLD only, 26,5% in NAFLD/MAFLD overlap, 48% in MAFLD with diabetes and overweight/obesity, and 16,7% in lean MAFLD. Male sex, higher CD4, triglycerides and BMI were associated with NAFLD/MAFLD. Significant liver fibrosis was associated with MAFLD with diabetes and overweight/obesity.
Regarding the secondary objective, a total of 888 PLWH were included in the longitudinal study (mean age 54,4 years, 77% male sex, mean follow-up time of two years). NAFLD was diagnosed in 285 (42,9%) PLWH, after excluding excessive alcohol intake and/or hepatic viral infection, and MAFLD in 305 (34,3%). In particular, MAFLD with BMI >25 kg/m2 was diagnosed in 244 (27,5%), MAFLD with diabetes in 86 (9,7%) and lean MAFLD in 33 (3.7%). Markov models showed that PLWH with BMI >25 kg/m2 had the higher probability of MAFLD and liver fibrosis progression, while PLWH with lean MAFLD had a higher probability of MAFLD regression and PLWH with MAFLD and diabetes had a higher probability of fibrosis regression.
Conclusions: PLWH showed a substantial overlap between NAFLD and MAFLD, but MAFLD with diabetes and/or overweight/obesity presents a higher risk of significant liver fibrosis. HIV-related and metabolic variables were independent predictors of NAFLD/MAFLD. The use of the new MAFLD diagnosis criteria in PLWH is more useful to evaluate PLWH needing an advanced screening and surveillance for their metabolic risk factors and liver fibrosis development.
Markov models represent dynamic developments of liver steatosis and/or fibrosis over a mean period of time of two years. MAFLD main criteria could be used in clinical practice to assess PLWH risk of progression of steatosis/fibrosis and related hepatic adverse outcomes.
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