Riassunto analitico
Background Demographic changes occurring in people living with HIV (PLWH) are similar to those of the general population, thanks to effective antiretroviral therapy. This scenario carries a heightened risk for non-infectious co-morbidities (NICM) and metabolic disorders such as non-alcoholic fatty liver disease (NAFLD) that should be considered as a multisystemic disease involving other organs. The evaluation of single comorbidities cannot entirely describe aging, therefore incorporation of geriatric tools could be useful in order to identify individuals more vulnerable to adverse outcomes and to provide suitable interventions. Frailty represents a more accurate measure of an individual’s biological age that may replace the traditional metric of chronological age. Objective of the study The objective of the study was to investigate the contribution of liver steatosis and significant fibrosis alone and in association (severe NAFLD) to frailty in PLWH in order to optimize the estimation of biological age. Methods Consecutive patients without hazardous alcohol intake attending Modena HIV Metabolic Clinic in 2018. Liver stiffness measurement (LSM) and associated controlled attenuation parameter (CAP) by transient elastography. Liver steatosis was diagnosed by CAP as follows: S0 (no steatosis; CAP<248 dB/m), S1 (mild steatosis; 248≥ CAP<268), S2 (moderate steatosis; 269≥ CAP<280), S3 (severe steatosis; CAP≥ 280) dB/m. Liver fibrosis was diagnosed by LSM as follows: stage F0-F1 (mild fibrosis, LSM<7.1 kPa), F2-F3 (significant fibrosis, 7.1>LSM<13), F4 (cirrhosis, LSM>13 kPa). Severe NAFLD was defined as the contemporary presence of liver steatosis (CAP≥248) and significant liver fibrosis or cirrhosis (stage >F2). Frailty was assessed using 36-Item frailty index (FI). We categorized PLWH according to FI score as fit (<0.25), frail (0.25-0.4), most frail (>0.4). Logistic regressions were built to explore the contribution of severe steatosis severe NAFLD to frailty using these covariates: age, male gender, diabetes and multimorbidity. Results We analyzed 707 PLWH. Mean age was 53.5 (8.15) years, 76.24% males, mean BMI 24.64 (4.21), 18.3% with type 2 diabetes, current median was CD4=700 μL (IQR=539-889), HIV-VL undetectable in 98.7% of cases. Severe NAFLD was present in 10.18%, frail and most-frail in 18.90 % and 3.92%, respectively.Severe NAFLD group showed a higher prevalence of obesity, waist circumference, elevated BMI, lower HDL cholesterol levels, higher total and LDL cholesterol levels, longer HIV duration and lower CD4 nadir, current use of NNRTI. Univariate analysis demonstrated that neurocognitive impairment (OR=5.08, 1.61-14.96), vitamin D insufficiency (OR=1.94, 1.18-3.24), obesity (OR=8.06, 4.44-14.55), diabetes (OR=3.24, 1.91-5.59) and osteoporosis (OR=0.37, 0.16-0.76) were statistically significant related to severe NAFLD. Logistic regression model showed as independent predictors for FI: age (OR=0.55, 0.35-0.86) male gender, (OR=0.55, 0.35-0.86), steatosis (OR=2.12, 1.3-3.45) and fibrosis (OR=1.95, 1.03-3.66) alone and in association (OR=9.19, 5.17-16.79), diabetes (OR=1.65, 0.99-2.74), multimorbidity (OR=2.46, 1.53-4.01). Conclusion This is the first study to explore the relationship between liver steatosis, severe NAFLD and frailty in PLWH. The main finding of this study is that severe NAFLD, but also steatosis alone increases the risk of frailty in PLWH by 9.2 and 2.1-fold, respectively. Frailty and severe NAFLD presented a positive linear association. Severe NAFLD contributes significantly to frailty and we may argue to suggest it as an indicator of metabolic age. From our study emerged that also steatosis alone was associated with frailty, implying that health care interventions that are proven to be effective, such as lifestyle changes, should be promoted in order to decrease the burden of frailty and NAFLD as well both in general population and in PLWH.
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