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Fatty Liver NAFLD in HIV: Higher
Prevalence, Metabolics & ALT/AST Predict
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Fatty Liver in HIV: higher prevalence, progresses faster, ALT/AST Predict- (02/02/22)
NASH Pipeline - (02/05/22)
Although awaiting additional data from trials, clinical assessment for fatty liver disease can be integrated into HIV care in most settings.
In this issue of AIDS, Maurice et al.[7] report a systematic review and meta-analysis of NAFLD, NASH, and hepatic fibrosis in HIV-monoinfected adults. Their findings are remarkable for several reasons. First, the analysis identifies a NAFLD prevalence in HIV-monoinfected patients of 35%, higher than prevalence estimates for the general population in North America, Europe, or worldwide [8,9]. In HIV-infected patients undergoing liver biopsy for further evaluation of elevated aminotransferases, NASH was seen is 45% and significant fibrosis in 22%. In similar studies in HIV-negative populations, NASH prevalence is 12-30% and significant fibrosis in 7% [10]. Though a number of factors can influence these rates, including race and ethnicity, and the prevalence of obesity and diabetes, taken together, these findings confirm that HIV-infected patients are at high risk for NASH, fibrosis, and related complications. Second, the meta-analysis confirms that metabolic factors, notably elevated BMI, insulin resistance, and dyslipidemia, confer the greatest increased risk of NAFLD in HIV infection, similar to the general population. CD4+ cell count was the only HIV-specific variable associated with NAFLD in the analysis, suggesting a role for immune recovery. Notably, age, time since HIV diagnosis, and duration of ART were not associated with increased risk.
NAFLD is common in HIV-monoinfected patients. Metabolic disorders are key risk factors of NAFLD independent of HIV parameters and predict its complications. The strong association between obesity and liver fibrosis in HIV-monoinfected patients supports the adipocentric concept of liver fibrogenesis in this population. This needs to be confirmed by additional studies. Our systematic review underlines the need for additional data on NAFLD in HIV infection as well as a better standardized assessment and management of the disease.
Based on radiological criteria, our review found a prevalence of NAFLD in HIV-monoinfected of 35%. Prevalence estimates in the general population vary significantly with diagnostic modality and study population. A recent systematic review has reported a worldwide prevalence of NAFLD diagnosed by imaging at 25%. Stratified by region, the prevalence in Asia, Europe and the United States America was 27, 24 and 24%, respectively [4]. However, the figure increases up to 70% in diabetic patients and over 90% among obese patients [25].
BMI (MD 2.92 95% CI 2.14-3.70, P < 0.00001), waist circumference [MD 8.05 (5.46-10.64) P < 0.00001], type 2 diabetes [OR 1.61 (1.09-2.39) P = 0.02], hypertension [OR 1.75 (1.27-2.41) P = 0.0006], high triglycerides [MD 61.52 (24.31-98.74) P = 0.001], high total cholesterol [MD 6.19 (0.93-11.45) P = 0.02], low HDL cholesterol [MD -4.21 (-6.82 to -1.59) P = 0.002], high LDL cholesterol [MD 5.80 (2.01-9.58) P = 0.003], high fasting glucose [MD 0.43 (0.18-0.68) P = 0.0007], high alanine aminotransferase [MD 15.98 (8.04-23.92) P < 0.0001], high aspartate aminotransferase (AST) [MD 5.27 (2.66-7.88) P < 0.0001] and high CD4+ T-cell count [MD 54.83 (11.55-98.11) P = 0.0]) were associated with NAFLD. Age, suppressed HIV viral load, duration of HIV infection, duration of HAART and CD4+ nadir were not associated with NAFLD (Fig. 3). There were insufficient data to meta-analyse the diagnosis of dyslipidaemia (based on the use of lipid-lowering drugs).
BMI (MD 1.38 95% CI 0.04-2.71 P = 0.04), fasting glucose [MD 0.80 (0.47-1.13) P < 0.00001] and AST level[MD 13.00 (4.34-21.65) P = 0.003] were associated with fibrosis, whereas male sex [OR 0.27 (0.15-0.51) P < 0.0001] and black ethnicity [OR 0.18 (0.08-0.44) P = 0.0002] were protective factors. CD4+ cell count (NASH) and duration of HIV infection (fibrosis) were the only HIV-specific variables with data for meta-analysis, neither of which were associated with the outcome of interest (Fig. 4). There was significant statistical heterogeneity for age (I2 = 85% P = 0.0002).
In HIV-negative populations, NAFLD and NASH are associated with increased cardiovascular and renal disease as well as all-cause mortality. Their findings are remarkable for several reasons. First, the analysis identifies a NAFLD prevalence in HIV-monoinfected patients of 35%, higher than prevalence estimates for the general population in North America, Europe, or worldwide. Although awaiting additional data from trials, clinical assessment for fatty liver disease can be integrated into HIV care in most settings.
Patients with metabolic risk factors, especially those with elevated aminotransferase levels, should be evaluated and managed following guidelines for the general population [17,18]. BMI is especially concerning given the rising prevalence of overweight and obesity in HIV-positive patients. weight gain was more strongly associated with increased risk of incident diabetes mellitus in HIV-positive vs. HIV-negative individuals (10 vs. 6% increased risk per 5-lb gain).. Perhaps the most important take-home message is that persistently elevated aminotransferase levels in HIV-infected patients should not be ignored or attributed to minor ART-related toxicities. They may be the first clue to significant liver disorders that can have major clinical consequences.
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