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NASH or NAFLD Tied to ASCVD-and NASH
to Cognitive Impairment-With HIV
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IAS 2023, July 23-26, 2023. Brisbane
Mark Mascolini
Nonalcoholic steatohepatitis (NASH) almost tripled odds of a high 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in an analysis of 319 older adults with HIV in Thailand [1]. In the same population, NASH independently doubled the odds of cognitive impairment. These analyses also linked nonalcoholic fatty liver disease (NAFLD) to high 10-year ASCVD risk but not to cognitive impairment. The findings echo earlier reports of NASH and NAFLD’s impact on ASCVD and cognitive impairment in the general population [2,3].
Researchers with the HIV-NAT Thai Red Cross AIDS Research Centre and other centers conducted this study to explore possible associations between NASH or NAFLD and ASCVD or cognitive impairment. They noted that rising prevalence of obesity around the world has driven growing concern about liver disease in the general population as well as in people with HIV. NAFLD prevalence may be similar in people with HIV and the general population, the researchers added, but HIV infection could boost risk of severe NAFLD forms like NASH and significant fibrosis.
To address these issues, the HIV-NAT team and collaborators conducted a cross-sectional study analyzing 2017-2018 data from an aging HIV cohort in Bangkok, Thailand. Cohort members had to be at least 50 years old and taking stable antiretroviral therapy, and they had to have two FibroScan metrics: continued attenuation parameter (CAP) and liver stiffness measurement (LSM).
The investigators defined NAFLD as a CAP of at least 248 dBm, while advanced liver fibrosis meant an LSM at or above 9.5 kPa. The researchers defined NASH with significant fibrosis (at least F2) and inflammation (NAS at least 4) as a FibroScan-AST or FAST score at or above 0.67. A score below 25 on a validated Thai version of the Montreal Cognitive Assessment (MoCA) indicated cognitive impairment. Intermediate 10-year ASCVD risk ran from 7.5% to 19.9% and high risk ran from 20% up.
The 319 study participants had a median age of 54 (interquartile range [IQR] 52 to 60) and 63% were men. Median HIV infection duration stood at 19 years (IQR 15 to 21), and 98% of participants had a viral load below 50 copies. Median body mass index (BMI) measured 23 kg/m2, within the normal range. Seventy-four people (23%) had NAFLD and 33 (10%) had advanced liver fibrosis. Sixty-six people (21%) had NASH with significant fibrosis and inflammation.
The researchers determined that 192 people (60%) had cognitive impairment, 103 (32%) had intermediate 10-year ASCVD risk , and 34 (11%) had high 10-year ASCVD risk.
Logistic regression analysis adjusted for age, sex, BMI, employment status, education, income, smoking, alcohol, diabetes, hypertension, and depression linked NASH with significant fibrosis and inflammation to almost tripled odds of 20% or higher 10-year ASCVD risk (adjusted odds ratio [aOR] 2.83, 95% confidence interval [CI] 1.11 to 7.26). NASH was not associated with intermediate 10-year ASCVD risk. The same kind of analysis tied NAFLD to tripled odds of a 20% or higher ASCVD risk (aOR 2.94, 95% CI 1.08 to 7.97). (Other researchers reviewed additional studies tying NAFLD to ASCVD in the general population [2].)
NASH independently doubled odds of cognitive impairment (aOR 2.11, 95% CI 1.09 to 3.90). When the researchers also adjusted this analysis for HIV-related variables like CD4/CD8 ratio, HIV duration, and antiretroviral regimen, NASH still independently doubled odds of cognitive impairment (aOR 2.01, 95% CI 1.02 to 3.98 ). NAFLD or advanced liver fibrosis raised chances of cognitive impairment, but these associations did not reach statistical significance. (In 2022 a 7-study meta-analysis did tie NAFLD to cognitive impairment in the general population-OR 1.44, 95% CI: 1.17-1.78 [3]).
The HIV-NAT investigators reminded attendees of the limitations inherent in this kind of analysis-its cross-sectional format making it impossible to suggest causality, the possibility of uncontrolled confounders, lack of HIV-negative controls, need for more robust cognitive impairment testing, and lack of liver biopsy confirmation of NAFLD and NASH.
References
1. Han WM, Hiransuthikul A, Apornpong T, et al. Association between non-alcohol steatohepatitis with significant activity and fibrosis and neurocognitive impairment in people with HIV. IAS 2023, July 23-26, 2023. Brisbane. Abstract MOPEB13.
2. Zhang D, Mi Z, Peng J, et al. Nonalcoholic fatty liver disease as an emerging risk factor and potential intervention target for atherosclerotic cardiovascular diseases. Cardiovasc Pharmacol. 2023;81:327-335. doi: 10.1097/FJC.0000000000001418. https://pubmed.ncbi.nlm.nih.gov/36917556/
3. Wang L, Sang B , Zheng Z. Risk of dementia or cognitive impairment in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Front Aging Neurosci. 2022;14:985109. doi: 10.3389/fnagi.2022.985109. https://pubmed.ncbi.nlm.nih.gov/36204558/
IAS: Association between non-alcohol steatohepatitis with significant activity and fibrosis and neurocognitive impairment in people with HIV - (08/02/23)
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