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Prevalence of nonalcoholic fatty liver disease using noninvasive techniques among children, adolescents, and youths living with HIV
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May 1 2022
Conclusion
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Larger and longitudinal studies addressing the evolution of liver disease in PHIV are needed. Clinicians should be aware of the risk and consider the need for screening. According to our results, the performance of scores based on clinical and analytical parameters for the identification of patients at risk is poor among youths. Despite their limitations, imaging techniques should be considered when available. As specific therapeutic measures are under research, intensifying prevention of metabolic risk factors since childhood seems mandatory to avoid future comorbidities.
Seventy-six participants (59.2% women) with a median of 19 years old (interquartile range: 15.5-25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; P = 0.02) by noninvasive imaging techniques.
Abstract
Objective:
The prevalence of subclinical liver abnormalities is high among people with HIV, but data regarding perinatally HIV-infected children and adolescents (PHIV) are scarce. Noninvasive image techniques offer an opportunity to address nonalcoholic fatty liver disease (NAFLD) in a population in which the scores validated for adults have not been tested.
Design:
Prospective cross-sectional study including PHIV and uninfected controls.
Methods:
Noninvasive imaging techniques for the diagnosis of NAFLD and/or fibrosis were performed, and four scores to predict NAFLD were evaluated.
Study design and participants
We carried out a prospective longitudinal study in two tertiary hospitals in Madrid, Spain. PHIV followed up in the Spanish National Network of Children and Adolescents Living with HIV (CoRISpe) were included. Uninfected siblings, partners, and adolescents who attended for postexposure prophylaxis were included as controls, matched by sex and age (±2 years). HIV participants and uninfected controls were recruited at Hospital Universitario La Paz and Hospital General Universitario Gregorio Maran on in Madrid (Spain) from June 2018 to December 2020.
Results:
Seventy-six participants (59.2% women) with a median of 19 years old (interquartile range: 15.5-25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; P = 0.02) by noninvasive imaging techniques. The performance of scores based on clinical and analytical parameters was very poor. Although nonsignificant, overweight was more common among participants with NAFLD, who had a significantly higher BMI. Differences in HIV-related parameters between the groups were nonsignificant, except for the CD4+/CD8+ T-cells ratio, decreased among PHIV diagnosed with NAFLD (P = 0.04).
Conclusions:
The prevalence of NAFLD was high (28.9%) among PHIV, and only partially explained by overweight and metabolic syndrome defining factors. The scores based on clinical and analytical parameters did not accurately identify participants at risk. Therefore, liver ultrasound assessment should be considered for the screening of NAFLD among PHIV in routine clinical practice.
Introduction
Since the introduction of antiretroviral therapy (ART), HIV infection has turned into a chronic condition [1]. As a result of this increase in life expectancy, the quality of life of people with HIV is threatened by comorbidities, including liver, kidney, cardiovascular disease, or cancer [2,3]. Worldwide, the liver disease remains one of the major causes of morbidity and mortality among people with HIV [4,5]. However, thanks to the efficacy of direct-acting antivirals (DAA) to treat the hepatitis C virus (HCV), the burden of diseases associated with this virus is decreasing dramatically in areas with access to treatment. Instead, the weight of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis on chronic liver disease is increasing.
NAFLD is defined as a fat accumulation higher than 5% in the liver, encompassing different stages of abnormal liver ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis [3,6]. The increase in NAFLD keeps pace with the increasing prevalence of obesity, insulin resistance [7,8] and other components of the metabolic syndrome [9,10], and is linked to mitochondrial dysfunction [11] and the cytopathic effect of HCV infection [12]. Some reports suggest that NAFLD/NASH will turn into the first cause of liver disease in the general population, both for children and adults, and the first cause of liver transplant in western countries in years to come [3,10]. However, the diagnosis of NAFLD/NASH is challenging, and although we have very sensitive and specific noninvasive methods for steatosis and fibrosis diagnosis in our daily clinical practice, to date, liver biopsy is considered the gold standard [13]. Scores combining clinical and laboratory parameters, such as the hepatic steatosis index (HSI) [14] or triglycerides and glucose (TyG) [15], have been validated in adults for screening and are able to predict NAFLD in the adult population. The AST to platelet ratio index [16] and the fibrosis-4 index and NAFLD fibrosis score [17] are recommended to detect fibrosis. None of these scores has been validated for children [18,19].
New, noninvasive imaging techniques as transient elastography (TE) or point shear wave elastography (p-SWE) offer the possibility to stratify the degrees of steatosis [13,20], assessing hepatic rigidity in a quantitative way and can be combined with the mentioned scores to improve accuracy. Their main limitation is a low sensitivity for the diagnosis of early stages of NAFLD/NASH, according to the European Association for the Study of the Liver [21]. However, up today, the use of noninvasive imaging techniques is recommended for the diagnosis and follow-up both in adults and children [16,21,22].
Among people with HIV, data suggest an increased prevalence of NAFLD [23-29] ranging from 28.8% [30] to 48.0% [31] when the diagnosis is based on imaging techniques to 57.1% [32] to 72.6% [25] when based on liver biopsy. Although the pathogenesis of NAFLD/NASH is unclear and most probably multifactorial, in the context of HIV infection, authors have suggested a potential deleterious effect of the chronic inflammation and activation of the immune system secondary to the virus [28,33-35] and its treatment [36,37]. In the unique population of perinatally HIV-infected children who face lifelong exposure to antiretroviral treatment and its metabolic consequences, and the deleterious effects of the virus itself [18] these phenomena have been described since birth [38-40]. However, data addressing the prevalence of NAFLD in this population are scarce [41]. The reliability of noninvasive assessment of NAFLD, including clinical scores in the population of adults living with HIV, has been the focus of intense research, but their use among children and youths has not been established [17]. Although hypertransaminasemia is quite common during follow-up in people with HIV its significance remains unknown [40].
The aim of this study was to determine the prevalence of subclinical liver abnormalities based on the use of noninvasive image techniques (TE/p-SWE) in perinatally HIV-infected children and youths (PHIV). Secondary objectives included the description of clinical, epidemiological, virological, and immunological determinants and evaluation of clinical scores for the diagnosis of NAFLD among children and youths.
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