Dataset Information

Human Immunodeficiency Virus Is Associated With Elevated FibroScan-Aspartate Aminotransferase (FAST) Score.

ABSTRACT:

Background

Whether human immunodeficiency virus (HIV) infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-aspartate aminotransferase (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS ≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort.

Methods

Vibration-controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women with HIV (WWH) and 381 women without HIV (WWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score.

Results

Median age of WWH and WWOH was 51 years and 48 years, respectively. Most (90%) WWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WWH compared to WWOH (6.3% vs 1.8%, respectively; P = .001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (P = .002), and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (P < .001). In analysis limited to WWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score.

Conclusions

Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons with HIV are warranted.

SUBMITTER: Price JC

PROVIDER: S-EPMC10200299 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Human Immunodeficiency Virus Is Associated With Elevated FibroScan-Aspartate Aminotransferase (FAST) Score.

Price Jennifer C JC Ma Yifei Y Kuniholm Mark H MH Adimora Adaora A AA Fischl Margaret M French Audrey L AL Golub Elizabeth T ET Konkle-Parker Deborah D Minkoff Howard H Ofotokun Ighovwerha I Plankey Michael M Sharma Anjali A Tien Phyllis C PC

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20221201 12

<h4>Background</h4>Whether human immunodeficiency virus (HIV) infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-aspartate aminotransferase (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS ≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated ...[more]

PMID: 35511608

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Project description:BackgroundCurrently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their ability to assess disease progression or treatment effect is unknown. We aimed to assess the association between FAST score and histological endpoints.MethodsWe conducted a post-hoc analysis using data from a prior randomised, double-blind, placebo-controlled, phase 2b trial at 143 sites across 16 countries. Patients (aged 18-75 years) with biopsy-confirmed NASH, fibrosis stage 1-3, and a Non-alcoholic fatty liver disease Activity Score (NAS) ≥4 were enrolled between January 2017 and September 2018, and randomly assigned to receive once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg or placebo for 72 weeks. A subgroup analysis of patients with FAST score and histological data in the pooled semaglutide treatment and placebo arms at baseline and week 72 was performed. The original trial is registered at ClinicalTrials.gov, NCT02970942.FindingsA total of 122 patients were included in this post-hoc analysis (93 received semaglutide and 29 received placebo). FAST score reduction was associated with achieving the primary endpoint of NASH resolution without worsening of fibrosis in the pooled semaglutide group (area under the receiver operating curve 0.69; 95% confidence interval [CI] 0.58, 0.81). Mean FAST score reduction from baseline to week 72 was greatest in patients who met the primary endpoint vs those who did not in both the semaglutide (-0.40 [95% CI -0.84, 0.04] vs -0.22 [95% CI -0.74, 0.30] points; p = 0.002) and placebo groups (-0.25 [95% CI -0.72, 0.23] vs 0.00 [95% CI -0.50, 0.50] points; p = 0.047). Similarly, mean reductions in FAST score at week 72 were greater in those with NAS improvement vs those without in the semaglutide and placebo groups (≥1 point, -0.36 [95% CI -0.82, 0.11] vs -0.08 [95% CI -0.53, 0.38] points [p < 0.001] and -0.25 [95% CI -0.64, 0.14] vs -0.06 [95% CI -0.40, 0.53] points [p = 0.001]; ≥2 points, -0.40 [95% CI -0.86, 0.06] vs -0.14 [95% CI -0.56, 0.28] points [p < 0.001] and -0.29 [95% CI -0.67, 0.09] vs -0.05 [95% CI -0.40, 0.50] points; [p < 0.001]). A FAST score reduction of more than 0.22 points after semaglutide treatment was associated with meeting the primary endpoint (sensitivity 78%; specificity 60%; positive likelihood ratio 1.26; negative likelihood ratio 0.25; odds ratio 4.93).InterpretationThe potential of the FAST score as a non-invasive monitoring tool to identify histological changes following treatment requires further evaluation and validation.FundingNovo Nordisk A/S.

Project description:Vibration controlled transient elastography (FibroScan) is used to predict the severity of liver fibrosis and steatosis. In pediatrics, few studies have been performed directly comparing liver histologic features with FibroScan liver stiffness measurements (LSMs) and controlled attenuation parameters (CAPs). The FibroScan-aspartate aminotransferase (FAST) score, which predicts liver disease severity in adult nonalcoholic fatty liver disease (NAFLD), has not been analyzed in children. The aims of this study were to determine if LSM and CAP correlated with liver histologic fibrosis stage and steatosis grade, respectively, and to determine the predictive capacity of FAST in pediatric NAFLD. Research participants (n = 216) included those with FibroScan within 90 days of a liver biopsy. The ability of LSM, CAP, and FAST to predict severity of liver disease was analyzed by Spearman correlation, linear regression, and receiver operating characteristic and C statistic. Significant correlations were identified between LSM and Ishak fibrosis stages, with the strongest correlation occurring in the non-NAFLD group (Spearman r = 0.47, p < 0.0001). LSM adequately predicted Ishak stages F0-2 versus F3-F6 (area under the receiver operating characteristic curve [AUROC], 0.73 for all; 0.77 for non-NAFLD). CAP strongly predicted histologic steatosis grade (r = 0.84; p < 0.0001; AUROC, 0.98). FAST had acceptable discriminatory ability for significant liver disease (AUROC, 0.75). A FAST cutoff ≥0.67 had a sensitivity of 89% but a specificity of only 62% at determining significant liver disease. This study encompasses one of the largest pediatric cohorts describing the accuracy of FibroScan LSM and CAP to predict liver histologic fibrosis stage and steatosis grade, respectively. In order to determine specific LSM, CAP, and FAST cut-off values for fibrosis stages, steatosis grades, and significant liver disease, respectively, a much larger cohort is necessary and will likely entail the need for multicentered studies.

Project description:BackgroundThe FibroScan-AST (FAST) score was recently described to detect patients with nonalcoholic steatohepatitis (NASH) having elevated nonalcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 4) and significant fibrosis (≥ F2) on liver biopsy (NASH+ NAS ≥ 4 + F ≥ 2).AimThe aim of this study was to validate the FAST score in Indian patients with NAFLD and to derive optimal cut-offs.MethodsSixty patients with biopsy-proven NAFLD [men: 38 (63.3%), age 40 (32-52) years] with all parameters for assessing the FAST score within 3 months of liver histology were retrospectively analysed.ResultsHistological NASH was present in 17 patients (28.3%), while 11 (18.3%) patients had NASH + NAS ≥ 4 + F ≥ 2. The area under the curve (AUROC) of the FAST score for discriminating NASH + NAS ≥ 4 + F ≥ 2 was 0.81. Using cut-offs by Newsome et al, the rule-out cut-off (FAST: ≤ 0.35) had a negative predictive value (NPV) of 0.88 [sensitivity: 0.91, specificity: 0.14, negative likelihood ratio (LR): 0.64], while the rule-in cut-off (FAST: ≥ 0.67) had a positive predictive value (PPV) of 0.33 (sensitivity: 0.73, specificity: 0.67, positive LR: 2.22). Fifteen (25%) patients were correctly classified as per histology, while 28 (46.67%) patients fell in the grey zone. On recalculating the optimal cut-offs for our patients, the rule-out cut-off (FAST: ≤ 0.55) had an NPV of 0.95 (sensitivity: 0.90, specificity: 0.45, negative LR: 0.21), while the optimal rule-in cut-off (FAST: ≥ 0.78) had a PPV of 0.70 (sensitivity: 0.64, specificity 0.94, positive LR: 10.39). With these cut-offs, 27 (45%) patients fell in the grey zone and 29 (48.3%) were correctly classified as per histology, performing better than the cut-offs by Newsome et al (P < 0.001).ConclusionThe FAST score demonstrates good AUROC for detecting NASH with significant fibrosis and inflammation on histology. Cut-offs should be recalibrated based on prevalence of disease.Lay summaryIndia has a high burden of NAFLD with an estimated 25 million patients at potential risk for significant liver disease. Liver biopsy remains the gold standard for diagnosing NASH, although its application in routine clinical practice is limited. Noninvasive tests for the simultaneous detection of steatosis, inflammation and fibrosis are thus the need of the hour. The FAST score has been recently suggested for the noninvasive detection of NASH with significant fibrosis (≥ F2) and inflammation (NAS ≥ 4) on liver biopsy. We validated the utility of the FAST score for detecting NASH with significant fibrosis and inflammation on liver biopsy in Indian patients with NAFLD. This noninvasive, easy-to-use and nonproprietary FAST score can correctly classify disease severity in more than 50% patients. However, our results suggest that cut-offs should be recalibrated based on the anticipated prevalence of NASH + NAS ≥ 4 + F ≥ 2 in the given population.

Dataset Information

Human Immunodeficiency Virus Is Associated With Elevated FibroScan-Aspartate Aminotransferase (FAST) Score.

Background

Methods

Results

Conclusions

Publications

Human Immunodeficiency Virus Is Associated With Elevated FibroScan-Aspartate Aminotransferase (FAST) Score.

Similar Datasets

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