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Metabolomic profiling to predict histologic progression of liver fibrosis in patients with HIV and HBV coinfection: 20% have fibrosis progression in 3 years
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One in 5 With HIV/HBV Has Fibrosis Progression in 3 Years; Culprit Metabolites Identified
AASLD 2023, The Liver Meeting, November 10-14, 2023, Boston
Mark Mascolini
Almost 20% of 60 people coinfected with HIV and HBV had biopsy-confirmed liver fibrosis progression in 3 years [1]. Nearly everyone with and without worsening fibrosis had HIV and HBV loads below 200 copies/mL or IU/mL. Tzu-Hao Lee from Houston's Baylor College of Medicine and colleagues in the Hepatitis B Research Network (HBRN) [2] pinned down patterns of circulating bioactive metabolites linked to liver fibrosis progression.
HBRN collaborators collected clinical data, plasma samples, and liver biopsies when each person entered the study group. They did a second liver biopsy 3 or more years later. The researchers also collected plasma samples within 24 weeks of the first (baseline) biopsy to quantify 563 metabolites including fatty acids, amino acids, and bile acids. They adjusted metabolite expression by sex, age, body mass index (BMI), HIV and HBV load, HCV coinfection, and medications for HIV, diabetes, and abnormal lipids. They aimed to determine the initial rate of advanced liver fibrosis (Ishak score above 3) and progression (worsening Ishak score) from the first to the 3-year biopsy.
This analysis involved 108 people with HIV/HBV, 11 of whom had advanced fibrosis on their initial biopsy. Among 60 people with a second biopsy a median 3.6 years later, 11 (18%) had fibrosis progression. The 11 people with progression were a few years older than the 49 without progression (average 53.1 vs 50.5) and had a marginally lower BMI (22.5 vs 25.9 kg/m2)-but a strikingly higher though still normal average ALT liver enzyme (39.0 vs 24.0 U/L).
Progressors differed little from nonprogressors in other measures: sex, 100% and 95.8% male; HBV DNA below 200 IU/mL, 90.9% and 87.8%; HIV RNA below 200 copies, 100% and 95.9%; and CD4 count, 562 and 558. One or 2 people in each group had HCV coinfection or got treated for diabetes. About one quarter of each group took lipid-lowering drugs. A 2021 publication on the HBRN study group includes additional information, but no fibrosis progression could be detected at that point [3].
The metabolite analysis linked baseline serum levels of amino acids to advanced fibrosis at baseline (P = 0.00248). Baseline serum levels of 10 metabolites were significantly associated with liver fibrosis progression: triacylglycerols (P < 0.00001), alcohols (P = 0.00017), carboxylic acids (P = 0.00034), glycerophospholipids (P = 0.00037), fatty acids (P = 0.00091), biogenic amines (P = 0.00100), epoxide (P = 0.00377), hydroxyperoxide (P = 0.00622), sugars (P = 0.01573), and acylcarnitines (P = 0.02088).
The BRN team proposed that further work "could elucidate pathways and biomarkers predictive of liver disease in this high-risk group."
References
1. Lee TH, Sterling RK, Lucas J, et al. Metabolomic profiling to predict histologic progression of
liver fibrosis in patients with HIV and HBV coinfection. AASLD 2023, The Liver Meeting, November 10-14, 2023, Boston.
2. ClinicalTrials.gov. HBV-HIV Coinfection Research Network. ClinicalTrials.gov ID NCT01924455. https://clinicaltrials.gov/study/NCT01924455
3. Sterling RK, King WC, Khalili M, et al. A prospective study evaluating changes in histology, clinical and virologic outcomes in HBV-HIV co-infected adults in North America. Hepatology. 2021;74:1174-1189. doi: 10.1002/hep.31823. https://journals.lww.com/hep/abstract/2021/09000/a_prospective_study_evaluating_changes_in.6.aspx
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