Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients - 13/02/22
, David Rojo c , Isidoro Martínez a, b , Juan Berenguer b, d, e , Juan González-García b, f, g , Oscar Brochado-Kith a, b , Amanda Fernández-Rodríguez a, b , Cristina Díez b, d, e , Víctor Hontañon b, f, g , Leire Pérez-Latorre b, d, e , Rafael Micán b, f, g , Coral Barbas c , Salvador Resino a, b, ⁎, 1 , María Angeles Jiménez-Sousa a, b, ⁎, 1 on behalf of the ESCORIAL Study Group
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Abstract |
Background |
A better understanding of the evolution of cirrhosis after hepatitis C virus (HCV) clearance is essential since the reversal of liver injury may not happen. We aimed to assess the evolution of plasma metabolites after direct-acting antivirals (DAAs) therapy and their association with liver disease scores in HIV/HCV-coinfected patients with advanced HCV-related cirrhosis.
Methods |
We performed a prospective study in 49 cirrhotic patients who started DAAs therapy. Data and samples were collected at baseline and 36 weeks after SVR. Metabolomics analysis was carried out using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Inflammation-related biomarkers were analyzed using ProcartaPlex Immunoassays.
Results |
At 36 weeks after SVR, patients experienced significant decrease in taurocholic acid, 2,3-butanediol, and LPC(18:0); while several phosphatidylcholines (LPC(16:1), LPC(18:1), LPC(20:4), and PC(16:0/9:0(CHO))/PC(16:0/9:0(COH)), 2-keto-n-caproic acid/2-keto-isocaproic acid and N-methyl alanine increased, compared to baseline. The plasma decrease in taurocholic acid was associated with a reduction in Child-Turcotte-Pugh (CTP) (AMR=3.39; q-value=0.006) and liver stiffness measurement (LSM) (AMR=1.06; q-value<0.001), the plasma increase in LPC(20:4) was related to a reduction in LSM (AMR=0.98; q-value=0.027), and the rise of plasma 2-keto-n-caproic acid/2-keto-isocaproic acid was associated with a reduction in CTP (AMR=0.35; q-value=0.004). Finally, plasma changes in taurocholic acid were directly associated with inflammation-related biomarkers, while changes in LPC(20:4) were inversely associated.
Conclusions |
Plasma metabolomic profile changed after HCV clearance with all oral-DAAs in HIV/HCV-coinfected with advanced HCV-related cirrhosis. Changes in plasma levels of LPC (20: 4), 2-keto-n-caproic acid/2-keto-isocaproic acid, and taurocholic acid were related to improvements in cirrhosis scores and inflammatory status of patients.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | The metabolomic profile changes after SVR with DAAs in HIV/HCV-coinfected patients. |
• | The metabolite changes are linked to improvements in cirrhosis scores (CTP and LSM). |
• | Plasma taurocholic acid and LPC(20:4) levels are related to the inflammatory state. |
Abbreviations : HIV, HCV, DAAs, LPC, CTP, AMR, LSM, SVR, PCR, cART, INR, GC-MS, LC-MS, QC, MSD, ESI, PLS-DA, LOOCV, VIP, GLMM, MELD, FDR, PC, LPS, IL, sRANKL, OPG, PD, siCAM, IFN, svCAM, PAI, TNFRI, OxPL, BCAA, LPE
Keywords : Chronic hepatitis C, HIV, Cirrhosis, Metabolomics, DAAs therapy, HCV elimination
Plan
Vol 147
Article 112623- mars 2022 Retour au numéro
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