Modifications of Liver Stiffness and CXCL4, TGF-β1 and HGF Are Similar in HCV- and HIV/HCV-infected Patients After DAAs

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 11

PMID 33972651

Authors

Mercedes Marquez-Coello

Ana Arizcorreta

Maria Rodriguez-Pardo

Francisco Illanes-Alvarez

Denisse Marquez

Sara Cuesta-Sancho

Jose-Antonio Giron-Gonzalez

Affiliations

Soon will be listed here.

Abstract

The objective of this work was to identify predictive factors of fibrosis regression after direct antiviral agents (DAAs) in HCV-monoinfected and HIV/HCV-coinfected patients. This was a prospective study of HCV-monoinfected (n = 20), HIV/HCV-co-infected (n = 66) patients and healthy controls (n = 15). Patients had started DAAs and achieved sustained virological response. Liver stiffness (LS) and serum concentrations of profibrotic transforming growth factor (TGF)-β1 and CXC chemokine ligand 4 (CXCL4) and antifibrotic HGF hepatocyte growth factor (HGF) were analyzed at baseline (M0) and 12 months after starting DAAs (M12). A M12 LS achievement of ≤ 9.5 kPa was considered the cutoff point to discharge from a liver clinic. The LS decrease from M0 to M12 was 34%. No significant differences were observed in LS decline between HCV- and HIV/HCV-infected individuals. Changes of serum CXCL4, TGF-β1 and HGF levels did not correlate with LS improvement. 16 out from 56 patients (28%) with a baseline LS > 9.5 achieved a M12 LS ≤ 9.5. HCV-monoinfected and HIV/HCV coinfected patients experienced a significant reduction of LS after sustained virological response. This improvement did not correlate with changes in serum profibrotic or antifibrotic markers. A 29% of those with a baseline LS > 9.5 achieved a LS under this cutoff point.

References

Huh C, Factor V, Sanchez A, Uchida K, Conner E, Thorgeirsson S . Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A. 2004; 101(13):4477-82. PMC: 384772. DOI: 10.1073/pnas.0306068101. View

Sacchi P, Cima S, Corbella M, Comolli G, Chiesa A, Baldanti F . Liver fibrosis, microbial translocation and immune activation markers in HIV and HCV infections and in HIV/HCV co-infection. Dig Liver Dis. 2014; 47(3):218-25. DOI: 10.1016/j.dld.2014.11.012. View

Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C . Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet. 2019; 393(10179):1453-1464. DOI: 10.1016/S0140-6736(18)32111-1. View

Chau G, Lui W, Chi C, Chau Y, Li A, Kao H . Significance of serum hepatocyte growth factor levels in patients with hepatocellular carcinoma undergoing hepatic resection. Eur J Surg Oncol. 2007; 34(3):333-8. DOI: 10.1016/j.ejso.2006.12.007. View

Macias J, Berenguer J, Japon M, Giron J, Rivero A, Lopez-Cortes L . Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology. 2009; 50(4):1056-63. DOI: 10.1002/hep.23136. View

Panasiuk A, Zak J, Kasprzycka E, Janicka K, Prokopowicz D . Blood platelet and monocyte activations and relation to stages of liver cirrhosis. World J Gastroenterol. 2005; 11(18):2754-8. PMC: 4305910. DOI: 10.3748/wjg.v11.i18.2754. View

Vispo E, Barreiro P, del Valle J, Maida I, de Ledinghen V, Quereda C . Overestimation of liver fibrosis staging using transient elastography in patients with chronic hepatitis C and significant liver inflammation. Antivir Ther. 2009; 14(2):187-93. DOI: 10.1177/135965350901400214. View

Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera L, Perez-Guzman E . Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. Clin Infect Dis. 2003; 36(4):491-8. DOI: 10.1086/367643. View

Rallon N, Barreiro P, Soriano V, Garcia-Samaniego J, Lopez M, Benito J . Elevated TGF-β1 levels might protect HCV/ HIV-coinfected patients from liver fibrosis. Eur J Clin Invest. 2010; 41(1):70-6. DOI: 10.1111/j.1365-2362.2010.02381.x. View

10.

Abdelgawad M, El-Zakzok H, Salah M, El-Mezayen H . Diagnostic accuracy of hepatocyte growth factor, Fas/CD95 and Endostatin for non-invasive assessment of hepatic fibrosis in biopsy-proven hepatitis C virus patients. Infect Genet Evol. 2020; 85:104526. DOI: 10.1016/j.meegid.2020.104526. View

11.

Corma-Gomez A, Macias J, Tellez F, Freyre-Carrillo C, Morano L, Rivero-Juarez A . Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals. Clin Infect Dis. 2019; 71(9):2354-2362. DOI: 10.1093/cid/ciz1140. View

12.

Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M . Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005; 128(2):343-50. DOI: 10.1053/j.gastro.2004.11.018. View

13.

Neuman M, Benhamou J, Malkiewicz I, Ibrahim A, Valla D, Martinot-Peignoux M . Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis. J Viral Hepat. 2002; 9(2):134-40. DOI: 10.1046/j.1365-2893.2002.00343.x. View

14.

Singh S, Muir A, Dieterich D, Falck-Ytter Y . American Gastroenterological Association Institute Technical Review on the Role of Elastography in Chronic Liver Diseases. Gastroenterology. 2017; 152(6):1544-1577. DOI: 10.1053/j.gastro.2017.03.016. View

15.

Medina J, Caveda L, Sanz-Cameno P, Arroyo A, Martin-Vilchez S, Majano P . Hepatocyte growth factor activates endothelial proangiogenic mechanisms relevant in chronic hepatitis C-associated neoangiogenesis. J Hepatol. 2003; 38(5):660-7. DOI: 10.1016/s0168-8278(03)00053-9. View

16.

Zaldivar M, Pauels K, von Hundelshausen P, Berres M, Schmitz P, Bornemann J . CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology. 2010; 51(4):1345-53. DOI: 10.1002/hep.23435. View

17.

Marin-Serrano E, Rodriguez-Ramos C, Diaz-Garcia F, Martin-Herrera L, Fernandez-Gutierrez-Del-Alamo C, Giron-Gonzalez J . Hepatocyte growth factor and chronic hepatitis C. Rev Esp Enferm Dig. 2010; 102(6):365-71. DOI: 10.4321/s1130-01082010000600004. View

18.

Akhtar E, Manne V, Saab S . Cirrhosis regression in hepatitis C patients with sustained virological response after antiviral therapy: a meta-analysis. Liver Int. 2014; 35(1):30-6. DOI: 10.1111/liv.12576. View

19.

Hezode C, Castera L, Roudot-Thoraval F, Bouvier-Alias M, Rosa I, Roulot D . Liver stiffness diminishes with antiviral response in chronic hepatitis C. Aliment Pharmacol Ther. 2011; 34(6):656-63. DOI: 10.1111/j.1365-2036.2011.04765.x. View

20.

Lin Z, Xin Y, Dong Q, Wang Q, Jiang X, Zhan S . Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011; 53(3):726-36. DOI: 10.1002/hep.24105. View