Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents

Hae Won Yoo, Jun Yong Park, Sang Gyune Kim, Young Kul Jung, Sae Hwan Lee, Moon Young Kim, Dae Won Jun, Jae Young Jang, Jin Woo Lee, Oh Sang Kwon, Hae Won Yoo, Jun Yong Park, Sang Gyune Kim, Young Kul Jung, Sae Hwan Lee, Moon Young Kim, Dae Won Jun, Jae Young Jang, Jin Woo Lee, Oh Sang Kwon

Abstract

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN.Clinical trials registration: ClinicalTrials.gov (NCT02865369).

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
Study design and selection of patients.
Figure 2
Figure 2
(a) Comparison of changes in liver stiffness, APRI, and FIB-4 index. (b) Distribution of fibrosis stage across different time points.

References

    1. Sangiovanni A, et al. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology. 2006;43:1303–1310. doi: 10.1002/hep.21176.
    1. Singal, A. G., Volk, M. L., Jensen, D., Di Bisceglie, A. M. & Schoenfeld, P. S. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin. Gastroenterol. Hepatol.8, 280–288. 10.1016/j.cgh.2009.11.018 (2010).
    1. Gotte M, Feld JJ. Direct-acting antiviral agents for hepatitis C: structural and mechanistic insights. Nat. Rev. Gastroenterol. Hepatol. 2016;13:338–351. doi: 10.1038/nrgastro.2016.60.
    1. Camma C, et al. Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data. Hepatology. 2004;39:333–342. doi: 10.1002/hep.20073.
    1. Poynard T, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002;122:1303–1313. doi: 10.1053/gast.2002.33023.
    1. Carmona I, Cordero P, Ampuero J, Rojas A, Romero-Gomez M. Role of assessing liver fibrosis in management of chronic hepatitis C virus infection. Clin. Microbiol. Infect. 2016;22:839–845. doi: 10.1016/j.cmi.2016.09.017.
    1. Martinez SM, Crespo G, Navasa M, Forns X. Noninvasive assessment of liver fibrosis. Hepatology. 2011;53:325–335. doi: 10.1002/hep.24013.
    1. Schmoyer, C. J., Kumar, D., Gupta, G. & Sterling, R. K. Diagnostic Accuracy of Noninvasive Tests to Detect Advanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage Renal Disease. Clin. Gastroenterol. Hepatol.18, 2332–2339. 10.1016/j.cgh.2020.02.019 (2020).
    1. Patel K, Sebastiani G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Rep. 2020;2:100067. doi: 10.1016/j.jhepr.2020.100067.
    1. European Association for Study of, L. & Asociacion Latinoamericana para el Estudio del, H. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J. Hepatol.63, 237–264. 10.1016/j.jhep.2015.04.006 (2015).
    1. Degos F, et al. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: A multicenter prospective study (the FIBROSTIC study) J. Hepatol. 2010;53:1013–1021. doi: 10.1016/j.jhep.2010.05.035.
    1. Castera L, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343–350. doi: 10.1053/j.gastro.2004.11.018.
    1. Zarski JP, et al. Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: The ANRS HCEP-23 study. J. Hepatol. 2012;56:55–62. doi: 10.1016/j.jhep.2011.05.024.
    1. Wai CT, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–526. doi: 10.1053/jhep.2003.50346.
    1. Sterling RK, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–1325. doi: 10.1002/hep.21178.
    1. Poster Session 2: Advances in Imaging and Noninvasive Markers of Fibrosis; Bile Acids, Cholangiocyte Biology, and Experimental Cholestasis. 62, 594A-624A. 10.1002/hep.28218 (2015).
    1. Team, R. C. R: A Language and Environment for Statistical Computing. (2020).
    1. Pons M, et al. Non-invasive prediction of liver-related events in patients with HCV-associated compensated advanced chronic liver disease after oral antivirals. J. Hepatol. 2020;72:472–480. doi: 10.1016/j.jhep.2019.10.005.
    1. Calvaruso V, Craxi A. Hepatic benefits of HCV cure. J. Hepatol. 2020;73:1548–1556. doi: 10.1016/j.jhep.2020.08.006.
    1. Sangiovanni A, et al. Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis. J. Hepatol. 2020;73:593–602. doi: 10.1016/j.jhep.2020.03.030.
    1. Waziry R, et al. Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression. J. Hepatol. 2017;67:1204–1212. doi: 10.1016/j.jhep.2017.07.025.
    1. Li DK, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study. Hepatology. 2018;67:2244–2253. doi: 10.1002/hep.29707.
    1. Nahon, P. et al. Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs. Gastroenterology155, 1436–1450 e1436. 10.1053/j.gastro.2018.07.015 (2018).
    1. Fernandes FF, et al. Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response. J. Gastroenterol. Hepatol. 2019;34:2187–2195. doi: 10.1111/jgh.14707.
    1. Dolmazashvili E, et al. Regression of liver fibrosis over a 24-week period after completing direct-acting antiviral therapy in patients with chronic hepatitis C receiving care within the national hepatitis C elimination program in Georgia: results of hepatology clinic HEPA experience. Eur. J. Gastroenterol. Hepatol. 2017;29:1223–1230. doi: 10.1097/MEG.0000000000000964.
    1. Knop V, et al. Regression of fibrosis and portal hypertension in HCV-associated cirrhosis and sustained virologic response after interferon-free antiviral therapy. J. Viral Hepat. 2016;23:994–1002. doi: 10.1111/jvh.12578.
    1. Lledo GM, et al. Regression of liver fibrosis after curing chronic hepatitis C with oral antivirals in patients with and without HIV coinfection. AIDS. 2018;32:2347–2352. doi: 10.1097/QAD.0000000000001966.
    1. Kronfli N, et al. Liver fibrosis in HIV-Hepatitis C virus (HCV) co-infection before and after sustained virologic response: what is the best non-invasive marker for monitoring regression? Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa702.
    1. Facciorusso A, et al. Long-term liver stiffness assessment in hepatitis C virus patients undergoing antiviral therapy: Results from a 5-year cohort study. J. Gastroenterol. Hepatol. 2018;33:942–949. doi: 10.1111/jgh.14008.
    1. Yoo JJ, et al. The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years. J Clin Med. 2019;8:1. doi: 10.3390/jcm8122065.
    1. Singh, S., Facciorusso, A., Loomba, R. & Falck-Ytter, Y. T. Magnitude and Kinetics of Decrease in Liver Stiffness After Antiviral Therapy in Patients With Chronic Hepatitis C: A Systematic Review and Meta-analysis. Clin. Gastroenterol. Hepatol.16, 27–38. 10.1016/j.cgh.2017.04.038 (2018).
    1. Chan J, et al. Direct-acting antiviral therapy for chronic HCV infection results in liver stiffness regression over 12 months post-treatment. Dig. Dis. Sci. 2018;63:486–492. doi: 10.1007/s10620-017-4749-x.
    1. Malin JJ, et al. Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection. HIV Med. 2019;20:230–236. doi: 10.1111/hiv.12705.
    1. Conti F, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J. Hepatol. 2016;65:727–733. doi: 10.1016/j.jhep.2016.06.015.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner