Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study.
antiviral treatment
hepatitis C
hepatocellular carcinoma
liver stiffness
Journal
Journal of viral hepatitis
ISSN: 1365-2893
Titre abrégé: J Viral Hepat
Pays: England
ID NLM: 9435672
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
07
09
2021
received:
23
05
2021
accepted:
23
09
2021
pubmed:
29
9
2021
medline:
3
2
2022
entrez:
28
9
2021
Statut:
ppublish
Résumé
The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
26-34Informations de copyright
© 2021 John Wiley & Sons Ltd.
Références
Daniel KE, Saeian K, Rizvi S. Real-world experiences with direct-acting antiviral agents for chronic hepatitis C treatment. J Viral Hepat. 2020;27:195-204. https://doi.org/10.1111/jvh.13218
Pawlotsky JM, Feld JJ, Zeuzem S, et al. From non-A, non-B hepatitis to hepatitis C virus cure. J Hepatol. 2015;62:S87-S99. https://doi.org/10.1016/j.jhep.2015.02.006
El-Sherif O, Jiang ZG, Tapper EB, et al. Baseline factors associated with improvements in decompensated cirrhosis after direct-acting antiviral therapy for hepatitis c virus infection. Gastroenterology. 2018;154:2111-2121.e8. https://doi.org/10.1053/j.gastro.2018.03.022
Moon AM, Green PK, Rockey DC, et al. Hepatitis C eradication with direct-acting anti-virals reduces the risk of variceal bleeding. Aliment Pharmacol Ther. 2019;51:364-373. https://doi.org/10.1111/apt.15586
Singal AG, Volk ML, Jensen D, et al. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280-288.e1. https://doi.org/10.1016/j.cgh.2009.11.018
BrunoS, StroffoliniT, ColomboM, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007;45:579-587. https://doi.org/10.1002/hep.21492
Poynard T, McHutchison J, Davis GL, et al. Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C. Hepatology. 2000;32:1131-1137. https://doi.org/10.1053/gast.2002.33023
Shiratory Y, Imazeki F, Moriyama M, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med. 2000;132:517-524. https://doi.org/10.7326/0003-4819-132-7-200004040-00002
Metwally MA, Zein CO, Zein NN. Regression of hepatic fibrosis and cirrhosis in patients with chronic hepatitis C treated with interferon-based therapy. Gastroenterology. 2003;124:156. https://doi.org/10.1016/s0016-5085(03)00352-4
Rinaldi L, Perrella A, Guarino M, et al. Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study. J Transl Med. 2019;17:292. https://doi.org/10.1186/s12967-019-2033-x
Carrat F, Fontaine H, Dorival C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet. 2019;393(10179):1453-1464. https://doi.org/10.1016/S0140-6736(18)32111-1
Piñero F, Mendizabal M, Ridruejo E, et al. Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma. Liver Int. 2019;39:1033-1043. https://doi.org/10.1111/liv.14041
The French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology. 1994;20(1 Pt 1):15-20. https://doi.org/10.1002/hep.1840200104
Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38:1449-1457. https://doi.org/10.1016/j.hep.2003.09.022
Rinaldi L, Valente G, Piai G. Serial liver stiffness measurements and monitoring of liver-transplanted patients in a real-rife clinical practice. Hepat Mon. 2016;16:e41162. https://doi.org/10.5812/hepatmon.41162
Erman A, Sathya A, Nam A, et al. Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: a systematic review and meta-analysis. J Viral Hepat. 2018;25:502-513. https://doi.org/10.1111/jvh.12846
Vergniol J, Foucher J, Terrebonne E, et al. Non-invasive test for fibrosis and liver stiffness predict 5-year outcome of patients with chronic hepatitis C. Gastroenterology. 2011;140:1970-1979. https://doi.org/10.1053/j.gastro.2011.02.058
Chekuri S, Nickerson J, Bichoupan K, et al. Liver stiffness decreases rapidly in response to successful hepatitis c treatment and then plateaus. PLoS One. 2016;11:e0159413.
Hsu WF, Lai HC, Su WP, et al. Rapid decline of noninvasive fibrosis index values in patients with hepatitis C receiving treatment with direct-acting antiviral agents. BMC Gastroenterol. 2019;19:63. https://doi.org/10.1186/s12876-019-0973-5
Sporea I, Lupușoru R, Mare R, et al. Dynamics of liver stiffness values by means of transient elastography in patients with HCV liver cirrhosis undergoing interferon free treatment. J Gastrointestin Liver Dis. 2017;26:145-150. https://doi.org/10.15403/jgld.2014.1121.262.dyn
Bachofner JA, Valli PV, Kröger A, et al. Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index. Liver Int. 2017;37:369-376. https://doi.org/10.1111/liv.13256
Chung T, Ghany MG, Kim AY, et al. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis c virus infection. Clin Infect Dis. 2018;67:1477-1492. https://doi.org/10.1093/cid/ciy585
European Association for Study of Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63:199-236. https://doi.org/10.1016/j.jhep.2015.03.025
European Association for the Study of the Liver, European Organization for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908-943. https://doi.org/10.1016/j.jhep.2011.12.001
Boursier J, Zarski JP, de Ledinghen V, et al. Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatology. 2013;57:1182-1191. https://doi.org/10.1002/hep.25993
Deterding K, Höner zu Siederdissen C, Port K, et al. Improvement of liver function parameters in advanced HCV-associated liver cirrhosis by IFN-free antiviral therapies. Aliment Pharmacol Ther. 2015;42:889-901. https://doi.org/10.1111/apt.13343
Camma C, Di Bona D, Schepis F, 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. https://doi.org/10.1002/hep.20073
Tripodi A, Fracanzani LA, Chantarangkul V, et al. Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol. 2017;66:248-250. https://doi.org/10.1016/j.jhep.2016.09.025
Khalili M, Kleiner DE, King DC, et al. Hepatic steatosis and steatohepatitis in a large North American cohort of adults with chronic hepatitis B. Am J Gastroenterol. 2021;116(8):1686-1697. https://doi.org/10.14309/ajg.0000000000001257
Rinaldi L, Nascimbeni F, Giordano M, et al. Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis. World J Gastroenterol. 2017;23:1458-1468. https://doi.org/10.3748/wjg.v23.i8.1458
Di Francia R, Rinaldi L, Cillo M, et al. Antioxidant diet and genotyping as tools for the prevention of liver disease. Eur Rev Med Pharmacol Sci. 2016;20:5155-5163.
Di Francia R, Rinaldi L, Troisi A, et al. Effect of anti-oxidant agents in patients with hepatocellular diseases. Eur Rev Med Pharmacol Sci. 2015;19:3993-3995.
Fraquelli M, Rigamonti C, Casazza G, et al. Etiology-related determinants of liver stiffness values in chronic viral hepatitis B or C. J Hepatol. 2011;54:621-628. https://doi.org/10.1016/j.jhep.2010.07.017
Lombardi R, Airaghi L, Targher G, et al. Liver fibrosis by fibroscan® independently of established cardiovascular risk parameters associates with macrovascular and microvascular complications in patients with type 2 diabetes. Liver Int. 2020;40:347-354. https://doi.org/10.1111/liv.14274
Lombardi R, Petta S, Pisano G, et al. FibroScan identifies patients with non-alcoholic fatty liver disease and cardiovascular damage. Clin Gastroenterol Hepatol. 2020;18:517-519. https://doi.org/10.1016/j.cgh.2018.11.011
Sasso FC, Rinaldi L, Lascar N, et al. Role of tight glycemic control during acute coronary syndrome on CV outcome in type 2 diabetes. J Diabetes Res. 2018;2018:3106056. https://doi.org/10.1155/2018/3106056
Sasso FC, Pafundi PC, Gelso A, et al. High HDL cholesterol: a risk factor for diabetic retinopathy? Findings from NO BLIND study. Diabetes Res Clin Pract. 2019;150:236-244. https://doi.org/10.1016/j.diabres.2019.03.028
Adinolfi LE, Petta S, Fracanzani AL, et al. Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: a prospective multicentre study. Atherosclerosis. 2020;296:40-47. https://doi.org/10.1016/j.atherosclerosis.2020.01.010
European Association for the Study of the Liver. EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol. 2021;75(3):659-689. https://doi.org/10.1016/j.jhep.2021.05.025
Rinaldi L, Guarino M, Perrella A, et al. Role of liver stiffness measurement in predicting HCC occurrence in direct-acting antivirals setting: a real-life experience. Dig Dis Sci. 2019;64:3013-3019. https://doi.org/10.1007/s10620-019-05604-8
Kobayashi N, Iijima H, Tada T, et al. Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response. Eur J Gastroenterol Hepatol. 2018;30:546-551. https://doi.org/10.1097/meg.0000000000001106
Fehily SR, Papaluca T, Thompson AJ. Long-term impact of direct-acting antiviral agent therapy in HCV cirrhosis: critical review. Semin Liver Dis. 2019;39:341-353. https://doi.org/10.1055/s-0039-1685538
Lenti MV, Pasina L, Cococcia S, et al. Mortality rate and risk factors for gastrointestinal bleeding in elderly patients. Eur J Int Med. 2019;61:54-61. https://doi.org/10.1016/j.ejim.2018.11.003
Valente G, Rinaldi L, Sgambato M, et al. Conversion from twice-daily to once- daily tacrolimus in stable liver transplant patients: effectiveness in a real-world setting. Transplant Proc. 2013;45:1273-1275. https://doi.org/10.1016/j.transproceed.2013.02.021
Ascione A, Fontanella L, Imparato M, et al. Mortality from liver cirrhosis and hepatocellular carcinoma in Western Europe over the last 40 years. Liver Int. 2017;37:1193-1201. https://doi.org/10.1111/liv.13371
Rinaldi L, Folliero V, Palomba L, et al. Sonoporation by microbubbles as gene therapy approach against liver cancer. Oncotarget. 2018;9:32182-32190. https://doi.org/10.18632/oncotarget.25875