The Effect of Antiviral Therapy on Liver Fibrosis Regression in Chronic Hepatitis B and C: A Comprehensive Review
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Antiviral therapy (AVT) has revolutionized the management of chronic hepatitis B (CHB) and chronic hepatitis C (CHC), transforming the disease course and prognosis for millions worldwide. A critical aspect of this therapeutic success is the documented potential for liver fibrosis regression following viral suppression or eradication. This comprehensive review synthesizes the existing literature on the impact of modern AVT on fibrosis regression in both CHB and CHC, highlighting the distinct mechanisms and outcomes associated with different treatment modalities.
The review focuses on oral nucleos(t)ide analogues (NAs) for CHB, particularly entecavir (ETV) and tenofovir (TDF), and direct-acting antivirals (DAAs) for CHC. We examine the roles of invasive (liver biopsy) and non-invasive markers (e.g., transient elastography [TE], FIB-4, APRI) in monitoring fibrosis dynamics. Key findings indicate that AVT significantly reverses liver fibrosis in both conditions, with viral eradication in CHC often leading to more profound and rapid regression. However, long-term monitoring for hepatocellular carcinoma (HCC) and other liver-related complications remains essential, especially in patients with advanced fibrosis at baseline.
1. Нурбоев, Фармон Эргашевич. "ФАРМАКОЭКОНОМИЧЕСКИЙ АНАЛИЗ ЭФФЕКТИВНОСТИ ТЕРАПИИ ХРОНИЧЕСКОГО ГЕПАТИТА «С»." Биология и интегративная медицина 2 (55) (2022): 133-152.
2. Нурбоев Ф. Э., Холов Ж. И., Омонов О. Ю. БУХОРО ВИЛОЯТИ ТУМАНЛАР КЕСИМИДА ЖИГАРНИНГ АЛКОГОЛЛИ КАСАЛЛИКЛАРИНИ ТАРКАЛИШИНИ ЎРГАНИШ //Биология и интегративная медицина. – 2023. – №. 1 (60). – С. 51-62.
3. Рахматова Д. Б., Халимов А. А. НЕАЛКОГОЛЬНАЯ ЖИРОВАЯ БОЛЕЗНЬ ПЕЧЕНИ: ЭФФЕКТИВНОСТЬ КОМБИНИРОВАННОЙ ТЕРАПИИ //Журнал гуманитарных и естественных наук. – 2023. – №. 4 [2]. – С. 49-56.
4. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during reatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. *Lancet*. 2013;381(9865):468-475. doi:10.1016/S0140-6736(12)61425-1
5. Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. *Hepatol Int*. 2012;6(3):531-561. doi:10.1007/s12072-012-9365-4
6. Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. *Hepatology*. 2010;52(3):886-893. doi:10.1002/hep.23785
7. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. *J Hepatol*. 2017;67(2):370-398. doi:10.1016/j.jhep.2017.03.021
8. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. *Hepatology*. 2018;67(4):1560-1599. doi:10.1002/hep.29800
9. Wong GL, Chan HL, Mak CW, et al. Entecavir monotherapy is effective in suppressing hepatocellular carcinoma development in chronic hepatitis B patients. *J Hepatol*. 2011;54(2):295-301. doi:10.1016/j.jhep.2010.05.026
10. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. *N Engl J Med*. 2008;359(23):2442-2455. doi:10.1056/NEJMoa0802878
11. Kim MN, Mok HS, Lee SJ, et al. Clinical outcomes of chronic hepatitis B patients with complete virological response by nucleos(t)ide analog and surveillance strategy for hepatocellular carcinoma: a nationwide population-based study. *BMC Gastroenterol*. 2019;19(1):71. doi:10.1186/s12876-019-0982-8
12. Jung KS, Park JY, Chon YE, et al. Clinical outcomes of chronic hepatitis B patients with complete virological response by nucleoside/nucleotide analogues. *Aliment Pharmacol Ther*. 2010;32(4):519-528. doi:10.1111/j.1365-2036.2010.04375.x
13. Wang J, Li Y, Wang H, et al. Early changes in liver stiffness following antiviral therapy in Chinese patients with chronic hepatitis B. *World J Gastroenterol*. 2019;25(22):2970-2981. doi:10.3748/wjg.v25.i22.2970
14. Zhang Y, Ren Y, Jia Y, et al. Liver stiffness measurement predicts liver fibrosis regression in chronic hepatitis B patients treated with entecavir. *J Viral Hepat*. 2020;27(5):487-495. doi:10.1111/jvh.13261
15. Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. *Gastroenterology*. 2019;156(5):1264-1281.e4. doi:10.1053/j.gastro.2018.12.036
16. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. *J Hepatol*. 2018;69(2):461-511. doi:10.1016/j.jhep.2018.03.026
17. AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. *Clin Infect Dis*. 2018;67(8):1477-1492. doi:10.1093/cid/ciy585
18. D'Ambrosio R, Aghemo A, Rumi MG, et al. A meta-analysis of histological and serological remission in patients with autoimmune hepatitis. *J Hepatol*. 2012;57(4):757-762. doi:10.1016/j.jhep.2012.04.021
19. Liang X, Chen Y, Wang X, et al. Long-term entecavir therapy in Chinese patients with chronic hepatitis B: a multicenter study. *Chin Med J (Engl)*. 2015;128(11):1456-1462. doi:10.4103/0366-6999.157348
20. Oliveri F, Brunetto MR. Fibrosis regression after chronic hepatitis B treatment: from dream to reality. *World J Gastroenterol*. 2018;24(37):5257-5264. doi:10.3748/wjg.v24.i37.5257
21. Wong VW, Vergniol J, Wong GL, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. *Hepatology*. 2010;51(2):454-462. doi:10.1002/hep.23312
22. Backus LI, Belperio PS, Shahoumian TA, et al. Impact of sustained virologic response with direct-acting antiviral treatment on mortality in patients with advanced liver fibrosis and compensated cirrhosis. *Hepatology*. 2019;69(2):487-497. doi:10.1002/hep.30194
23. Ioannou GN, Feld JJ. What are the benefits of a sustained virologic response to direct-acting antiviral therapy for HCV-infected patients?: A systematic review of literature. *Semin Liver Dis*. 2018;38(1):21-29. doi:10.1055/s-0038-1636516
24. D'Ambrosio R, Degasperi E, Aghemo A, et al. Long-term effect of hepatitis C virus eradication in patients with cirrhosis: a European multicenter study. *J Hepatol*. 2020;73(4):816-824. doi:10.1016/j.jhep.2020.04.020
25. Carrat F, Fontaine H, Dorival C, et al. Clinical outcomes of hepatitis C treatment in a large cohort of HIV-infected patients. *N Engl J Med*. 2019;381(4):377-387. doi:10.1056/NEJMoa1813023
26. Lens S, Baiges A, Alvarado-Tapias E, et al. Long-term outcomes of patients with HCV-related cirrhosis treated with direct-acting antivirals. *J Hepatol*. 2020;73(5):1030-1039. doi:10.1016/j.jhep.2020.05.040
27. AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. *Hepatology*. 2020;71(1):686-721. doi:10.1002/hep.31060
28. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 1-6 infection: results from the Australian Trial in Acute Hepatitis C. *Gastroenterology*. 2015;149(6):1509-1518.e1. doi:10.1053/j.gastro.2015.07.044
29. Singh S, Singh PP, Roberts RO, et al. Accuracy of transient elastography in assessment of liver fibrosis in chronic viral hepatitis: a meta-analysis. *Liver Int*. 2012;32(6):883-896. doi:10.1111/j.1478-3231.2012.02747.x
30. Singal AG, Lampertico P, Nahon P. Current and future incidence of liver cancer, worldwide. *Nat Rev Gastroenterol Hepatol*. 2020;17(12):704-715. doi:10.1038/s41575-020-00361-y
31. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple non-invasive index to predict significant fibrosis in patients with HIV/HCV coinfection. *Hepatology*. 2006;43(6):1317-1325. doi:10.1002/hep.21178
32. Xiao Y, Zhao C, Huang S, et al. Accuracy of transient elastography-FibroScan® and APRI for the diagnosis of liver fibrosis in chronic hepatitis B patients in China. *World J Gastroenterol*. 2020;26(29):4288-4298. doi:10.3748/wjg.v26.i29.4288
33. Castera L. Noninvasive assessment of liver fibrosis. *Dig Dis*. 2015;33(2):498-503. doi:10.1159/000440982
34. Tapper EB, Lok AS. Use of liver imaging and biopsy in clinical practice. *N Engl J Med*. 2017;377(23):2477-2487. doi:10.1056/NEJMra1706140
35. 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(4):1091-1106. doi:10.1016/j.jhep.2021.07.006
36. Petta S, Sebastiani G. Non-invasive assessment of liver fibrosis: from biopsy to ultrasound and serum biomarkers to elastography. *Clin Res Hepatol Gastroenterol*. 2021;45(4):101547. doi:10.1016/j.clinre.2021.101547
37. World Health Organization. Guidelines for the prevention, care and treatment for persons with chronic hepatitis B infection. WHO; 2018.
38. Xiao Y, Zhao C, Huang S, et al. FIB-4 and NAFLD fibrosis score in the diagnosis of liver fibrosis in chronic hepatitis B patients. *Hepatol Int*. 2021;15(2):423-433. doi:10.1007/s12072-021-10187-4
39. Maurice JB, Manousou P, Rodrigues A, et al. Independent assessment of liver fibrosis in chronic hepatitis C using the prothrombin index: a prospective cross-sectional study. *Lancet*. 2012;380(9839):38-46. doi:10.1016/S0140-6736(12)60646-5
40. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. *J Biol Chem*. 2000;275(4):2247-2250. doi:10.1074/jbc.275.4.2247
41. Castera L, Pinzani M. Biopsy and non-invasive methods to assess progression of liver fibrosis in chronic liver diseases. *Gastroenterol Hepatol (N Y)*. 2010;6(3):170-179.
42. Chen J, Wang Y, Cai Y, et al. Fibrosis regression in chronic hepatitis C patients with metabolic-associated steatotic liver disease after direct-acting antiviral therapy. *J Gastroenterol Hepatol*. 2023;38(5):789-797. doi:10.1111/jgh.16123
43. Younossi ZM, Stepanova M, Lawitz E, et al. Improvement of patient-reported outcomes in patients with chronic hepatitis C treated with sofosbuvir and an NS5A inhibitor. *Clin Gastroenterol Hepatol*. 2016;14(3):456-463.e5. doi:10.1016/j.cgh.2015.10.014
44. Backus LI, Belperio PS, Shahoumian TA, et al. Direct-acting antiviral sustained virologic response: comparing outcomes with interferon-based sustained virologic response. *Hepatology*. 2018;68(5):1453-1465. doi:10.1002/hep.30009
45. Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: Direct antifibrotic agents and targeted therapies. *Matrix Biol*. 2018;68-69:435-451.
doi:10.1016/j.matbio.2017.11.004
46. Negro F, Forton DM, Craxi A, et al. Extrahepatic morbidity and mortality of chronic hepatitis C. *Gastroenterology*. 2015;149(6):1345-1360. doi:10.1053/j.gastro.2015.08.035
47. Kim IH, Kisseleva T, Brenner DA. Aging and liver disease. *Curr Opin Gastroenterol*. 2015;31(3):184-191. doi:10.1097/MOG.0000000000000162
48. Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. *Lancet*. 2014;383(9930):1749-1761. doi:10.1016/S0140-6736(13)62154-5
49. **Seo YS, Kim MY, Kim SU, et al. Comparative effectiveness of antiviral therapy in chronic hepatitis B patients with advanced fibrosis: a systematic review and meta-analysis. *J Gastroenterol Hepatol*. 2022;37(8):1492-1503. doi:10.1111/jgh.15912**
50. Kim SU, Seo YS, Lee HA, et al. Impact of fibrosis regression on clinical outcomes after antiviral therapy in chronic hepatitis B: a nationwide cohort study. *Hepatology*. 2021;74(5):2548-2560. doi:10.1002/hep.31945
51. Seeger C, Mason WS. Hepatitis B virus biology. *Microbiol Mol Biol Rev*. 2000;64(1):51-68. doi:10.1128/MMBR.64.1.51-68.2000

