Evaluation of Non-invasive Scores Before and After Direct-acting Antiviral Treatment in Patients with Chronic Hepatitis C

Öz

The sustained virological response is achieved in patients with chronic hepatitis C infection using direct-acting antiviral (DAA) therapy. However, it is not known whether there is a decrease in liver fibrosis level. Non-invasive serum scores are successful in determining the level of liver fibrosis before treatment. There are no adequate studies in the literature about the use of these scores after treatment. This study aimed to determine the change in inflammation and fibrosis levels after treatment by using non-invasive scores. Adult patients who applied to the Karabuk University Training and Research Hospital between January 2019 and January 2020 and used DAA treatment were included in the study. Clinical and laboratory findings of the cases were recorded retrospectively from the hospital information system. Fibrosis-4 (FIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), γ glutamate transpeptidase-platelet ratio (GPR) and AST / ALT ratio scores were calculated before and after (24th week) treatment. Forty-two patients with a mean age of 56.4 were evaluated. 52% of these patients were women. All patients developed a sustained virological response. Genotype 1b was the most common (67 %). The most commonly used treatment regimen (60 %) was paritaprevir + ritonavir + ombitasvir + dasabuvir. After treatment compared to pretreatment, mean AST value decreased from 24.69 to 20.67, mean ALT value decreased from 20.57 to 15.31 and APRI from 0.33 to 0.29 (p=0.01; p=0.03; p=0.01, respectively). Although not statistically significant, FIB-4 was low after treatment. In conclusion, the use of non-invasive serum biomarker scores may be useful in the follow-up of chronic hepatitis C cases using DAA treatment.

Anahtar Kelimeler

• chronic hepatitis C
• direct-acting antiviral
• genotype
• non-invasive scores

Kronik Hepatit C Olgularında Doğrudan Etkili Antiviral Tedavi Öncesi ve Sonrası Non-invaziv Skorların Değerlendirilmesi

Öz

Doğrudan etkili antiviral (DEA) tedavi kullanan kronik hepatit C enfeksiyonu olan hastalarda kalıcı virolojik yanıt sağlanmaktadır. Ancak karaciğer fibrozu düzeyinde gerileme olup olmadığı bilinmemektedir. Non-invaziv serum skorları, tedavi öncesi karaciğer fibrozu düzeyini saptamada başarılıdır. Bu skorların tedavi sonrası kullanımı konusunda litetatürde yeterli çalışma bulunmamaktadır. Bu çalışma, non-invaziv skorları kullanarak tedavi sonrası inflamasyon ve fibroz düzeyindeki değişimi belirlemeyi amaçlamıştır. Karabük Üniversitesi Eğitim ve Araştırma Hastanesi’ne, Ocak 2019 ile Ocak 2020 tarihleri arasında başvurup DEA tedavi kullanan erişkin hastalar çalışmaya alınmıştır. Olgularının klinik ve laboratuvar bulguları, hastane bilgi sisteminden geriye dönük olarak kaydedilmiştir. Tedavi öncesi ve sonrası (24. hafta) Fibrosis-4 (FIB-4), aspartat aminotransferaz (AST) - trombosit oranı indeksinin (APRI), γ glutamat peptidaz-trombosit oranı (GPR) ve AST/ALT oranı skorları hesaplanmıştır. Yaş ortalaması 56,4 olan 42 hasta incelenmiştir. Bu hastaların % 52’si kadın idi. Tüm hastalarda kalıcı virolojik yanıt gelişmiştir. En sık (% 67) genotip 1b saptanmıştır. En çok kullanılan tedavi rejiminin (% 60) paritaprevir + ritonavir + ombitasvir + dasabuvir olduğu belirlenmiştir. Tedavi öncesine göre tedavi sonrası, ortalama AST değeri 24,69’dan 20,67’ye, ortalama ALT değeri 20,57’den 15,31’e ve APRI 0,33’den 0,29’a azalmıştır (sırasıyla p=0,01; p=0,03; p=0,01). İstatistiksel açıdan anlamlı olmasa da FIB-4 de tedavi sonrası düşük bulunmuştur. Sonuç olarak, DEA tedavi kullanan kronik hepatit C olguların takibinde, non-invaziv serum biyobelirteç skorlarının kullanımı yararlı olabilir.

Anahtar Kelimeler

• doğrudan etkili antiviral
• genotip
• kronik hepatit C
• non-invaziv skorlar

Kaynakça

1. Abdel Alem S, Elsharkawy A, El Akel W, et al. Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients. Expert Rev Gastroenterol Hepatol. 2019;13(10):1009-16. https://doi.org/10.1080/17474124.2019.1653183
2. Alem SA, Said M, Anwar I, et al. Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort. J Med Virol. 2018;90(9):1508-15. https://doi.org/10.1002/jmv.25210
3. Bachofner JA, Valli PV, Kroger 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(3):369-76. https://doi.org/10.1111/liv.13256
4. D’Ambrosio R, Degasperi E, Aghemo A, et al. Serological tests do not predict residual fibrosis in hepatitis C cirrhotics with a sustained virological response to interferon. PLoS One. 2016 ;11(6):e0155967. doi:10.1371/journal.pone.0155967. PMID: 27304619; PMCID: PMC4909284. https://doi.org/10.1371/journal.pone.0155967
5. Ghoneim S, Butt MU, Trujillo S, Asaad I. FIB-4 Regression with direct-acting antiviral therapy in patients with hepatitis C infection: a safety-net hospital experience. Front Med (Lausanne). 2020;7:359. PMID: 32793612; PMCID: PMC7387643. https://doi.org/10.3389/fmed.2020.00359
6. Gutierrez JA, Lawitz EJ, Poordad F. Interferon-free, direct-acting antiviral therapy for chronic hepatitis C. J Viral Hepat. 2015;22(11):861-70. https://doi.org/10.1111/jvh.12422
7. Jaroszewicz J, Flisiak-Jackiewicz M, Lebensztejn D, Flisiak R. Current drugs in early development for treating hepatitis C virus-related hepatic fibrosis. Expert Opin Investig Drugs. 2015;24(9):1229-39. https://doi.org/10.1517/13543784.2015.1057568
8. European Association for Study of L and 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. 2015;63(1):237-64. https://doi.org/10.1016/j.jhep.2015.04.006

9. Holmberg SD, Lu M, Rupp LB, et al. Noninvasive serum fibrosis markers for screening and staging chronic hepatitis C virus patients in a large US cohort. Clin Infect Dis. 2013;57(2):240-6. https://doi.org/10.1093/cid/cit245
10. Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology. 2003;125(6):1695-704. https://doi.org/10.1053/j.gastro.2003.08.032
11. Kotronen A and Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28(1):27-38. https://doi.org/10.1161/ATVBAHA.107.147538
12. Lam BP, Jeffers T, Younoszai Z, Fazel Y and Younossi ZM. The changing landscape of hepatitis C virus therapy: focus on interferon-free treatment. Therap Adv Gastroenterol. 2015;8(5):298-312. https://doi.org/10.1177/1756283X15587481
13. Lin MS, Lin HS, Chung CM, et al. Serum aminotransferase ratio is independently correlated with hepatosteatosis in patients with HCV: a cross-sectional observational study. BMJ Open. 2015;5:e008797. https://doi.org/10.1136/bmjopen-2015-008797
14. Lledo GM, Carrasco I, Benitez-Gutierrez LM, et al. Regression of liver fibrosis after curing chronic hepatitis C with oral antivirals in patients with and without HIV coinfection. AIDS. 2018;32(16):2347-52. https://doi.org/10.1097/QAD.0000000000001966
15. Lu M, Li J, Zhang T, et al. Serum biomarkers indicate long-term reduction in liver fibrosis in patients with sustained virological response to treatment for HCV infection. Clin Gastroenterol Hepatol. 2016;14(7):1044- 55 e3. https://doi.org/10.1016/j.cgh.2016.01.009
16. Preveden T, Veres B, Ruzic M, et al. Non-invasive assessment of liver fibrosis in HCV patients compared to liver biopsy: the experience of tertiary level Hospital in Serbia. Minerva Med. 2019. https://doi.org/10.23736/S0026-4806.19.06109-3
17. Sayyar M, Saidi M, Zapatka S, Deng Y, Ciarleglio M and Garcia-Tsao G. Platelet count increases after viral elimination in chronic HCV, independent of the presence or absence of cirrhosis. Liver Int. 2019;39(11):2061-5. https://doi.org/10.1111/liv.14203
18. Tada T, Kumada T, Toyoda H, et al. Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response. J Gastroenterol Hepatol. 2017;32(12):1982-8. https://doi.org/10.1111/jgh.13788
19. Tozun N, Ozdogan O, Cakaloglu Y, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect. 2015;21(11):1020-6. https://doi.org/10.1016/j.cmi.2015.06.028
20. Tuzuner U GB, Ozdemir M, Feyzioglu B, Baykan M. Seven-year genotype distribution among hepatitis C patients in a city in the central Anatolia region of Turkey. Viral Hepatitis Journal. 2018;24(1):12-7. https://doi.org/10.4274/vhd.0013
21. Wang LS, D’Souza LS and Jacobson IM. Hepatitis C-a clinical review. J Med Virol. 2016;88(11):1844-55. https://doi.org/10.1002/jmv.24554
22. Zhao Y, Thurairajah PH, Kumar R, Tan J, Teo EK and Hsiang JC. Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination: a population study of ex-substance users in Singapore. Hepatobiliary Pancreat Dis Int. 2019;18(2):143-8. https://doi.org/10.1016/j.hbpd.2018.12.002