Potent Antiviraller Arasında Fark Var mı? Tenofovir ve Entekavirin Noninvaziv Biyobelirteçler Üzerindeki 5 Yıllık Etkilerinin Karşılaştırılması

Yıl 2020, Cilt: 19 Sayı: 3, 116 - 122, 30.12.2020

Serkan Yalaki , Mehmet Suat Yalçın

https://doi.org/10.17941/agd.629736

Öz

Amaç: Kronik karaciğer hastalıklarının morbidite ve mortalitesi karaciğer fibrozisinin derecesi ile yakından ilişikilidir. Karaciğer fibrozisinin artık geri
dönüşümlü olduğu ve tedavi ile geri döndürülebildiği bilinmektedir. Bu
çalışmada, kronik hepatit B hastalarındaki fibrozisin gerilemesinde potent antivirallerin etkinliği non-invaziv testler üzerinde araştırılmış; şayet iyileşme yönünde etkinlikleri varsa aralarında bir farkın olup olmadığını araştırılmıştır.

Gereç ve Yöntem: Karaciğer biyopsisi
yapılan kronik hepatit B hastalarının tıbbi kayıtları sistematik olarak
incelendi ve uygunluk açısından tarandı. Potent antiviral tedavi başlanan ve 5
yıl boyunca alan naif hastalar seçildi. Bu hastaların çalışılan non-invaziv biyobelirteçlerinin (AAR, API, APRI, FIB-4, PLT, MPV) başlangıç, 3. yıl ve 5. yıl değerleri karşılaştırıldı.

Bulgular: Tenofovir ve entecavir alan
hastalarda APRI, AAR, API, MPV ve PLT dağılımları açısından 3 ölçüm arasında
istatistiksel olarak anlamlı bir fark vardı (Friedman p <0,05). Bazal ve 3.
yıl, bazal ve 5. yıl değerleri arasında APRI, AAR, API, MPV ve PLT ölçümleri açısından
post-hoc ikili karşılaştırmalara göre istatistiksel olarak anlamlı bir fark
vardı (Wilcoxon p <0,016 Bonferroni düzeltmesi). Bu değerlerdeki iyileşme
açısından iki ilaç arasında belirgin bir fark saptanmadı (Mann-Whitney U, p>0,05).

Sonuç: Kronik karaciğer hastalıklarının tanısında ve
tedavi takibinde karaciğer biyopsisinin altın standart olduğu bilinmektedir. Bununla
birlikte, biyopsi her zaman mümkün olmayabilir. Verilen tedavinin karaciğer
histopatolojisi üzerinde yaptığı iyileşmeyi takip edebilmek için invaziv olmayan birkaç
test kullanılabilir. Kr hepatit B hastalarında fibrozisteki iyileşme üzerinde potent antiviraller etkin ancak bu etkinlik açısından aralarında fark
yoktur.

Anahtar Kelimeler

Entekavir, Fibrozis, Kr hepatit B, Noninvaziv test, Tenofovir

IS THERE A DIFFERENCE BETWEEN POTENT ANTIVIRALS? COMPARISON OF 5-YEAR CHANGES OF TENOFOVIR AND ENTECAVIR ON NONINVASIVE MARKERS

Öz

Objective: The
morbidity and mortality of chronic liver diseases are closely related to the
degree of liver fibrosis. It is known that liver fibrosis is now reversible and
can be reversed with treatment. In this study, the effectiveness of potent
antivirals in the regression of fibrosis in chronic hepatitis B patients was
investigated on non-invasive tests; if there is a difference between them, it
is investigated whether there is a difference between them.

Materials and Methods: Medical records of chronic hepatitis B patients who underwent liver
biopsy were systematically reviewed and screened for compliance. Potent
antiviral treatment was initiated and selected naive patients who received for
5 years. The non-invasive biomarkers (AAR, API, APRI, FIB-4, PLT, MPV) of these
patients were compared at baseline, 3rd year and 5th year.

Results: There
was a statistically significant difference in APRI, AAR, API, MPV and PLT
distributions between ten measurements in tenofovir and entecavir patients
(Friedman p <0.05). There was a statistically significant difference between
baseline and 3rd year, baseline and 5th year values in terms of APRI, AAR, API,
MPV and PLT measurements compared to post-hoc binary comparisons (Wilcoxon p
<0.016 Bonferroni correction). There was no significant difference between
these two drugs in terms of improvement in these values (Mann-Whitney U, p>
0.05).

Conclusion: It is
known that liver biopsy is the gold standard in the diagnosis and follow-up of
chronic liver diseases. However, biopsy may not always be possible. Several
non-invasive tests can be used to monitor the improvement of treatment on liver
histopathology. Potential antivirals are effective on the recovery of fibrosis
in patients with chronic hepatitis B, but there is no difference in this efficacy.

Anahtar Kelimeler

Entecavir, Fibrosis, Hepatitis B, Non-invasive tests, Tenofovir

Kaynakça

• 1. European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection - Journal of Hepatology 2012 Jul;57(1):167-85. Doi: 10.1016/j.jhep.2012.02.010. 2. Zani C, Pasquale L, Bressanelli M, Puoti M, Paris B, Coccaglio R, et al. The epidemiological pattern of chronic liver diseases in a community undergoing voluntary screening for hepatitis B and C. Dig Liver Dis 2011; 43: 653 – 8. Doi: 10.1016/j.dld.2011.03.0073. Serkan Yalaki, Mehmet Suat Yalçın, Avşar Zerman. Malign Karaciğer Kitleleri, 127 Olgunun Retrospektif Değerlendirilmesi Van Tıp Derg 25(1): 17-21, 2018 Doi: 10.5505/vtd.2018.363494. Hammel P, Couvelard A, O’Toole D, Ratouis A, Sauvanet A, Flejou JF, et al. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med 200; 344: 418-423. Doi: 10.1056/NEJM2001020834406045. Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL et al. Long-Term Entecavir Therapy Results in the Reversal of Fibrosis/Cirrhosis and Continued Histological Improvement in Patients with Chronic Hepatitis B. Hepatology, Vol. 52, No. 3, 2010. Doi: 10.1002/hep.237856. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. The Lancet Volume 381, Issue 9865, 9–15 February 2013, Pages 468-475. Doi: 10.1016/S0140-6736(12)61425-17. Iloeje UH, Yang HI, Jen CL, Su J, Wang LY, You SL, et al. Risk and predictors of mortality associated with chronic hepatitis B infection. Clin Gastroenterol Hepatol 2007; 5: 921–31. Doi: 10.1016/j.cgh.2007.06.0158. Dienstag JL, Goldin RD, Heathcote EJ, Hann HW, Woessner M, Stephenson SL, et al. Histological outcome during long-term lamivudine therapy. Gastroenterology 2003; 124: 105–17. Doi: 10.1053/gast.2003.500139. Ke W, Liu L, Zhang C, Ye X, Gao Y, Zhou S, et al. Comparison of efficacy and safety of tenofovir and entecavir in chronic hepatitis B virus infection: a systematic review and meta-analysis. PloS one. 2014;9(6):e98865. Doi: 10.1371/journal.pone.009886510. Dogan UB, Kara B, Gumurdulu Y, Soylu A, Akin MS. Comparison of the efficacy of tenofovir and entecavir for the treatment of nucleos(t)ide-naive patients with chronic hepatitis B. The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology. 2012;23(3):247–52. Doi: 10.4318/tjg.2012.0380 11. Park JW, Kwak KM, Kim SE, Jang MK, Suk KT, Kim DJ et al. Comparison of the long-term efficacy between entecavir and tenofovir in treatment- naïve chronic hepatitis B patients. BMC Gastroenterology volume 17, Article number: 39 (2017). Doi: 10.1186/s12876-017-0596-712. Giannini E, Botta F, Fasoli A, Ceppa P, Risso D, Lantieri PB, et al. Progressive liver functional impairment is associated with an increase in AST/ALT ratio. Dig Dis Sci 1999; 44: 1249 –53. Doi: 10.1023/a:102660923109413. Poynard T, Bedossa P. Age and platelet count: A simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups. J Viral Hepat 1997; 4:199-208.14. Shin WG, Park SH, Jang MK, Hahn TH, Kim JB, Lee MS, et al. Aspartate aminotransferase to platelet ratio index (APRI) can predict liver fibrosis in chronic hepatitis B. Dig LiverDis 2008; 40:267-74. Doi: 10.1016/j.dld.2007.10.01115. Sterling RK, Lissen E, Clumerk N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvazive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006; 43:1317-25. Doi: 10.1002/hep.2117816. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003; 38:518-26. Doi: 10.1053/jhep.2003.5034617. Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. Performance of the aspartate aminotransferase -to- platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011; 53:726-36. Doi: 10.1002/hep.2410518. Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review. Ann Intern Med. 2013; 158: 807-20. Doi: 10.7326/0003-4819-158-11-201306040-0000519. Park SY, Kang KH, Park JH, Lee JH, Cho CM, Tak WY, et al. Clinical efficacy of AST/ALT ratio and platelet counts as predictors of degree of fibrosis in HBV infected patients without clinically evident liver cirrhosis. Korean J Gastroenterol. 2004; 43: 246–51.20. Karasu Z, Tekin F, Ersoz G, Gunsar F, Batur Y, Ilter T, et al. Liver fibrosis is associated with decreased peripheral platelet count in patients with chronic hepatitis B and C. Dig Dis Sci 2007; 52(6):1535-9. Doi:10.1007/s10620-006-9144-y21. Purnak T, Olmez S, Torun S, Efe C, Sayilir A, Ozaslan E, et al. Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis. Clin Res Hepatol Gastroenterol. 2013; 37:41–6. Doi: 10.1016/j.clinre.2012.03.035 22. Ceylan B, Fincanci M, Yardimci C, Eren G, Tözalgan Ü, Müderrisoğlu C et al. Can mean platelet volume determine the severity of liver fibrosis or inflammation in patients with chronic hepatitis B? Eur J Gastroenterol Hepatol 2013; 25(5):606-12. Doi: 10.1097/MEG.0b013e32835d08da23. Ting-Tsung Chang, Yun-Fan Liaw, Shun-Sheng Wu, Eugene Schiff, Kwang-Hyub Han, Ching-Lung Lai et al. Long-Term Entecavir Therapy Results in the Reversal of Fibrosis/Cirrhosis and Continued Histological Improvement in Patients with Chronic Hepatitis B. Hepatology, Vol. 52, No. 3, 2010. Doi: 10.1002/hep.2378524. Patrick Marcellin, Edward Gane, Maria Buti, Nezam Afdhal, William Sievert, Ira M Jacobson et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. The Lancet Volume 381, Issue 9865, 9–15 February 2013, Pages 468-475. Doi: 10.1016/S0140-6736(12)61425-125. Basar Ö, Yımaz B, Ekiz F, Ginis Z, Altınbas A, Aktas B et al. Non-invasive tests in prediction of liver fibrosis in chronic hepatitis B and comparison with post-antiviral treatment results. Clinics and Research in Hepatology and Gastroenterology 2013; 37, 152—158. Doi: 10.1016/j.clinre.2012.07.00326. Koksal AR, Alkim H, Boga S, Ergun M, Bayram M, Ozguven BY et al. Effect of Entecavir and Tenofovir Treatment on Noninvasive Fibrosis Scores: Which One Is Better? American Journal of Therapeutics 2016; 23, e429–e438. Doi: 10.1097/MJT.0000000000000203