Comparison of Invasive and Non-Invasive Liver Fibrosis Indicators in Chronic Hepatitis B Patients

Öz

Background: Liver biopsy is the gold standard for staging fibrosis. This procedure is quite difficult, has complications and is invasive. Various scores were defined using biochemical tests to define the fibrosis stage and it was aimed to define the fibrosis stage without biopsy. Materials and Methods: The study included 156 patients who were followed up with a diagnosis of chronic viral hepatitis B and had a liver biopsy performed at the Infectious Diseases and Clinical Microbiology Clinic of Harran University Faculty of Medicine Hospital between 2010 and 2022. The patients were divided into two groups according to the ISHAK scoring system. Patients with no fibrosis and mild fibrosis were grouped as F0 (Stage 0, 1, 2), and patients with moderate-severe fibrosis were grouped as F1 (Stage 3, 4, 5). FIB-4, APRI, AAR, KING, AGAP, FIBROQ, FI, FCI, GPR, GUCI and ALBI scores were calculated using age, gender, complete blood count and some biochemical parameters. Results: 74,4% (n = 116) of the patients were in the F0 group and 25,6% (n = 40) were in the F1 group. The median age of the patients was 39.00 [49-31] years. 89 of the patients were male (57,1%) and 67 (42,9%) were female. While the difference between FIB-4(p<0.001), APRİ(p<0.001), KING(p<0.001), AGAP(p<0.001) and GUCI(p<0.001) scores was found to be statistically significant, no significant difference was found between other scores. According to ROC analysis, the non-invasive score with the highest diagnostic performance was GUCI (0.796), and the cut-off value for this score was ≥0.70. Conclusions: In the study, GUCI was found to be a useful score, especially in terms of diagnostic performance. Considering the negative effects of liver biopsy, such as being an invasive procedure and carrying the risk of complications, it can be said that non-invasive scoring systems will be useful in predicting fibrosis.

Anahtar Kelimeler

• Chronic HBV
• Fibrosis
• Non-invasive
• Hepatitis
• GUCI

Kronik Hepatit B Hastalarında İnvaziv Ve Non-İnvaziv Karaciğer Fibrozis Göstergelerinin Karşılaştırılması

Öz

Amaç: Karaciğer biyopsisi fibrozisin evrelenmesi için altın standarttır. Bu işlem oldukça güç, kompli-kasyonları olan ve invaziv bir işlemdir. Bu çalışmada kronik viral hepatit B tanılı hastalarda karaciğer fibrozisini öngörmede kullanılan non-invaziv yöntem sonuçlarının karaciğer biyopsi sonuçlarıyla karşılaştırılması amaçlandı. Materyal ve metod: Çalışmaya 2010-2022 yılları arasında Harran Üniversitesi Tıp Fakültesi Hastanesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji kliniğinde kronik viral hepatit B tanısıyla takip edilen ve karaciğer biyopsisi yapılmış olan 156 hasta dahil edildi. İSHAK skorlama sistemine göre hastalar iki gruba ayrıldı. Fibrozisi olmayan ve hafif fibrozisi olan hastalar F0 (Evre 0, 1, 2), orta-ağır fibrozisi olan hastalar ise F1 (Evre 3, 4, 5) olarak gruplandırıldı. Yaş, cinsiyet, hemogram ve biyokimyasal bazı parametreler kullanılarak FIB-4, APRI, AAR, KING, AGAP, FIBROQ, FI, FCI, GPR, GUCI ve ALBI skorları hesaplandı. Bulgular: Hastaların %74,4’ü (n = 116) F0, %25,6’sı (n=40) ise F1 grubunda yer alıyordu. Hastaların yaş medyanı 39.00 [49-31] yıldı. Hastaların 89’u erkek (%57,1) ve 67’si (%42,9) kadındı. FIB-4 (p<0.001), APRİ (p<0.001), KING (p<0.001), AGAP (p<0.001) ve GUCI (p<0.001) skorlamaları arasın-daki fark istatistiksel açıdan anlamlı bulunurken diğer skorlamalar arasında anlamlı farklılık saptan-madı. ROC analizine göre tanı performansı en yüksek olan non-invaziv skor GUCI (0.796) idi ve bu skor için kesme değeri ≥0.70 olarak bulundu. Sonuç: Çalışmada özellikle tanısal performans bakımından GUCI yararlı bir skor olarak tespit edildi. Karaciğer biyopsisinin invaziv bir işlem olması, komplikasyon riskini taşıması gibi negatif etkileri göz önünde bulundurulduğunda non-invaziv skorlama sistemlerinin fibrozisi tahmin etmede yararlı olacağı söylenebilir.

Anahtar Kelimeler

• Kronik HBV
• Fibrozis
• Non-invaziv
• Hepatit
• GUCI

Kaynakça

1. 1. Lee HW, Lee JS, Ahn SH. Hepatitis B Virus Cure: Targets and Future Therapies. International journal of molecular sciences. 2020;22(1): 213-224.
2. 2. Sant'Anna TB, Araujo NM. Hepatitis B Virus Genotype D: An Overview of Molecular Epidemiology, Evolutionary His-tory, and Clinical Characteristics. Microorganisms. 2023;11(5): 1101-1105.
3. 3. Koc Ö M, Robaeys G, Yildirim B, Posthouwer D, Hens S, Koek GH. Horizontal hepatitis B virus transmission through non-sexual close contact in Turkish chronic hepatitis B pa-tients living outside of Turkey. Acta gastro-enterologica Belgica. 2018;81(4):503-508.
4. 4. Parikh P, Ryan JD, Tsochatzis EA. Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection. An-nals of translational medicine. 2017;5(3):40-53.
5. 5. Enomoto M, Morikawa H, Tamori A, Kawada N. Noninva-sive assessment of liver fibrosis in patients with chronic hepatitis B. World journal of gastroenterology. 2014;20(34):12031-12038.
6. 6. Wai C-T, 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 (Baltimore, Md). 2003;38(2):518-526.
7. 7. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive in-dex to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology (Baltimore, Md). 2006;43(6):1317-1325.
8. 8. Okdemir S, Cakmak E. A novel non-invasive score for the prediction of advanced fibrosis in patients with chronic hepatitis B. Ann Hepatol. 2022;27(1):100544. doi: 10.1016/j.aohep.2021.100544.

9. 9. Ohta T, Sakaguchi K, Fujiwara A, Fujioka S, Iwasaki Y, Makino Y, et al. Simple surrogate index of the fibrosis stage in chronic hepatitis C patients using platelet count and serum albumin level. Acta medica Okayama. 2006;60(2):77-84.
10. 10. Lemoine M, Shimakawa Y, Nayagam S, Khalil M, Suso P, Lloyd J, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Af-rica. Gut. 2016;65(8):1369-1376.
11. 11. Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, et al. Assessment of liver function in pa-tients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. Journal of clinical oncology : official journal of the American Society of Clinical Oncolo-gy. 2015;33(6):550-558.
12. 12. Islam S, Antonsson L, Westin J, Lagging M. Cirrhosis in hepatitis C virus-infected patients can be excluded using an index of standard biochemical serum markers. Scandinavi-an journal of gastroenterology. 2005;40(7):867-872.
13. 13. Hsieh Y-Y, Tung S-Y, Lee I-L, Lee K, Shen C-H, Wei K-L, et al. FibroQ: an easy and useful noninvasive test for predict-ing liver fibrosis in patients with chronic viral hepatitis. Chang Gung Med J. 2009;32(6):614-622.
14. 14. Cross TJ, Rizzi P, Berry PA, Bruce M, Portmann B, Harrison PM. King's Score: an accurate marker of cirrhosis in chronic hepatitis C. European journal of gastroenterology & hepa-tology. 2009;21(7):730-738.
15. 15. Asfuroğlu-Kalkan E, Soykan İ. Kronik Hepatit B Hastalarında Fibrozisi Belirlemede Noninvazif Skorlama Sistemlerinin Yeri. Klimik Journal/Klimik Dergisi. 2022;35(3): 164-170.
16. 16. Ahmad W, Ijaz B, Javed FT, Gull S, Kausar H, Sarwar MT, et al. A comparison of four fibrosis indexes in chronic HCV: development of new fibrosis-cirrhosis index (FCI). BMC gastroenterology. 2011;11(4): 1-10.
17. 17. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepati-tis. Journal of hepatology. 1995;22(6):696-699.
18. 18. Zeng DW, Dong J, Liu YR, Jiang JJ, Zhu YY. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection. World journal of gastro-enterology. 2016;22(29):6663-6672.
19. 19. Cheng R, Tan N, Luo H, Kang Q, Xu X. Noninvasive Methods for Detecting Advanced Liver Fibrosis and Cirrhosis in Pa-tients with Chronic Hepatitis B: A Single-Center Retrospec-tive Study. Infection and drug resistance. 2023;16(9):6323-6331.
20. 20. Aygün, C., Gözel, N., Demirel, U., Yalnız, M., Özercan, İ. H., & Bahcecioğlu, İ. H. Kronik viral hepatit B tanısı olan has-talarda serum GGT düzeyi ile karaciğer fibrozu ilişkisi. Fırat Tıp Dergisi. 2010;15(2): 74-78.
21. 21. Akgül F, Çakırca TD. Kronik Hepatit B Hastalarında Fibrozisi Belirlemede Noninvazif Skorlama Sistemlerinin Yeri. Kocaeli Med J 2023;12 (2): 210-215.
22. 22. Karacaer Z, Avcı Ö, Yılmaz Karadağ F. King's Score may be More Effective in the Determination of Severe Fibrosis in Chronic Hepatitis B Infections. Viral Hepatitis Journal/Viral Hepatit Dergisi. 2017;23(1): 20-25.
23. 23. Ben Ayed H, Koubaa M, Yaich S, Rekik K, Ben Jemaa T, Maaloul I, et al. A new combined predicting model using a non-invasive score for the assessment of liver fibrosis in patients presenting with chronic hepatitis B virus infection. Medecine et maladies infectieuses. 2019;49(8):607-615.
24. 24. Fujita K, Oura K, Yoneyama H, Shi T, Takuma K, Nakahara M, et al. Albumin-bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C. Hepatology research : The official journal of the Japan So-ciety of Hepatology. 2019;49(7):731-742.
25. 25. Hu YC, Liu H, Liu XY, Ma LN, Guan YH, Luo X, et al. Value of gamma-glutamyltranspeptidase-to-platelet ratio in diag-nosis of hepatic fibrosis in patients with chronic hepatitis B. World journal of gastroenterology. 2017;23(41):7425-7432.