Diagnostic validity of serum YKL-40 as a non-invasive diagnostic marker of oesophageal varices in cirrhotic hepatitis C virus patients

Springer Science and Business Media LLC - Tập 12 - Trang 1-15 - 2022
Abdelfattah Hanno1, Ali M. EL-Kady1, Essam Bedewy1, Reham A. Abo Elwafa2, Mohammed S. Ahmed1
1Tropical Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Tóm tắt

Liver cirrhosis is the last phase of chronic hepatitis C virus infection. During the compensated phase, portal pressure is still below the point where varices start to form. On the contrary, decompensated individuals have clinically significant portal hypertension. YKL-40 protein is categorized as an inflammatory protein and is related to various different variables in expressing the severity of hepatic fibrosis, including hepatic venous pressure gradient. The objective of this research was to evaluate the diagnostic validity of serum YKL-40 in cirrhotic hepatitis C virus patients as a predictive non-invasive marker for the diagnosis of oesophageal varices and to compare it to other non-invasive clinical, laboratory, and ultrasonographic parameters, as well as endoscopy with and without treatment modalities. The present research was done on 80 participants visiting the Tropical Medicine Department at the Main University Hospital in Alexandria; they were divided into four groups, group I (n = 20) cirrhotic patients with no oesophageal varices, group II (n = 20) with small varices, group IIIa (n = 20) with large varices, and group IIIb same patients of group IIIa but after disappearance of varices by band ligation and medical treatment with carvedilol and group IV as apparently healthy control. YKL-40 in serum was evaluated using ELISA. Serum YKL-40 was statistically significantly higher in all cirrhotic patients than healthy controls (p = <0.001). Furthermore, it was statistically significantly greater in patients with small varices compared to those without varices (p = <0.001) and in large varices rather than no varices or small varices (p < 0.001) and (p < 0.001) respectively. However, there was no statistically significant difference between IIIa and IIIb (p = 0.881). In all tested groups, there was no correlation between serum YKL-40 and FIB-4 or APRI. However, only participants in group I exhibited a significant negative correlation between serum YKL-40 and AST/ALT ratio, whereas subjects in groups II and IIIa exhibited no significant correlation. Serum YKL-40 could be used as a sensitive non-invasive predictor for diagnosis and grading of oesophageal varices but not for follow up after treatment.

Tài liệu tham khảo

The Polaris Observatory HCV Collaborators (2017) Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2(3):161–176 Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L, Sheron N (2018) Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies. J Hepatol 69(3):718–735 Esmat G, El-Sayed MH, Hassany M, Doss W, Waked I (2018) One step closer to elimination of hepatitis C in Egypt. Lancet Gastroenterol Hepatol 3(10):665 McCormick PA, Nolan N (2004) Palpable epigastric liver as a physical sign of cirrhosis: a prospective study. Eur J Gastroenterol Hepatol 16(12):1331–1334 Sherlock S, Dooley J (2011) Hepatic cirrhosis. Sherlocks dis. Liver biliary Syst. Wiley-Blackwell, Oxford de Franchis R (2010) Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 53(4):762–768 de Franchis R, Dell'Era A, Iannuzzi F (2004) Diagnosis and treatment of portal hypertension. Dig Liver Dis 36(12):787–798 Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W (2007) Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 46(3):922–938 Albillos A, Bañares R, González M, Ripoll C, Gonzalez R, Catalina MV, Molinero LM (2007) Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension: a meta-analysis. Am J Gastroenterol 102(5):1116–1126 Groszmann RJ, Wongcharatrawee S (2004) The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology 39(2):280–282 Reiberger T, Ferlitsch A, Payer BA, Pinter M, Schwabl P, Stift J, Trauner M, Peck-Radosavljevic M (2012) Noninvasive screening for liver fibrosis and portal hypertension by transient elastography--a large single center experience. Wien Klin Wochenschr 124(11-12):395–402 Tao H, Yang JJ, Shi KH, Huang C, Zhang L, Lv XW, Li J (2014) The significance of YKL-40 protein in liver fibrosis. Inflamm Res 63(4):249–254 Tran A, Benzaken S, Saint-Paul MC, Guzman-Granier E, Hastier P, Pradier C, Barjoan EM, Demuth N, Longo F et al (2000) Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease. Eur J Gastroenterol Hepatol 12(9):989–993 Saitou Y, Shiraki K, Yamanaka Y, Yamaguchi Y, Kawakita T, Yamamoto N, Sugimoto K, Murata K, Nakano T (2005) Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease. World J Gastroenterol 11(4):476–481 Johansen JS, Christoffersen P, Møller S, Price PA, Henriksen JH, Garbarsch C, Bendtsen F (2000) Serum YKL-40 is increased in patients with hepatic fibrosis. J Hepatol 32(6):911–920 Smith GE, Cerham JH, Ivnik RJ (2003) Diagnostic validity. In: Tulsky DS, Saklofske DH, Chelune GJ, Heaton RK, Ivnik RJ, Bornstein R, Prifitera A, Ledbetter MF (eds) Clinical interpretation of the WAIS-III and WMS-III. Academic, Cambridge, pp 273–301 Brown HS, Halliwell M, Qamar M, Read AE, Evans JM, Wells PN (1989) Measurement of normal portal venous blood flow by Doppler ultrasound. Gut 30(4):503–509 Li Q, Ren X, Lu C, Li W, Huang Y, Chen L (2017) Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN: a retrospective cohort study. Medicine (Baltimore) 96(12):e6336 Giannini EG, Zaman A, Kreil A, Floreani A, Dulbecco P, Testa E, Sohaey R, Verhey P, Peck-Radosavljevic M et al (2006) Platelet count/spleen diameter ratio for the noninvasive diagnosis of esophageal varices: results of a multicenter, prospective, validation study. Am J Gastroenterol 101(11):2511–2519 Nyblom H, Björnsson E, Simrén M, Aldenborg F, Almer S, Olsson R (2006) The AST/ALT ratio as an indicator of cirrhosis in patients with PBC. Liver Int 26(7):840–845 Wynn TA, Barron L (2010) Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 30(3):245–257 Mehta P, Ploutz-Snyder R, Nandi J, Rawlins SR, Sanderson SO, Levine RA (2008) Diagnostic accuracy of serum hyaluronic acid, FIBROSpect II, and YKL-40 for discriminating fibrosis stages in chronic hepatitis C. Am J Gastroenterol 103(4):928–936 Sumanth K, Kurpad S, Venkataswamy L, Chandrappa M (2018) Correlative study of hyaluronic acid and YKL-40 with conventional markers for cirrhosis of liver. J Gastroenterol Hepatol 3:14 Sira MM, El-Araby HA, Ghoneim EM, Konsowa HA-S, El-Mwafy EH, Elhenawy IA (2016) Serum YKL-40 (chitinase-3-like protein 1) compared to APRI and FIB-4 in predicting liver fibrosis in children with chronic hepatitis C. Arch Hepat Res 1:15–20 Wang D, Lu JG, Wang Q, Du XL, Dong R, Wang P, Zhao L, Jiang X, Yuan LJ (2012) Increased immunohistochemical expression of YKL-40 in the spleen of patients with portal hypertension. Braz J Med Biol Res 45(3):264–272 Abruzzi A, Fried B, Alikhan SB (2016) Coinfection of schistosoma species with hepatitis B or hepatitis C viruses. Adv Parasitol 91:111–231 Yan L, Deng Y, Zhou J, Zhao H, Wang G (2018) Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT. Infection 46(3):385–393 Qi R, Jin X, Shi H, Wang C, Li H, Shi X (2019) Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension. Ann Hepatol 18(6):898–901 Tripathi D, Hayes PC (2010) The role of carvedilol in the management of portal hypertension. Eur J Gastroenterol Hepatol 22(8):905–911 Abbasi A, Bhutto AR, Butt N, Munir SM, Dhillo AK (2011) Frequency of portal hypertensive gastropathy and its relationship with biochemical, haematological and endoscopic features in cirrhosis. J Coll Physicians Surg Pak 21(12):723–726