Role of Serum M2BPGi Levels on Diagnosing Significant Liver Fibrosis and Cirrhosis in Treated Patients with Chronic Hepatitis B Virus Infection

Overview

Journal Clin Transl Gastroenterol

Specialty Gastroenterology

Date 2018 Jun 20

PMID 29915243

Citations 16

Authors

Lung-Yi Mak

Danny Ka-Ho Wong

Ka-Shing Cheung

Wai-Kay Seto

Ching-Lung Lai

Man-Fung Yuen

Affiliations

Soon will be listed here.

Abstract

Background: Mac-2-binding protein glycosylation isomer (M2BPGi), a novel serum marker for liver fibrosis, was seldom studied in chronic hepatitis B (CHB). We aimed to evaluate its role on diagnosing significant fibrosis and cirrhosis in treated CHB patients.

Methods: CHB patients treated with nucleos(t)ide analogues (NAs) with baseline liver biopsies and retrievable serum samples were recruited. Paired liver biopsies were performed in patient subgroups at 1 and 3 years.

Results: In total, 327 NA-treated CHB patients (M:F = 229:98; median age 38.1 years) were recruited. The median M2BPGi values were 0.26, 0.34, 0.57 and 1.21 cutoff index (COI), in liver histology with Ishak F0-1, F2, F3 and F4, respectively (p < 0.01). M2BPGi levels correlated with the Ishak scores (ρ = 0.312, p < 0.001). Using the cutoff values of 0.25, 0.45 and 0.96 COI for ≥F2, ≥F3 and F4, the AUROCs were 0.653, 0.795 and 0.914, respectively. Multivariate analysis with several other serum indices showed that M2BPGi was the most significant independent factor for ≥F3 (OR: 8.197, 95% CI: 2.699-24.897, p < 0.001). In patient subgroups with serial liver biopsies, both the proportion of F3/F4 and M2BPGi decreased at 1 year (8.3% vs. 2.8% and 0.32 vs. 0.21 COI, respectively; both p < 0.001). Histological fibrosis progression after ≥3 years of NA therapy accompanied with an increase in M2BPGi level, compared to patients without progression (+0.14 vs -0.03 COI, p = 0.045).

Conclusion: Serum M2BPGi is a reliable non-invasive marker for diagnosing ≥F2, ≥F3 and F4. It is the only significant marker for ≥F3 among several other indices. NA produced concordant dynamic changes in M2BPGi levels and histological fibrosis.

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References

Fraser J, Gibson P . Mechanisms by which food intake elevates circulating levels of hyaluronan in humans. J Intern Med. 2005; 258(5):460-6. DOI: 10.1111/j.1365-2796.2005.01564.x. View

Nishikawa H, Enomoto H, Iwata Y, Kishino K, Shimono Y, Hasegawa K . Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein for patients with chronic hepatitis B and C: a comparative study. J Viral Hepat. 2016; 23(12):977-984. DOI: 10.1111/jvh.12575. View

Nishikawa H, Takata R, Enomoto H, Yoh K, Kishino K, Shimono Y . Proposal of a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin-positive Mac-2-binding protein in chronic hepatitis C. Hepatol Res. 2016; 47(3):E74-E84. DOI: 10.1111/hepr.12724. View

Nakamura Y, Aikata H, Fukuhara T, Honda F, Morio K, Morio R . Liver fibrosis assessment by FibroScan compared with pathological findings of liver resection specimen in hepatitis C infection. Hepatol Res. 2016; 47(8):767-772. DOI: 10.1111/hepr.12815. View

Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M . Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005; 128(2):343-50. DOI: 10.1053/j.gastro.2004.11.018. View

Nishikawa H, Enomoto H, Iwata Y, Hasegawa K, Nakano C, Takata R . Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level and high-sensitivity C-reactive protein concentration in autoimmune hepatitis. Hepatol Res. 2015; 46(7):613-21. DOI: 10.1111/hepr.12596. View

Cheung K, Seto W, Wong D, Mak L, Lai C, Yuen M . Wisteria floribunda agglutinin-positive human Mac-2 binding protein predicts liver cancer development in chronic hepatitis B patients under antiviral treatment. Oncotarget. 2017; 8(29):47507-47517. PMC: 5564582. DOI: 10.18632/oncotarget.17670. View

ISHAK K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F . Histological grading and staging of chronic hepatitis. J Hepatol. 1995; 22(6):696-9. DOI: 10.1016/0168-8278(95)80226-6. View

Kuno A, Ikehara Y, Tanaka Y, Ito K, Matsuda A, Sekiya S . A serum "sweet-doughnut" protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis. Sci Rep. 2013; 3:1065. PMC: 3545220. DOI: 10.1038/srep01065. View

10.

Afdhal N, Bacon B, Patel K, Lawitz E, Gordon S, Nelson D . Accuracy of fibroscan, compared with histology, in analysis of liver fibrosis in patients with hepatitis B or C: a United States multicenter study. Clin Gastroenterol Hepatol. 2014; 13(4):772-9.e1-3. DOI: 10.1016/j.cgh.2014.12.014. View

11.

Schiff E, Lee S, Chao Y, Yoon S, Bessone F, Wu S . Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2010; 9(3):274-6. DOI: 10.1016/j.cgh.2010.11.040. View

12.

Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson I . Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2012; 381(9865):468-75. DOI: 10.1016/S0140-6736(12)61425-1. View

13.

Papastergiou V, Tsochatzis E, Burroughs A . Non-invasive assessment of liver fibrosis. Ann Gastroenterol. 2014; 25(3):218-231. PMC: 3959378. View

14.

Umemura T, Joshita S, Sekiguchi T, Usami Y, Shibata S, Kimura T . Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein Level Predicts Liver Fibrosis and Prognosis in Primary Biliary Cirrhosis. Am J Gastroenterol. 2015; 110(6):857-64. DOI: 10.1038/ajg.2015.118. View

15.

Abe M, Miyake T, Kuno A, Imai Y, Sawai Y, Hino K . Association between Wisteria floribunda agglutinin-positive Mac-2 binding protein and the fibrosis stage of non-alcoholic fatty liver disease. J Gastroenterol. 2014; 50(7):776-84. DOI: 10.1007/s00535-014-1007-2. View

16.

Poynard T, Morra R, Halfon P, Castera L, Ratziu V, Imbert-Bismut F . Meta-analyses of FibroTest diagnostic value in chronic liver disease. BMC Gastroenterol. 2007; 7:40. PMC: 2175505. DOI: 10.1186/1471-230X-7-40. View

17.

Volpi N, Schiller J, Stern R, Soltes L . Role, metabolism, chemical modifications and applications of hyaluronan. Curr Med Chem. 2009; 16(14):1718-45. DOI: 10.2174/092986709788186138. View

18.

Yamada N, Sanada Y, Tashiro M, Hirata Y, Okada N, Ihara Y . Serum Mac-2 binding protein glycosylation isomer predicts grade F4 liver fibrosis in patients with biliary atresia. J Gastroenterol. 2016; 52(2):245-252. DOI: 10.1007/s00535-016-1235-8. View

19.

Ura K, Furusyo N, Ogawa E, Hayashi T, Mukae H, Shimizu M . Serum WFA(+) -M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C. Aliment Pharmacol Ther. 2015; 43(1):114-24. DOI: 10.1111/apt.13431. View

20.

Kojiro M, Shimamatsu K, Kage M . Pathomorphologic comparison of hepatitis C virus-related and hepatitis B virus-related cirrhosis bearing hepatocellular carcinoma. Princess Takamatsu Symp. 1995; 25:179-84. View