Clinical Validation of Preoperative Serum Markers for Liver Fibrosis in Living Donor Liver Transplantation Recipients

Overview

Journal Surg Today

Specialty General Surgery

Date 2024 Sep 24

PMID 39317845

Authors

Takahiro Tomino

Shinji Itoh

Takeo Toshima

Shohei Yoshiya

Yuki Bekki

Norifumi Iseda

Takuma Izumi

Yuriko Tsutsui

Katsuya Toshida

Tomoharu Yoshizumi

Affiliations

Soon will be listed here.

Abstract

Purpose: To validate the reliability of fibrosis markers as predictors of graft survival in living donor liver transplantation (LDLT) recipients.

Methods: We reviewed data retrospectively, from 163 patients who underwent adult LDLT with preoperative measurements of type IV collagen (CIV), Mac-2 binding protein glycosylation isomer (M2BPGi), and hyaluronic acid (HA). Patients were divided into high and low groups for each biomarker, based on optimal cutoff values, and graft loss within 6 months was evaluated in each group.

Results: The high CIV level group showed significantly lower 6-month graft survival rates and significantly higher rates of postoperative sepsis and sepsis from pneumonia. However, the groups with high and low M2BPGi levels and those with high and low HA levels did not show significant differences in 6-month graft survival rates or rates of postoperative sepsis. Multivariate analysis revealed that a CIV level ≥ 590 was a significant predictor of graft loss within 6 months, postoperative sepsis, and sepsis from pneumonia.

Conclusion: Unlike other fibrosis markers, preoperative CIV levels can predict graft survival, postoperative sepsis, and sepsis from pneumonia after LDLT.

Citing Articles

Surgical treatment for hepatocellular carcinoma in era of multidisciplinary strategies.

Takamoto T, Mihara Y, Nishioka Y, Ichida A, Kawaguchi Y, Akamatsu N Int J Clin Oncol. 2025; 30(3):417-426.

PMID: 39907863 PMC: 11842484. DOI: 10.1007/s10147-025-02703-7.

References

Mak K, Chen L, Lee T . Codistribution of collagen type IV and laminin in liver fibrosis of elderly cadavers: immunohistochemical marker of perisinusoidal basement membrane formation. Anat Rec (Hoboken). 2013; 296(6):953-64. DOI: 10.1002/ar.22694. View

Mizuno M, Shima T, Oya H, Mitsumoto Y, Mizuno C, Isoda S . Classification of patients with non-alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers. Hepatol Res. 2016; 47(2):216-225. DOI: 10.1111/hepr.12710. View

Angulo P, Kleiner D, Dam-Larsen S, Adams L, Bjornsson E, Charatcharoenwitthaya P . Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015; 149(2):389-97.e10. PMC: 4516664. DOI: 10.1053/j.gastro.2015.04.043. View

Shirabe K, Bekki Y, Gantumur D, Araki K, Ishii N, Kuno A . Mac-2 binding protein glycan isomer (M2BPGi) is a new serum biomarker for assessing liver fibrosis: more than a biomarker of liver fibrosis. J Gastroenterol. 2018; 53(7):819-826. DOI: 10.1007/s00535-017-1425-z. View

Bekki Y, Yoshizumi T, Shimoda S, Itoh S, Harimoto N, Ikegami T . Hepatic stellate cells secreting WFA -M2BP: Its role in biological interactions with Kupffer cells. J Gastroenterol Hepatol. 2016; 32(7):1387-1393. DOI: 10.1111/jgh.13708. View

Ito K, Murotani K, Nakade Y, Inoue T, Nakao H, Sumida Y . Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein levels and liver fibrosis: A meta-analysis. J Gastroenterol Hepatol. 2017; 32(12):1922-1930. DOI: 10.1111/jgh.13802. View

Guechot J, Laudat A, Loria A, Serfaty L, Poupon R, Giboudeau J . Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clin Chem. 1996; 42(4):558-63. View

Neuman M, Cohen L, Nanau R . Hyaluronic acid as a non-invasive biomarker of liver fibrosis. Clin Biochem. 2015; 49(3):302-15. DOI: 10.1016/j.clinbiochem.2015.07.019. View

Yoshizumi T, Itoh S, Shimokawa M, Inokuchi S, Harada N, Takeishi K . Simultaneous splenectomy improves outcomes after adult living donor liver transplantation. J Hepatol. 2020; 74(2):372-379. DOI: 10.1016/j.jhep.2020.08.017. View

10.

Yoshiya S, Harada N, Toshima T, Toshida K, Kosai Y, Tomino T . Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria. Surg Today. 2023; 54(1):64-72. DOI: 10.1007/s00595-023-02710-z. View

11.

Yoshizumi T, Mori M . Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy. Surg Today. 2019; 50(1):21-29. PMC: 6949207. DOI: 10.1007/s00595-019-01881-y. View

12.

Yoshizumi T, Ikegami T, Bekki Y, Ninomiya M, Uchiyama H, Iguchi T . Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era. Liver Transpl. 2013; 20(3):323-32. DOI: 10.1002/lt.23804. View

13.

Mizuno S, Das B, Iizawa Y, Kato H, Murata Y, Tanemura A . Pretransplant Serum Hyaluronic Acid Can Be a Biomarker as a Prognostic Predictor in Adult-to-Adult Living Donor Liver Transplantation. Transplant Proc. 2017; 49(1):102-108. DOI: 10.1016/j.transproceed.2016.11.019. View

14.

Mittler J, Heinrich S, Koch M, Hoppe-Lotichius M, Hadian A, Weinmann A . Elderly Patients with Hepatocellular Carcinoma Benefit from Liver Transplantation as Much as Younger Ones. Liver Cancer. 2023; 12(2):171-177. PMC: 10267523. DOI: 10.1159/000528830. View

15.

Toshima T, Harada N, Itoh S, Tomiyama T, Toshida K, Morita K . What Are Risk Factors for Graft Loss in Patients Who Underwent Simultaneous Splenectomy During Living-donor Liver Transplantation?. Transplantation. 2024; 108(7):1593-1604. DOI: 10.1097/TP.0000000000004952. View

16.

Ikegami T, Yoshizumi T, Sakata K, Uchiyama H, Harimoto N, Harada N . Left lobe living donor liver transplantation in adults: What is the safety limit?. Liver Transpl. 2016; 22(12):1666-1675. DOI: 10.1002/lt.24611. View

17.

Ikegami T, Shirabe K, Yoshiya S, Yoshizumi T, Yamashita Y, Harimoto N . A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation. Surg Today. 2013; 44(2):233-40. DOI: 10.1007/s00595-013-0523-7. View

18.

Mazzoran L, Tamaro G, MANGIAROTTI M, Marchi P, Baracetti S, Gerini U . Effects of interferon therapy on fibrosis serum markers in HCV-positive chronic liver disease. Eur J Gastroenterol Hepatol. 1998; 10(2):125-31. DOI: 10.1097/00042737-199802000-00005. View

19.

Ogawa E, Furusyo N, Toyoda K, Takeoka H, Otaguro S, Hamada M . Transient elastography for patients with chronic hepatitis B and C virus infection: Non-invasive, quantitative assessment of liver fibrosis. Hepatol Res. 2007; 37(12):1002-10. DOI: 10.1111/j.1872-034X.2007.00160.x. View

20.

Stefano J, Guedes L, de Souza A, Vanni D, Alves V, Carrilho F . Usefulness of collagen type IV in the detection of significant liver fibrosis in nonalcoholic fatty liver disease. Ann Hepatol. 2020; 20:100253. DOI: 10.1016/j.aohep.2020.08.070. View