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Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study

Abstract

Background & Aim

Search for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remains an important issue. This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation in patients with HBV-ACLF.

Methods

45 consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among these patients, 11 received both plasma exchange (PE) and a single transplantation of UC-MSCs (group A), while 34 received only PE (group B). The primary endpoint was survival at 24 months.

Results

Compared with group B, levels of albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin time (PT), international normalized ratio (INR) and model for end-stage liver disease score in group A improved significantly at 4 weeks after transplantation (p < 0.05). Levels of albumin, PT and INR in group A were also markedly improved at 24 months (p < 0.05). Group A had significantly higher cumulative survival rate at 24 months (54.5 % v.s. 26.5 %, p = 0.015 by log rank test). Between the two groups, levels of creatinine, White blood cell, hemoglobin and platelet were similar. HBeAg loss and hepatocellular carcinoma incidence were similar at 24 months. Group assignment (relative risk: 2.926, 95%confidence interval: 1.043–8.203, p = 0.041) was an independent predictor for survival at 24 months. Success rate of UC-MSC transplantation was 100 % in group A. No severe adverse event was observed in any patient.

Conclusion

UC-MSC transplantation is safe and effective for HBV-ACLF patients treated with PE and entecavir. It further improves the hepatic function and survival.

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Fig. 1

Abbreviations

HBV-ACLF:

Hepatitis B virus related acute-on-chronic liver failure

LT:

Liver transplantation

ALS:

Artificial liver support systems

PE:

Plasma exchange

ETV:

Entecavir

MSCs:

Mesenchymal stem cells

BM-MSCs:

Bone marrow-derived MSCs

UC-MSCs:

Umbilical cord-derived MSCs

INR:

International normalized ratio

PTA:

Prothrombin activity

PLT:

Platelet

HBsAg:

Hepatitis B surface antigen

NAs:

Nucleos(t)ide analogs

HCV:

Hepatitis C virus

HDV:

Hepatitis D virus

HIV:

Human immunodeficiency virus

HCC:

Hepatocellular carcinoma

AFP:

Alpha-fetoprotein

CT:

Computed tomography

USG:

Ultrasonography

PT:

Prothrombin time

CBC:

Complete blood count

MELD:

Model for end-stage liver disease

SD:

Standard deviation

ALT:

Alanine amnotransferase

AST:

Aspartate aminotransferase

TBIL:

Total bilirubin

DBIL:

Direct bilirubin

Cr:

Creatinine

WBC:

White blood cell

HGB:

Hemoglobulin

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Acknowledgments

We kindly thank Prof. Jin-Hui Yang for his theoretical support and for permitting us to carry out this study. We thank Mr. Hong-Wei Wang from Shenzhen Baike Cell Engineering Research Institute for providing human UC-MSCs and instructing the clinical application of UC-MSCs. We thank interventional radiologists Prof. Ying-Chun Li and Song-Wei Li for their technical support in performing transplantation of UC-MSCs via the hepatic artery.

Author information

Correspondence to Wan Yue-Meng.

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The authors declare that they have no conflicts of interest.

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Li, Y., Xu, Y., Wu, H. et al. Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study. Stem Cell Rev and Rep 12, 645–653 (2016). https://doi.org/10.1007/s12015-016-9683-3

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Keywords

  • Acute-on-chronic liver failure
  • Mesenchymal stem cell
  • Plasma exchange
  • Hepatitis b virus
  • Antiviral agents