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Novel strategy of sirolimus plus thymalfasin and huaier granule on tumor recurrence of hepatocellular carcinoma beyond the UCSF criteria following liver transplantation: A single center experience.

Authors
  • Zhou, Lin1, 2
  • Pan, Li-Chao1, 2
  • Zheng, Yong-Gen1, 2
  • Du, Guo-Sheng1
  • Fu, Xiao-Qian1
  • Zhu, Zhi-Dong1
  • Song, Ji-Yong1
  • Liu, Zhi-Jia1
  • Su, Xiang-Zheng2
  • Chen, Wen2
  • Zheng, De-Hua1
  • Suo, Long-Long1
  • Yang, Shao-Zhen1
  • 1 Department of Hepatobiliary Surgery, Organ Transplant Institute, Chinese PLA 309th Hospital, Beijing 100091, P.R. China. , (China)
  • 2 Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China. , (China)
Type
Published Article
Journal
Oncology Letters
Publisher
Spandidos Publications
Publication Date
Oct 01, 2018
Volume
16
Issue
4
Pages
4407–4417
Identifiers
DOI: 10.3892/ol.2018.9226
PMID: 30214575
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18). The SRL+ group had significantly longer recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1-year: 100%, 3-year: 94.4%, 5-year: 77.8%; DFS, 1-year: 88.9%, 3-year: 55.6%, 5-year: 50.0%). Furthermore, compared with pre-LT values and the control group, the SRL+ group had significantly lower serum α-fetoprotein (AFP) levels (both P<0.0001) and percentage of Forkhead box P3 (FoxP3)+ Treg lymphocytes (P<0.001) during the first year. In the SRL+ group, FoxP3+/cluster of differentiation (CD)8+ Treg lymphocyte percentages decreased significantly following LT (P<0.001); however, CD8+/CD3+ T-cells significantly increased (P<0.001). Levels of serum AFP and FoxP3+ Treg cells increased when tumors relapsed, and decreased to near-normal when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and Treg levels, while increasing CD8+ T cells, indicating an associated mechanism among them. In conclusion, SRL+ therapy appears to be safe and effective in preventing HCC recurrence following LT with no significant adverse events, and warrants further investigation.

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