Skip to main content

Advertisement

SpringerLink
Log in

The decreased risk of hepatocellular carcinoma in hepatitis B virus-related cirrhotic portal hypertension patients after laparoscopic splenectomy and azygoportal disconnection

  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH).

Methods

A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan–Meier curves, and logistic regression to estimate survival and risk differences.

Results

Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan–Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928–8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343–0.776; P = 0.002).

Conclusion

Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A (2023) Cancer statistics 2023. CA Cancer J Clin 73:17–48

    Article  PubMed  Google Scholar 

  2. Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. The Lancet 391:1301–1314

    Article  Google Scholar 

  3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249

    Article  PubMed  Google Scholar 

  4. Petrick JL, Florio AA, Koshiol J, Pfeiffer RM, Yang BY, Yu K, Chen CJ, Yang HI, Lee MH, McGlynn KA (2020) Prediagnostic concentrations of circulating bile acids and hepatocellular carcinoma risk: REVEAL-HBV and HCV studies. Int J Cancer 147:2743–2753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen WQ, Zheng RS, Baade PD, Zhang SW, Zeng HM, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China 2015. CA Cancer J Clin 66:115–132

    Article  PubMed  Google Scholar 

  6. Cholongitas E, Papatheodoridis GV, Goulis J, Vlachogiannakos J, Karatapanis S, Ketikoglou J, Vasiliadis T, Kontos G, Karlaftis A, Akriviadis E (2015) The impact of newer nucleos(t)ide analogues on patients with hepatitis B decompensated cirrhosis. Ann Gastroenterol 28:109

    PubMed  PubMed Central  Google Scholar 

  7. Yang JQ, Pan GD, Guan LJ, Liu ZP, Wu YR, Liu Z, Lu WC, Li S, Xu HL, Ouyang GQ (2022) The burden of primary liver cancer caused by specific etiologies from 1990 to 2019 at the global, regional, and national levels. Cancer Med 11:1357–1370

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association (2019) The guidelines of prevention and treatment for chronic hepatitis B (2019 version). Zhonghua Gan Zang Bing Za Zhi 27:938–961

    Google Scholar 

  9. Armengol C, Sarrias MR, Sala M (2018) Hepatocellular carcinoma: present and future. Med Clin 150:390–397

    Article  Google Scholar 

  10. Chen XP, Wu ZD, Huang ZY, Qiu FZ (2005) Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism. Br J Surg 92:334–339

    Article  PubMed  Google Scholar 

  11. Bai DS, Jin SJ, Qian JJ, Zhang C, Zhou BH, Jiang GQ (2021) Modified (Bai-Jiang style) vagus nerve-preserving versus conventional laparoscopic splenectomy and azygoportal disconnection: a randomized clinical trial. Surg Endosc 35:1786–1795

    Article  PubMed  Google Scholar 

  12. Bai DS, Chen P, Jin SJ, Qian JJ, Jiang GQ (2018) Vagus nerve-preserving versus conventional laparoscopic splenectomy and azygoportal disconnection. Surg Endosc 32:2696–2703

    Article  PubMed  Google Scholar 

  13. Williamson EJ, Forbes A, White IR (2014) Variance reduction in randomised trials by inverse probability weighting using the propensity score. Stat Med 33:721–737

    Article  PubMed  Google Scholar 

  14. Wang YD, Ye H, Ye ZY, Zhu YQ, Xie ZJ, Zhu JH, Liu JM, Zhao T (2008) Laparoscopic splenectomy and azygoportal disconnection for bleeding varices with hypersplenism. J Laparoendosc Adv Surg Tech A 18:37–41

    Article  PubMed  Google Scholar 

  15. Bai DS, Zhou BH, Qian JJ, Zhang C, Jin SJ, Jiang GQ (2020) Effects of laparoscopic splenectomy and azygoportal disconnection on liver synthesis function and cirrhosis: a 2-year prospective study. Surg Endosc 34:5074–5082

    Article  PubMed  Google Scholar 

  16. Manieri E, Herrera-Melle L, Mora A, Tomás-Loba A, Leiva-Vega L, Fernández DI, Rodríguez E, Morán L, Hernández-Cosido L, Torres JL, Seoane LM, Cubero FJ, Marcos M, Sabio G (2019) Adiponectin accounts for gender differences in hepatocellular carcinoma incidence. J Exp Med 216:1108–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cao ZX, Chen XP, Wu ZD (2003) Effects of splenectomy in patients with cirrhosis undergoing hepatic resection for hepatocellular carcinoma. World J Gastroenterol 9:2460–2463

    PubMed  Google Scholar 

  18. Cao ZX, Chen XP, Wu ZD (2003) Changes of immune function in patients with liver cirrhosis after splenectomy combined with resection of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2:562–565

    CAS  PubMed  Google Scholar 

  19. Akahoshi T, Hashizume M, Tanoue K, Shimabukuro R, Gotoh N, Tomikawa M, Sugimachi K (2002) Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor beta-1. J Gastroenterol Hepatol 17:59–65

    Article  CAS  Google Scholar 

  20. Cho JJ, Hocher B, Herbst H, Jia JD, Ruehl M, Hahn EG, Riecken EO, Schuppan D (2000) An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis. Gastroenterology 118:1169–1178

    Article  CAS  PubMed  Google Scholar 

  21. Han YM, Liu QY, Hou J, Gu Y, Zhang Y, Chen ZB, Fan J, Zhou WP, Qiu SJ, Zhang YH, Dong T, Li N, Jiang ZP, Zhu H, Zhang Q, Ma YW, Zhang LF, Wang QQ, Yu YZ, Li N, Cao XT (2018) Tumor-induced generation of splenicerythroblast-like Ter-cells promotes tumor progression. Cell 173:634–648.e612

    Article  CAS  PubMed  Google Scholar 

  22. Shi HF, Han XQ, Sun YY, Shang C, Wei M, Ba XQ, Zeng XL (2018) Chemokine (C-X-C motif) ligand 1 and CXCL2 produced by tumor promote the generation of monocytic myeloid-derived suppressor cells. Cancer Sci 109:3826–3389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kasai M, Leclerc JC, McVay-Boudreau L, Shen FW, Cantor H (1979) Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo. J Exp Med 149:1260–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lv YF, Wu HF, Lau WY, Zheng JF, Wu JC, Zeng M (2021) Impact of total splenectomy on peripheral lymphocytes and their subsets in patients with hypersplenism associated with cirrhotic portal hypertension. Sci Rep 11:21246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ma SH, Shi YX, Pang YK, Dong F, Cheng H, Hao S, Xu J, Zhu XF, Yuan WP, Cheng T, Zheng GG (2014) Notch1-induced T cell leukemia can be potentiated by microenvironmental cues in the spleen. J Hematol Oncol 7:71

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ugel S, Peranzoni E, Desantis G, Chioda M, Walter S, Weinschenk T, Ochando JC, Cabrelle A, Mandruzzato S, Bronte V (2012) Immune tolerance to tumor antigens occurs in a specialized environment of the spleen. Cell Rep 2:628–639

    Article  CAS  PubMed  Google Scholar 

  27. Yusuke H, Toshiro O, Tetsuro S, Takuto Y, Kyogo I, Hiroyuki T, Koji O (2019) Immunological consequences following splenectomy in patients with liver cirrhosis. Exp Ther Med 18:848–856

    Google Scholar 

  28. Halazun KJ, Hardy MA, Rana AA, Woodland DC, Luyten EJ, Mahadev S, Witkowski P, Siegel AB, Brown RS, Emond JC (2009) Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg 250:141–151

    Article  PubMed  Google Scholar 

  29. Aino H, Sumie S, Niizeki T, Kuromatsu R, Tajiri N, Nakano M, Satani M, Okamura S, Shimose S, Miyahara K, Torimura T (2016) The systemic inflammatory response as a prognostic factor for advanced hepatocellular carcinoma with extrahepatic metastasis. Mol Clin Oncol 5:83–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Qiao WY, Wang Q, Hu CX, Zhang YH, Li JJ, Sun Y, Yuan CW, Wang W, Liu BY, Zhang YH (2022) Interim efficacy and safety of PD-1 inhibitors in preventing recurrence of hepatocellular carcinoma after interventional therapy. Front Immunol 13:6564

    Article  Google Scholar 

  31. Yao JL, Zhu XD, Wu ZH, Wei Q, Cai YB, Zheng Y, Hu XY, Hu H, Zhang XY, Pan HM, Zhong X, Han WD (2022) Efficacy and safety of PD-1 inhibitor combined with antiangiogenic therapy for unresectable hepatocellular carcinoma: a multicenter retrospective study. Cancer Med 11:3612–3622

    Article  CAS  PubMed Central  Google Scholar 

  32. Chen HK, Li ZL, Qiu LM, Dong XQ, Chen G, Shi YJ, Cai LS, Liu WH, Ye HH, Zhou Y, Ouyang JH, Cai ZX, Liu XL (2022) Personalized neoantigen vaccine combined with PD-1 blockade increases CD8 tissue-resident memory T-cell infiltration in preclinical hepatocellular carcinoma models. J Immunother Cancer 10:e004389

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 82173353) and the top talent scientific research project of “six one projects” (LGY2018028).

Author information

Author notes

  1. Tian-Ming Gao, Kun-Qing Xiao, and Xiao-Xing Xiang have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, 98 West Nantong Rd, Yangzhou, 225001, China

    Tian-Ming Gao, Kun-Qing Xiao, Xiao-Xing Xiang, Sheng-Jie Jin, Jian-Jun Qian, Chi Zhang, Bao-Huan Zhou, Dou-Sheng Bai & Guo-Qing Jiang

  2. Department of Digestive Diseases, Clinical Medical College, Yangzhou University, 98 West Nantong Rd, Yangzhou, 225001, China

    Xiao-Xing Xiang

  3. The Administration Office, Yangzhou Blood Center, Yangzhou, 225001, China

    Hua Tang

Authors
  1. Tian-Ming Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kun-Qing Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-Xing Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sheng-Jie Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Jun Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bao-Huan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hua Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dou-Sheng Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guo-Qing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dou-Sheng Bai or Guo-Qing Jiang.

Ethics declarations

Disclosures

Tian-Ming Gao, Kun-Qing Xiao, Xiao-Xing Xiang, Sheng-Jie Jin, Jian-Jun Qian, Chi Zhang, Bao-Huan Zhou, Hua Tang, Dou-Sheng Bai, and Guo-Qing Jiang have no conflicts of interest or financial ties to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 121 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, TM., Xiao, KQ., Xiang, XX. et al. The decreased risk of hepatocellular carcinoma in hepatitis B virus-related cirrhotic portal hypertension patients after laparoscopic splenectomy and azygoportal disconnection. Surg Endosc 37, 8522–8531 (2023). https://doi.org/10.1007/s00464-023-10454-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-023-10454-7

Keywords

Search

Navigation