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Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients

Abstract

Background

Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC.

Methods

From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome.

Results

Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018–1.660; P = 0.036) and RFS (1.314; 1.062–1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004–2.151; P = 0.047).

Conclusions

In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.

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References

  1. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6.

    Article  Google Scholar 

  2. Wong M, Huang J, George J, Huang J, Leung C, Eslam M, et al. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol. 2019;16:57–73.

    Article  Google Scholar 

  3. Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3:1683–91.

    Article  Google Scholar 

  4. Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-medicare database. Hepatology. 2011;54:463–71.

    Article  Google Scholar 

  5. Li R, Li W, Lun Z, Zhang H, Sun Z, Kanu JS, et al. Prevalence of metabolic syndrome in Mainland China: a meta-analysis of published studies. BMC Public Health. 2016;16:296.

    Article  Google Scholar 

  6. Yang M, Wei L. Impact of NAFLD on the outcome of patients with chronic hepatitis B in Asia. Liver Int. 2022.

  7. Dhir M, Melin AA, Douaiher J, Lin C, Zhen WK, Hussain SM, et al. A review and update of treatment options and controversies in the management of hepatocellular carcinoma. Ann Surg. 2016;263:1112–25.

    Article  Google Scholar 

  8. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358–80.

    Article  Google Scholar 

  9. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.

    Article  Google Scholar 

  10. Wang MD, Li C, Liang L, Xing H, Sun LY, Quan B, et al. Early and Late Recurrence of Hepatitis B Virus-Associated Hepatocellular Carcinoma. Oncologist. 2020;25:e1541-1541e1551.

    CAS  Article  Google Scholar 

  11. Xu XF, Xing H, Han J, Li ZL, Lau WY, Zhou YH, et al. risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China. JAMA Surg. 2019;154:209–17.

    Article  Google Scholar 

  12. Wu JC, Huang YH, Chau GY, Su CW, Lai CR, Lee PC, et al. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol. 2009;51:890–7.

    Article  Google Scholar 

  13. Sohn W, Paik YH, Kim JM, Kwon CH, Joh JW, Cho JY, et al. HBV DNA and HBsAg levels as risk predictors of early and late recurrence after curative resection of HBV-related hepatocellular carcinoma. Ann Surg Oncol. 2014;21:2429–35.

    Article  Google Scholar 

  14. Du ZG, Wei YG, Chen KF, Li B. Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution’s experience with 398 consecutive patients. Hepatobiliary Pancreat Dis Int. 2014;13:153–61.

    CAS  Article  Google Scholar 

  15. Anstee QM, Reeves HL, Kotsiliti E, Govaere O, Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol. 2019;16:411–28.

    Article  Google Scholar 

  16. Borena W, Strohmaier S, Lukanova A, Bjørge T, Lindkvist B, Hallmans G, et al. Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults. Int J Cancer. 2012;131:193–200.

    CAS  Article  Google Scholar 

  17. Jinjuvadia R, Patel S, Liangpunsakul S. The association between metabolic syndrome and hepatocellular carcinoma: systemic review and meta-analysis. J Clin Gastroenterol. 2014;48:172–7.

    CAS  Article  Google Scholar 

  18. Pawlik TM, Soubrane O. Metabolic syndrome-associated hepatocellular carcinoma: questions still unanswered. J Hepatol. 2015;63:8–9.

    Article  Google Scholar 

  19. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–5.

    CAS  Article  Google Scholar 

  20. Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2010;375:181–3.

    Article  Google Scholar 

  21. [Expert recommendations on standardized diagnosis and treatment for fatty liver disease in China (2019 revised edition)]. Zhonghua Gan Zang Bing Za Zhi. 2019;27:748–53.

  22. Yu JJ, Shen F, Chen TH, Liang L, Han J, Xing H, et al. Multicentre study of the prognostic impact of preoperative bodyweight on long-term prognosis of hepatocellular carcinoma. Br J Surg. 2019;106:276–85.

    CAS  Article  Google Scholar 

  23. Strasberg SM, Phillips C. Use and dissemination of the brisbane 2000 nomenclature of liver anatomy and resections. Ann Surg. 2013;257:377–82.

    Article  Google Scholar 

  24. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  Google Scholar 

  25. Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243:229–35.

    Article  Google Scholar 

  26. Gu D, Reynolds K, Wu X, Chen J, Duan X, Reynolds RF, et al. Prevalence of the metabolic syndrome and overweight among adults in China. Lancet. 2005;365:1398–405.

    Article  Google Scholar 

  27. Xing Y, Xu S, Jia A, Cai J, Zhao M, Guo J, et al. Recommendations for revision of Chinese diagnostic criteria for metabolic syndrome: a nationwide study. J Diabetes. 2018;10:232–9.

    Article  Google Scholar 

  28. Ma WY, Yang CY, Shih SR, Hsieh HJ, Hung CS, Chiu FC, et al. Measurement of Waist Circumference: midabdominal or iliac crest. Diabetes Care. 2013;36:1660–6.

    CAS  Article  Google Scholar 

  29. Yoshida N, Takayama T, Midorikawa Y, Higaki T, Nakayama H, Moriguchi M, et al. Surgical outcomes in patients with hepatocellular carcinoma associated with metabolic syndrome. World J Surg. 2015;39:471–7.

    Article  Google Scholar 

  30. Cauchy F, Zalinski S, Dokmak S, Fuks D, Farges O, Castera L, et al. Surgical treatment of hepatocellular carcinoma associated with the metabolic syndrome. Br J Surg. 2013;100:113–21.

    CAS  Article  Google Scholar 

  31. Viganò L, Conci S, Cescon M, Fava C, Capelli PD et al. Liver resection for hepatocellular carcinoma in patients with metabolic syndrome: a multicenter matched analysis with HCV-related HCC. J Hepatol. 2015;63:93–101.

  32. Tian Y, Lyu H, He Y, Xia Y, Li J, Shen F. Comparison of hepatectomy for patients with metabolic syndrome-related HCC and HBV-related HCC. J Gastrointest Surg. 2018;22:615–23.

    Article  Google Scholar 

  33. Jia HD, Liang L, Li C, Wu H, Wang H, Liang YJ, et al. Long-term surgical outcomes of liver resection for hepatocellular carcinoma in patients with HBV and HCV co-infection: a multicenter observational study. Front Oncol. 2021;11:700228.

    Article  Google Scholar 

  34. Wu Y, Dong Y, Duan S, Zhu D, Deng L. Metabolic syndrome, inflammation, and cancer. Mediators Inflamm. 2017;2017:8259356.

    PubMed  PubMed Central  Google Scholar 

  35. Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–21.

    CAS  Article  Google Scholar 

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Acknowledgment

This study was supported by the National Natural Science Foundation of China (No. 81972726), Dawn Project Foundation of Shanghai (No. 21SG36), Adjunct Talent Fund of Zhejiang Provincial People’s Hospital (No. 2021-YT), the Natural Science Foundation of Shanghai (No. 22ZR1477900) and Shanghai Science and Technology Committee Rising-Star Program (No. 22QA1411600).

Funding

The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

Authors

Contributions

Conception: M-DW, S-CT, CL, L-YS, XX, WYL, TY; Study design: M-DW, Y-YZ, TY; Administrative support: Y-YZ, FS, TY; Data collection and acquisition: M-DW, CL, S-CT, XX, Y-JL, F-BL, W-MG, X-MW, Y-HZ; Data analysis: M-DW, S-CT, CL, L-QY, Y-KD; Manuscript preparation: M-DW, CL, S-CT, L-YS, XX, L-HG, TY; Critical revision: WYL, FS, Y-YZ, TY; Final approval of manuscript: All authors.

Corresponding authors

Correspondence to Feng Shen MD, PhD, Yong-Yi Zeng MD or Tian Yang MD.

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The study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Boards of all the participating hospitals.

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Wang, MD., Tang, SC., Li, C. et al. Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients. Ann Surg Oncol (2022). https://doi.org/10.1245/s10434-022-12529-6

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  • DOI: https://doi.org/10.1245/s10434-022-12529-6