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Liver Resection for Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: a Multicenter Propensity Matching Analysis with HBV-HCC

  • Tian YangEmail author
  • Lun-Yang Hu
  • Zhen-Li Li
  • Kai Liu
  • Han Wu
  • Hao Xing
  • Wan Yee Lau
  • Timothy M. Pawlik
  • Yong-Yi Zeng
  • Ya-Hao Zhou
  • Wei-Min Gu
  • Hong Wang
  • Ting-Hao Chen
  • Jun Han
  • Chao Li
  • Ming-Da Wang
  • Meng-Chao Wu
  • Feng ShenEmail author
Original Article
  • 86 Downloads

Abstract

Background

The incidence of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Higher perioperative risks may be anticipated due to underlying steatohepatitis, while long-term outcomes after liver resection are unknown. We sought to investigate outcomes after liver resection for NAFLD-HCC versus hepatitis B virus (HBV)-HCC using propensity score matching (PSM).

Methods

Consecutive patients who underwent liver resection for HCC between 2003 and 2014 were identified from a multicenter database. Patients with NAFLD-HCC were matched one-to-one to patients with HBV-HCC.

Results

Among 1483 patients identified, 96 (6.5%) had NAFLD-HCC and 1387 (93.5%) had HBV-HCC. Patients with NAFLD-HCC were older (median age 57 vs. 50 years), more often overweight (50.0% vs. 37.5%), less often to have cirrhosis (30.2% vs. 72.5%) and liver dysfunction (Child-Pugh B: 4.2% vs. 10.7%), had larger tumor size (median 7.2 vs. 6.2 cm) yet had better tumor differentiation (27.1% vs. 17.6%) compared with patients with HBV-HCC (all P < 0.05). Perioperative mortality and morbidity were comparable between the two groups (1.0% vs. 1.4% and 20.8% vs. 23.2%, both P > 0.05). No differences were noted in median OS and RFS among patient with NAFLD-HCC versus HBV-HCC before or after PSM.

Conclusion

While patients with NAFLD-HCC had different clinical characteristics than patients with HBV-HCC, liver resection resulted in similar perioperative outcomes and comparable OS and RFS among patients with NAFLD-HCC and HBV-HCC.

Keywords

Hepatocellular carcinoma Hepatectomy Non-alcoholic fatty liver disease Hepatitis B virus Overall survival Recurrence-free survival 

Abbreviations

HCC

hepatocellular carcinoma

HBV

hepatitis B virus

HCV

hepatitis C virus

NAFLD

non-alcoholic fatty liver disease

NASH

non-alcoholic steatohepatitis

HEV

hepatitis E virus

BMI

body mass index

ASA

American Society of Anesthesiologists

AST

aspartate transaminase

ALT

alanine aminotransferase

AFP

alpha-fetoprotein

CT

computed tomography

MRI

magnetic resonance imaging

PSM

propensity score matching

OS

overall survival

RFS

recurrence-free survival

95% CI

95% confidence interval.

Notes

Author’s Contribution

Conception: Tian Yang, Wan Yee Lau, Feng Shen; Study design: Tian Yang, Lun-Yang Hu, Zhen-Li Li, Jun Han, Hao Xing, Han Wu; Administrative support: Meng-Chao Wu, Feng Shen; Data collection and acquisition: Chao Li, Ming-Da Wang, Yong-Yi Zeng, Ya-Hao Zhou, Ting-Hao Chen, Wei-Min Gu, Hong Wang; Data analysis: Hao Xing, Zhen-Li Li, Jun Han, Tian Yang; Manuscript preparation: Tian Yang, Lun-Yang Hu, Zhen-Li Li, Kai Liu, Jun Han, Hao Xing, Han Wu; Critical revision: Wan Yee Lau, Timothy M. Pawlik, Feng Shen; Final approval of manuscript: All authors.

Funding Information

This work was supported in part by the National Natural Science Foundation of China (No. 81472284 and 81672699), and Shanghai Pujiang Program (No. 16PJD004).

Compliance with Ethical Standards

The study was performed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies of all the six enrolled hospitals.

References

  1. 1.
    Gerbes A, Zoulim F, Tilg H, Dufour JF, Bruix J, Paradis V, Salem R, Peck-Radosavljevic M, Galle PR, Greten TF, Nault JC, Avila MA. Gut roundtable meeting paper: selected recent advances in hepatocellular carcinoma. Gut 2018;67(2):380–8.CrossRefGoogle Scholar
  2. 2.
    Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology 2004;127(5):1372–80.CrossRefGoogle Scholar
  3. 3.
    Bertuccio P, Turati F, Carioli G, Rodriguez T, La Vecchia C, Malvezzi M, Negri E. Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol 2017;67(2):302–9.CrossRefGoogle Scholar
  4. 4.
    Goh GB, Chang PE, Tan CK. Changing epidemiology of hepatocellular carcinoma in Asia. Best Pract Res Clin Gastroenterol 2015;29(6):919–28.CrossRefGoogle Scholar
  5. 5.
    Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313–21.CrossRefGoogle Scholar
  6. 6.
    Pascale A, Pais R, Ratziu V. An overview of nonalcoholic steatohepatitis: past, present and future directions. J Gastrointestin Liver Dis 2010;19(4):415–23.Google Scholar
  7. 7.
    De Minicis S, Day C, Svegliati-Baroni G. From NAFLD to NASH and HCC: pathogenetic mechanisms and therapeutic insights. Curr Pharm Des 2013;19(29):5239–49.CrossRefGoogle Scholar
  8. 8.
    Adams LA, Lymp JF, St SJ, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129(1):113–21.CrossRefGoogle Scholar
  9. 9.
    Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010;51(5):1820–32.CrossRefGoogle Scholar
  10. 10.
    Birjandi M, Ayatollahi SM, Pourahmad S, Safarpour AR. Prediction and Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) and Identification of Its Associated Factors Using the Classification Tree Method. Iran Red Crescent Med J 2016;18(11):e32858.CrossRefGoogle Scholar
  11. 11.
    Reddy SK, Steel JL, Chen HW, DeMateo DJ, Cardinal J, Behari J, Humar A, Marsh JW, Geller DA, Tsung A. Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology 2012;55(6):1809–19.CrossRefGoogle Scholar
  12. 12.
    Pais R, Fartoux L, Goumard C, Scatton O, Wendum D, Rosmorduc O, Ratziu V. Temporal trends, clinical patterns and outcomes of NAFLD-related HCC in patients undergoing liver resection over a 20-year period. Aliment Pharmacol Ther 2017;46(9):856–63.CrossRefGoogle Scholar
  13. 13.
    Piscaglia F, Svegliati-Baroni G, Barchetti A, Pecorelli A, Marinelli S, Tiribelli C, Bellentani S. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study. Hepatology 2016;63(3):827–38.CrossRefGoogle Scholar
  14. 14.
    Yang T, Lu JH, Lau WY, Zhang TY, Zhang H, Shen YN, Alshebeeb K, Wu MC, Schwartz M, Shen F. Perioperative blood transfusion does not influence recurrence-free and overall survivals after curative resection for hepatocellular carcinoma: A Propensity Score Matching Analysis. J Hepatol 2016;64(3):583–93.Google Scholar
  15. 15.
    Strasberg SM, Phillips C. Use and dissemination of the brisbane 2000 nomenclature of liver anatomy and resections. Ann Surg 2013;257(3):377–82.CrossRefGoogle Scholar
  16. 16.
    Yang T, Zhang J, Lu JH, Yang GS, Wu MC, Yu WF. Risk factors influencing postoperative outcomes of major hepatic resection of hepatocellular carcinoma for patients with underlying liver diseases. World J Surg 2011. 35(9): 2073–82.CrossRefGoogle Scholar
  17. 17.
    Yang T, He H, Yuan J, et al. Surgery for hepatocellular carcinoma presenting with variceal bleeding: The eastern experience. J Surg Oncol 2016. 113(2): 165–74.CrossRefGoogle Scholar
  18. 18.
    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(2):205–13.CrossRefGoogle Scholar
  19. 19.
    Rubin DB, Thomas N. Matching using estimated propensity scores: relating theory to practice. Biometrics 1996;52(1):249–64.CrossRefGoogle Scholar
  20. 20.
    Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat 1985;39:33–8.Google Scholar
  21. 21.
    Yang T, Tabrizian P, Zhang H, Lau WY, Han J, Li ZL, Wang Z, Wu MC, Florman S, Schwartz ME, Shen F. Comparison of patterns and outcomes of liver resection for hepatocellular carcinoma: East vs West. Clin Gastroenterol Hepatol 2017;15(12):1972–4.CrossRefGoogle Scholar
  22. 22.
    Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013;10(11):686–90.CrossRefGoogle Scholar
  23. 23.
    Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018;15(1):11–20.CrossRefGoogle Scholar
  24. 24.
    Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J, Colombo M, Craxi A, Crespo J, Day CP, Geier A, Kondili LA, Lazarus JV, Loomba R, Manns MP, Marchesini G, Negro F, Petta S, Ratziu V, Romero-Gomez M, Sanyal A, Schattenberg JM, Tacke F, Trautwein C, Wei L, Zeuzem S, Razavi H. Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol 2018. DOI:  https://doi.org/10.1016/j.jhep.2018.05.036.
  25. 25.
    Fan JG, Kim SU, Wong VW. New trends on obesity and NAFLD in Asia. J Hepatol 2017;67(4):862–73.CrossRefGoogle Scholar
  26. 26.
    Wong VW, Wong GL, Yeung DK, Lau TK, Chan CK, Chim AM, Abrigo JM, Chan RS, Woo J, Tse YK, Chu WC, Chan HL. Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy. J Hepatol 2015;62(1):182–9.CrossRefGoogle Scholar
  27. 27.
    Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, Hunt S. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015;62(6):1723–30.CrossRefGoogle Scholar
  28. 28.
    Mittal S, Sada YH, El-Serag HB, Kanwal F, Duan Z, Temple S, May SB, Kramer JR, Richardson PA, Davila JA. Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population. Clin Gastroenterol Hepatol 2015;13(3):594–601.e1.CrossRefGoogle Scholar
  29. 29.
    Mittal S, El-Serag HB, Sada YH, Kanwal F, Duan Z, Temple S, May SB, Kramer JR, Richardson PA, Davila JA. Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2016;14(1):124–31.e1.CrossRefGoogle Scholar
  30. 30.
    Zoller H, Tilg H. Nonalcoholic fatty liver disease and hepatocellular carcinoma. Metabolism 2016;65(8):1151–60.CrossRefGoogle Scholar
  31. 31.
    Pocha C, Kolly P, Dufour JF. Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Problem of Growing Magnitude. Semin Liver Dis 2015;35(3):304–17.CrossRefGoogle Scholar
  32. 32.
    Wakai T, Shirai Y, Sakata J, Korita PV, Ajioka Y, Hatakeyama K. Surgical outcomes for hepatocellular carcinoma in nonalcoholic fatty liver disease. J Gastrointest Surg 2011;15(8):1450–8.CrossRefGoogle Scholar
  33. 33.
    Salomao M, Yu WM, Brown RS Jr, Emond JC, Lefkowitch JH. Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. Am J Surg Pathol 2010;34(11):1630–6.Google Scholar
  34. 34.
    Viganò L, Conci S, Cescon M, Fava C, Capelli P, D'Errico A, Torzilli G, Di TL, Giuliante F, Vecchio FM, Salizzoni M, David E, Pinna AD, Guglielmi A, Capussotti L. Liver resection for hepatocellular carcinoma in patients with metabolic syndrome: A multicenter matched analysis with HCV-related HCC. J Hepatol 2015;63:93–101.CrossRefGoogle Scholar
  35. 35.
    Ertle J, Dechêne A, Sowa JP, Penndorf V, Herzer K, Kaiser G, Schlaak JF, Gerken G, Syn WK, Canbay A. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011;128(10):2436–43.CrossRefGoogle Scholar
  36. 36.
    Younes R, Bugianesi E. Should we undertake surveillance for HCC in patients with NAFLD. J Hepatol 2018;68(2):326–34.CrossRefGoogle Scholar
  37. 37.
    Rich N, Singal AG. Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Potential New Challenge for Hepatocellular Carcinoma Surveillance. Gastroenterology 2016;151(6):1246–8.CrossRefGoogle Scholar
  38. 38.
    Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67(1):358–80.CrossRefGoogle Scholar
  39. 39.
    EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69(1):182–236.Google Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2018

Authors and Affiliations

  • Tian Yang
    • 1
    Email author
  • Lun-Yang Hu
    • 1
    • 2
  • Zhen-Li Li
    • 1
  • Kai Liu
    • 1
  • Han Wu
    • 1
  • Hao Xing
    • 1
  • Wan Yee Lau
    • 1
    • 3
  • Timothy M. Pawlik
    • 4
  • Yong-Yi Zeng
    • 5
  • Ya-Hao Zhou
    • 6
  • Wei-Min Gu
    • 7
  • Hong Wang
    • 8
  • Ting-Hao Chen
    • 9
  • Jun Han
    • 1
  • Chao Li
    • 1
  • Ming-Da Wang
    • 1
  • Meng-Chao Wu
    • 1
  • Feng Shen
    • 1
    Email author
  1. 1.Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.Department of Clinical MedicineSecond Military Medical UniversityShanghaiChina
  3. 3.Faculty of MedicineThe Chinese University of Hong KongHong KongChina
  4. 4.Department of Surgery, Wexner Medical CenterOhio State UniversityColumbusUSA
  5. 5.Department of Hepatobiliary Surgery, Mengchao Hepatobiliary HospitalFujian Medical UniversityFuzhouChina
  6. 6.Department of Hepatobiliary SurgeryPu’er People’s HospitalPu’erChina
  7. 7.The First Department of General SurgeryThe Fourth Hospital of HarbinHarbinChina
  8. 8.Department of General SurgeryLiuyang People’s HospitalLiuyangChina
  9. 9.Department of General SurgeryZiyang First People’s HospitalZiyangChina

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