N-Acetylcysteine Prevents Post-embolization Syndrome in Patients with Hepatocellular Carcinoma Following Transarterial Chemoembolization

Abstract

Background

Post-embolization syndrome is a common complication after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). N-acetylcysteine (NAC) is known to ameliorate liver damage from several causes.

Aim

To determine the efficacy of intravenous NAC in the prevention of post-embolization syndrome in HCC patients following TACE.

Methods

In this study, patients with HCC admitted for TACE were prospectively enrolled. All patients were randomized stratified by Child A or B to receive NAC or placebo. The NAC group received intravenous NAC 24 h prior to TACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h, then continuous infusion 6.25 mg/h for 48 h after the procedure). The placebo group received an infusion of 5% glucose solution until 48 h after procedure. The post-embolization syndrome was defined as: T ≥ 38.5 c and serum ALT > 3 times of pretreatment value.

Results

In total, 111 HCC patients were enrolled; 57 were randomly assigned to NAC group and 54 to placebo group. The incidence of post-embolization syndrome was lower in NAC group (24.6%) compared to placebo group (48.2%); P = 0.01. On multivariate analysis, receiving IV NAC (P = 0.03) and HCC diameter (P < 0.01) were associated with developing post-embolization syndrome. Post-TACE liver decompensation was documented in 26/111 (23.4%) patients. There was no difference in the incidence of post-TACE liver decompensation between NAC and placebo group.

Conclusions

In this study, intravenous NAC administration reduces the incidence of post-embolization syndrome after TACE in patients with HCC. However, it does not prevent post-TACE liver decompensation.

Trial Registration Number

This study was registered with Thai Clinical Trial Registry (TCTR20150313002).

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

Fig. 1
Fig. 2

Abbreviations

TACE:

Transarterial chemoembolization

HCC:

Hepatocellular carcinoma

NAC:

N-acetylcysteine

BCLC:

Barcelona clinic liver center

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

MELD:

Model for end-stage liver disease

PV:

Portal vein

AST:

Aspatate aminotransferase

ALT:

Alanine aminotransferase

5-FU:

5-Fluorouracil

WBC:

White blood cell

References

  1. 1.

    El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–1127.

    CAS  Article  Google Scholar 

  2. 2.

    Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–1255.

    Article  Google Scholar 

  3. 3.

    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.

    Article  Google Scholar 

  4. 4.

    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442.

    CAS  Article  Google Scholar 

  5. 5.

    Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology. 2004;127:S179–188.

    CAS  Article  Google Scholar 

  6. 6.

    Chan AO, Yuen MF, Hui CK, Tso WK, Lai CL. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer. 2002;94:1747–1752.

    Article  Google Scholar 

  7. 7.

    Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol. 2001;12:321–326.

    CAS  Article  Google Scholar 

  8. 8.

    Li CP, Chao Y, Chen LT, et al. Fever after transcatheter arterial chemoembolization for hepatocellular carcinoma: incidence and risk factor analysis. Scand J Gastroenterol. 2008;43:992–999.

    CAS  Article  Google Scholar 

  9. 9.

    Wigmore SJ, Redhead DN, Thomson BN, et al. Postchemoembolisation syndrome–tumour necrosis or hepatocyte injury? Br J Cancer. 2003;89:1423–1427.

    CAS  Article  Google Scholar 

  10. 10.

    Tasneem AA, Abbas Z, Luck NH, Hassan SM, Faiq SM. Adverse events following transarterial chemoembolization for hepatocellular carcinoma and factors predicting such events. J Pak Med Assoc. 2013;63:239–244.

    PubMed  Google Scholar 

  11. 11.

    Prescott LF, Critchley JA. The treatment of acetaminophen poisoning. Annu Rev Pharmacol Toxicol. 1983;23:87–101.

    CAS  Article  Google Scholar 

  12. 12.

    Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137:856–864, 864 e851.

    PubMed Central  Google Scholar 

  13. 13.

    Wang C, Chen K, Xia Y, et al. N-acetylcysteine attenuates ischemia–reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway. PLoS ONE. 2014;9:e108855.

    Article  Google Scholar 

  14. 14.

    Hsieh CC, Hsieh SC, Chiu JH, Wu YL. Protective effects of N-acetylcysteine and a prostaglandin E1 analog, alprostadil, against hepatic ischemia: reperfusion injury in rats. J Tradit Complement Med. 2014;4:64–71.

    Article  Google Scholar 

  15. 15.

    Sun Y, Pu LY, Lu L, Wang XH, Zhang F, Rao JH. N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia–reperfusion injury. World J Gastroenterol. 2014;20:15289–15298.

    CAS  Article  Google Scholar 

  16. 16.

    Min YW, Kim J, Kim S, et al. Risk factors and a predictive model for acute hepatic failure after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Liver Int. 2013;33:197–202.

    CAS  Article  Google Scholar 

  17. 17.

    Jun CH, Ki HS, Lee HK, et al. Clinical significance and risk factors of postembolization fever in patients with hepatocellular carcinoma. World J Gastroenterol. 2013;19:284–289.

    Article  Google Scholar 

  18. 18.

    Mason MC, Massarweh NN, Salami A, Sultenfuss MA, Anaya DA. Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma. HPB (Oxford). 2015;17:1137–1144.

    Article  Google Scholar 

  19. 19.

    Lauterburg BH, Corcoran GB, Mitchell JR. Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest. 1983;71:980–991.

    CAS  Article  Google Scholar 

  20. 20.

    Nguyen-Khac E, Thevenot T, Piquet MA, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011;365:1781–1789.

    CAS  Article  Google Scholar 

  21. 21.

    Ogasawara S, Chiba T, Ooka Y, et al. A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization. Hepatology. 2018;67:575–585.

    CAS  Article  Google Scholar 

  22. 22.

    Garwood ER, Fidelman N, Hoch SE, Kerlan RK Jr, Yao FY. Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction. Liver Transpl. 2013;19:164–173.

    Article  Google Scholar 

  23. 23.

    Huang YS, Chiang JH, Wu JC, Chang FY, Lee SD. Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test. Am J Gastroenterol. 2002;97:1223–1227.

    Article  Google Scholar 

  24. 24.

    Schmidt-Arras D, Rose-John S. IL-6 pathway in the liver: from physiopathology to therapy. J Hepatol. 2016;64:1403–1415.

    CAS  Article  Google Scholar 

  25. 25.

    Yamaguchi K, Itoh Y, Yokomizo C, et al. Blockade of IL-6 signaling exacerbates liver injury and suppresses antiapoptotic gene expression in methionine choline-deficient diet-fed db/db mice. Lab Invest. 2011;91:609–618.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This work was funded by Faculty of Medicine and Chulabhorn International College of Medicine, Thammasat University, Thailand, and Gastrointestinal Association of Thailand.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sith Siramolpiwat.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Siramolpiwat, S., Punjachaipornpon, T., Pornthisarn, B. et al. N-Acetylcysteine Prevents Post-embolization Syndrome in Patients with Hepatocellular Carcinoma Following Transarterial Chemoembolization. Dig Dis Sci 64, 3337–3345 (2019). https://doi.org/10.1007/s10620-019-05652-0

Download citation

Keywords

  • Hepatocellular carcinoma
  • N-acetylcysteine
  • Post-embolization syndrome
  • Liver cancer