Pain relief may also be achieved with procedure-based therapy, especially in the setting of metastatic HCC. Radiotherapy has been widely shown to mitigate pain due to bone and lymph node metastases and should be regarded as safe and effective palliation for metastatic HCC symptoms.7,22 Current EASL clinical practice guidelines similarly suggest palliative radiotherapy for patients suffering from pain caused by an unambiguous bone metastasis.19 However, given its ability to relieve pain more quickly, RFA may be more effective for treating cancer-induced bone pain.23 Moreover, Kashima et al achieved pain reduction in 96.6% of patients with metastatic HCC through RFA compared to studies reporting relief in 50–90% of patients through radiotherapy. TACE has also been shown to relieve CIBP and may be preferable to radiotherapy since it also achieves palliation more quickly.8

Less conventional procedure-based therapies for HCC pain relief have also been explored. Hokotate et al9 successfully treated a Japanese patient’s metastatic HCC pain with bone cement therapy, suggesting this as a clinical avenue warranting further research. Electroacupuncture has been shown to alleviate pain in advanced HCC patients as well; however, the onset of significant pain relief was slow, which calls for supplementation with traditional analgesics for this method to be effective.24Transcranial direct current stimulation (tDCS) may prove an effective therapy to alleviate visceral HCC pain.11 Multiple sessions of tDCS over the primary motor cortex generated analgesic responses in HCC patients experiencing visceral pain, where relief appeared by the fifth session and persisted for a month. This method may be especially promising because it carries negligible risk and device application is simple. While the analgesic mechanisms of tDCS are not fully understood, resting membrane potential modulation beneath the active electrode and its effects in other parts of the pain-processing network generated by motor cortex-directed inhibition of somatosensation is thought to play a role.

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HCC pain constitutes a serious concern for both patients and providers. It can markedly and negatively impact HRQoL and may result from the spread of HCC itself or LRT. While treating HCC pain can be clinically challenging due to underlying hepatic impairment, hepatologists have developed analgesic treatment recommendations to bypass the risks of toxic metabolite accumulation and to avoid aggravating hepatic decompensation. Moreover, procedure-based pain therapies such as TACE, radiotherapy, and RFA have been shown to alleviate pain caused by extrahepatic HCC spread. Less studied therapies such as electroacupuncture and tDCS have demonstrated promise and should be explored further. In light of these developments and the disparity between hepatologists and nonhepatologists regarding analgesic preference for cirrhotic patients, coordinated multidisciplinary care between providers may be the optimal route for effective pain management. When used in conjunction with methodical pain assessment, up-to-date clinician knowledge of various forms of HCC pain presentation, and proper analgesic therapy, we hope improved pain management in HCC patients may be achieved.


The authors report no conflicts of interest in this work.

Nathaniel Christian-Miller,1 Catherine Frenette2

1Scripps Clinical Research, Scripps, San Diego, CA, USA; 2Scripps Center for Organ and Cell Transplantation, Scripps Green Hospital, La Jolla, CA, USA 


1. Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: a comprehensive review. World J Hepatol. 2015;7(26):2648–2663.

2. Kaiser K, Mallick R, Butt Z, Mulcahy MF, Benson AB, Cella D. Important and relevant symptoms including pain concerns in hepatocellular carcinoma (HCC): a patient interview study. Support Care Cancer. 2014;22(4):919–926.

3. Sun VC, Sarna L. Symptom management in hepatocellular carcinoma. Clin J Oncol Nurs. 2008;12(5):759–766.

4. Kumar M, Panda D. Role of supportive care for terminal stage hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4(suppl 3):S130–S139.

5. Mittal S, El-serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(suppl):S2–S6.

6. Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis – a practical guide. Aliment Pharmacol Ther. 2013;37(12):1132–1156.

7. Seong J, Koom WS, Park HC. Radiotherapy for painful bone metastases from hepatocellular carcinoma. Liver Int. 2005;25(2):261–265.

8. Nagata Y, Nakano Y, Abe M, Takahashi M, Kohno S. Osseous metastases from hepatocellular carcinoma: embolization for pain control. Cardiovasc Intervent Radiol. 1989;12(3):149–153.

9. Hokotate H, Baba Y, Churei H, Nakajo M, Ohkubo K, Hamada K. Pain palliation by percutaneous acetabular osteoplasty for metastatic hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2001;24(5):346–348.

10. Carr BI, Pujol L. Pain at presentation and survival in hepatocellular carcinoma. J Pain. 2010;11(10):988–993.

11. Ibrahim NM, Abdelhameed KM, Kamal SMM, Khedr EMH, Kotb HIM. Effect of transcranial direct current stimulation of the motor cortex on visceral pain in patients with hepatocellular carcinoma. Pain Med. 2018;19(3):550–560.

12. Chwistek M. Recent advances in understanding and managing cancer pain. F1000Res. 2017;6:945.

13. Deutsch M, Vasiliou K, Papatheodoridis GV. Hepatocellular carcinoma presenting with pleuritic pain. Eur J Intern Med. 2006;17(3):222.

14. Benzakoun J, Ronot M, Lagadec M, et al. Risks factors for severe pain after selective liver transarterial chemoembolization. Liver Int. 2017;37(4):583–591.

15. Hsieh YC, Yap YS, Hung CH, Chen CH, Lu SN, Wang JH. Factors related to postoperative pain among patients who underwent radiofrequency ablation of hepatocellular carcinoma. Clin Radiol. 2013;68(6):600–607.

16. Narayanan G, Froud T, Lo K, Barbery KJ, Perez-rojas E, Yrizarry J. Pain analysis in patients with hepatocellular carcinoma: irreversible electroporation versus radiofrequency ablation-initial observations. Cardiovasc Intervent Radiol. 2013;36(1):176–182.

17. Ge PS, Runyon BA. Treatment of patients with cirrhosis. N Engl J Med. 2016;375(21):2104–2105.

18. Soleimanpour H, Safari S, Shahsavari Nia K, Sanaie S, Alavian SM. Opioid drugs in patients with liver disease: a systematic review. Hepat Mon. 2016;16(4):e32636.

19. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol. Epub 2018 Apr 5:doi: 10.1016/j.jhep.2018.03.019.

20. National Comprehensive Cancer Network. Adult Cancer Pain (2.2017). 2018. Available from: Accessed January 15, 2018.

21. Chandok N, Watt KD. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85(5):451–458.

22. Kalogeridi MA, Zygogianni A, Kyrgias G, et al. Role of radiotherapy in the management of hepatocellular carcinoma: a systematic review. World J Hepatol. 2015;7(1):101–112.

23. Kashima M, Yamakado K, Takaki H, et al. Radiofrequency ablation for the treatment of bone metastases from hepatocellular carcinoma. AJR Am J Roentgenol. 2010;194(2):536–541.

24. Xu L, Wan Y, Huang J, Xu F. Clinical analysis of electroacupuncture and multiple acupoint stimulation in relieving cancer pain in patients with advanced hepatocellular carcinoma. J Cancer Res Ther. 2018;14(1):99–102.

Source: Journal of Hepatocellular Carcinoma.
Originally published July 18, 2108.