Changes in real-life practice for hepatocellular carcinoma patients in the Republic of Korea over a 12-year period: A nationwide random sample study

Autoři: Beom Kyung Kim aff001;  Do Young Kim aff001;  Kwang-Hyub Han aff001;  Jinsil Seong aff003
Působiště autorů: Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea aff001;  Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea aff002;  Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Backgrounds & aims

Comprehensive analyses through nationwide hepatocellular carcinoma (HCC) registries are important to understand health care issues. We assessed changes in real-life practice for HCC over a long time period.


The Korean Liver Cancer Association and the Korean Central Cancer Registry jointly established the nationwide cohorts of newly diagnosed HCC patients between 2003 and 2005 and between 2008 and 2014. According to sorafenib reimbursement in the Republic of Korea (January 2011), patients were divided into early (E-Cohort: 2003~2010) and late (L-Cohort: 2011~2014) cohorts.


L-Cohort (n = 4776) comprised patients with older age (60.8 vs. 58.3 years), higher proportions of patients with well-preserved liver function (75.6% vs. 68.2%) and non-viral etiologies (28.6% vs. 19.4%), and lower proportion of patients with Barcelona Clinic Liver Cancer [BCLC] 0~A stage (46.2% vs. 53.9%) than E-Cohort (n = 8203) (all p<0.05). Proportions of patients undergoing curative treatments were higher in L-Cohort than in E-Cohort (55.0% vs. 35.1%, 23.2 vs. 11.3%, and 17.3% vs. 9.6% in BCLC 0A, B, and C stages, respectively; all p<0.05). Accordingly, compared with that in E-Cohort, overall survival in L-Cohort significantly improved in patients with BCLC 0~A, B, and C stages (all p<0.05). As first-line treatment, 62.4% underwent locoregional treatments (LRTs), whereas only 9.7% received sorafenib, among BCLC stage C patients in L-Cohort.


For the past 12 years, curative treatments became more widely available to BCLC 0~A, B, and C stage patients, generally improving prognosis. Despite sorafenib reimbursement, LRTs remain the mainstay of first-line treatment for BCLC C stage patients.

Klíčová slova:

Cancer detection and diagnosis – Cancer treatment – Etiology – Hepatitis B virus – Hepatitis C virus – Hepatocellular carcinoma – Prognosis – South Korea


1. Yang JD, Roberts LR. Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol. 2010;7: 448–458. doi: 10.1038/nrgastro.2010.100 20628345

2. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365: 1118–1127. doi: 10.1056/NEJMra1001683 21992124

3. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362: 1907–1917. doi: 10.1016/S0140-6736(03)14964-1 14667750

4. Kim BH, Park JW. Epidemiology of liver cancer in South Korea. Clin Mol Hepatol. 2018;24: 1–9. doi: 10.3350/cmh.2017.0112 29249129

5. Sung JL. Hepatitis B virus eradication strategy for Asia. The Asian Regional Study Group. Vaccine. 1990;8 Suppl: S95–99 doi: 10.1016/0264-410x(90)90227-d 2139290

6. Choi J, Han S, Kim N, Lim YS. Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus-endemic population. Hepatology. 2017;66: 1454–1463. doi: 10.1002/hep.29321 28628942

7. Korea Central Cancer Registry, National Cancer Center. Annual report of cancer statistics in Korea in 2014. Ministry of Health and Welfare 2016.

8. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359: 378–390. doi: 10.1056/NEJMoa0708857 18650514

9. Kang D, Han Z, Oh GH, Joo Y, Choi HJ, Song JJ. Down-Regulation of TGF-beta Expression Sensitizes the Resistance of Hepatocellular Carcinoma Cells to Sorafenib. Yonsei Med J. 2017;58: 899–909. doi: 10.3349/ymj.2017.58.5.899

10. Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, et al. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol. 2018;4: 661–669.29543938

11. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389: 2492–2502. doi: 10.1016/S0140-6736(17)31046-2 28434648

12. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391: 1163–1173. doi: 10.1016/S0140-6736(18)30207-1 29433850

13. Lee S, Kim BK, Kim SU, Park Y, Chang S, Park JY, et al. Efficacy of sorafenib monotherapy versus sorafenib-based loco-regional treatments in advanced hepatocellular carcinoma. PLoS One. 2013;8: e77240. doi: 10.1371/journal.pone.0077240 24155932

14. Costentin CE, Ferrone CR, Arellano RS, Ganguli S, Hong TS, Zhu AX. Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy. Liver Cancer. 2017;6: 360–374. doi: 10.1159/000481315 29234639

15. European Association For The Study Of The L, European Organisation For R, Treatment Of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56: 908–943. doi: 10.1016/j.jhep.2011.12.001 22424438

16. Bruix J, Sherman M, American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53: 1020–1022. doi: 10.1002/hep.24199 21374666

17. Park JW. [Practice guideline for diagnosis and treatment of hepatocellular carcinoma]. Korean J Hepatol. 2004;10: 88–98 15218342

18. 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015;9: 267–317. doi: 10.5009/gnl14460 25918260

19. 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: 358–380. doi: 10.1002/hep.29086 28130846

20. Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28: 1067–1077. doi: 10.1111/j.1365-2036.2008.03816.x 18657133

21. Kim BH, Lim YS, Kim EY, Kong HJ, Won YJ, Han S, et al. Temporal improvement in survival of patients with hepatocellular carcinoma in a hepatitis B virus-endemic population. J Gastroenterol Hepatol. 2018;33: 475–483. doi: 10.1111/jgh.13848 28612951

22. Lee HW, Kim BK. Hepatocellular Carcinoma Prediction Models for Patients with Chronic Hepatitis B Virus Infection in the Era of Potent Antiviral Therapy. J Liver Cancer. 2018;18: 87–93

23. Yoo JJ, Kim W, Kim MY, Jun DW, Kim SG, Yeon JE, et al. Recent research trends and updates on nonalcoholic fatty liver disease. Clin Mol Hepatol. 2019;25: 1–11. doi: 10.3350/cmh.2018.0037 30086613

24. Ha KH, Kim DJ. Trends in the Diabetes Epidemic in Korea. Endocrinol Metab (Seoul). 2015;30: 142–146. doi: 10.3803/EnM.2015.30.2.142 26194073

25. Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11: e1001624. doi: 10.1371/journal.pmed.1001624 24691105


27. Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015;21: 3826–3842. doi: 10.3748/wjg.v21.i13.3826 25852267

28. Lee HS, Kim KM, Yoon JH, Lee TR, Suh KS, Lee KU, et al. Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol. 2002;20: 4459–4465. doi: 10.1200/JCO.2002.02.013 12431969

29. Chen RX, Gan YH, Ge NL, Chen Y, Ma H, Wang Y, et al. Comparison of transarterial chemoembolization with radiofrequency ablation for unresectable Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma: a propensity score matching. J Gastroenterol Hepatol. 2016;31: 442–449. doi: 10.1111/jgh.13077 26259976

30. Agarwal PD, Phillips P, Hillman L, Lucey MR, Lee F, Mezrich JD, et al. Multidisciplinary Management of Hepatocellular Carcinoma Improves Access to Therapy and Patient Survival. J Clin Gastroenterol. 2017;51: 845–849.28877082

31. Sangiovanni A, Triolo M, Iavarone M, Forzenigo LV, Nicolini A, Rossi G, et al. Multimodality treatment of hepatocellular carcinoma: How field practice complies with international recommendations. Liver Int. 2018;38: 1624–1634. doi: 10.1111/liv.13888 29791968

32. Lee YG, Oh S, Kimm H, Koo DH, Kim DY, Kim BS, et al. Practice Patterns Regarding Multidisciplinary Cancer Management and Suggestions for Further Refinement: Results from a National Survey in Korea. Cancer Res Treat. 2017;49: 1164–1169. doi: 10.4143/crt.2016.517 28231425

33. Tang A, Bashir MR, Corwin MT, Cruite I, Dietrich CF, Do RKG, et al. Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review. Radiology. 2018;286: 29–48. doi: 10.1148/radiol.2017170554 29166245

34. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68: 723–750. doi: 10.1002/hep.29913 29624699

35. Choi SH, Seong J. Stereotactic Body Radiotherapy: Does It Have a Role in Management of Hepatocellular Carcinoma? Yonsei Med J. 2018;59: 912–922. doi: 10.3349/ymj.2018.59.8.912 30187697

36. Choi SH, Seong J. Strategic application of radiotherapy for hepatocellular carcinoma. Clin Mol Hepatol. 2018;24: 114–134. doi: 10.3350/cmh.2017.0073 29439305

Článek vyšel v časopise


2019 Číslo 10
Nejčtenější tento týden