Skip Navigation
Skip to contents

JLC : Journal of Liver Cancer

OPEN ACCESS
SEARCH
Search

Articles

Page Path
HOME > J Liver Cancer > Volume 20(1); 2020 > Article
Original Article
Hepatocellular Carcinoma in Korea Between 2008 and 2011: an Analysis of Korean Nationwide Cancer Registry
Jun Sik Yoon1*, Han Ah Lee2*, Jun Yong Park3, Bo Hyun Kim4, In Joon Lee5, Young Eun Chon6, Suk Kyun Hong7, Dong Hyeon Lee8, Hyun-Joo Kong9, Young-Joo Won9, Eunyang Kim9, Jeong-Hoon Lee10orcid
Journal of Liver Cancer 2020;20(1):41-52.
DOI: https://doi.org/10.17998/jlc.20.1.41
Published online: March 31, 2020
  • 3,344 Views
  • 178 Downloads
  • 13 Citations

1Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

10Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

2Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

4Center for Liver Cancer, Research Institute and Hospital, Goyang, Korea

5Department of Radiology, National Cancer Center, Goyang, Korea

6Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea

7Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

8Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea

9Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea

Corresponding author : Jeong-Hoon Lee Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel. +82-2-2072-2228, Fax. +82-2-743-6701 E-mail; JHLeeMD@snu.ac.kr
*The first two authors contributed equally to this study.
• Received: December 31, 2019   • Revised: February 6, 2020   • Accepted: February 7, 2020

Copyright © 2020 The Korean Liver Cancer Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Backgrounds/Aims
    Backgrounds/Aims: In Korea, hepatocellular carcinoma (HCC) is the sixth most common cancer and results in the second-highest cancer death rate among all cancers. We aimed to describe the characteristics of patients who were newly diagnosed with HCC in Korea between 2008 and 2011.
  • Methods
    The Korean Primary Liver Cancer Registry (KPLCR) is a random sample consisting of approximately 15% of patients with newly diagnosed primary liver cancer registered in the Korean Central Cancer Registry. We investigated the baseline characteristics, treatment modalities, and overall survival (OS) of patients with HCC registered in the KPLCR between 2008 and 2011.
  • Results
    A total of 6,083 patients were histologically or radiologically diagnosed with HCC. The hepatitis B virus was the predominant HCC etiology (72.0%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stages 0, A, B, C, and D accounted for 8.6%, 39.7%, 11.5%, 33.8%, and 6.9%, respectively. Transarterial therapy (41.7%) was the most commonly performed initial treatment, followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapies (10.6%). The overall rate of adherence to the BCLC treatment guideline was only 37.7%. The 1-, 3-, and 5-year OS rates were 65.6%, 46.2%, and 36.8%, respectively.
  • Conclusions
    Between 2008 and 2011, approximately half of patients with HCC (48.3%) were candidates for curative treatment (BCLC stage 0 or A), but one-third of patients (33.8%) had advanced HCC (BCLC stage C). Transarterial therapy was the most commonly conducted initial treatment and the 5-year OS rate was 36.8% in this period.
Primary liver cancer is the sixth most common cancer and results in the second-highest cancer death rate among all cancers in Korea [1-3]. Hepatocellular carcinoma (HCC) accounts for more than 80-90% of primary liver cancer cases [4,5]. Korea is a hepatitis B virus (HBV)-endemic area, and chronic hepatitis B accounts for 62-75% of HCC etiology [6-8]. As the prevalence of chronic hepatitis B increases with age, the incidence and mortality rates of HCC are highest among the economically active working-age (40-59 years) group [9]. Therefore, HCC imposes the highest economic burden among all cancers in Korea [10]. To reduce the development of HCC and improve the prognosis of patients with HCC, a large number of studies regarding the management of HCC are published every year in Korea. Accurate information on the characteristics and overall survival (OS) of patients with HCC is essential to establish an optimal strategy for managing HCC. However, there has been a lack of large-scale, nationwide data to represent the typical characteristics of Korean patients with HCC. Therefore, we aimed to describe the baseline characteristics, treatment modalities, and OS of patients newly diagnosed with HCC utilizing a nationwide population-based cancer registry in Korea.
1. Study population
The study population was selected from the patients registered in the Korean Primary Liver Cancer Registry (KPLCR). The KPLCR is a random sample consisting of approximately 15% of patients newly diagnosed with primary liver cancer registered in the Korean Central Cancer Registry (KCCR), which is a nationwide cancer registry and includes more than 95% of all cancer cases in Korea. The patients in the KPLCR were selected from the KCCR using a probability proportional to size method and stratification by region in a given year. Therefore, the KPLCR is a representative group of patients with newly diagnosed HCC in Korea. We investigated the patients registered in the KPLCR between 2008 and 2011. All patients included in the study were diagnosed with HCC histologically or radiologically [11,12]. We also performed survival analyses among patients who underwent the initial treatment within 120 days from their diagnosis or received best supportive care (designated as the treatment group). Because the median doubling time of an HCC lesion is approximately 117 days [13], patients who received the initial treatment more than 120 days after their diagnosis date were likely to receive the treatment at a more advanced tumor stage than their initial tumor stage. Therefore, we excluded patients who received treatment more than 120 days after the initial date of diagnosis in the survival analyses. Because the KPLCR data in our study were collected as part of the KCCR in accordance with the Cancer Control Act, the need for institutional review board approval was waived.
2. Basic statistics
Individual information about the study population was obtained from medical records at the hospital where the diagnosis was made. KCCR-trained registry recorders in each hospital investigated the medical records. Data were extracted using a standardized case record form and validated by statisticians at the KCCR and the KPLCR. Collected data included not only baseline characteristics such as demographic, laboratory, and tumor variables, but also treatment modalities and OS of the patients. All of the tumor variables were assessed by diagnostic imaging such as dynamic computed tomography (CT) or magnetic resonance imaging (MRI). Both the modified Union for International Cancer Control (mUICC) staging system [14,15] and the Barcelona Clinic Liver Cancer (BCLC) staging system [16] were adapted as staging systems for HCC.
3. Overall survival
The OS was measured from the date of the HCC diagnosis until death from any cause. The date of the HCC diagnosis was defined as the date when the patient underwent dynamic CT or MRI for the HCC diagnosis. Death certificate data were obtained from national statistical data collected by the Korean Ministry of Government Administration and Home Affairs. Individual data of patients' vital statistics were identified using 13-digit unique resident registration numbers issued to all Koreans. Final data cut-off date was December 31, 2017. The OS rates were obtained from the patients with HCC classified according to their baseline characteristics. The survival curves were also constructed according to the subgroups classified by the underlying liver functions and tumor stages using the Kaplan-Meier method. The survival differences were compared by the log-rank test. The survival analyses were conducted using R version 3.5.2 (http://www.r-project.org) with P <0.05 considered statistically significant.
1. Study population
Between 2008 and 2011, 6,146 patients were registered in the KPLCR. Of these, 63 patients were histologically diagnosed with other malignancies and excluded from the study. Therefore, 6,083 patients were selected as the study population. Among the patients with HCC, we excluded 1) patients who received their initial treatment more than 120 days from the date of diagnosis (n=103) and 2) patients lacking information on treatment modalities (n=6). As a result, 5,974 patients were selected as the treatment group. The treatment group consisted of patients who received active treatment (n=4,679) and those who received best supportive care (n=1,295). The flow diagram of the study population is shown in Supplementary Fig. 1.
2. Basic statistics

1) Baseline characteristics

The baseline characteristics of the study population (n=6,083) are presented in Table 1. The median age of the study population was 59 years (range, 2-98 years), and the majority were male (78.7%). HBV was the predominant etiology (72.0%), followed by alcohol (13.4%), hepatitis C virus (12.0%), and others (2.5%). When the underlying liver function was estimated according to Child-Turcotte-Pugh (CTP) class, 71.0%, 23.7%, and 5.1% of patients were in CTP classes A, B, and C, respectively. According to the mUICC staging system, stage II (37.5%) was the most common, followed by stage III (26.1%), stage I (14.1%), stage IV-A (12.3%), and stage IV-B (9.9%). According to the BCLC staging system, stage A (39.7%) was the most common, followed by stage C (33.8%), stage B (11.5%), stage 0 (8.6%), and stage D (6.9%). A solitary tumor was observed in 61.5% of the patients, and the median maximal diameter of tumors was 3.0 cm. Vascular invasions to the portal vein and hepatic vein were observed in 24.3% and 5.6% of the patients, respectively. Lymph node metastasis and distant metastasis were observed in 7.1% and 9.9% of patients, respectively.

2) Initial treatment modality

As shown in Table 2, of the patients in the treatment group (n=5,974), 17.6% underwent surgical therapies (i.e., surgical resection and liver transplantation), 54.2% underwent locoregional therapies (i.e., local ablation therapy, transarterial therapy, and a combination of local ablation and transarterial therapy), 3.7% underwent systemic therapy, 1.0% underwent external beam radiation therapy, 21.7% underwent best supportive care, and 1.7% underwent miscellaneous therapies (i.e., combination therapies other than transarterial therapy and local ablation therapy). Transarterial therapy (41.7%) was the most commonly performed therapy or procedure as an initial treatment, followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapies (10.6%). The majority of local ablation therapies was radiofrequency ablation (594/636, 99.4%). Among the transarterial therapies, conventional transarterial chemoembolization with or without a gelatin sponge was the most frequently performed procedure (2,407/2,493, 96.6%). Sorafenib was the most commonly used agent for systemic therapy (175/224, 78.1%).
The treatment modalities used at each BCLC stage are presented in Fig. 1. For BCLC stage 0 or A, transarterial therapy (41.8%) was the most commonly conducted initial treatment, followed by surgical therapy (27.3%) and local ablation therapy (19.4%). , and it was for BCLC stages B and C as well. BCLC stages B and C. Although systemic therapy is a standard treatment modality of BCLC stage C, it was conducted in only 9.5% of patients with BCLC stage C. For BCLC stage D, best supportive care was the most commonly conducted treatment modality. We show the rates of adherence to the BCLC treatment guideline according to each BCLC stage in Supplementary Table 1. The overall adherence rate of the total study population was only 37.4%. We also show the treatment modalities according to each mUICC stage in Supplementary Fig. 2. Transarterial therapy was the most commonly conducted initial treatment for mUICC stages I-III. For mUICC stage IV, best supportive care was the most commonly conducted treatment modality.

3) Baseline characteristics according to treatment modalities

The baseline characteristics of the patients treated with surgical therapies including surgical resection (n=998) and liver transplantation (n=55) are presented in Supplementary Table 2. Most patients treated with surgical resection had a good performance status of 0 or 1 (99.4%) and well-preserved liver function of CTP class A (95.4%). Of the patients treated with surgical resection, 21.2%, 53.6%, and 25.2% had a maximal tumor diameter measuring ≤2, 2-5, and ≥5 cm, respectively; 85.9% of these tumors were solitary. In the case of liver transplantation, more than half of the patients had poor liver function of CTP class B or C (53.8%) and multiple tumors (50.9%).
The baseline characteristics of the patients treated with locoregional therapies including local ablation therapy (n=636), transarterial therapy (n=2,493), and a combination of local ablation and transarterial therapy (n=108) are presented in Supplementary Table 3. Most patients had a good performance status of 0 or 1 (98.0%, 96.4%, and 98.8% of patients treated with local ablation therapy, transarterial therapy, and combination therapy, respectively) and well-preserved liver function classified as CTP class A (80.8 %, 75.1%, and 78.8% of patients treated with local ablation therapy, transarterial therapy, and combination therapy, respectively). The proportion of patients with multiple tumors and the median maximal diameter of tumors were highest in patients treated with transarterial therapy (43.1% and 3.0 cm), followed by combination therapy (32.7% and 2.0 cm) and local ablation therapy (15.6% and 1.9 cm).
The baseline characteristics of the patients treated with other therapies, including systemic therapy (n=224), external beam radiation therapy (n=61), best supportive care (n=1,295), and miscellaneous therapies (n=104), are presented in Supplementary Table 4. The proportions of patients with a poor performance status (≥2) and poor liver function (CTP class B or C) were the highest in patients treated with best supportive care (23.6% and 58.0%), followed by external beam radiation therapy (13.2% and 53.4%) and systemic therapy (7.9% and 39.2%). The proportion of patients with multiple tumors and the median maximal diameter of tumors were highest in patients treated with systemic therapy (67.0% and 7.0 cm), followed by best supportive care (59.1% and 6.0 cm) and external beam radiation therapy (47.5% and 4.2 cm)
3. Overall survival
The OS rates of the patients in the HCC group classified according to their baseline characteristics and their initial treatment modalities are presented in Table 3. The 1-, 3-, and 5-year OS rates for the entire study population were 65.6%, 46.2%, and 36.8%, respectively (Fig. 2A). All of the variables included in the formula of the CTP class (presence of ascites and hepatic encephalopathy, the serum levels of bilirubin and albumin, and prothrombin time) showed a good discriminatory performance on the prognosis of patients with HCC (all log-rank P <0.001; Supplementary Fig. 3). All of the survival curves according to CTP class (Fig. 2B), mUICC stage (Fig. 2C), and BLCL stage (Fig. 2D) showed significant survival differences (all log-rank P <0.001). We also performed post hoc analyses of log-rank tests for multiple comparisons between each survival curve. We found significant survival differences among all CTP classes and all vHCC stages (all pairwise comparisons of log-rank P <0.001).
The aim of this study was to investigate the baseline characteristics, treatment modalities, and OS of patients with newly diagnosed HCC in Korea. We analyzed 6,083 patients with HCC registered in the KPLCR, which is a representative group of patients with newly diagnosed HCC in Korea, between 2008 and 2011. We found that approximately half of the patients with HCC (48.3%) were candidates for curative treatment (BCLC stage 0 or A), but one-third of patients (33.8%) had advanced HCC (BCLC stage C). Transarterial therapy (41.7%) was the most commonly conducted initial treatment, followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapy (10.6%). The 1-, 3-, and 5-year OS rates were 65.6%, 46.2%, and 36.8%, respectively.
The nationwide surveillance program for HCC in a high-risk population (i.e., patients over 40 years of age who had chronic hepatitis B, chronic hepatitis C, or liver cirrhosis) was started in 2003 in Korea. As a result, early detection of HCC has gradually been increasing over time. We compared the results of this study (KPLCR data between 2008 and 2011) with the KPLCR data between 2003 and 2005 (data extracted from http://www.livercancer.or.kr). The proportion of patients with mUICC stage I increased from 10.7% in the 2003-2005 period to 14.1% in the 2008-2011 period. Moreover, 64.2%, 27.0%, and 8.8% of patients in the 2003-2005 period were in CTP class A, B, and C, respectively, whereas 71.0%, 23.8%, and 5.1% of patients in the 2008-2011 period were in CTP class A, B, and C, respectively. These data indicate that the detection of patients with early TNM-stage HCC with well-preserved liver function has been increasing over time. Therefore, the 1-, 3-, and 5-year OS rates also increased from 54.8%, 35.0%, and 26.4% in the 2003-2005 period to 65.6%, 46.2%, and 36.8% in the 2008-2011 period, respectively.
Approximately half of the patients with HCC (48.3%) were candidates for curative treatment (BCLC stage 0 or A) in this study. The detection rate of BCLC stage 0 or A was higher than that in Western countries (approximately 30%), where nationwide surveillance programs are yet to be implemented [17,18]. However, the detection rate was lower than that in Japan (62.5%) where a nationwide surveillance program began in 1980 [19]. Probably owing to this reason, the 5-year survival rate of Korean patients with HCC in this study (36.8%) was higher than that in Western countries (9.6-18.0%) [20-22], but lower than that in Japan (50.8%) during a similar study period [23]. The reason patients with HCC in Korea had a lower 5-year survival rate than patients in Japan is not only because of the low detection rate of BCLC stage 0 or A (48.3% vs. 62.5%), but also because of the high detection rate of BCLC stage C or D (40.6% vs. 6.0%) [19]. Intensive surveillance for detecting HCC at earlier stages might be required to improve the survival of patients with HCC in Korea.
In the present study, the most commonly conducted initial treatment was transarterial therapy (41.7%), followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapy (10.6%). Transarterial therapy was the most commonly performed treatment for all HCC stages except mUICC stage IV or BCLC stage D, which was consistent with results in Western countries [17]. However, the overall rate of adherence to BCLC treatment guidelines was only 37.4%, which was lower than that of Western countries (58.1-70.6%) [24-26]. In particular, the adherence rates of BCLC stage 0 or A and BCLC stage C were as low as 47.4% and 9.5%, respectively. Liver transplantation, one of the standard treatment modalities for BCLC stage 0 or A, was performed in only 0.7% of the patients with BCLC stage 0 or A stage. Moreover, approximately half of the patients in BCLC stage C underwent other therapies rather than the recommended systemic therapy; 39.8%, 8.1%, and 2.4% were treated with transarterial therapy, surgical resection, and local ablation therapy, respectively. The discrepancies of the real-world treatment from the recommended treatment are thought to be caused by an extreme shortage of liver donors and the low anticipated survival benefit of systemic therapy.
In conclusion, we have shown that, between 2008 and 2011, approximately half of Korean patients newly diagnosed with HCC had BCLC stage 0 or A, but one-third of the patients had BCLC stage C. Transarterial therapy was the most commonly conducted initial treatment, and the 5-year OS was 36.8% in this period. We believe that the results described here will contribute to the clinical management of HCC and promote future study.
Supplementary datas can be found with this article online http://www.e-jlc.org/html/https://doi.org/10.17998/jlc.20.1.41.
Supplementary Table 1.
Adherence rates of the BCLC treatment guideline in each Barcelona Clinic Liver Cancer stage and total study population
jlc-20-1-41-suppl1.pdf
Supplementary Table 2.
Baseline characteristics of the patients treated with surgical therapies (n=1,053)
jlc-20-1-41-suppl2.pdf
Supplementary Table 3.
Baseline characteristics of the patients treated with locoregional therapies (n=3,237)
jlc-20-1-41-suppl3.pdf
Supplementary Table 4.
Baseline characteristics of the patients treated with systemic therapy, external beam radiation therapy, best supportive care, and miscellaneous therapies (n=1,684)
jlc-20-1-41-suppl4.pdf
Supplementary Fig. 1.
Flow diagram of the study population. KPLCR, Korean Primary Liver Cancer Registry; HCC, hepatocellular carcinoma.
jlc-20-1-41-suppl5.pdf
Supplementary Fig. 2.
The initial treatment modality of the study population according to the modified Union for International Cancer Control staging system. * Combination therapy is defined as the combined treatment of local ablation therapy and transarterial therapy; Miscellaneous therapies are defined as unclassifiable treatment modalities (i.e., combination therapies other than transarterial therapy and local ablation therapy).
jlc-20-1-41-suppl6.pdf
Supplementary Fig. 3.
Cumulative survival curves for the subgroups according to the presence of ascites (A) and hepatic encephalopathy (B), the serum levels of bilirubin (C) and albumin (D), and prolongation (seconds) of prothrombin time (E).
jlc-20-1-41-suppl7.pdf
This study was supported by Korean Liver Cancer Association Research Award (recipient: J. H. L). The database used in this study was provided by the Korean Central Cancer Registry, Ministry of Health and Welfare, South Korea, and the Korean Liver Cancer Association.

The authors declare no conflicts of interest relevant to this article.

Figure 1.
The initial treatment modality of the study population (A) and subgroups according to the Barcelona Clinic Liver Cancer (BCLC) stage 0 (B), stage A (C), stage B (D), stage C (E), and stage D (F). * Combination therapy is defined as the combined treatment of local ablation therapy and transarterial therapy; Miscellaneous therapies are defined as unclassifiable treatment modalities (i.e., combination therapies other than transarterial therapy and local ablation therapy).
jlc-20-1-41f1.jpg
Figure 2.
Overall survival curves for the study population (A) and subgroups divided by the Child-Turcotte-Pugh classes (B) and the modified Union for International Cancer Control stages (C) and the Barcelona Clinic Liver Cancer stages (D).
jlc-20-1-41f2.jpg
Table 1.
Baseline characteristics of the study population (n = 6,083)
Variable Value
Demographic variable
 Age (years) 59.0 (51.0-68.0)
 Sex (male) 4,790 (78.7)
 Diabetes 1,401 (23.0)
 Hypertension 1,808 (29.7)
 Body mass index (kg/m2) 23.7 (21.7-25.8)
 Smoking 2,657 (43.7)
 Etiology (n=5,291, missing values=792)
  HBV* 3,810 (72.0)
  HCV 636 (12.0)
  Alcohol 711 (13.4)
  Others 134 (2.5)
 Performance status (n=4,162, missing values=1,921)
  0 3,231 (77.6)
  1 641 (15.4)
  2 159 (3.8)
  3 74 (1.8)
  4 57 (1.4)
 Ascites (n=6,006, missing values=77)
  None 4,509 (75.1)
  Mild 964 (16.1)
  Moderate to severe 533 (8.9)
 Encephalopathy (n=6,045, missing values=38)
  None 5,894 (97.5)
  Mild to moderate (grade 1 or 2) 119 (2.0)
  Severe (grade 3 or 4) 32 (0.5)
Laboratory variables
 Total bilirubin (mg/dL) 1.0 (0.70-1.60)
 Serum albumin (g/dL) 3.8 (3.2-4.2)
 Alanine aminotransferase (IU/L) 38.0 (24.0-61.0)
 Platelet count (109/L) 139.0 (95.0-199.0)
 Prothrombin time (INR) 1.11 (1.04-1.22)
 Creatinine (mg/dL) 0.90 (0.74-1.00)
 Sodium (mmol/L) 139.0 (136.0-141.0)
 Glucose (mg/dL) 109.0 (94.0-139.0)
 Total cholesterol (mg/dL) 155.0 (130.0-182.0)
 Alpha-fetoprotein (ng/mL) 47.4 (7.3-785.0)
 PIVKA-II (mAU/mL) 144.5 (30.0-1,373.0)
 Child-Turcotte-Pugh class (n=5,719, missing values=364)
  A 4,063 (71.0)
  B 1,362 (23.8)
  C 294 (5.1)
 MELD score 8.6 (7.3-11.1)
 MELD-Na score 10.1 (8.0-13.8)
Tumor variable
 Tumor number (n=6,061, missing values=22)
  1 3,725 (61.5)
  2 826 (13.6)
  3 247 (4.1)
  4 95 (1.6)
  ≥5 1,168 (19.3)
 Maximal tumor diameter (cm) 3.0 (2.0-5.4)
 Portal vein invasion 1,477 (24.3)
 Hepatic vein invasion 339 (5.6)
 Bile duct invasion 159 (2.6)
 Lymph node metastasis 431 (7.1)
 Distant metastasis 602 (9.9)
 Modified UICC stage (n=6,045, missing values=38)
  Stage I 854 (14.1)
  Stage II 2,267 (37.5)
  Stage III 1,577 (26.1)
  Stage IV-A 746 (12.3)
  Stage IV-B 601 (9.9)
 BCLC stage (n=5,697, missing values=386)
  0 489 (8.6)
  A 2,260 (39.7)
  B 658 (11.5)
  C 1,923 (33.8)
  D 391 (6.9)

Values are presented as median (interquartile range) or number (%).

HBV, hepatitis B virus; HCV, hepatitis C virus; INR, international normalized ratio; PIVKA-II, protein induced by vitamin K absence-II; MELD, model for end-stage liver disease; UICC, Union for International Cancer Control; BCLC, Barcelona Clinic Liver Cancer.

* Patients co-infected with HBV and HCV (n=87) were also included;

Performance status was defined as follows: 0, fully active without symptoms; 1, ambulatory with symptoms; 2, bedridden <50% of the time; 3, bedridden >50% of the time but capable of self-care; 4, bedridden 100% of the time and incapable of self-care.

Table 2.
The initial treatment modality of the patients in the treatment group (n = 5,974)
Treatment modality Value
Surgical resection 998 (16.7)
Liver transplantation 55 (0.9)
Local ablation therapy 636 (10.6)
 RFA 594
 PEI 37
 Other local ablation 5
Transarterial therapy 2,493 (41.7)
 Conventional TACE 2,407
 TACE with drug-eluting beads 64
 Radioembolization 7
 HAIC 82
Combination therapy* 108 (1.8)
Systemic therapy 224 (3.7)
 Sorafenib 175
 Other systemic agents 77
External beam radiation therapy 61 (1.0)
Best supportive care 1,295 (21.7)
Miscellaneous therapies 104 (1.7)

Values are presented as number (%) unless otherwise indicated.

RFA, radiofrequency ablation; PEI, percutaneous ethanol injection; TACE, transarterial chemoembolization; HAIC, hepatic arterial infusional chemotherapy.

* Combination therapy is defined as the combined treatment of local ablation therapy and transarterial therapy;

Miscellaneous therapies are defined as unclassifiable treatment modalities (i.e., combination therapies other than transarterial therapy and local ablation therapy).

Table 3.
Overall survival rates (%) of the study population according to the baseline characteristics and the initial treatment modalities
Variable Value Year
1 2 3 4 5
All case 6,083 (100) 65.6 54.3 46.2 40.9 36.8
Age (years, n=6,078, missing values=5)
 <40 187 (3.1) 59.9 50.8 43.9 40.6 40.1
 40-49 982 (16.2) 61.7 51.8 44.8 40.4 38.7
 50-59 1,955 (32.2) 68.1 57.7 50.3 45.6 41.5
 60-69 1,696 (27.9) 68.6 57.3 49.1 43.6 39.1
 ≥70 1,258 (20.77) 61.8 47.4 37.5 30.4 24.3
Sex (n=6,083, missing values=0)
 Male 4,790 (78.7) 64.6 53.3 45.0 39.8 35.8
 Female 1,293 (21.3) 69.5 57.9 50.8 45.1 40.4
Ascites (n=6,006, missing values=77)
 None 4,509 (75.1) 76.2 64.4 55.8 49.9 45.1
 Mild 964 (16.1) 37.9 27.4 21.1 17.1 14.3
 Moderate to severe 533 (8.9) 26.6 18.6 12.2 9.9 9.0
Encephalopathy (n=6,045, missing values=38)
 None 5,894 (97.5) 66.5 55.1 47.0 41.7 37.5
 Mild to moderate (grade 1 or 2) 119 (2.0) 37.8 28.6 20.2 13.4 11.8
 Severe (grade 3 or 4) 32 (0.5) 28.1 28.1 18.8 18.8 18.8
Serum albumin (g/dL, n=5,871, missing values=212)
 <2.8 524 (8.9) 35.7 25.2 19.3 17.0 15.1
 2.8-3.5 1,730 (29.5) 53.0 40.9 32.1 25.8 21.3
 >3.5 3,617 (61.6) 76.6 65.6 57.5 52.0 47.7
Serum bilirubin (mg/dL, n=5,900, missing values=83)
 <2.0 4,842 (82.1) 72.0 60.3 51.4 45.9 41.4
 2.0-3.0 522 (8.8) 48.1 36.8 30.1 23.9 20.7
 >3.0 536 (9.1) 28.4 21.5 18.5 15.1 13.6
Prothrombin time (INR, n=5,733, missing values=350)
 <1.7 5,599 (97.7) 66.8 55.5 47.3 41.8 37.5
 1.7-2.3 99 (1.7) 38.4 28.3 24.2 20.2 17.2
 >2.3 35 (0.6) 20.0 20.0 17.1 14.3 14.3
Child-Turcotte-Pugh classification (n=5,719, missing values=375)
 A 4,063 (71.2) 77.3 66.0 57.0 51.1 46.4
 B 1,354 (23.7) 42.2 30.4 23.5 19.0 15.6
 C 291 (5.1) 20.6 15.1 11.0 8.9 8.6
Tumor number (n=6,061, missing values=22)
 1 3,725 (61.5) 75.6 65.4 57.1 51.7 47.0
 2 826 (13.6) 75.3 59.8 49.2 41.4 36.8
 3 247 (4.1) 74.5 55.5 42.1 32.0 25.1
 4 95 (1.6) 55.8 41.1 32.6 25.3 21.1
 ≥5 1,168 (19.3) 26.1 15.8 11.3 9.2 7.8
Maximal tumor diameter (cm, n=6,040, missing values=43)
 <2 1,185 (19.6) 90.0 81.5 72.7 66.3 59.7
 2-4.9 2,346 (38.8) 83.4 71.9 61.8 54.4 48.8
 5-9.9 1,180 (19.5) 52.3 37.2 28.7 24.1 22.1
 ≥10 1329 (22.0) 24.6 14.4 10.8 9.6 8.1
Portal vein invasion (n=6,083, missing values=0)
 None 4,606 (75.7) 79.1 67.5 57.9 51.5 46.4
 Yes 1,477 (24.3) 23.6 13.1 9.6 7.9 6.7
Hepatic vein invasion (n=6,083, missing values=0)
 None 5,744 (94.4) 68.1 56.7 48.4 42.8 38.5
 Yes 329 (5.6) 24.5 13.3 8.6 8.6 8.0
Bile duct invasion (n=6,083, missing values=0)
 None 5,924 (97.4) 66.5 55.1 46.9 41.5 37.4
 Yes 159 (2.6) 34.0 23.9 19.5 18.2 15.1
T classification (n=6,041, missing values=42)
 T1 860 (14.2) 93.3 86.6 78.0 72.3 65.5
 T2 2,396 (39.7) 84.0 73.0 63.4 56.8 51.7
 T3 1,954 (32.3) 51.1 36.3 28.1 22.7 19.4
 T4 831 (13.8) 18.7 9.7 6.4 5.7 4.8
N classification (n=6,083, missing values=0)
 N0 5,652 (92.9) 69.2 57.6 49.1 43.5 39.1
 N1 431 (7.1) 19.0 10.9 8.1 7.0 6.0
M classification (n=6,083, missing values=0)
 M0 5,481 (90.1) 71.1 59.3 50.7 44.9 40.4
 M1 602 (9.9) 16.1 8.6 5.3 4.8 4.0
Distant metastasis sites (n=569, missing values=33)
 Bone 93 (16.3) 14.0 3.2 2.2 1.1 1.1
 Lung 260 (45.7) 16.2 8.1 5.0 4.6 3.5
 Distant lymph node 64 (11.2) 15.6 7.8 6.2 4.7 4.7
 Lung and bone 31 (5.4) 6.5 3.2 0.0 0.0 0.0
 Bone and distant lymph node 11 (1.9) 36.4 9.1 9.1 9.1 9.1
 Lung and distant lymph node 29 (5.1) 3.4 3.0 0.0 0.0 0.0
 Bone and lung and distant lymph node 9 (1.6) 11.1 0.0 0.0 0.0 0.0
 Others 72 (12.7) 16.7 12.5 8.3 8.3 6.9
Modified UICC stage (n=6,045, missing values=38)
 Stage I 854 (14.1) 93.4 86.8 78.2 72.6 65.7
 Stage II 2,267 (37.5) 86.5 75.7 66.1 59.2 54.0
 Stage III 1,577 (26.1) 59.0 42.8 33.4 26.9 23.1
 Stage IV-A 746 (12.3) 24.5 13.4 9.2 7.8 6.6
 Stage IV-B 601 (9.9) 16.0 8.5 5.3 4.8 4.0
BCLC stage (n=5,697, missing values=386)
 0 489 (8.6) 97.5 93.5 87.7 81.2 74.0
 A 2,259 (39.7) 89.2 78.4 68.5 61.5 56.0
 B 657 (11.5) 72.3 54.2 41.1 32.4 27.4
 C 1,919 (33.7) 37.9 25.8 19.6 17.0 14.6
 D 373 (6.5) 18.8 13.4 9.4 7.8 7.5
Initial treatment modalities (n=5,974, missing values=109)
 Surgical resection 998 (17.6) 93.1 88.0 81.4 77.5 74.4
 Liver transplantation 55 (0.9) 89.1 83.6 80.0 78.2 78.2
 Local ablation therapy 636 (10.6) 94.2 86.5 78.0 71.4 65.1
 Transarterial therapy 2,493 (41.7) 72.8 57.0 45.4 37.8 32.0
 Combination therapy* 108 (1.8) 94.4 84.3 79.6 72.2 65.7
 Systemic therapy 224 (3.7) 18.8 9.4 6.2 5.8 4.5
 External beam radiation therapy 61 (1.0) 24.6 13.1 8.2 6.6 4.9
 Best supportive care 1,295 (21.7) 25.6 17.2 14.1 11.9 10.0
 Miscellaneous therapies 104 (1.7) 45.2 23.1 12.5 8.7 5.8

Values are expressed as median (interquartile range) or number (%).

INR, international normalized ratio; UICC, Union for International Cancer Control; BCLC, Barcelona Clinic Liver Cancer.

* Combination therapy is defined as the combined treatment of local ablation therapy and transarterial therapy;

Miscellaneous therapies are defined as unclassifiable treatment modalities (i.e., combination therapies other than transarterial therapy and local ablation therapy).

  • 1. Statistics Korea. Annual report on the causes of death statistics 2017. Daejeon, Statistics Korea. 2018.
  • 2. Kweon SS. Updates on cancer epidemiology in Korea, 2018. Chonnam Med J 2018;54:90−100.ArticlePubMedPMC
  • 3. National Cancer Center. Korea Central Cancer Registry. Annual report of cancer statistics in Korea in 2016. Goyang: National Cancer Center. 2018.
  • 4. McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis 2015;19:223−238.ArticlePubMedPMC
  • 5. European Association For The Study Of The Live, European Organisation For Research And Treatment Of Cance. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:908−943.ArticlePubMed
  • 6. Lee YS, Seo YS, Kim JH, Lee J, Kim HR, Yoo YJ, et al. Can more aggressive treatment improve prognosis in patients with hepatocellular carcinoma? A direct comparison of the Hong Kong liver cancer and Barcelona clinic liver cancer algorithms. Gut Liver 2018;12:94−101.ArticlePubMedPDF
  • 7. 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.ArticlePubMed
  • 8. Kwak HW, Park JW, Nam BH, Yu A, Woo SM, Kim TH, et al. Clinical outcomes of a cohort series of patients with hepatocellular carcinoma in a hepatitis B virus-endemic area. J Gastroenterol Hepatol 2014;29:820−829.ArticlePubMed
  • 9. Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019;25:93−159.ArticlePubMedPMC
  • 10. Lee KS, Chang HS, Lee SM, Park EC. Economic burden of cancer in Korea during 2000-2010. Cancer Res Treat 2015;47:387−398.ArticlePubMedPDF
  • 11. Yu SJ. A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016. Clin Mol Hepatol 2016;22:7−17.ArticlePubMedPMCPDF
  • 12. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Disease. Management of hepatocellular carcinoma. Hepatology 2005;42:1208−1236.ArticlePubMed
  • 13. 13Sheu JC, Sung JL, Chen DS, Yang PM, Lai MY, Lee CS, et al. Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterology 1985;89:259−266.ArticlePubMed
  • 14. Kudo M, Kitano M, Sakurai T, Nishida N. General Rules for the Clinical and Pathological Study of Primary Liver Cancer, Nationwide Follow-Up Survey and Clinical Practice Guidelines: the outstanding achievements of the Liver Cancer Study Group of Japan. Dig Dis 2015;33:765−770.ArticlePubMed
  • 15. Ueno S, Tanabe G, Nuruki K, Hamanoue M, Komorizono Y, Oketani M, et al. Prognostic performance of the new classification of primary liver cancer of Japan (4th edition) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res 2002;24:395−403.ArticlePubMed
  • 16. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329−338.ArticlePubMedPDF
  • 17. Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int 2015;35:2155−2166.ArticlePubMedPMC
  • 18. El-Serag HB, Davila JA. Surveillance for hepatocellular carcinoma: in whom and how? Therap Adv Gastroenterol 2011;4:5−10.ArticlePubMedPMC
  • 19. Kudo M. Japan’s successful model of nationwide hepatocellular carcinoma surveillance highlighting the urgent need for global surveillance. Liver Cancer 2012;1:141−143.ArticlePubMedPMC
  • 20. Goutté N, Sogni P, Bendersky N, Barbare JC, Falissard B, Farges O. Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country. J Hepatol 2017;66:537−544.ArticlePubMed
  • 21. Altekruse SF, McGlynn KA, Dickie LA, Kleiner DE. Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992-2008. Hepatology 2012;55:476−482.ArticlePubMed
  • 22. El -Serag HB. Hepatocellular carcinoma. N Engl J Med 2011;365:1118−1127.ArticlePubMed
  • 23. Kudo M, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, et al. Report of the 20th Nationwide Follow-up Survey of Primary Liver Cancer in Japan. Hepatol Res 2020;50:15−46.ArticlePubMedPMC
  • 24. Guarino M, Tortora R, de Stefano G, Coppola C, Morisco F, Salomone Megna A, et al. Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: results of Progetto Epatocarcinoma Campania. J Gastroenterol Hepatol 2018;33:1123−1130.ArticlePubMed
  • 25. Leoni S, Piscaglia F, Serio I, Terzi E, Pettinari I, Croci L, et al. Adherence to AASLD guidelines for the treatment of hepatocellular carcinoma in clinical practice: experience of the Bologna Liver Oncology Group. Dig Liver Dis 2014;46:549−555.ArticlePubMed
  • 26. Radu P, Groza I, Iancu C, Al Hajjar N, Andreica V, Sparchez Z. Treatment of hepatocellular carcinoma in a tertiary Romanian center. Deviations from BCLC recommendations and influence on survival rate. J Gastrointestin Liver Dis 2013;22:291−297.PubMed

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Hepatocellular carcinoma incidence is decreasing in Korea but increasing in the very elderly
      Young Eun Chon, Seong Yong Park, Han Pyo Hong, Donghee Son, Jonghyun Lee, Eileen Yoon, Soon Sun Kim, Sang Bong Ahn, Soung Won Jeong, Dae Won Jun
      Clinical and Molecular Hepatology.2023; 29(1): 120.     CrossRef
    • Surgical resection versus ablation for early hepatocellular carcinoma: The debate is still open
      Bo Hyun Kim
      Clinical and Molecular Hepatology.2022; 28(2): 174.     CrossRef
    • Cause of death and cause-specific mortality for primary liver cancer in South Korea: A nationwide population-based study in hepatitis B virus-endemic area
      Bo Hyun Kim, Dahhay Lee, Kyu-Won Jung, Young-Joo Won, Hyunsoon Cho
      Clinical and Molecular Hepatology.2022; 28(2): 242.     CrossRef
    • Impact of expanding hepatitis B treatment guidelines: A modelling and economic impact analysis
      Young‐Suk Lim, Sang Hoon Ahn, Jae‐Jun Shim, Homie Razavi, Devin Razavi‐Shearer, Dong Hyun Sinn
      Alimentary Pharmacology & Therapeutics.2022; 56(3): 519.     CrossRef
    • Surveillance for hepatocellular carcinoma: It is time to move forward
      Bo Hyun Kim, Yuri Cho, Joong-Won Park
      Clinical and Molecular Hepatology.2022; 28(4): 810.     CrossRef
    • Therapeutic Decision Making in Hepatocellular Carcinoma According to Age and Child–Pugh Class: A Nationwide Cohort Analysis in South Korea
      Sunmin Park, Chai Hong Rim, Young Kul Jung, Won Sup Yoon, Alessandro Granito
      Canadian Journal of Gastroenterology and Hepatology.2021; 2021: 1.     CrossRef
    • Outcome of Immune Checkpoint Inhibitor and Molecular Target Agent Combination for Advanced Hepatocellular Carcinoma: Beyond Sorafenib Era
      Nae-Yun Heo
      The Korean Journal of Gastroenterology.2021; 77(3): 145.     CrossRef
    • Rare Case of Pyogenic Brain Abscess after Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma: Case Report and Literature Review
      Jun-Ho Myeong, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
      Journal of Liver Cancer.2021; 21(1): 81.     CrossRef
    • Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry
      Jun Sik Yoon, Han Ah Lee, Hwi Young Kim, Dong Hyun Sinn, Dong Ho Lee, Suk Kyun Hong, Ju-Yeon Cho, Jonggi Choi, Young Chang, Hyun-Joo Kong, Eunyang Kim, Young-Joo Won, Jeong-Hoon Lee
      Journal of Liver Cancer.2021; 21(1): 58.     CrossRef
    • Glucose Variability and Risk of Hepatocellular Carcinoma in Patients with Diabetes: A Nationwide Population-Based Study
      Jeong-Ju Yoo, Eun Ju Cho, Kyungdo Han, Soo Seong Heo, Bo-Yeon Kim, Dong Wook Shin, Su Jong Yu
      Cancer Epidemiology, Biomarkers & Prevention.2021; 30(5): 974.     CrossRef
    • Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein improves diagnostic accuracy for hepatocellular carcinoma
      Han Ah Lee, Yoo Ra Lee, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Yeon Seok Seo
      World Journal of Gastroenterology.2021; 27(28): 4687.     CrossRef
    • Hepatocellular Carcinoma in Korea between 2012 and 2014: an Analysis of Data from the Korean Nationwide Cancer Registry
      Young Eun Chon, Han Ah Lee, Jun Sik Yoon, Jun Yong Park, Bo Hyun Kim, In Joon Lee, Suk Kyun Hong, Dong Hyeon Lee, Hyun-Joo Kong, Eunyang Kim, Young-Joo Won, Jeong-Hoon Lee
      Journal of Liver Cancer.2020; 20(2): 135.     CrossRef
    • Efficacy of Local Treatments for Hepatocellular Carcinoma Involving the Inferior Vena Cava and/or Right Atrium
      Han Ah Lee, Chai Hong Rim
      Journal of Hepatocellular Carcinoma.2020; Volume 7: 435.     CrossRef

    • PubReader PubReader
    • ePub LinkePub Link
    • Cited
      CITED
      export Copy
      Close
    • XML DownloadXML Download
    • XML DownloadDownload Citation
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Hepatocellular Carcinoma in Korea Between 2008 and 2011: an Analysis of Korean Nationwide Cancer Registry
      J Liver Cancer. 2020;20(1):41-52.   Published online March 31, 2020
      Close
    Related articles

    JLC : Journal of Liver Cancer