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The diagnostic value of circulating tumor DNA in hepatitis B virus induced hepatocellular carcinoma: a systematic review and meta-analysis
Young Chang, Soung Won Jeong, Jae Young Jang, Hyuksoo Eun, Young‑Sun Lee, Do Seon Song, Su Jong Yu, Sae Hwan Lee, Won Kim, Hyun Woong Lee, Sang Gyune Kim, Seongho Ryu, Suyeon Park
J Liver Cancer. 2022;22(2):167-177.   Published online September 29, 2022
DOI: https://doi.org/10.17998/jlc.2022.09.19
  • 524 Views
  • 31 Downloads
AbstractAbstract PDFSupplementary Material
Background
/Aim: New biomarkers are urgently needed to aid in the diagnosis of early stage hepatocellular carcinoma (HCC). We performed a meta-analysis on the diagnostic utility of circulating tumor DNA (ctDNA) levels in patients with hepatitis B virus-induced HCC.
Methods
We retrieved relevant articles from PubMed, Embase, and the Cochrane Library up to February 8, 2022. Two subgroups were defined; one subset of studies analyzed the ctDNA methylation status, and the other subset combined tumor markers and ctDNA assays. Pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) were analyzed.
Results
Nine articles including 2,161 participants were included. The overall SEN and SPE were 0.705 (95% confidence interval [CI], 0.629-0.771) and 0.833 (95% CI, 0.769-0.882), respectively. The DOR, PLR, and NLR were 11.759 (95% CI, 7.982-17.322), 4.285 (95% CI, 3.098- 5.925), and 0.336 (0.301-0.366), respectively. The ctDNA assay subset exhibited an AUC of 0.835. The AUC of the combined tumor marker and ctDNA assay was 0.848, with an SEN of 0.761 (95% CI, 0.659-0.839) and an SPE of 0.828 (95% CI, 0.692-0.911).
Conclusions
Circulating tumor DNA has promising diagnostic potential for HCC. It can serve as an auxiliary tool for HCC screening and detection, especially when combined with tumor markers.
Clinical characteristics and prognosis of Korean patients with hepatocellular carcinoma with respect to etiology
Wonjoon Jang, Hye Won Lee, Jae Seung Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim
J Liver Cancer. 2022;22(2):158-166.   Published online September 27, 2022
DOI: https://doi.org/10.17998/jlc.2022.09.18
  • 543 Views
  • 28 Downloads
AbstractAbstract PDFSupplementary Material
Background
/Aim: The profile of patients with hepatocellular carcinoma (HCC) has changed globally; the role of etiology in predicting prognosis of HCC patients remains unclear. We aimed to analyze the characteristics and prognosis of Korean patients with HCC according to disease etiology.
Methods
This retrospective observational study included patients diagnosed with HCC between 2010 and 2014 in a single center in Korea. Patients with HCC aged <19 years old, had coinfection with other viral hepatitis, had missing follow-up data, were Barcelona Clinic Liver Cancer stage D, or died before 1 month were excluded.
Results
A total of 1,595 patients with HCC were analyzed; they were classified into the hepatitis B virus (HBV) group (1,183 [74.2%]), hepatitis C virus (HCV) group (146 [9.2%]), and non-B non-C (NBNC) group (266 [16.7%]). The median overall survival of all patients was 74 months. The survival rates at 1, 3, and 5 years were 78.8%, 62.0% and 54.9% in the HBV group; 86.0%, 64.0%, and 48.6% in the HCV group; and 78.4%, 56.5%, and 45.9% in the NBNC group, respectively. NBNC-HCC has a poorer prognosis than other causes of HCC. Survival was significantly longer in the HBV group with early-stage HCC than in the NBNC group. Furthermore, survival was shorter in patients with early-stage HCC and diabetes mellitus (DM) than in those without DM.
Conclusions
The etiology of HCC affected clinical characteristics and prognosis to some extent. NBNC-HCC patients showed shorter overall survival than viral-related HCC patients. Additionally, the presence of DM is an additional important prognostic factor in patients with early-stage HCC.
Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: a retrospective observational study
Jeong Yun Jang, Jinhong Jung, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jin-hong Park, Sang Min Yoon
J Liver Cancer. 2022;22(2):136-145.   Published online September 16, 2022
DOI: https://doi.org/10.17998/jlc.2022.08.18
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AbstractAbstract PDFSupplementary Material
Background
/Aim: We aimed to investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) in elderly patients with small hepatocellular carcinomas (HCC).
Methods
Eighty-three patients (89 lesions) with HCC who underwent SBRT between January 2012 and December 2018 were reviewed in this retrospective observational study. The key inclusion criteria were as follows: 1) age ≥75 years, 2) contraindications for hepatic resection or percutaneous ablative therapies, 3) no macroscopic vascular invasion, and 4) no extrahepatic metastasis.
Results
The patients were 75-90 years of age, and 49 (59.0%) of them were male. Most patients (94.0%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Seventy-four patients (89.2%) had Child-Pugh class A hepatic function before SBRT. The median tumor size was 1.6 cm (range, 0.7-3.5). The overall median follow-up period was 34.8 months (range, 7.3-99.3). The 5-year local tumor control rate was 90.1%. The 3-year and 5-year overall survival rate was 57.1% and 40.7%, respectively. Acute toxicity grade ≥3 was observed in three patients (3.6%) with elevated serum hepatic enzymes; however, no patient experienced a worsening of the Child-Pugh score to ≥2 after SBRT. None of the patients developed late toxicity (grade ≥3).
Conclusions
SBRT is a safe treatment option with a high local control rate in elderly patients with small HCC who are not eligible for other curative treatments.
Indications for open hepatectomy in the era of laparoscopic liver resection: a high volume single institutional study
Sung Jun Jo, Jinsoo Rhu, Jong Man Kim, Gyu-Seong Choi, Jae-Won Joh
J Liver Cancer. 2022;22(2):146-157.   Published online September 14, 2022
DOI: https://doi.org/10.17998/jlc.2022.08.22
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  • 30 Downloads
AbstractAbstract PDFSupplementary Material
Background
/Aim: Since the introduction of laparoscopy for liver resection in the 1990s, the performance of laparoscopic liver resection (LLR) has been steadily increasing. However, there is currently no data on the extent to which laparoscopy is used for liver resection. Herein, we investigated the extent to which laparoscopy is performed in liver resection and sought to determine whether surgeons prefer laparoscopy or laparotomy in the posterosuperior (PS) segment.
Methods
For this retrospective observational study, we enrolled patients who had undergone liver resection at the Samsung Medical Center between January 2020 and December 2021. The proportion of LLR in liver resection was calculated, and the incidence and causes of open conversion were investigated.
Results
A total of 1,095 patients were included in this study. LLR accounted for 79% of the total liver resections. The percentage of previous hepatectomy (16.2% vs. 5.9%, P<0.001) and maximum tumor size (median 4.8 vs. 2.8, P<0.001) were higher in the open liver resection (OLR) group. Subgroup analysis revealed that tumor size (median 6.3 vs. 2.9, P<0.001) and surgical extent (P<0.001) in the OLR group were larger than those in the LLR group. The most common cause of open conversion (OC) was adhesion (57%), and all OC patients had tumors in the PS.
Conclusions
We investigated the recent preference of practical surgeons in liver resection, and found that surgeons preferred OLR to LLR when treating a large tumor located in the PS.
Effect of direct-acting antivirals for hepatitis C virus-related hepatocellular carcinoma recurrence and death after curative treatment
Young-Hwan Ahn, Heirim Lee, Ji Eun Han, Hyo Jung Cho, Jae Youn Cheong, Bumhee Park, Soon Sun Kim
J Liver Cancer. 2022;22(2):125-135.   Published online June 28, 2022
DOI: https://doi.org/10.17998/jlc.2022.05.24
  • 858 Views
  • 42 Downloads
  • 1 Citation
AbstractAbstract PDFSupplementary Material
Background
/Aim: There has been a long-standing debate about the association of directacting antiviral (DAA) therapy and hepatocellular carcinoma (HCC) recurrence. This study aimed to investigate the association between DAA therapy and HCC recurrence after curative therapy.
Methods
We retrospectively enrolled 1,021 patients with HCV-related (hepatitis C virus) HCC who underwent radiofrequency ablation (RFA), liver resection, or both as the first treatment modality from January 2007 to December 2016 and without a history of HCV therapy before HCC treatment from a nationwide database. The effect of HCV treatment on HCC recurrence and all-cause mortality was also investigated.
Results
Among the 1,021 patients, 77 (7.5%) were treated with DAA, 14 (1.4%) were treated with interferon-based therapy, and 930 (91.1%) did not receive HCV therapy. DAA therapy was an independent prognostic factor for lower HCC recurrence rate (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.006-0.289; P=0.001 for landmarks at 6 months after HCC treatment and HR, 0.05; 95% CI, 0.007-0.354; P=0.003 for landmarks at 1 year). Furthermore, DAA therapy was associated with lower all-cause mortality (HR, 0.049; 95% CI, 0.007-0.349; P=0.003 for landmarks at 6 months and HR, 0.063; 95% CI, 0.009-0.451; P=0.006 for landmarks at 1 year).
Conclusions
DAA therapy after curative HCC treatment can decrease HCC recurrence and all-cause mortality compared to interferon-based therapy or no antiviral therapy. Therefore, clinicians should consider administering DAA therapy after curative HCC treatment in patients with HCV-related HCC.

Citations

Citations to this article as recorded by  
  • Is direct-acting antiviral treatment beneficial or harmful for patients with hepatitis C virus-related hepatocellular carcinoma?
    Hye Won Lee
    Journal of Liver Cancer.2022; 22(2): 91.     CrossRef
The dual role of transforming growth factor-beta signatures in human B viral multistep hepatocarcinogenesis: early and late responsive genes
Jeong Eun Yoo, Ji Hae Nahm, Young-Joo Kim, Youngsic Jeon, Young Nyun Park
J Liver Cancer. 2022;22(2):115-124.   Published online May 20, 2022
DOI: https://doi.org/10.17998/jlc.2022.04.20
  • 1,009 Views
  • 51 Downloads
AbstractAbstract PDFSupplementary Material
Background
/Aim: Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis.
Methods
The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry.
Results
The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers.
Conclusions
The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis.
Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma
Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
J Liver Cancer. 2022;22(1):30-39.   Published online March 21, 2022
DOI: https://doi.org/10.17998/jlc.2022.02.25
  • 1,919 Views
  • 87 Downloads
AbstractAbstract PDFSupplementary Material
Background
/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.
The effects of immune checkpoint modulators on the clinical course of patients with resectable hepatocellular carcinoma
Jihyun An, Hyo Jeong Kang, Eunsil Yu, Han Chu Lee, Ju Hyun Shim
J Liver Cancer. 2022;22(1):40-50.   Published online March 17, 2022
DOI: https://doi.org/10.17998/jlc.2022.03.06
  • 1,532 Views
  • 81 Downloads
AbstractAbstract PDFSupplementary Material
Background
/Aim: Immune checkpoint proteins regulating T-cell mediated anti-tumor immunity have been reported to affect clinical outcomes in multiple malignancies. This study aimed to investigate the prognostic effect of histological expression of immune checkpoint proteins in patients with resected hepatocellular carcinoma (HCC).
Methods
A total of 221 patients with HCC who underwent curative resection were included. Expression of programmed-cell death ligand-1 (PD-L1) in tumor cells (tPD-L1) and tumor infiltrating mononuclear cells (TIMCs) (iPD-L1), programmed-cell death-1 in TIMCs (iPD-1), and cytotoxic T lymphocyte antigen-4 in TIMCs (iCTLA-4) were measured immunohistochemically.
Results
Histo-positivity for iCTLA-4, iPD-1, iPD-L1, and tPD-L1 was 32.1%, 42.5%, 35.3%, and 14.9%, respectively. Multivariate logistic analyses revealed that male sex and tumor >5 cm were variables related to iCTLA-4 positivity (odds ratio [OR], 0.46 and 1.94, respectively; P<0.05). Poor differentiation was related to PD-L1 expression in both tumor cells and TIMCs (OR, 2.88 and 3.46, respectively; P<0.05). Microvascular invasion was significantly associated only with iPD-L1 (OR, 2.24; P<0.05). In time-dependent outcome analyses, expression of immune checkpoint proteins in TIMCs (i.e., iCTLA-4, iPD-1, and iPD-L1) was significantly related to longer overall survival and non-cancer-related survival (all P<0.05), but not to time-to-recurrence or cancer-specific deaths. Concurrent activation of the PD-1:PD-L1 and CTLA-4 pathways predicted improved outcomes in terms of overall survival and non-cancer related survival (P=0.06 and P=0.03, respectively).
Conclusions
Immune checkpoint proteins upregulated in TIMCs in HCC tissues have individual and additive effects in prolonging the survival of patients, specifically in terms of survival not related to cancer recurrence.
The effect of nucleos(t)ide analogues on clinical outcomes of patients treated with transarterial chemoembolization and radiofrequency ablation for hepatitis B virus-related hepatocellular carcinoma
Jae Min Park, Won Hyeok Choe, Jeong Han Kim, So Young Kwon, Byung Chul Yoo
J Liver Cancer. 2021;21(2):155-162.   Published online September 30, 2021
DOI: https://doi.org/10.17998/jlc.2021.09.22
  • 1,733 Views
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AbstractAbstract PDFSupplementary Material
Background
/Aims: Because hepatitis B virus (HBV) replication has been known to play an important role in cancer recurrence after curative treatment of HBV-related hepatocellular carcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs) might decrease the recurrence rate and improve patient survival.
Methods
The retrospective cohort study enrolled 73 patients with chronic hepatitis B who were treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), respectively.
Results
Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were dead during a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazard ratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B (vs. class A/non cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associated with HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was an independent unfavorable prognostic factor for survival. During NAs therapy, TDF was superior to ETV for complete viral response at 1 year after the date of combination of TACE and RFA (P=0.016). However, the risks of HCC recurrence and survival were not significantly different between those treated with TDF versus ETV.
Conclusions
TDF was superior to ETV for achieving complete viral response. However, the recurrence and mortality after TACE and RFA for HBV-related HCC were not significantly different between patients treated with TDF versus ETV.
Transarterial chemoembolization using drug-eluting bead compared with radiofrequency ablation for treatment of single small hepatocellular carcinoma: a pilot non-randomized trial
Tae Hoon Kim, Na Hye Kim, Jin Dong Kim, Young Nam Kim, Yu Jin Kim, Eun Jung Kim, Ki Deok Yoo, Choong Heon Ryu, Ha Hun Song, Hyun Kim
J Liver Cancer. 2021;21(2):146-154.   Published online August 11, 2021
DOI: https://doi.org/10.17998/jlc.2021.05.20
  • 2,085 Views
  • 110 Downloads
  • 1 Citation
AbstractAbstract PDFSupplementary Material
Background
/Aims: Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC.
Methods
In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications.
Results
Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively (P=1.000). During mean follow-up of 87.6 months (95% confidence interval: 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group (P=0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEBTACE vs. 17.2% and 36.3% in RFA group (P=0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event.
Conclusions
Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible.

Citations

Citations to this article as recorded by  
  • Comparable Outcomes in Early Hepatocellular Carcinomas Treated with Trans-Arterial Chemoembolization and Radiofrequency Ablation
    Benjamin Wei Rong Tay, Daniel Q. Huang, Muthiah Mark, Neo Wee Thong, Lee Guan Huei, Lim Seng Gee, Low How Cheng, Lee Yin Mei, Prem Thurairajah, Lim Jia Chen, Cheng Han Ng, Wen Hui Lim, Darren Jun Hao Tan, Da Costa Maureen, Kow Wei Chieh Alfred, Iyer Shrid
    Biomedicines.2022; 10(10): 2361.     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
J Liver Cancer. 2021;21(1):58-68.   Published online March 31, 2021
DOI: https://doi.org/10.17998/jlc.21.1.58
Retraction in: J Liver Cancer 2022;22(2):207
  • 3,011 Views
  • 180 Downloads
  • 9 Citations
AbstractAbstract PDFSupplementary Material
Background
/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death in Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2015.
Methods
Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative sample of patients newly diagnosed with HCC in Korea, were analyzed. A total of 1,558 patients with HCC registered in the KPLCR in 2015 were investigated.
Results
The median age was 61.0 years (interquartile range, 54.0-70.0 years), and men accounted for 79.7% of the subjects. Hepatitis B virus infection was the most common underlying liver disease (58.1%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stage 0, A, B, C, and D HCCs accounted for 14.2%, 31.5%, 7.6%, 39.0%, and 7.8% of patients, respectively. Transarterial therapy (32.1%) was the most commonly performed initial treatment, followed by surgical resection (23.2%), best supportive care (20.2%), and local ablation therapy (10.7%). Overall, 34.5% of patients were treated in accordance with the BCLC guidelines: 59.2% in stage 0/A, 48.4% in stage B, 18.1% in stage C, and 71.6% in stage D. The 1-, 3-, and 5-year OS rates were 67.1%, 50.9%, and 27.0%, respectively.
Conclusions
In 2015, approximately 45% of Korean HCC cases were diagnosed at a very early or early stage, and 35% of patients underwent potentially curative initial treatment. BCLC guidance was followed in 34.5% of patients; in patients with stage B or C disease, there was relatively low adherence.

Citations

Citations to this article as recorded by  
  • 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 tumor size on hepatectomy outcomes in hepatocellular carcinoma: a nationwide propensity score matching analysis
    Suk Kyun Hong, Kwang-Woong Lee, Sola Lee, Su young Hong, Sanggyun Suh, Eui Soo Han, YoungRok Choi, Nam-Joon Yi, Kyung-Suk Suh
    Annals of Surgical Treatment and Research.2022; 102(4): 193.     CrossRef
  • Efficacy and feasibility of surgery and external radiotherapy for hepatocellular carcinoma with portal invasion: A meta-analysis
    Han Ah Lee, Yeon Seok Seo, In-Soo Shin, Won Sup Yoon, Hye Yoon Lee, Chai Hong Rim
    International Journal of Surgery.2022; 104: 106753.     CrossRef
  • Yoon et al. Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry
    Jeong-Hoon Lee
    Journal of Liver Cancer.2022; 22(2): 207.     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
  • Treatment patterns for hepatocellular carcinoma in patients with Child–Pugh class B and their impact on survival: A Korean nationwide registry study
    Dongsub Jeon, Gi‐Won Song, Han Chu Lee, Ju Hyun Shim
    Liver International.2022; 42(12): 2830.     CrossRef
  • Metastatic breast cancer from a hepatocellular carcinoma: a case report
    Hyewon Bang, Nam-Hee Kim, Seung Hye Choi, Si Hyun Bae, Eun Sun Jung, Ki Ouk Min, Yong Hwa Eom
    Korean Journal of Clinical Oncology.2022; 18(2): 93.     CrossRef
  • Current Status and Future Directions of Hepatocellular Carcinoma Surveillance Test Based on Cost-effective Analysis
    Jihyun An
    The Korean Journal of Gastroenterology.2021; 78(5): 255.     CrossRef
Prediction of Post-resection Prognosis Using the ADV Score for Huge Hepatocellular Carcinomas ≥13 cm
Shin Hwang, Ki-Hun Kim, Deok-Bog Moon, Chul-Soo Ahn, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Gil-Chun Park
J Liver Cancer. 2021;21(1):45-57.   Published online March 31, 2021
DOI: https://doi.org/10.17998/jlc.21.1.45
  • 2,290 Views
  • 63 Downloads
AbstractAbstract PDF
Background
/Aims: Multiplication of α-fetoprotein, des-γ-carboxy prothrombin, and tumor volume (ADV score) is a surrogate marker for post-resection prognosis of hepatocellular carcinoma (HCC). This study aimed to validate the predictive power of the ADV score-based prognostic prediction model for patients with solitary huge HCC.
Methods
Of 3,018 patients, 100 patients who underwent hepatic resection for solitary HCC ≥13 cm between 2008 and 2012 were selected.
Results
The median tumor diameter and tumor volume were 15.0 cm and 886 mL, respectively. Tumor recurrence and overall survival (OS) rates were 70.7% and 66.0% at one year and 84.9% and 34.0% at five years, respectively. Microvascular invasion (MVI) was the only independent risk factor for disease-free survival (DFS) and OS. DFS and OS, stratified by ADV score with 1-log intervals, showed significant prognostic contrasts (P=0.007 and P=0.017, respectively). DFS and OS, stratified by ADV score with a cut-off of 8-log, showed significant prognostic contrasts (P=0.014 and P=0.042, respectively). The combination of MVI and ADV score with a cut-off of 8-log also showed significant prognostic contrasts in DFS (P<0.001) and OS (P=0.001) considering the number of risk factors. Prognostic contrast was enhanced after combining the MVI and ADV score.
Conclusions
The prognostic prediction model with the ADV score could reliably predict the risk of tumor recurrence and long-term patient survival outcomes in patients with solitary huge HCCs ≥13 cm. The results of this study suggest that our prognostic prediction models can be used to guide surgical treatment and post-resection follow-up for patients with huge HCCs.
Incidence and Clinical Features of Hepatitis C Virus-associated Hepatocellular Carcinoma Patients without Liver Cirrhosis in Hepatitis B Virus-endemic Area
Jongbeom Shin, Jung Hwan Yu, Young-Joo Jin, Jin-Woo Lee
J Liver Cancer. 2021;21(1):34-44.   Published online March 31, 2021
DOI: https://doi.org/10.17998/jlc.21.1.34
  • 2,280 Views
  • 72 Downloads
AbstractAbstract PDF
Background
/objective: Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC.
Methods
The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically.
Results
Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients.
Conclusions
HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.
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
J Liver Cancer. 2020;20(2):135-147.   Published online September 30, 2020
DOI: https://doi.org/10.17998/jlc.20.2.135
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  • 10 Citations
AbstractAbstract PDFSupplementary Material
Background
/Aims: Considering the high prevalence and mortality of hepatocellular carcinoma (HCC) in Korea, accurate statistics for HCC are important. We evaluated the characteristics of Korean patients with newly diagnosed HCC.
Methods
We retrospectively evaluated data from the Korean Primary Liver Cancer Registry (KPLCR). The baseline characteristics, treatment modalities, and overall survival (OS) of 4,572 patients with HCC registered in the KPLCR between 2012 and 2014 were investigated.
Results
At the time of HCC diagnosis, the median age was 60.0 years, with male predominance (79.6%). Hepatitis B virus infection was the most common etiology (59.1%). The rates of Barcelona Clinic Liver Cancer (BCLC) stages 0, A, B, C, and D at diagnosis were 3.9%, 36.9%, 12.5%, 39.4%, and 7.3%, respectively. The proportion of very early or early stage HCC at diagnosis (BCLC stage 0 or A) in the 2012-2014 cohort was significantly lower than that in the 2008-2011 cohort (40.8% vs. 48.3%, P<0.001). Transarterial therapy (37.5%) was the most commonly performed initial treatment, followed by surgical resection (19.8%), best supportive care (19.1%), and local ablation (10.6%). The median OS was 2.9 years, and the 1-, 3-, and 5-year OS rates were 67.7%, 49.3% and 41.9%, respectively. The OS rate of the 2012-2014 cohort was significantly higher than that of the 2008-2011 cohort (log-rank, P<0.001).
Conclusions
The OS of HCC patients registered in the KPLCR between 2012 and 2014 significantly improved. Nevertheless, as about half of the HCC patients were diagnosed at an advanced stage, vigorous and optimized HCC screening strategies should be implemented.

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    Clinical and Molecular Hepatology.2023; 29(1): 120.     CrossRef
  • Surgical resection versus ablation for early hepatocellular carcinoma: The debate is still open
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  • 2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

    Korean Journal of Radiology.2022; 23(12): 1126.     CrossRef
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    Journal of Liver Cancer.2021; 21(1): 58.     CrossRef
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    Jeong-Yeon Cho, Sun-Hong Kwon, Eui-Kyung Lee, Jeong-Hoon Lee, Hye-Lin Kim
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Sang Yi Moon, Sang Young Han, Yang-Hyun Baek
    Kosin Medical Journal.2021; 36(2): 161.     CrossRef
Infiltration of T Cells and Programmed Cell Death Ligand 1-expressing Macrophages as a Potential Predictor of Lenvatinib Response in Hepatocellular Carcinoma
Pil Soo Sung, Sung Woo Cho, Jaejun Lee, Hyun Yang, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
J Liver Cancer. 2020;20(2):128-134.   Published online September 30, 2020
DOI: https://doi.org/10.17998/jlc.20.2.128
  • 2,171 Views
  • 83 Downloads
  • 5 Citations
AbstractAbstract PDF
Background
/Aims: Lenvatinib was recently proven to be non-inferior to sorafenib in treating unresectable hepatocellular carcinoma (HCC) in a phase-3 randomized controlled trial. In this study, we investigated whether the response to lenvatinib was affected by tumor immunogenicity.
Methods
Between May 2019 and April 2020, nine patients with intermediate-to-advanced HCC, who were treated with lenvatinib after liver biopsy, were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed on specimens obtained from liver biopsy.
Results
Among the nine patients enrolled, four showed objective responses (complete responses+partial responses). Immunohistochemical staining for CD3, CD68, and programmed cell death ligand 1 (PD-L1) demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing macrophages in intra-tumoral and peri-tumoral tissues compared to those without objective responses. A significant difference in the numbers of infiltrated T cells, both in the intra-tumoral (P<0.01) and peri-tumoral regions (P<0.05), were identified between responders and non-responders. Regarding the number of infiltrated macrophages, no significant difference was found between the responders and non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than that in non-responders (P<0.05).
Conclusions
Tumor immunogenicity, as indicated by T cell and PD-L1-positive macrophage infiltration, affects lenvatinib response in unresectable HCC.

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    Journal for ImmunoTherapy of Cancer.2022; 10(5): e003618.     CrossRef
  • Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
    Pil Soo Sung
    Clinical and Molecular Hepatology.2022; 28(3): 333.     CrossRef
  • Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go
    Pil Soo Sung, Isaac Kise Lee, Pu Reun Roh, Min Woo Kang, Jaegyoon Ahn, Seung Kew Yoon
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection
    Pil Soo Sung, Eui-Cheol Shin
    Journal of Clinical Medicine.2021; 10(2): 221.     CrossRef
  • Preferential Expression of Programmed Death Ligand 1 Protein in Tumor-Associated Macrophages and Its Potential Role in Immunotherapy for Hepatocellular Carcinoma
    Dong-Jun Park, Pil-Soo Sung, Gil-Won Lee, Sung-Woo Cho, Sung-Min Kim, Byung-Yoon Kang, Won-Hee Hur, Hyun Yang, Soon-Kyu Lee, Sung-Hak Lee, Eun-Sun Jung, Chang-Ho Seo, Joseph Ahn, Ho-Joong Choi, Young-Kyoung You, Jeong-Won Jang, Si-Hyun Bae, Jong-Young Cho
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JLC : Journal of Liver Cancer