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Guideline
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma
Received November 5, 2022  Accepted November 7, 2022  Published online December 9, 2022  
DOI: https://doi.org/10.17998/jlc.2022.11.07    [Epub ahead of print]
  • 437 Views
  • 18 Downloads
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Editorial
Is direct-acting antiviral treatment beneficial or harmful for patients with hepatitis C virus-related hepatocellular carcinoma?
Hye Won Lee
J Liver Cancer. 2022;22(2):91-92.   Published online September 29, 2022
DOI: https://doi.org/10.17998/jlc.2022.09.20
  • 610 Views
  • 32 Downloads
PDF
Original Articles
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.
Review Article
Liquid biopsy for early detection and therapeutic monitoring of hepatocellular carcinoma
Eun-Ji Choi, Young-Joon Kim
J Liver Cancer. 2022;22(2):103-114.   Published online September 22, 2022
DOI: https://doi.org/10.17998/jlc.2022.09.08
  • 885 Views
  • 60 Downloads
AbstractAbstract PDFSupplementary Material
Advances in our knowledge of the molecular characteristics of hepatocellular carcinoma (HCC) have enabled significant progress in the detection and therapeutic prediction of HCC. As a non-invasive alternative to tissue biopsy, liquid biopsy examines circulating cellular components such as exosomes, nucleic acids, and cell-free DNA found in body fluids (e.g., urine, saliva, ascites, and pleural effusions) and provides information about tumor characteristics. Technical advances in liquid biopsy have led to the increasing adoption of diagnostic and monitoring applications for HCC. This review summarizes the various analytes, ongoing clinical trials, and case studies of United States Food and Drug Administrationapproved in vitro diagnostic applications for liquid biopsy, and provides insight into its implementation in managing HCC.
Case Report
Multidisciplinary approach for hepatocellular carcinoma arising from cirrhotic liver with Budd-Chiari syndrome: a case report
Sangmi Kim, Ji Hoon Kim, Ji Won Han, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Pil Soo Sung
J Liver Cancer. 2022;22(2):202-206.   Published online September 20, 2022
DOI: https://doi.org/10.17998/jlc.2022.09.17
  • 555 Views
  • 16 Downloads
AbstractAbstract PDF
Budd-Chiari syndrome (BCS) is defined by the obstruction of the hepatic venous outflow between the small hepatic veins and the junction of the inferior vena cava (IVC) with the right atrium. BCS with IVC obstruction occasionally progresses to hepatocellular carcinoma (HCC). Here, we report the case of a patient with HCC arising from a cirrhotic liver with BCS, in whom the hepatic portion of the IVC was obstructed, and who had a favorable outcome with a multidisciplinary approach and IVC balloon angioplasty.
Original Article
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
  • 942 Views
  • 29 Downloads
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.
Case Report
Hepatocellular carcinoma with Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava with long-term follow-up: a case report
Choong Hee Kim, Gwang Hyeon Choi, Hee Young Na, Chang Jin Yoon, Jai Young Cho, Sangmi Jang, Ji Hye Kim, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong
J Liver Cancer. 2022;22(2):194-201.   Published online September 15, 2022
DOI: https://doi.org/10.17998/jlc.2022.08.24
  • 545 Views
  • 14 Downloads
AbstractAbstract PDF
Membranous obstruction of the inferior vena cava (MOVC) is a rare subset of Budd-Chiari syndrome (BCS) with a subacute onset that is often complicated by cirrhosis and hepatocellular carcinoma (HCC). Here we report a case of recurrent HCC in a patient with cirrhosis and BCS that was treated with several episodes of transarterial chemoembolization followed by surgical tumorectomy, whereas the MOVC was successfully treated with balloon angioplasty followed by endovascular stenting. The patient was followed up for 9.9 years without anticoagulation and experienced no stent thrombosis. After the tumorectomy, the patient was HCC-free for 4.4 years of follow-up.
Original Article
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
  • 656 Views
  • 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.
Case Reports
Hepatocellular carcinoma diagnosed in a patient who had Fontan operation 30 years ago: a case report
Moon Haeng Hur, Haeryoung Kim, Jeong-Hoon Lee
J Liver Cancer. 2022;22(2):188-193.   Published online August 31, 2022
DOI: https://doi.org/10.17998/jlc.2022.08.17
  • 692 Views
  • 20 Downloads
AbstractAbstract PDF
The Fontan operation is performed in patients with a single ventricle. As the systemic venous return is directly connected to the pulmonary circulation during this procedure, chronic hepatic congestion is induced, leading to Fontan-associated liver disease (FALD) including liver cirrhosis and hepatocellular carcinoma (HCC). In this report, we present a case of HCC diagnosed in a patient who underwent the Fontan operation 30 years ago. The patient underwent regular surveillance for FALD, which revealed a 4 cm-sized hepatic mass with elevated serum alpha-fetoprotein. After surgical treatment, there was no evidence of HCC recurrence during 3 years of follow-up. As the risk of HCC and Fontan-associated liver cirrhosis increases with the duration elapsed since the operation, regular surveillance should be emphasized. Serial follow-up of serum alpha-fetoprotein levels and abdominal imaging are necessary to achieve early and accurate diagnosis of HCC in post-Fontan patients.
Novel management of expected post-radiotherapy complications in hepatocellular carcinoma patients: a case report
Sung Hoon Chang, Tae Suk Kim, Yong Hwan Jeon, Nuri Hyun Jung, Dae Hee Choi
J Liver Cancer. 2022;22(2):183-187.   Published online August 24, 2022
DOI: https://doi.org/10.17998/jlc.2022.08.03
  • 578 Views
  • 23 Downloads
AbstractAbstract PDF
In recent years, radiotherapy (RT) has been used to treat hepatocellular carcinoma (HCC) at each stage. This clinical trend has developed with the increasing improvement of RT techniques, which show clinical results comparable to those of other treatment modalities. Intensity-modulated radiotherapy uses a high radiation dose to improve treatment effectiveness. However, the associated radiation toxicity can damage adjacent organs. Radiation-induced gastric damage with gastric ulcers is a complication of RT. This report presents a novel management strategy for preventing post-RT gastric ulcers. We present the case of a 53-year-old male patient diagnosed with HCC, who experienced gastric ulcer after RT. Before the second round of RT, the patient was administered a gas-foaming agent, which was effective in preventing RT complications.
Original Article
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
Case Report
Fibrolamellar hepatocellular carcinoma that was successfully treated with surgical resection: a case report
Seong Kyun Na
J Liver Cancer. 2022;22(2):178-182.   Published online June 22, 2022
DOI: https://doi.org/10.17998/jlc.2022.06.10
  • 670 Views
  • 31 Downloads
AbstractAbstract PDF
Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare malignant hepatic cancer with characteristics that differ from those of typical hepatocellular carcinoma (HCC). Unlike conventional HCC, FLHCC is common in young patients without any underlying liver disease and is known to be associated with a unique gene mutation. This cancer type is rare in Asia, with only a few cases being reported in Korea. We report a case of FLHCC in a young woman that successfully underwent surgical resection. The efficacy of alternative treatments, such as transarterial chemoembolization or systemic chemotherapies, has not yet been established. To conclude, early diagnosis and appropriate surgical resection are important for the treatment of FLHCC.
Notice of Retraction and Replacement
Original Article
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.

JLC : Journal of Liver Cancer