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Volume 17(2); September 2017
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Review Articles
Current Status of Research on Liver Cancer in Korea
Jae-Jun Shim
J Liver Cancer. 2017;17(2):105-110.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.105
  • 1,459 Views
  • 16 Downloads
AbstractAbstract PDF
Liver cancer is one of the leading causes of cancer-related death in Korea. Liver cancer imposes a considerable societal burden due to its high incidence and high mortality rate in younger patients, as compared to other cancers. However, interest in liver cancer among researchers and health-policy makers is low. In this review, recent trends in the number of published articles on liver cancer in Korea and internationally were analyzed. The key finding is that the rate of growth in the number of published articles on liver cancer is slowly decreasing and financial investment for research into liver cancer is very limited, despite the increasing research and development investment budget in Korea. Meanwhile, the rate of growth of research into liver cancer in China has recently increased markedly. Therefore, the scale and rate of growth of research into liver cancer in Korea should be enhanced.
Application of CRISPR/Cas9 in Treating Hepatitis B Virus
Ju-Yeon Cho
J Liver Cancer. 2017;17(2):111-116.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.111
  • 2,624 Views
  • 85 Downloads
AbstractAbstract PDF
The advent of oral antiviral agents has revolutionized hepatitis B treatment. It has led to decreased incidence and mortality related to hepatocellular carcinoma. However, although nucleos(t)ide analogs (NA) are fast and potent in inhibiting hepatitis B virus (HBV) polymerase and reverse transcriptase activity, complete cure of the virus is not possible. The complete eradication of HBV requires the covalently-closed-circular DNA (cccDNA) to be eliminated. Novel gene editing methods, such as zing finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/ Cas9) system, designed to target specific DNA sequences has great potential for therapeutic application. Among these, the CRISPR/Cas9 system may be the most feasible approach to eradicate HBV cccDNA. Further studies are needed to develop a more efficient and safer
method
of delivery using the CRISPR/Cas9 system to achieve complete cure of chronic hepatitis B.
Non-alcoholic Fatty Liver Disease and Hepatocellular Carcinoma
Hyunwoo Oh, Dea Won Jun
J Liver Cancer. 2017;17(2):117-125.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.117
  • 2,934 Views
  • 108 Downloads
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) is one of the most common life-threatening cancers worldwide. Recently, many patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have progressed to HCC even in the absence of cirrhosis. As the morbidity of metabolic syndrome increases, the proportion of HCC associated with NAFLD is expected to increase gradually. A new mechanism for the development of HCC in NAFLD has been identified; Diabetes mellitus, insulin resistance, obesity, lipotoxicity, gut dysbiosis are risk factors. Inflammatory cytokines such as adipokines, leptin, tumor necrosis factor-α, interlukin-8, nuclear factor-κB constitute dysplasia-carcinoma sequence. At the time of diagnosis, NAFLD/ NASH related HCC tend to progress to larger and in advanced tumor-node-metastasis stages compared to viral hepatitis related HCC. But there are no guidelines for early detection of NAFLD-related HCC. So, it is essential to study the screening program for the early detection of NAFLD-related HCC and precise methods for NAFLD.
Original Articles
17-DMAG has the Potentiated Anticancer Effects Against Hepatocellular Carcinoma Cells by Transfection of the Gene Encoding Hepatitis B Viral X Protein
Chul-Seung Lee, Ok-Hee Kim, Ha-Eun Hong, Sang-Jin Jeon, Seong-Soo Wong, Say-June Kim
J Liver Cancer. 2017;17(2):126-135.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.126
  • 1,644 Views
  • 13 Downloads
AbstractAbstract PDF
Background
/Aims: Hepatitis B viral protein X (HBx) is implicated in the pathogenesis of hepatocellular carcinoma (HCC) as well as the elevation of heat shock proteins (HSPs) after hepatitis B virus (HBV) infection. We thus investigated the anticancer effects of an HSP90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in HBxtransfected hepatocellular carcinoma cells.
Methods
pcDNA-HBx was made by inserting the HBx gene derived from the HBV-infected patient into pcDNA3.1 using the restriction enzymes (XbaI/HindIII). HBx-expressing HepG2 cells were then generated by transfecting HepG2 cells with pcDNA containing HBx gene. To compare the anticancer effects of 17-DMAG between pcDNA-HBx transfected HepG2 cells and the control cells (pcDNA-transfected HepG2 cells), we performed various molecular studies, including Ez-cytox proliferation assay, Western blot analysis, and flow cytometry.
Results
17-DMAG inhibited the proliferation of pcDNA-HBx transfected HepG2 cells better than control cells (P<0.05). After treating with a various concentration of 17-DMAG (50–1,000 nM), pcDNA-HBx transfected HepG2 cells exhibited higher expression of pro-apoptotic proteins (c-caspase-3, c-caspase-8, and c-caspase-9) than did control cells (P<0.05). pcDNAHBx transfected HepG2 cells showed higher activities of caspase-3, caspase-8, and caspase-9 than did control cells (P<0.05). Finally, we found that the expression of pro-apoptotic proteins (PARP and c-caspase-3) was considerably decreased by the use of a caspase inhibitor suggesting that 17-DMAG induces the cell death of HepG2 cells caspase-dependently.
Conclusions
Our study strongly suggests that 17-DMAG has antiviral effects against HBV as well as anticancer effects against HepG2 cells. Thus, the application of 17-DMAG appears to be particularly advantageous to the HCC patients related with HBV infection.
Incidence of Primary Liver Cancer in Subjects with Chronic Hepatitis B in Korean National Liver Cancer Screening Program
In Seung Choi, Chi Hyuck Oh, So Young Park, Sung Eun Ahn, Seong Jin Park, Hyun Rim Choi, Byung-Ho Kim, Jae-Jun Shim
J Liver Cancer. 2017;17(2):136-143.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.136
  • 3,079 Views
  • 39 Downloads
  • 3 Citations
AbstractAbstract PDF
Background
/Aims: To optimize efficacy of National Liver Cancer Screening Program (NLCSP) for subjects with chronic hepatitis B (CHB), it is needed to know the incidence of liver cancer and its predisposing factors in the program.
Methods
From January 2010 to December 2014, all the hepatitis B surface antigen (HBsAg) positive participants who received at least two or more abdominal ultrasonography under NLCSP were retrospectively enrolled in a single tertiary hospital. Annual incidence of primary liver cancer was calculated and related clinical factors were investigated.
Results
During 5 years, 541 subjects were enrolled. Mean age was 53 years old and 292 subjects (54%) were receiving antiviral agents. Liver cirrhosis (LC) was diagnosed in 212 (39.2%). Mean follow-up time was 2.36 years and 15 hepatocellular carcinoma and 1 intrahepatic cholangiocarcinoma were diagnosed. Annual incidence of primary liver cancer was 9.8 per 1,000 patient year. Cumulative incidence at 1, 3, and 5 year was 0.6%, 2.6%, and 6.4%, respectively. In multivariate analyses, LC (hazard ratio [HR] 8.74, 95% confidence interval [CI] 1.97–38.71, P=0.024), age (HR 1.08, 95% CI 1.01–1.15, P=0.024) were significantly associated with cancer development.
Conclusions
Despite of high rate of oral antiviral therapy, incidence of primary liver cancer is not low in CHB patients in Korea. Old age and presence of LC are independently associated with higher risk of cancer development during surveillance. This study could be used as baseline data for quality control of NLCSP.

Citations

Citations to this article as recorded by  
  • Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval: Nationwide Cohort of Korea
    Heejin Bae, Sang Ah Lee, Jong Won Choi, Shin Hye Hwang, Sumi Park, Mi-Suk Park
    Yonsei Medical Journal.2021; 62(8): 758.     CrossRef
  • A Survey of Liver Cancer Specialists’ Views on the National Liver Cancer Screening Program in Korea
    Won Sohn, Young-Sun Lee, Jae Geun Lee, Jihyun An, Eun Sun Jang, Dong Ho Lee, Dong Hyun Sinn
    Journal of Liver Cancer.2020; 20(1): 53.     CrossRef
  • Discrepancy between the Actual Clinical Status of Patients with Hepatocellular Carcinoma and Expectations from Hepatocellular Carcinoma Surveillance: a Single-Center Study
    Nak Min Kim, Young Seok Doh, Ji Woong Jang, Seok-Hwan Kim, Hyuk Soo Eun, Jae Hyuck Jun, Sae Hee Kim, Il Hyun Baek, Sung Hee Jung
    Journal of Liver Cancer.2019; 19(1): 30.     CrossRef
Conventional versus Drug-eluting Beads Trans-arterial Chemoembolization for Treatment of Hepatocellular Carcinoma at Very Early and Early Stages
Kwang-Hun Lee, Seung-Moon Joo, Tae Jun Yum, Sang Hoon Jung
J Liver Cancer. 2017;17(2):144-152.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.144
  • 2,716 Views
  • 83 Downloads
  • 2 Citations
AbstractAbstract PDF
Background
/Aims: To retrospectively compare conventional and drug-eluting beads transarterial chemoembolization (C-TACE and DEB-TACE) for treatment of hepatocellular carcinoma (HCC) at very early and early stages.
Methods
We retrospectively compared patients treated with C-TACE (n=115) or DEB-TACE (n=103) from September 2009 to May 2016. All patients were in a very early (stage 0) or early stage (stage A) of the Barcelona Clinic Liver Cancer (BCLC) staging system, and all had Child– Pugh class A and ≤B7 liver status. Approval by the institutional review board was waived because the study was retrospective. The following parameters were evaluated: severe pain and bradycardia during TACE, post-embolization syndrome (PES), liver function change, complications, target tumor response, and conversion to another treatment modality. Numeric differences were assessed by the independent Student’s t-test for continuous variables and by chi-square test for categorical variables.
Results
Severe intractable pain and bradycardia during the TACE procedure were significantly more frequent in the C-TACE group than in the DEB-TACE group (P<0.001). The incidence and duration of PES were significantly higher in the C-TACE group than in the DEB-TACE group (P<0.001). The increase in liver enzymes was significantly higher in the C-TACE group than in the DEB-TACE group (P<0.001). The deterioration of the Child-Pugh class was significantly higher in the C-TACE group than in the DEB-TACE group (P =0.006). There was no significant difference in serious complications except localized bile duct dilatation between the groups. There was no significant difference between the groups in tumor response at both immediate and 1-year assessment. The conversion rate to other treatment modalities was significantly higher in the DEB-TACE group than in the C-TACE group (P<0.001).
Conclusions
DEB-TACE is better than C-TACE in terms of procedural safety as initial treatment in a very early or early stage of HCC.

Citations

Citations to this article as recorded by  
  • Current status of transarterial chemoembolization (TACE) agents in hepatocellular carcinoma treatment
    Roshana Saghafian Larijani, Nazanin Shabani Ravari, Navid Goodarzi, Shahram Akhlaghpour, Samaneh Saghafian Larijani, Mohammad Reza Rouini, Rassoul Dinarvand
    Journal of Drug Delivery Science and Technology.2022; 77: 103905.     CrossRef
  • 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
    Journal of Liver Cancer.2021; 21(2): 146.     CrossRef
A Case of Hepatocellular Carcinoma with Recurrent Peritoneal Metastasis after Hepatectomy Who Showed Complete Response by Surgical Resection
Hyo Young Lee, Jeong-Hoon Lee, Joon Yeul Nam, Young Chang, Hyeki Cho, Young Youn Cho, Eung Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
J Liver Cancer. 2017;17(2):153-157.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.153
  • 1,424 Views
  • 13 Downloads
AbstractAbstract PDF
Recurrence of hepatocellular carcinoma (HCC) after hepatic resection is quite common. Peritoneal recurrence has been considered incurable status and related to poor prognosis. Although peritoneal metastasectomy is a therapeutic option for some selected patients with a few peritoneal metastasis, the indication and therapeutic effect has not been clear. We report a
case
of a 61-year-old man achieving complete remission of recurrent peritoneal metastasis after repeated surgical resection by a multidisciplinary approach. Peritoneal metastasectomy might be a therapeutic option for selected patients with localized oligonodular peritoneal metastasis.
Case Reports
A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Treated by Hepatic Artery Injection Chemotherapy and Radiotherapy
Sang Jin Kim, Byoung Kuk Jang, Jae Seok Hwang
J Liver Cancer. 2017;17(2):158-162.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.158
  • 2,173 Views
  • 17 Downloads
  • 1 Citation
AbstractAbstract PDF
External beam radiotherapy, transarterial chemoembolization and sorafenib are currently standard treatments for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, hepatic arterial infusion chemotherapy has been applied to advanced stage HCC with a view to improving the therapeutic effect. We experienced a case of advanced HCC with clinical complete response after hepatic artery infusion chemotherapy and radiation therapy and report that.

Citations

Citations to this article as recorded by  
  • A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Treated by Hepatic Arterial Infusion Chemotherapy and Radiotherapy
    Jin Yong Lee, Jeong-Ju Yoo, Seong Joon Chun, Sun Hyun Bae, Jae Myeong Lee, Sang Gyune Kim, Young Seok Kim
    Journal of Liver Cancer.2020; 20(1): 78.     CrossRef
Acute Pulmonary Infarction Complicated with Thromboembolism as the First Manifestation of Hepatocellular Carcinoma
Chae June Lim, ji Yun Hong, Chung Hwan Jun, Sung Kyu Choi, Sung Bum Cho
J Liver Cancer. 2017;17(2):163-167.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.163
  • 1,592 Views
  • 19 Downloads
AbstractAbstract PDF
Acute pulmonary infarction by tumoral thromboemboli is an extremely rare fatal complication as the first clinical manifestation of hepatocellular carcinoma (HCC) patient with tumoral thrombi in the inferior vena cava. The treatment method has not been established and shown to very poor prognosis despite of trying various modalities such as anticoagulation, radiotherapy and thromboembolectomy. Here, we describe a 74-year-old man who was diagnosed with HCC that presented as pulmonary thromboembolism and subsequent pulmonary infarction as the first manifestation.
A Case of Abscopal Effect on Pulmonary Metastasis after Palliative Radiotherapy on Bone Metastasis of Hepatocellular Carcinoma
Do Seon Song, U Im Chang, Ho Jung An, Sung Hwan Kim, Jin Mo Yang
J Liver Cancer. 2017;17(2):168-173.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.168
  • 2,044 Views
  • 18 Downloads
AbstractAbstract PDF
The abscopal effect is a rare phenomenon that characterized by tumor regression of untreated metastatic lesions after a local radiotherapy. The mechanisms of abscopal effect are speculated to be associated with cytokine release and host immune system. In this case, we report a case of abscopal effect in a 64-year-old male with hepatocellular carcinoma with lung and bone metastasis, who had complete response in the lung after receiving radiation to the metastatic bone lesions.
A Case of Combined Hepatocellular-cholangiocarcinoma Mimicking Pyogenic Liver Abscess
Seung Suk Baek, Eileen L. Yoon, Hyun-Jung Kim, Kyung Eun Bae, Kyeongmee Park, Won-choong Choi
J Liver Cancer. 2017;17(2):174-181.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.174
  • 1,977 Views
  • 17 Downloads
AbstractAbstract PDF
Heterogeneous features of liver cancer can mimic liver abscess. Therefore it is essential to doublecheck tumor markers in the diagnosis of liver abscess. Herein, we report a case of combined hepatocellular-cholangiocarcinoma (cHC) occurred in an unrecognized chronic hepatitis B patient initially misdiagnosed as liver abscess. A 49-year old male initially presented with chill, right upper quadrant pain, and a liver mass. Mass showed peripheral enhancement in arterial phase of computed tomography, which was not typical for hepatocellular carcinoma (HCC). Strikingly elevated alpha-fetoprotein and fine needle aspirated pathology revealed HCC. Despite discordant image findings he was treated with transarterial chemoembolization. He was treated with sorafenib due to metastatic retrocaval lymphadenopathy afterwards. The mass presumed to be HCC progressed with sorafenib. It was surgically resected and he was finally confirmed as cHC. Discordant tumor markers with presumptive image findings should prompt the suspicion of rare type of primary liver cancer, the cHC.
A Case of Successful Living Donor Liver Transplantation after Downstaging of Hepatocellular Carcinoma with the Beyond Milan Criteria by Radioembolization, Hepatic Arterial Infusion Chemotherapy, and Stereotactic Body Radiation Therapy
Yeong Jin Kim, Yeon Seung Chung, Beom Kyung Kim, Jin Sil Sung, Do Young Kim
J Liver Cancer. 2017;17(2):182-185.   Published online September 30, 2017
DOI: https://doi.org/10.17998/jlc.17.2.182
  • 1,268 Views
  • 10 Downloads
AbstractAbstract PDF
Liver transplantation for patients with hepatocellular carcinoma (HCC) within the Milan criteria generally yields a 4-year overall survival rate of 75% and 4-year recurrence free survival rate of 83%. But, many HCC patients present with the disease beyond the Milan criteria. On the other hands, the overall survival of patients with advanced HCC with portal vein invasion is very poor. We report a
case
of successful living donor liver transplantation for advanced HCC with portal vein invasion by down-staging through radioembolization, hepatic arterial infusion chemotherapy, and stereotactic body radiation therapy.

JLC : Journal of Liver Cancer