Journal of Liver Cancer

Volume 14(2); September 2014

Review Articles

Pathogenic Mechanism of Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: Sun Min Kim, Joo Hyun Sohn; J Liver Cancer. 2014;14(2):63-72. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.63

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Abstract PDF: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic condition that shows excessive fat accumulation in hepatocytes without significant alcohol intake, other liver diseases and the history of using hepatotoxic drugs. Recently, the incidence of hepatocellular carcinoma (HCC) related to NAFLD is increasing. However, the pathogenic mechanism of HCC developed from NAFLD has not been fully known. The most important pathogenic factor which affects the development of HCC is cirrhosis itself from any causes including NAFLD. To date, it is considered that NAFLD can cause HCC through insulin resistance, oxidative stress, and inflammatory process. In NAFLD, insulin resistance and its resulting hyperinsulinemia increase insulin-like growth factor-1 (IGF-1), which leads to cell growth and inhibition of apoptosis. Furthermore, hyperinsulinemia activates c-Jun amino-terminal kinase 1 (JNK1), increases free fatty acid (FFA) and reactive oxygen species (ROS), and increases the level of some inflammatory cytokines. In addition to that, various molecular biologic mechanisms such as deregulated NF-κB signaling, disorder in PI3K-AKT-PTEN pathway, defect in one-carbon metabolism, and dysfunction of microRNAs are involved in the NAFLD-mediated carcinogenesis. Finally, intestinal dysbiosis may also play a role in the pathogenesis of HCC. These pathogenic mechanisms will be discussed shortly in this review. (J Liver Cancer 2014;14:63-72)

The Usefulness of Hepatic Venous Pressure Gradient in the Prediction of Hepatocellular Carcinoma: Ki Tae Suk; J Liver Cancer. 2014;14(2):73-79. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.73

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Abstract PDF: Hepatocellular carcinoma (HCC) is the final stage of portal hypertension in chronic liver disease and the sixth most common neoplasm in the world. Hepatic venous pressure gradient (HVPG) measurement is the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >10 mmHg. In this condition, the complications of portal hypertension might begin to appear. HVPG measurement is increasingly used in the clinical fields, and the HVPG is a robust surrogate marker in many clinical applications such as diagnosis of fibrosis, risk stratification, identification of patients with HCC who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. In addition, HVPG may be a useful predictive factor for the development of HCC and HVPG ≥12 mmHg may be suggested a predictor of survival in cirrhotic patients with earlystage HCC. However, in the field of HCC, few data are available about the role of HVPG. In this review, we are going to introduce HVPG and overview its usefulness in the prediction of HCC. (J Liver Cancer 2014;14:73-79)

The Issues for Improving Prognosis in Intermediate Stage of Hepatocellular Carcinoma: Yang Jae Yoo, Ji Hoon Kim; J Liver Cancer. 2014;14(2):80-88. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.80

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Abstract PDF: Hepatocellular carcinoma (HCC) is one of major malignant tumor with heterogeneity and poor prognosis. In contrast to other solid malignant tumors, the prognosis of HCC is affected by not only progression of tumor itself but also residual liver function. Therefore, diverse staging systems are developed in HCC and there was no universal consensus for best staging system. However, Barcelona Clinic Liver Cancer (BCLC) system, which was endorsed by Western expert guidelines, is most commonly used staging system. BCLC system defined intermediate stage as single tumor more than 5cm, 2-3 tumor more than 3cm or ≥ 4 tumor at any size with Child-Pugh A or B and performance status 0-1 and allocated transarterial chemoembolization (TACE) as primary treatment for this stage. Intermediate stage include heterogeneous patients population and inevitably showed diverse prognosis. Among HCC patients, about 20% belonged to intermediate stage and intermediate stage means relatively little progressed stage, fair liver function and performance status. Therefore, improvement of survival of intermediate HCC patients may be a cornerstone leading improvement of survival of overall HCC patients. Hence, the strategy for optimal classification and treatment modality for intermediate HCC patients at pre and post treatment to improve prognosis in this patients will be discussed in this review. (J Liver Cancer 2014;14:80-88)

New Techniques of Ultrasound-guided Radiofrequency Ablation for Hepatocellular Carcinoma: Min Woo Lee; J Liver Cancer. 2014;14(2):89-96. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.89

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Abstract PDF: In Korea, radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is most widely used under ultrasonography (US) guidance. With the technical development, small HCCs in challenging locations can be ablated effectively. Both fusion imaging and contrast-enhanced US is useful for identifying small inconspicuous HCCs on conventional US, thereby enable us to conduct successful RFA. Artificial ascites can enhance ultrasonic window and is helpful in avoiding thermal injury to the surrounding organs. Laparoscopy is also useful for guidance of RFA for subcapsular HCCs which are difficult to approach percutaneously. (J Liver Cancer 2014;14:89-96)

Original Articles

Characteristics and Survival of Korean Patients with Hepatocellular Carcinoma: A Nationwide Random Sample Study: Young-Suk Lim, Seung Hyung Kim, Seung Hyung Kim, Jae Seok Hwang, Kwang-Hyub Han; J Liver Cancer. 2014;14(2):97-107. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.97

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Abstract PDF

Background/Aim
s: Given the high incidence and mortality rate of hepatocellular carcinoma (HCC), ensuring high quality of registry data is important for the improvement of health service. Registries by voluntary reporting often lack case completeness and may cause selection bias. A statutory Korean Central Cancer Registry (KCCR) has case completeness and provides accurate information on HCC incidence, but provides limited information about HCC characteristics.
Methods
The Korean Liver Cancer Study Group (KLCSG) and the KCCR jointly built a nationwide cohort of patients who were diagnosed with HCC between 2003 and 2005. Out of 31,521 new HCC cases that were registered at the KCCR between 2003 and 2005, 4,630
case
s (14.7% of total HCC cases) were randomly selected and abstracted from 32 hospitals nationwide, and followed up until December 2011. After excluding 110 patients who met the exclusion criteria, a total of 4,520 HCC patients were analyzed.
Results
Mean age at the diagnosis of HCC was 57.1±10.8 years, and males comprised 81.0%. Hepatitis B was the predominant etiology (72%), and hepatitis C comprised 12%. Stage at diagnosis was 10%, 43%, 28%, 11% and 8% for modified International Union Against Cancer (mUICC) stages I, II, III, IV-A and IV-B, respectively. Initial treatment modalities were transarterial therapy in 53%, surgical resection in 10%, local ablation in 7%, and liver transplantation in 1%. The median survival was 1.4 years, and the 1-, 3-, and 5-year survival rates were 56%, 35% and 27%, respectively. Age, gender, Child-Pugh class, etiology, tumor stage at diagnosis, and treatment modality were factors independently related to survival.
Conclusions
About half of HCC patients are diagnosed at advanced stages in Korea. Curativeintent treatments are rarely applied to patients. This data provides unbiased information about the characteristics and outcome of HCC patients in Korea. (J Liver Cancer 2014;14:97- 107)

Citations

Citations to this article as recorded by

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
Subclassification of Barcelona Clinic Liver Cancer B and C hepatocellular carcinoma: A cohort study of the multicenter registry database
Sangheun Lee, Beom Kyung Kim, Kijun Song, Jun Yong Park, Sang Hoon Ahn, Seung Up Kim, Kwang‐Hyub Han, Do Young Kim
Journal of Gastroenterology and Hepatology.2016; 31(4): 842. CrossRef

Cirrhosis in Surgically Resected Hepatitis C-Associated Hepatocellular Carcinoma in a Hepatitis B Endemic Area: Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Jae-Won Joh, Seung Woon Paik, Byung Chul Yoo, Cheol Keun Park; J Liver Cancer. 2014;14(2):108-114. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.108

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Abstract PDF: Background/Aim
s: Cirrhosis has generally been considered a prerequisite for hepatitis C virus (HCV)-infected livers to develop hepatocellular carcinoma (HCC), but HCCs that arise in absence of cirrhosis has been reported. We assessed the prevalence and significance of cirrhosis in HCV-related HCC patients who underwent surgical resection.
Methods
A total of 78 HCC patients (65 male [83.3%]; mean age, 64.2 ± 8.6 years) were evaluated for the presence of cirrhosis. Cirrhosis was assessed based on histology, aspartate aminotransferase-to-platelet ratio index (APRI) as well as clinical criteria, such as ascites, varices, thrombocytopenia, splenomegaly, and radiographic configuration of cirrhosis.
Results
Based on histology, cirrhosis, septal fibrosis, periportal fibrosis and no fibrosis was noticed in 33.3%, 60.3%, 5.1% and 1.3% of patients, respectively. The clinical criteria of cirrhosis were present in 76.9% of patients. APRI > 1.0 was seen in 47.4% of patients. There was no evidence of cirrhosis in 18 patients (23.1%), either by histology or clinically. Cirrhosis by histology was an independent factor for overall survival [hazard ratio: 3.87 (95% CI: 1.24 – 12.00), P=0.019].
Conclusions
Quite proportion of HCC patients had no evidence of cirrhosis, either by histology or clinically. Careful follow-up for HCC may be necessary even for non-cirrhotic HCVinfected Korean patients. (J Liver Cancer 2014;14:108-114)

Follow-up of Hepatocellular Carcinoma After Transarterial Chemoembolization; The Concordance of Contrast Enhanced Ultrasonography and Lipiodol CT: Gene Hyun Bok, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim; J Liver Cancer. 2014;14(2):115-119. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.115

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Abstract PDF: Background/Aim
s: The aim of this study is to evaluate the concordance of contrast-enhanced ultrasonography (CEUS) and lipiodol computed tomography (L-CT) for the assessment of viable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).
Methods
We retrospectively reviewed the post-TACE CEUS and L-CT images of 65 consecutive HCCs in 41 patients to assess the presence of viable tumor tissue. Forty-seven HCCs in 31 patients that underwent post-TACE L-CT within 4 weeks of the CEUS examination were included. The degree of concordance between CEUS and L-CT and factors related to concordance were analyzed.
Results
The overall concordance of CEUS and LDCT was 78.7% (37/47). The concordance with L-CT for viable tumor and non-viable tumor tissue on CEUS was 95.2%, and 65.4% respectively (P<0.013). Diffuse tumors had a tendency for non-concordance (P=0.066). Although 3 of 4 lesions located in the hepatic dome were non-concordant, the sample size was too small to establish significance. The mean tumor size for concordant and non-concordant tumors was 2.9 and 3.0 cm, with no significant difference.
Conclusions
Although the concordance of CEUS and L-CT for viable tumor tissue was high, the concordance for non-viable tumor tissue was relatively low. Prospective studies using angiography as a gold standard should be performed in the future. (J Liver Cancer 2014;14:115-119)

Case Reports

A Case of Achieving Partial Remission with Combination of Radiation Therapy and Sorafenib inChild-Pugh Class B Patients with Hepatocellular Carcinoma with Main Portal Vein Invasion and Lymph Node Metastasis: Sang Youn Hwang, Seon-Mi Lee, Jung Woo Im, Joon Suk Kim, Sang Bu Ahn, Eun Kyeong Ji, Hyun-Cheol Kang, Cheol-Won Choi, Gwang-Mo Yang; J Liver Cancer. 2014;14(2):120-126. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.120

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Abstract PDF: Reserved liver function is one of the most important determinants of survivial in advanced hepatocellular carcinoma (HCC). Especially in cirrhotic patient with decompensated liver function, sorafenib for HCC with main portal vein invasion have limited efficacy and survival benefit. Therefore many clinicians or centers still try locoregional therapy (LRT) such as transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT and sorafenib in this situation. However this multidisciplinary approach may increase treatment related toxicity such as liver failure, etc. Recently, studies for combination of RT and sorafenib for HCC with portal vein invasion have been tried and reported not only better therapeutic efficacy, but also more hepatic toxicity.Based on above suggestions, we herein offer our experience of a patient that although achieved survival gain via partial remission of intrahepatic tumor and main portal vein thrombosis and metastatic lymph node by combination therapy of RT and sorafenib, finally expired due to hepatictoxicity. Further study, maybe regarding a combination of locoregional and systemic therapy, is necessary on how to manage decompenstated cirrhotic patients with HCC with main portal vein invasion. (J Liver Cancer 2014;14:120-126)

A Case of Positive Tumor Marker Response after Intra-arterial Deferoxamine Infusion Therapy in a Hepatocellular Carcinoma Patient with Decompensated Liver Function: Hyun Ju Kim, Wonseok Kang, Mi Na Kim, Beom Kyung Kim, Seung Up Kim, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han; J Liver Cancer. 2014;14(2):127-130. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.127

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Abstract PDF: Treatment of hepatocellular carcinoma is often very challenging when the underlying liver function is decompensated. Recent experimental and clinical studies showed that some chelating agents, including deferoxamine, display anti-proliferative actions against tumor cells, thereby exhibiting anti-cancer effect in certain cancers, including hepatocellular carcinoma. Based on previous studies, we herein offer our experience of positive tumor marker response after intra-arterial deferoxamine infusion in a patient presenting with advanced hepatocellular carcinoma with decompensated hepatic function. Validation of the efficacy of intra-arterial deferoxamine therapy in the setting of advanced hepatocellular carcinoma with underlying decompensated hepatic function is warranted. (J Liver Cancer 2014;14:127-130)

A Case of Hepatocellular Carcinoma with Improved Decompansated Liver Cirrhosis with Combination Treatment of Transarterial Chemoembolization and Radiofrequency Ablation: Hyung Min Yu, Won Hyeok Choe, So Young Kwon, Jeong Han Kim; J Liver Cancer. 2014;14(2):131-134. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.131

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Abstract PDF: A 54-year-old female patient with no medical history visited our hospital complaining of both pretibial pitting oedema for 6 months, and abdominal distension for 1 month. Computed tomography and magnetic resonance imaging revealed an 2.3cm sized tumour at segment 2 of the liver. Her Child-Turcotte-Pugh (CTP) class was C (score 11) at the initial visit. She was diagnosed as hepatocellular carcinoma (UICC stage II, BCLC stage D), and then she underwent conservative treatment for 1 month. After one month of conservative treatment, her liver function was improved to CTP class B (score 8), and then she underwent combination treatment of transarterial chemoembolization and radiofrequency ablation. However, her liver function was deteriorated gradually. She was transferred to other hospital for liver transplantation eventually. (J Liver Cancer 2014;14:131-134)

A Case Report of Transarterial Chemoembolization and Stereotactic Radiation Therapy before Liver Transplantation in a Decompensated Cirrhosis with Hepatocellular Carcinoma: Sang Hoon Kim, Joo Hee Park, Sang Jun Suh, Young Kul Jung, Hyung Joon Yim; J Liver Cancer. 2014;14(2):135-138. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.135

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Abstract PDF: Liver transplantation is the only curable treatment modality for hepatocellular carcinoma with advanced liver cirrhosis. While treatment outcome of the liver transplantation is improving, time needed to standby until the surgery is getting longer because of both the lack of liver donors and increasing demands for the transplantation. Therefore, importance of bridging therapy before the liver transplantation is recently highlighted. We herein report our recent experience about a patient who successfully undergone transarterial chemoembolization (TACE) and stereotactic radiation therapy (START) as bridging therapy and later had liver transplantation operation. (J Liver Cancer 2014;14:135-138)

Clinical Outcome of Completely Ablated Hepatocellular Carcinoma in Single Session in Patients with Decompensated Liver Cirrhosis: Min Seon Park, Soon Ho Um, Ho Sang Ryu, Yeon Seok Seo, Sun Young Yim, Chang Ho Jung, Tae Hyung Kim, Dae Hoe Gu; J Liver Cancer. 2014;14(2):139-142. Published online September 30, 2014; DOI: https://doi.org/10.17998/jlc.14.2.139

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Abstract PDF: Most cases of hepatocellular carcinoma (HCC) occur in the Asia-Pacific region and in patients with underlying hepatitis B and C viral infection. Although surgical resection is the gold standard for treatment of HCC, only a few patients are surgical candidates because of their lack of hepatic reserve. Liver transplantation, which eradicates HCC and replaces damaged noncancerous hepatic parenchyma, is regarded as the best treatment for HCC in patients with decompensated liver cirrhosis. However, the shortage of donors limit its widespread use. Furthermore, the long waiting time for liver transplantation allow for tumor progression and reduce patient survival. Given this long wait, there is a reasonable clinical need in the meantime for minimally invasive methods to avoid progression of HCC in patients with decompensated liver cirrhosis. We herein offer our experiences of therapeutic efficacy and complications of the procedure and the changes in liver function before and after TACE and radiofrequency ablation in patients with HCC and decompensated liver cirrhosis, defined as a Child-Pugh-Turcotte score above 7. (J Liver Cancer 2014;14:139-142)

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