Journal of Liver Cancer

Review Article

Second-line antidiabetic drugs: friend or foe of the liver: Jiwon Yang, Gunho Kim, Ju Hyun Shim, Jihyun An; J Liver Cancer. 2025;25(2):187-203. Published online June 26, 2025; DOI: https://doi.org/10.17998/jlc.2025.06.25

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Diabetes mellitus is a cardiometabolic risk factor associated with the development of various comorbidities and malignancies. It has a bidirectional relationship with chronic liver disease, promoting hepatic inflammation and fibrosis, which can ultimately progress to advanced liver diseases such as cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Therefore, the importance of antidiabetic treatment has been increasingly emphasized as a strategy for preventing liver-related diseases in diabetic patients. Metformin, a first-line antidiabetic agent, has been shown to be effective in improving hepatic steatosis and preventing progression to advanced liver disease. Recently updated international guidelines recommend the use of metformin as a chemopreventive agent for HCC in diabetic patients, albeit with a weak recommendation. Meanwhile, as metformin alone is often insufficient for blood glucose control and concurrent metabolic comorbidities are increasingly prevalent, new second-line antidiabetic agents have been developed: glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors. These novel antidiabetic agents have demonstrated cardiovascular benefits, and protective effects on liver-related outcomes and mortality in previous studies. However, due to the limited number of studies and the variability in study populations, their effects remain inconsistent across different studies. Furthermore, there are no established therapeutic guidelines for diabetic patients with liver disease. Therefore, this review aims to examine the association between the use of novel second-line antidiabetic agents and the risk of liver-related outcomes and mortality in this population.

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Exploring the Epidemiologic Burden, Pathogenetic Features, and Clinical Outcomes of Primary Liver Cancer in Patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Scoping Review
Mario Romeo, Fiammetta Di Nardo, Carmine Napolitano, Claudio Basile, Carlo Palma, Paolo Vaia, Marcello Dallio, Alessandro Federico
Diabetology.2025; 6(8): 79. CrossRef

Original Articles

Hepatocellular carcinoma in Korea: an analysis of the 2016-2018 Korean Nationwide Cancer Registry: Jihyun An, Young Chang, Gwang Hyeon Choi, Won Sohn, Jeong Eun Song, Hyunjae Shin, Jae Hyun Yoon, Jun Sik Yoon, Hye Young Jang, Eun Ju Cho, Ji Won Han, Suk Kyun Hong, Ju-Yeon Cho, Kyu-Won Jung, Eun Hye Park, Eunyang Kim, Bo Hyun Kim; J Liver Cancer. 2025;25(1):109-122. Published online March 4, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.20

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Backgrounds/Aims
Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018.
Methods
Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018.
Results
The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%).
Conclusions
Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

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Real-World Treatment Efficacy and Safety Profile of Sofosbuvir- and Velpatasvir-Based HCV Treatment in South Korea: Multicenter Prospective Study
Jae Hyun Yoon, Chang Hun Lee, Hoon Gil Jo, Ju-Yeon Cho, Jin Dong Kim, Jin Won Kim, Ga Ram You, Sung Bum Cho, Sung Kyu Choi
Viruses.2025; 17(7): 949. CrossRef

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

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Abstract PDF Supplementary 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.

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The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review
Amirhosein Sabaghian, Shahnam Shamsabadi, Saghar Momeni, Mobina Mohammadikia, Kiarash Mohebbipour, Samira Sanami, Sajjad Ahmad, Nahid Akhtar, Neeta Raj Sharma, Raja Babu Singh Kushwah, Yash Gupta, Ajit Prakash, Hamidreza Pazoki-Toroudi
Journal of Cancer Metastasis and Treatment.2024;[Epub] CrossRef
Recent Advances in Immune-based Therapy for Hepatocellular Carcinoma
Kyung Won Park, Tae Hoon Park, Eun Ji Jang, Pil Soo Sung
Journal of Digestive Cancer Research.2024; 12(2): 115. 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; J Liver Cancer. 2020;20(1):53-59. Published online March 31, 2020; DOI: https://doi.org/10.17998/jlc.20.1.53

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6 Citations

Abstract PDF Supplementary Material

Background/Aims
To reduce the cancer burden, the Korean government initiated the National Cancer Control Plan including the National Liver Cancer Screening Program (NLCSP). Ultrasonography examinations and α-fetoprotein tests at six-month intervals are currently offered for high-risk individuals. High-risk individuals are identified by reviewing the National Health Insurance Service claims data for medical use for the past two years using International Classification of Diseases Codes for specific liver disease. We surveyed the attitudes and opinions towards the NLCSP to understand the issues surrounding the NLCSP in Korea.
Methods
Altogether, 90 Korean Liver Cancer Association members participated in online and offline surveys between November and December 2019.
Results
Approximately one-quarter (27%) of the survey participants rated the NLCSP as very contributing and about two-thirds (68%) as contributing to some extent toward reducing hepatocellular carcinoma (HCC)-related deaths in Korea. Most (87.8%) responded that the current process of identifying high-risk individuals needs improvement. Many (78.9%) were concerned that the current process identifies individuals who use medical services and paradoxically misses those who do not. When asked for the foremost priority for improvement, solving ‘duplication issues between the NLCSP and private clinic HCC screening practices’ was the most commonly selected choice (23.3%).
Conclusions
The survey participants positively rated the role of the NLCSP in reducing liver cancer deaths. However, many participants rated the NCLSP as needing improvement in all areas. This survey can be a relevant resource for future health policy decisions regarding the NLCSP in Korea.

Citations

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Potential role of Fibrosis‐4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study
Sujeong Shin, Won Sohn, Yoosoo Chang, Yoosun Cho, Min‐Jung Kwon, Sarah H. Wild, Christopher D. Byrne, Seungho Ryu
Hepatology Research.2024; 54(6): 551. CrossRef
Recent Hepatocellular Carcinoma Managements in Korea: Focus on the Updated Guidelines in 2022
Yuri Cho, Bo Hyun Kim, Young-Suk Lim
Digestive Disease Interventions.2024; 08(03): 169. CrossRef
Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective
Myung Ji Goh, Dong Hyun Sinn, Jong Man Kim, Min Woo Lee, Dong Ho Hyun, Jeong Il Yu, Jung Yong Hong, Moon Seok Choi
Clinical and Molecular Hepatology.2023; 29(2): 197. CrossRef
Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study
Sun Hong Yoo, Soon Sun Kim, Sang Gyune Kim, Jung Hyun Kwon, Han-Ah Lee, Yeon Seok Seo, Young Kul Jung, Hyung Joon Yim, Do Seon Song, Seong Hee Kang, Moon Young Kim, Young-Hwan Ahn, Jieun Han, Young Seok Kim, Young Chang, Soung Won Jeong, Jae Young Jang, J
Journal of Liver Cancer.2023; 23(1): 189. CrossRef
Selecting the Target Population for Screening of Hepatic Fibrosis in Primary Care Centers in Korea
Huiyul Park, Eileen L. Yoon, Mimi Kim, Seon Cho, Jung-Hwan Kim, Dae Won Jun, Eun-Hee Nah
Journal of Clinical Medicine.2022; 11(6): 1474. CrossRef
Fibrosis Burden of Missed and Added Populations According to the New Definition of Metabolic Dysfunction-Associated Fatty Liver
Huiyul Park, Eileen L. Yoon, Mimi Kim, Jung-Hwan Kim, Seon Cho, Dae Won Jun, Eun-Hee Nah
Journal of Clinical Medicine.2021; 10(19): 4625. CrossRef

Case Report

A Case of the Effective Treatment of HCC with Bile Duct Invasion and Portal Vein Thrombosis: Jihyun An, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee; Journal of the Korean Liver Cancer Study Group. 2013;13(2):169-172. Published online September 30, 2013; DOI: https://doi.org/10.17998/jlc.13.2.169

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Abstract PDF: Bile duct invasion of hepatocellular caricinoma (HCC) is rare, ranging from 1.2% to 9%. Moreover, the standard treatment of HCC with bile duct invasion is not yet established. We report a case of HCC with bile duct invasion and portal vein thrombosis which was successfully treated by trasarterial chemoembolization and radiotherapy. A 38-year-old female patient visited our hospital due to right upper quadrant pain. The level of total and direct bilirubin was 6.8 and 4.0 mg/dL, respectively. Her blood test showed HBs Ag positive and the level of alpha-fetoprotein was 43,000 ng/mL. Her CT scan revealed lobulating hypervascular mass involving right hepatic lobe, portal vein and both intrahepatic ducts. We performed endoscopic biliary drainage using biliary stent. She had been diagnosed as HCC on endobiliary biopsy. She was treated with radiotherapy (RT) to portal vein thrombosis, and seven transarterial chemoembolizations. After of all, we carried out radiotherapy to hepatic vein thrombosis and residual HCC near hepatic vein. After the RT, she has been taken care at outpatient clinic without evidence of recurrence during 8 months.

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