Journal of Liver Cancer

Original Articles

Pain, analgesic use and misconceptions in patients with hepatocellular carcinoma: a cross-sectional survey: Jina Park, Jiwon Yang, Sung Won Chung, Won-Mook Choi, Ju Hyun Shim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Jonggi Choi; Received January 15, 2026 Accepted March 19, 2026 Published online April 29, 2026; DOI: https://doi.org/10.17998/jlc.2026.03.19 [Epub ahead of print]

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Abstract PDF Supplementary Material: Backgrounds/Aims
Cancer-related pain remains undertreated despite established guidelines. In hepatocellular carcinoma (HCC), underlying chronic liver disease may amplify concerns regarding analgesic safety. We aimed to evaluate pain prevalence, analgesic use, pain-related perceptions, and educational needs among patients with HCC.
Methods
We conducted a cross-sectional survey of 200 adult patients with HCC receiving systemic therapy at a tertiary referral center. A 30-item questionnaire assessed pain presence and intensity using a numeric rating scale (NRS), analgesic use patterns, liver-related safety concerns, opioid-related stigma, and educational needs. Clinical characteristics, including tumor burden and liver function, were analyzed in relation to pain and perception domains.
Results
Fifty-five patients (27.5%) reported current pain (mean NRS, 3.6±2.5; mean worst pain 5.2±2.8). Among them, 31 patients (56.3%) were using analgesics; however, 51.6% reported using them only when pain became unbearable. Misconceptions regarding analgesic safety were prevalent: 70.0% believed long-term analgesic use damages the liver, 56.0% believed analgesics are unsafe with impaired liver function, 46.5% associated opioids with addiction, and 30.0% hesitated due to the term “narcotic.” These beliefs were not associated with Child-Pugh class or serum albumin level. Extrahepatic metastasis was associated with higher liver-related concern scores and a trend toward increased pain prevalence. Patients with elementary school education or less had poorer pain scale knowledge and no prior counseling.
Conclusions
Pain undertreatment and safety-related misconceptions are common in HCC and appear independent of objective liver function. Structured, proactive education, particularly for patients with untreated pain and low educational attainment, may improve pain control in this population.

Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma: Jin Sun Kim, Won-Mook Choi, Ha-Il Kim, Sung Won Chung, Jonggi Choi, Danbi Lee, Kang Mo Kim; J Liver Cancer. 2025;25(1):79-90. Published online January 14, 2025; DOI: https://doi.org/10.17998/jlc.2024.12.27

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Backgrounds/Aims
Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
Methods
ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays.
Results
ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway.
Conclusions
Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Citations

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