Journal of Liver Cancer

Review Article

Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma: Lung-Yi Mak; J Liver Cancer. 2024;24(2):145-154. Published online August 5, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.03

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Chronic hepatitis B (CHB) infection is responsible for 40% of the global burden of hepatocellular carcinoma (HCC) with a high case fatality rate. The risk of HCC differs among CHB subjects owing to differences in host and viral factors. Modifiable risk factors include viral load, use of antiviral therapy, co-infection with other hepatotropic viruses, concomitant metabolic dysfunctionassociated steatotic liver disease or diabetes mellitus, environmental exposure, and medication use. Detecting HCC at early stage improves survival, and current practice recommends HCC surveillance among individuals with cirrhosis, family history of HCC, or above an age cut-off. Ultrasonography with or without serum alpha feto-protein (AFP) every 6 months is widely accepted strategy for HCC surveillance. Novel tumor-specific markers, when combined with AFP, improve diagnostic accuracy than AFP alone to detect HCC at an early stage. To predict the risk of HCC, a number of clinical risk scores have been developed but none of them are clinically implemented nor endorsed by clinical practice guidelines. Biomarkers that reflect viral transcriptional activity and degree of liver fibrosis can potentially stratify the risk of HCC, especially among subjects who are already on antiviral therapy. Ongoing exploration of these novel biomarkers is required to confirm their performance characteristics, replicability and practicability.

Citations

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Direct Viral Mechanisms Underlying the Onset of HBV-Related Hepatocellular Carcinoma and Implications for Therapeutic Strategies
Simone La Frazia, Alessia Magnapera, Lorenzo Piermatteo, Stefano D’Anna, Leonardo Duca, Valentina Svicher, Romina Salpini
Viruses.2026; 18(2): 185. CrossRef
Reply to: Comment on “Lower Incidence of Hepatocellular Carcinoma with Tenofovir Alafenamide in Chronic Hepatitis B: Evidence from a Large-Scale Cohort”
Jisoo Lee, Jae-Young Kim, Jeong-Ju Yoo, Hye Won Lee, Sang Gyune Kim, Young Seok Kim
JHEP Reports.2025; : 101371. CrossRef
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Scientific Reports.2025;[Epub] CrossRef
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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

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Abstract PDF Supplementary 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.

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Richard Donkor Amponsah, Emmanuel Addai Gyabaah, Moro Amidu, Zhao Cheng, Fazlur Rahman Talukdar
International Journal of Cancer.2026; 158(3): 511. CrossRef
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Jadranka Pavicic Saric, Dinka Lulic, Dunja Rogic, Stipislav Jadrijevic, Danko Mikulic, Tajana Filipec Kanizaj, Nikola Prpic, Laura Karla Bozic, Ivona Adamovic, Iva Bacak Kocman, Zrinka Sarec, Gorjana Erceg, Mirta Adanic, Petra Ozegovic Zuljan, Filip Jadri
International Journal of Molecular Sciences.2025; 26(19): 9584. CrossRef
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Edwin Wilbur Woodhouse, Tzu-Hao Lee, Susanna Naggie
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16S rRNA Next-Generation Sequencing May Not Be Useful for Examining Suspected Cases of Spontaneous Bacterial Peritonitis
Chan Jin Yang, Ju Sun Song, Jeong-Ju Yoo, Keun Woo Park, Jina Yun, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(2): 289. CrossRef
Methylated circulating tumor DNA in hepatocellular carcinoma: A comprehensive analysis of biomarker potential and clinical implications
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Cancer Treatment Reviews.2024; 128: 102763. CrossRef

Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma: Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; J Liver Cancer. 2022;22(1):30-39. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.02.25

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7 Citations

Abstract PDF Supplementary Material

Background/Aim
Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Methods
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
Results
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC=0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (< 5 cm; AUC=0.930) compared with AFP (AUC=0.802) or PIVKA-II (AUC=0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Conclusions
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.

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Zinnat Ara Moni, Zahid Hasan, Md. Shaheen Alam, Nitai Roy, Farhadul Islam
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