Hepatitis Viruses Infection Up-Regulating Fibrosis Signals in Hepatocellular Carcinoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background and objectives: In Taiwan, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is the most common cause of hepatocellular carcinoma (HCC). However, an increasing number of non-HBV and non-HCV (NBNC) patient with HCC is noted in recent years. The connection between NBNC patient and HCC remains unknown etiology. We aim to explore the difference of clinical manifestation, pathological findings in HCC patients with HBV, HCV or NBNC. Methods: A retrospective study analyzed 521 HCC patients with completed hepatic virus profile in a single medical center in Taiwan between 2011 to 2020. Differential Expression Gene analysis, xCell stromal cell analysis, and Gene Set Enrichment Analysis were employed to explore the different HCC oncogenesis of viral and NBNC groups. Results: There are 38 non-HBV and non-HCV related HCC (NBNC-HCC) patients. NBNC-HCC patients have lower Fib-4 index than HCV-HCC patients (3.191 vs 6.077, P=0.0019). Less NBNC-HCC patients have cirrhosis than HBV-HCC patients (44.4% vs 68.1%, p=0.0057). Less NBNC-HCC patients have Ishak score 5-6 than HCV-HCC patients (31.3% vs 75.6%, p=0.0025). DEG analysis showed differential expression in oncogene OIT314, AKR1B1015 and liver fibrosis related genes like COLEC1016, CXCL1417, and LINC0109318. GSEA and stromal cell analysis also showed differential gene expression in stellate cells and vascular endothelial cells. Conclusion: NBNC-HCC patients have lower percentage of cirrhosis or fibrosis than HBV-HCC and HCV-HCC patients. Different gene expression and cell type enrichment features was shown between viral and NBNC groups. Which indicated a different pathogenesis in NBNC-HCC compared with hepatitis viruses induced hepatocellular carcinoma.
Source: Biomedicines
Institutions: Tri-Service General Hospital, National Defense Medical Center
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7171821785
