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.
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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
Appropriate prediction of hepatocellular carcinoma (HCC) development is of paramount importance in terms of decision on antiviral therapy and HCC surveillance. To date, many HCC risk prediction models had been derived based on well-known risk factors such as age, male gender, the degree of fibrosis, and serum hepatitis B virus (HBV)-DNA load. Overall, such models showed high negative predictive values of approximately >90%, excluding the possibility of HCC development in 3 to 10 years with considerable accuracy. On the other hands, on the basis that potent antiviral therapy can substantially reduce the risk of HCC, its indications are steadily getting expanded for prevention of disease progression. Since antiviral therapy is a very strong disease modifier, the uniform application of HCC risk scores developed before the era of potent antiviral therapy would overestimate the risk of HCC. Furthermore, the tools to assess the fibrotic burden have remarkably evolved, from subjective determination based upon clinical symptom sign and ultrasonographic finding to more objective and delicate non-invasive tests based upon imaging and/or serological methods. Therefore, in the current era of potent antiviral therapy, the clinical significance of recently developed HCC risk models for patients with chronic HBV infection should be reappraised further.
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