Here’s a startling fact: even if you’ve been functionally cured of chronic hepatitis B, your risk of developing liver cancer isn’t entirely gone. But here’s where it gets controversial—researchers have now pinpointed a biomarker that could change how we predict this risk, and it’s not what you’d expect. Scientists from Hiroshima University and Gifu Kyoritsu University have discovered that Hepatitis B RNA serum levels can more accurately assess the likelihood of liver cancer in individuals who’ve achieved functional cures from chronic hepatitis B. This finding could revolutionize how we monitor and manage this high-risk group.
Chronic hepatitis B is a viral infection affecting the liver, significantly increasing the chances of liver cirrhosis and hepatocellular carcinoma (HCC, or liver cancer). Globally, it impacts approximately 296 million people. While treatments like nucleoside (nucleotide) analog (NA) therapy have made it possible to suppress viral replication and reduce disease progression, they often result in partial cures—where viral DNA becomes undetectable but antigens remain present. Functional cures, where both DNA and antigens are undetectable, are rare. Yet, even in these cases, the risk of HCC persists due to the hepatitis B virus’s unique ability to integrate into the host’s genome.
And this is the part most people miss—traditional biomarkers haven’t been reliable enough to predict HCC risk in functionally cured patients. That’s why the discovery of Hepatitis B viral RNA (HBV RNA) as a superior biomarker is such a game-changer. Researchers compared it to existing and proposed biomarkers, finding it to be far more effective in determining HCC risk.
Their groundbreaking study, published in Alimentary Pharmacology & Therapeutics (https://doi.org/10.1111/apt.70483) on December 2, 2025, sheds new light on this critical issue. According to Takashi Kumada, a leading researcher on the study, ‘The introduction of NA medications has significantly improved outcomes for chronic hepatitis B patients. However, because HBV integrates into the host genome, a complete cure remains out of reach. This makes reliable biomarkers essential for predicting HCC in these patients.’
The study involved a retrospective analysis of 311 chronic hepatitis B patients treated with NA therapy at Ogaki Municipal Hospital between December 2000 and May 2024. Among these patients, 88.5% had the predominant HBV genotype C. Researchers analyzed medical records, including NA therapy details, serum hepatitis B surface antigen (HBsAg), and serum HBV DNA levels. They also examined stored serum samples for newer biomarkers like HBV core-related antigen (HBcrAg) and HBV RNA.
Of the 311 patients who achieved undetectable HBV DNA levels, 132 had quantifiable HBV RNA, and 229 had quantifiable HBcrAg. Over a median follow-up period of 7.8 years, 31 patients developed HCC. The key takeaway? Patients with detectable HBV RNA levels had a 3.2-fold higher risk of HCC, independent of traditional risk factors. Kumada notes, ‘HBV RNA has been overlooked because HBV is a DNA virus, but its predictive power for cancer development is surprisingly strong.’
Here’s where it gets even more intriguing—the study suggests that chronic hepatitis B patients with quantifiable HBV RNA levels, especially those with concurrent liver dysfunction (ALBI grade 2–3), are at particularly high risk and should be monitored more closely. However, Kumada emphasizes that these findings, based on a single-center study, need validation through multicenter research. ‘We’re eager to collaborate with other institutions to confirm these results,’ he adds. Such validation could also determine if the findings apply to other HBV genotypes.
Co-authored by Hidenori Toyoda, Satoshi Yasuda, Yuichi Koshiyama, Takanori Ito, Tomoyuki Akita, and Junko Tanaka, the study was supported by a grant from Roche Diagnostics Japan.
Now, here’s a thought-provoking question for you: If HBV RNA proves to be as reliable as this study suggests, could it reshape how we approach liver cancer prevention in hepatitis B patients? Share your thoughts in the comments—do you think this biomarker could be the breakthrough we’ve been waiting for, or are there still too many unknowns?
