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Temporal mutation profile discerns which patients with HBV will develop HCC

Researchers from Taiwan developed a temporal mutation profile that discerns which patients with hepatitis B virus are more likely to develop hepatocellular carcinoma within 5 years, according to recent findings published in Hepatology.

Ming-Whei Yu

“Here, we show a set of 10 HBV-[single nucleotide polymorphisms (SNPs)] associated with a statistically increased risk for HCC, each with a greater than 1.8-fold OR value after taking into account HBV genotype,” Ming-Whei Yu, PhD, professor of epidemiology and preventive medicine at National Taiwan University College of Public Health, and colleagues wrote. “Our whole viral genome analysis highlights the importance of progressive accumulation of a set of HBV mutations for hepatitis B progression to HCC in addition to well-established predictors such as HBV genotype and viral load.”

Previous studies associated viral load, genotype and certain mutations with progression from chronic HBV to HCC, the researchers wrote. However, those studies only used a small number of sequences whereas Yu and colleagues scanned the entire HBV genome.

In a cohort of patients with HBV, the researchers assessed blood obtained no more than 20 years prior to diagnosis from 117 patients who developed HCC and 118 patients who did not. Using logistic regression based on five periods to diagnosis, the researchers examined the relationship between each SNP and HCC development, while adjusting for HBV genotype.

They found 31 SNPs significantly associated with time to diagnosis, 24 of which could be analyzed with full-length data from the cohort. The 10 best SNP candidates had ORs ranging between 1.89 and 8.68 (P ≤ .0304) and were further confirmed using 163 HBV sequences from nine Asian regions that were assessed after HCC diagnosis.

The prevalence and mutation score of these SNPs increased as time moved closer to HCC diagnosis. When compared with a score of 0, the OR for a score of 1 was 2.17, for a score of 2 it was 4.21, for a score of 3 it was 8.15 and for a score of 4 it was 9.15. This mutation score outperformed HBV-DNA levels, viral genotype and other risk factors while showing increasing accuracy over time when the time to diagnosis was less than 4.5 years (area under the curve = 0.83-0.89; sensitivity = 72.7-94.1%; specificity = 58.3-70.5%).

The most noteworthy finding — according to the researchers — was that mutations continuously increased up until the clinical onset of HCC and that a mutation score would help predict short-term risk for HCC.

“The mutation score may be useful for both monitoring hepatitis B progression and early detection of HCC,” Yu and colleagues wrote. “A further study using deep sequencing to determine the importance of quantifying mutants for mutation tracking is warranted.” – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.