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ILCA 2013: High HBV Viral Load Raises Risk of Progression to Liver Cancer


Hepatitis B patients with high HBV DNA levels, indicating active viral replication, are more likely to experience progression of abnormal liver nodules to hepatocellular carcinoma, researchers reported at the 7th International Liver Cancer Association Annual Conference (ILCA 2013) last month in Washington, DC.

Over years or decades, chronic hepatitis B virus (HBV) infection can lead to serious liver disease including advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), a form of primary liver cancer. HCC typically occurs in people who already have cirrhosis, but this is not always the case. The impact of continued HBV replication on progression to liver cancer is not fully understood.

Researchers from Seoul Paik Hospital and Inje University Medical School in South Korea conducted a study to better understand how dysplastic nodules, or clusters of abnormal hepatocytes without histological evidence of malignancy, progress to frank liver cancer.

Recent advances in diagnostic imaging have made it possible to detect small dysplastic nodules in people at high risk for HCC, the investigators noted as background, which may offer opportunities for early treatment and improved survival.

This retrospective analysis included clinical, laboratory, and radiological data from 52 people diagnosed with dysplastic nodules in the liver, presumably caused by chronic HBV infection, between January 2003 and December 2012.

A majority of study participants (71%) were men and the mean age was 59 years. They were classified as having high or low viral load, defined as HBV DNA above or below 10,000 copies/mL; 20 people (39%) had low HBV viral load. One-quarter were hepatitis B "e" antigen (HBeAg) positive and alanine aminotransferase (ALT) levels were within the normal range. 60% had a Child-Pugh score of A (indicating least risk of progression), while 27% had a score of B and 14% had a score of C.

All dysplastic nodules were detected by abdominal computed tomography, or CT scans. Patients were followed for at least 12 months (median 26 months) after detection.


  • Patients had an average of 1.78 dysplastic nodules, with a mean size of 1.0 cm.
  • 29 dysplastic nodules (55%) progressed to HCC, over an average interval of 26 months from the time of nodule detection.
  • Overall cumulative HCC progression rates among patients with dysplastic nodules were at 10% at 1 year, 40% at 3 years, and 64% at 5 years.
  • Risk of developing HCC varied according to Child-Pugh score; while nodules tended to be more common among people with decompensated cirrhosis, the difference between Child-Pugh scores did not reach statistical significance:

o   A: 10% at 1 year, 28% at 3 years, and 53% at 5 years;

o   B: 0%, 58%, and 72%, respectively;

o   C: 29%, 52%, and 100%, respectively.

  • Risk of progression to HCC varied significantly according to HBV DNA level:

o   Low viral load: 0% at 1 year, 8% at 3 years, and 26% at 5 years;

o   High viral load: 16%, 54%, and 88%, respectively.

  • In a multivariate analysis, high HBV viral load was the only independent predictor of dysplastic nodule progression to HCC, with an odds ratio of 6.9 for high vs low HBV DNA, or nearly 7-fold higher risk.
  • Child-Pugh score, size and number of dysplastic nodules, and patient age and sex were not significant risk factors for progression to HCC.

"Higher HBV viremia (HBV DNA >10,000 copies/mL) at the time of diagnosis of [dysplastic nodules] was an independent predictor of HBV associated HCC in patients with [dysplastic nodules]," the researchers concluded.

Based on these findings, they suggested that "maintenance of an inactive carrier state might be essential to reduce the risk of progression" from HBV-associated dysplastic nodules to HCC.

These results are consistent with recent findings reported at this years EASL International Liver Congress showing that long-term treatment with tenofovir (Viread) significantly reduces the risk of liver cancer in people with HBV. Another study indicated that avoiding heavy alcohol consumption also reduces the risk of HCC in people with hepatitis B.



SY Jeong, SH Rya, WJ Yoon, et al.Risk Factors for Progression from Dysplastic Nodules to Overt Hepatocellular Carcinomas in Patients with Chronic Hepatitis B Infection: Long Term Follow-Up in Korea. 7th International Liver Cancer Association Annual Conference (ILCA 2013). Washington, DC. September 13-15, 2013. Abstract P-100.