Hepatitis B Core-Related Antigen Levels Linked to Liver Cancer Risk

September 12, 2019

By Marilynn Larkin

NEW YORK (Reuters Health) - Hepatitis B core-related antigen (HBcrAg) levels are an independent risk factor for liver cancer in patients with chronic HBV infection, a retrospective analysis reveals.

The best way to manage chronic hepatitis B patients with intermediate viral load (IVL) is "debatable," Drs. Tai-Chung Tseng and Jia-Horng Kao of National Taiwan University Hospital in Taipei told Reuters Health in a joint email.

"Our data suggested that HBcrAg should be (assessed) in IVL patients since the cutoff level of 10 KU/mL could stratify their hepatocellular carcinoma (HCC) risks into two distinct groups," they explained. "Antiviral treatment could be considered in IVL patients with a high HBcrAg level (> 10 KU/mL) to reduce their HCC risks over time."

"However, these findings need future prospective studies for validation," they said. "In addition, the HBcrAg assay has not yet been approved by the EMA or FDA, and still remains a research tool."

Drs. Tseng, Kao and colleagues collected data on 2,666 adults (61% men) at Taiwan University Hospital who were positive for hepatitis B surface antigen, infected with HBV genotypes B or C, and did not have liver cirrhosis, who had a long-term follow-up at the National Taiwan University Hospital. Age at enrollment varied from 28 to over age 60, and the mean follow-up was 16 years.

At baseline, 29.11% had ALT levels of 40 U/L or more; 19.35% were HBeAg (hepatitis B e antigen)-positive; 47.67% had HBcrAg <10 KU/mL; 20.59% had IVL (2,000-19,999 IU/mL); and 39.01% had high viral loads (HBV DNA level ≥ 20,000 IU/mL).

None received antiviral treatment during follow-up.

As reported online August 27 in Gastroenterology, 209 patients developed HCC (incidence rate, 4.91 cases/1000 person-years). The baseline level of HBcrAg was associated with HCC development, and the HBcrAg level was an independent risk factor in multivariable analysis.

In a subgroup of hepatitis B antigen-negative patients with IVL and normal alanine aminotransferase levels, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 4.89).

By contrast, HCC risk did not differ significantly between patients with high levels of HBcrAg and either IVL or high VL. (20,000 IU/mL or more).

However, those with IVL and a low level of HBcrAg had a low risk of HCC overall, with an annual incidence rate of 0.10%.

Dr. Ira Jacobson, Director of Hepatology at NYU Langone Health in New York City, commented in an email to Reuters Health, "For over a decade, the HBV DNA level in a patient's blood has been known to be a major predictor of the long term-risks of cirrhosis and liver cancer. But refinement of our ability to predict outcome is needed to strengthen our ability to make decisions about which patients to treat or monitor for liver cancer."

"In this study of a very large HBV-infected patient cohort...the authors correlated HBcrAg level in serum with long-term risk of liver cancer and found a strong correlation between cancer and higher levels," he said. "In patients with IVL levels, in whom there has been controversy about the need for long-term antiviral therapy, the strong relationship between viral levels and risk of cancer was still present, constituting a strong argument for treating these patients."

"It would have been of interest to study HBcrAg patients in the low viral level category, for whom all existing guidelines advise no treatment at present, although the authors positively correlated the risk of HCC in this (group) with an assay for quantitative hepatitis B surface antigen that has become commercially available recently but is not in widespread clinical use," he added.

Like Drs. Tseng and Kao, Dr. Jacobson noted that "HBcrAg itself is available only as a research assay at present, but doubtless this study will fuel additional interest in HBcrAg as not only a prognostic marker, but also as a marker of potential success with investigational therapies."

SOURCE: http://bit.ly/2LzIRLz

Gastroenterol 2019.