Serum Hep B Virus RNA Levels Useful When Deciding When to Stop Treatment

By Will Boggs, MD

August 26, 2020

NEW YORK (Reuters Health) - Patients with chronic hepatitis B who have undetectable serum hepatitis B virus (HBV) RNA can safely undergo cessation of entecavir antiviral treatment, according to a new study.

"Serum HBV RNA reflects an important intermediate in the life cycle of the virus, and at undetectable levels, patients may stand a chance of stopping their treatment," Dr. Wai-Kay Seto of The University of Hong Kong, Queen Mary Hospital, told Reuters Health by email. "However, if serum HBV RNA is positive, disease relapse is almost certain after treatment discontinuation."

Long-term anti-HBV treatment with nucleos(t)ide analogue (NUC) therapy results in persistent virological suppression and reduces the risk of liver-related complications. Improvements in clinical outcomes persist once hepatitis B surface antigen (HBsAg) seroclearance is achieved, but it remains unclear how best to identify patients that will safely discontinue NUC treatment.

Dr. Seto and colleagues investigated the role of HBV RNA, HBsAg, serum hepatitis B core-related antigen (HBcrAg), and covalently closed circular DNA (cccDNA) levels in patients with chronic HBV and low serum HBsAg levels with reference to guideline-recommended criteria for treatment cessation.

The study included 114 patients who ceased entecavir treatment following sustained virological suppression and 175 similar patients who refused treatment cessation.

At 48 weeks off treatment, 58.1% of patients had HBV DNA levels above 2,000 IU/mL (the primary marker of recurrence) and 59.7% had HBV RNA levels of 44.6 U/mL or higher.

Higher serum HBV RNA (44.6 U/mL or higher) at treatment cessation was associated with a three-fold greater risk of HBV DNA above 2,000 IU/mL during follow-up, whereas higher serum HBsAg levels showed only a borderline association and age, treatment duration, consolidation duration, and HBcrAg were not associated with the risk of recurrence.

Off-treatment HBV RNA levels of 44.6 U/mL and higher were associated with rates of recurrence above 90%, while the combination of HBV RNA undetectability and HBsAg <10 IU/mL was associated with a cumulative 48-week rate of recurrence of only 9.1%.

Among patients with undetectable HBV RNA at treatment cessation, there were no cases of HBV DNA >2,000 IU/mL from week 24 onwards, the researchers report in Gut.

"For a chronic hepatitis B patient who is stable on long-term therapy, consider checking his serum HBV RNA," Dr. Seto said. "If it is undetectable, and together with other favorable parameters (a low serum HBsAg level), treatment cessation can be considered."

"While serum HBV RNA can help identify patients suitable for treatment cessation, the proportion of suitable patients will be small," he cautioned. "For the majority of patients on currently available treatment regimens, treatment may have to be long-term."

Dr. Seto added, "While we only included Asian patients, it is possible that the results may be generalizable to patients of other ethnicities, since there are no significant differences in viral kinetics when comparing patients of different populations. Future studies in other populations will be required."

Dr. Robert G. Gish, an independent consultant and medical director of the Hepatitis B Foundation, told Reuters Health by email, "Quantitative HBsAg is our current best test for predicting clearance of HBsAg and relapse after stopping NUC therapy."

"With quantitative HBV RNA, we could refine stopping rules and also guide how to monitor patients often therapy," added Dr. Gish, who was not involved in the new work.

Dr. Yun-Fan Liaw of Chang Gung University and Memorial Hospital, in Taipei, Taiwan, who recently reviewed predictors of HBsAg seroclearance after cessation of NUC in patients with HBeAg-negative chronic hepatitis B, pointed out several shortcomings of this study in an email interview with Reuters Health, including the fact that its inclusion and exclusion criteria resulted in only 14.7% of patients being included in the study.

He concluded, "The quantitative HBsAg assay is stable, reproducible, and the commercial price is far cheaper than HBV DNA and has been widely utilized clinically over 10 years. Unless the predictive values of HBV RNA are far better than HBsAg, it is not practical to replace or add-on to the HBsAg assay for this purpose."

The study was done in collaboration with Abbott Laboratories, which sells the m2000 system used to measure HBV RNA in the study. The company funded the study and employed two of the authors.

SOURCE: Gut, online August 5, 2020.