Predictors of sustained virologic response after discontinuation of nucleos(t)ide analog treatment for chronic hepatitis B

Abstract

Background/Aims:The aim of this study was to identify the predictors for relapse after discontinuation of oral nucleos(t)ide analog treatment for chronic hepatitis B (CHB).Patients and Methods:We evaluated patients who were receiving long-term, regular antiviral therapy with nucleos(t)ide analogs, and subsequently achieved the discontinuation criteria from the Asia-Pacific guideline. After they voluntarily discontinued the drug therapy, data were prospectively collected to observe the potential virologic relapse, and the parameters that predicted recurrence were analyzed.Results:Sixty-five patients met the inclusion criteria, and were included in this study. Twenty-eight patients relapsed, and the accumulative recurrence rates at the 3-month, 6-month, and 1-year follow-ups were 13.85%, 32.31%, and 49.23%, respectively. There was no difference in the accumulative recurrence rate 12 months after discontinuation among patients who were positive or negative for the hepatitis B e antigen (HBeAg) before they received the medication. Logistic regression analysis revealed that the time to complete response, age at discontinuation, and HBsAg levels at discontinuation affected the rate of relapse.Conclusions:Among patients who received orally administrated nucleos(t)ide analogs, serum levels of HBsAg, age at discontinuation, and the time to complete response might be used as a guide to discontinue treatment. Among younger patients, those with low serum HBsAg levels, and those with an earlier complete response, the risk of relapse is lower and discontinuation is much safer.

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation Among Asian Patients With Chronic Hepatitis B: A Systematic Review

“…The cessation criteria were described in all studies. Ten studies discontinued NAs according to the APASL stopping criterion . One study discontinued NAs according to the recommendation from the National Health Plan of Taiwan, China; the clinical physician’s opinion; and sufficient discussion between physicians and patients .…”

“…The low detection limit of HBV DNA ranged from <12 to <1,000 IU/mL. Ten studies reported values of HBsAg at EOT that ranged from 39.8 to 794.3 IU/mL . The duration of the off‐treatment follow‐up ranged from 12 to 157 months.…”

“…All the studies described the definition of off‐therapy virological relapse, which was defined as the reappearance of a serum HBV DNA level >1,000 IU/mL or >2,000 IU/mL after stopping NAs treatment according to studies. Seven studies described the definition of off‐therapy clinical relapse, which was defined as an increase of serum HBV DNA >2,000 IU/mL and serum ALT levels >2× the ULN . The therapy, stopping rules, duration of consolidation therapy, off‐therapy follow‐up duration, and events definitions are listed in Table .…”

“…Off‐treatment events including virological relapse, clinical relapse, and HBsAg loss were analyzed. The definition of virological relapse varied across studies: reappearance of HBV DNA to >1,000 IU/mL from an undetectable level during the off‐treatment period and reappearance of HBV DNA to >2,000 IU/mL from an undetectable level during the off‐treatment period . The definition of clinical relapse was the reappearance of HBV DNA to >2,000 IU/mL from an undetectable level and an increase of ALT levels to >2× the upper limit of normal (ULN).…”

Health-related quality of life in patients with chronic hepatitis B during antiviral treatment and off-treatment

“…There are several problems associated with long-term NUC treatment, including development of drug resistance, poor adherence, economic burdens, and psychological stressors 9,10. The Asian Pacific Association for the Study of the Liver (APASL) Guidelines recommend that NUC treatment for CHB could be considered successful after serum HBV DNA is undetectable, HBeAg seroconversion has occurred, and alanine aminotransferase levels have normalized for at least 12 months.…”