Managing Nucleos(t)ide Analog Treatment in Patients With Chronic Hepatitis B

Pegylated-interferon (PEG-IFN) added to nucleos(t)ide analog (NA) treatment may be associated with hepatitis B surface antigen (HbsAg) decline and once HbsAg-seroclearance is achieved, discontinuation of NA is not associated with a higher risk for HbsAg-reversion, according to results of 2 studies presented at The American Association for the Study of Liver Diseases’ The Liver Meeting, held November 8 to 12, 2019 in Boston, Massachusetts.

PEG-IFN treatment has been associated with more significant declines of HbsAg in patients with chronic hepatitis B and the PEG-IFN add-on to NA treatment has been increasingly used in regimens aiming for functional cure. Additionally, PEG-IFN add-on therapy may help attain loss of HbsAg, thus allowing for discontinuation of NA. Therefore, a randomized controlled study investigated the dynamics of HbsAg in patients with chronic HBV who are hepatitis B envelope antigen (HbeAg)-negative, and are receiving long-term NA and who received add-on PEG-IFN.¹

In total, 89 patients who were HbeAg-negative were included and randomly assigned 2:1 to receive either add-on PEG-IFN alda-2a (180 µg per week) or continue NA monotherapy. The primary endpoint was HbsAg decline >1 log IU/mL at week 48 from baseline.

Results showed that the addition of PEG-IFN to long-term NA is associated with substantial HbsAg decline and limited HbsAg clearance in patients with chronic HBV who were HbeAg-negative. At week 48, no patient who received NA monotherapy achieved a decline in HbsAg >1 log10, compared with 6 (10%) patients in the PEG-IFN add-on group (P <.0001). Further, at week 48, 5 (8.6%) patients in the PEG-IFN add-on group demonstrated HbsAg clearance, compared with no patients in the NA monotherapy group (P <.0001). PEG-IFN was safe and well-tolerated in most patients but serious adverse events were reported in 3 patients.

Once patients with chronic HBV demonstrate HbsAg-seroclearance, it is recommended to discontinue NA treatment—though more evidence is needed. Kim et al conducted a multicenter study to evaluate whether discontinuation of NA treatment was as safe as continuation of treatment once HbsAg-clearance was achieved.

In total, 327 patients who achieved HbsAg-seroclearance during NA treatment were included: the NA-discontinuation group comprised 173 (52.9%) patients who discontinued NA treatment within 2 months of HbsAg-seroclearance and the NA-continuation group included 154 (47.1%) patients who continued NA treatment. The primary endpoint was HbsAg reversion; secondary endpoints included the development of HCC.

Results suggested that the discontinuation of NA was not associated with a higher risk for either HbsAg-reversion (hazard ratio [HR], 0.70) or development of hepatocellular carcinoma (HR, .33). However, HbsAg reversion was associated with an aminotransferase lvel of >40 IU/L at the time of HbsAg-seroclearance (HR, 3.13), and with >2 regimens of NA treatment (HR, 3.71). Further, HbsAg reversion was independently associated with higher risk for hepatocellular carcinoma development (HR, 11.78).

Overall, the results of these 2 studies suggested that PEG-IFN add-on to NA treatment aids in achieving HbsAg-seroclearance in patients with chronic HBV and once HbsAg-seroclearance is achieved, NA treatment is safe to discontinue without any associated risk of HbsAg-reversion.

References

1. Farag MS, Fung SK, Van Campenhour M, et al. Addition of peginterferon alfa-2a increases HBsAg decline in HBEAG-negative chonris hepatitis B patiented treated with long-term nucleos(t)ide analogue thereapy: results from a multicenter randomized controlled trial. (PAS study). Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 0195.

2. Kim MA, Lee JH, Lim YS, et al. The discontinuation of nucleos(t)ide analogue treatment is not associated with higher risk of HBsAg-seroconversion after antiviral-induced HBsAg-seroclearance: A multicenter cohort study. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 0198.