Author information

¹Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Electronic address: m.j.sonneveld@erasmusmc.nl.

²Department of Internal Medicine, Koahsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

³Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

⁴Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

⁵Faculty of Medicine, Prince of Songkla University, Hatyai, Thailand.

⁶Department of Medicine, State Key Laboratory for Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong.

⁷Department of Gastroenterology & Hepatology, Kumamoto University, Kumamoto, Japan.

⁸Institute of Liver Studies, King's College Hospital, London, United Kingdom.

⁹Department of Gastroenterology, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Athens, Greece.

¹⁰Hepatology Unit, University Hospital of Pisa, Pisa, Italy.

¹¹Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.

¹²Viral Hepatitis Research Laboratory, INSERM Unit 1052, Lyon, France.

¹³Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.

¹⁴Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

¹⁵Department of Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.

¹⁶Liver Unit, Hospital Universitari Vall d'Hebron and Ciberehd del Intituto Carlos III de Barcelona, Barcelona, Spain.

Abstract

Background & aims: Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up.

Methods: We studied the association between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment at follow-up at week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss was in a multicenter cohort of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy.

Results: We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio [HR], 1.576; P < .001) and a lower chance of HBsAg loss (HR, 0.454; P < .001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P < .001) and a lower chance of HBsAg loss (HR, 0.263; P < .001). A combination of both HBsAg <100 IU/mL and HBV DNA <100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg >100 IU/mL and HBV DNA >100 IU/mL (P < .001).

Conclusions: Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg <100 IU/mL with HBV DNA <100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.