Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-negative chronic hepatitis B: A multicentre cohort study
Milan J. Sonneveld, Shao‐Ming Chiu, Jun Yong Park, Sylvia M. Brakenhoff, Apichat Kaewdech, Wai‐Kay Seto, Yasuhito Tanaka, Ivana Carey, Μargarita Papatheodoridi, P. Colombatto, Florian van Bömmel, Thomas Berg, Fabien Zoulim, Sang Hoon Ahn, George Ν. Dalekos, Nicole S. Erler, Maurizia Rossana Brunetto, Heiner Wedemeyer, Markus Cornberg, Man‐Fung Yuen, Kosh Agarwal, André Boonstra, Marı́a Buti, Teerha Piratvisuth, George Papatheodoridis, Chien‐Hung Chen, Benjamin Maasoumy
Abstract
Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain illusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Chronic hepatitis B patients who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pre-treatment HBV DNA levels and1 clinical relapse (defined as HBV DNA >2,000 IU/mL + ALT > 2x ULN or retreatment) and2 HBsAg loss after NUC withdrawal. We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 weeks (IQR 156 – 262). Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/mL; and were low (<20,000 IU/mL) in 150 (20%) and high (>20,000 IU/mL) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels <20,000 IU/mL versus 60% among patients with pretreatment HBV DNA levels >20,000 IU/mL, whereas the cumulative probabilities of HBsAg loss were 17.5% versus 5% (p<0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/mL were independently associated with a reduced likelihood of clinical relapse (adjusted HR 0.379, p<0.001) and with an increased chance of HBsAg loss (adjusted HR 2.872, p<0.001). Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of EOT viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. A subgroup of chronic hepatitis B patients may not require retreatment after stopping antiviral therapy. In this study comprising 757 chronic hepatitis B patients from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal, and to guide intensity of off-treatment monitoring.