Distribution of patients by guideline-defined disease phase and/or grey zones in B-Clear, an international multicentre clinical trial

초록

Background and aims: Many patients ( pts) with chronic hepatitis B virus (CHB) lie in a grey zone (GZ) (i.e. they do not fit into a guideline-defined disease phase). We evaluated the distribution and characteristics of CHB pts enrolled in B-Clear, who were not on nucleos (t)ide analog (NA) therapy, by guideline-defined disease phase and GZ. Method: B-Clear is an ongoing trial (NCT04449029) to assess the efficacy and safety of bepirovirsen (GSK3228836, BPV)-an antisense oligonucleotide- in pts with CHB. Pts not on NA (N = 230) were categorised as HBeAg positive (eAg+) chronic infection, eAg+ chronic hepatitis, HBeAg negative (eAg-) chronic infection, and eAg- chronic hepatitis, based on HBV DNA, alanine aminotransferase (ALT) and eAg status at baseline as per EASL 2017, AASLD 2018 and APASL 2015 CHB guidelines. In addition, ‘Strict’ or ‘Common’ criteria were applied based upon eAg status and ALT cut-offs of 35/25 IU/ml [males/females] or 40/33 IU/ml [males/females], respectively. Pts in the GZ were categorised into four groups: A (eAg+, normal ALT), B (eAg+, high ALT), C (eAg-, normal ALT), D (eAg-, high ALT). Results: Of the four guideline-defined disease phases, the highest proportion of pts were eAg+ chronic hepatitis (EASL 16.2%; AASLD 18.8%) or eAg- chronic hepatitis (EASL 16.2%; APASL 8.7%) (Figure); however, the majority of patients (55.5%, 65.9% and 81.2%) fell in the GZ using EASL, AASLD and APASL guidelines, respectively. Most pts in the GZ were eAg-. GZ C was the most common GZ group: 48.5% (EASL), 36.2% (AASLD) and 48.5% (APASL); however, the proportion of pts in other GZ groups differed by guideline. The EASL guidelines had the lowest proportion of pts in the GZ for Asian (48.8%), Black (75%) and White (60.8%) pts. The APASL guidelines had the highest proportion in the GZ for Asian (86%) and Black (95%) pts, while AASLD guidelines had the highest proportion of pts in the GZ for White pts (74.7%). When the criterion for HBV DNA was removed, the highest proportion of GZ pts fell into the eAg-, normal ALT category (52.2% ‘Common’; 40.4% ‘Strict’) and eAg-, high ALT category (21.7% ‘Common’; 33.5% ‘Strict’) Conclusion: Most pts enrolled in B-Clear lie in the GZ. There is a need to understand how best to categorise pts with CHB to improve their overall management. Observations may be limited by the inclusion criteria of the study. [on behalf of the B-Clear study group].