Wang Tingyan, Campbell Cori, Stockdale Alexander J, Todd Stacy, McIntyre Karl, Frankland Andrew, Jaworski Jakub, Glampson Ben, Papadimitriou Dimitri, Mercuri Luca, Mayer Erik, Jones Christopher R, Salih Hizni, Roadknight Gail, Little Stephanie, Noble Theresa, Várnai Kinga A, Davis Cai, Heinson Ashley I, George Michael, Borca Florina, English Louise, Romão Luis, Ramlakhan David, Woods Kerrie, Davies Jim, Nastouli Eleni, Khakoo Salim I, Gelson William, Cooke Graham S, Barnes Eleanor, Matthews Philippa C
NIHR Oxford Biomedical Research Centre, Oxford, UK.
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
JHEP Rep. 2024 Oct 9;7(1):101229. doi: 10.1016/j.jhepr.2024.101229. eCollection 2025 Jan.
BACKGROUND & AIMS: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.
Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase, and with liver fibrosis/cirrhosis.
We retrieved data from 1,885 adults on NA treatment (median follow-up 6.2 years, IQR 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n = 1,367, discrimination: 0.93, entropy: 0.90): class 1 'long term suppression' (n = 827, 60.5%), class 2 'timely virological suppression' (n = 254, 18.6%), class 3 'persistent moderate viraemia' (n = 140, 10.2%), class 4 'persistent high-level viraemia' (n = 44, 3.2%), and class 5 'slow virological suppression' (n = 102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n = 518). Alanine transaminase decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all <0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had twofold increased hazards of fibrosis/cirrhosis compared with class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02).
Heterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression.
Treatment recommendations for people living with chronic hepatitis B virus (HBV) infection are becoming less stringent, meaning that more of the population will be eligible to receive therapy with nucleos(t)ide analogue agents. We explored outcomes of HBV treatment in a large UK dataset, describing different responses to treatment, and showing that the viral load is not completely suppressed after 1 year in about one in five cases, associated with an increased risk of liver complications. As treatment is rolled out more widely, patients and clinicians need to be aware of the potential for incomplete virologic responses. The findings can support the identification of high-risk individuals, improve early fibrosis and cirrhosis prediction, guide monitoring and preventive interventions, and support public health elimination goals.
对于接受核苷（酸）类似物（NA）治疗的慢性乙型肝炎（CHB）患者，乙肝病毒载量（VL）的动态变化及其与肝脏疾病的关系尚不清楚。我们旨在研究VL的纵向变化模式及其与CHB临床结局的关联。
利用英国六个中心常规收集的大规模电子健康记录，这些记录由国家卫生与保健研究健康信息协作中心（NIHR HIC）整理，我们应用潜在类别混合模型来研究接受NA治疗的成年人的VL轨迹模式。我们评估了VL轨迹与丙氨酸转氨酶以及肝纤维化/肝硬化的关联。
我们检索了1885名接受NA治疗的成年人的数据（中位随访6.2年，四分位间距3.7 - 9.3年），共21691次VL测量值（每位患者中位10次，四分位间距5 - 17次）。从推导队列（n = 1367，辨别力：0.93，熵：0.90）中识别出五个VL类别：1类“长期抑制”（n = 827，60.5%），2类“及时病毒学抑制”（n = 254，18.6%），3类“持续中度病毒血症”（n = 140，10.2%），4类“持续高水平病毒血症”（n = 44，3.2%），5类“缓慢病毒学抑制”（n = 102，7.5%）。验证队列（n = 518）的模型辨别力为0.93，熵为0.88。在VL抑制组（1、2、5类；均P < 0.001）中，丙氨酸转氨酶随时间有不同程度下降，但在持续病毒血症组（3、4类）中未显著改善。与1类相比，5类患者发生纤维化/肝硬化的风险增加两倍（调整后风险比，2.00；95%置信区间，1.33 - 3.02）。
CHB患者对NA治疗存在病毒学反应异质性，超过20%表现出潜在的次优反应。缓慢病毒学抑制与肝脏疾病进展相关。
慢性乙型肝炎病毒（HBV）感染患者的治疗建议正变得不那么严格，这意味着更多人群将有资格接受核苷（酸）类似物治疗。我们在一个大型英国数据集中探索了HBV治疗的结局，描述了不同的治疗反应，并表明约五分之一的病例在1年后病毒载量未被完全抑制，这与肝脏并发症风险增加相关。随着治疗更广泛地推广，患者和临床医生需要意识到病毒学反应不完全的可能性。这些发现有助于识别高危个体，改善早期纤维化和肝硬化预测，指导监测和预防性干预，并支持公共卫生消除目标。
