Patel Nishi H, Chen Annie Y, Osiowy Carla, Durkalski Mauldin Valerie, Lee William M, Coffin Carla S, Karvellas Constantine J
Department of Medicine, Cross-Appointment to Microbiology and Infectious Diseases, Snyder Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Liver Int. 2025 Jul;45(7):e70175. doi: 10.1111/liv.70175.
BACKGROUND & AIMS: Only 25% of hepatitis B-related acute liver failure (HBV-ALF) patients survive without liver transplantation (transplant-free survival, TFS). There is limited study of immunological and virological profiles in these patients. We analysed the association between hepatitis B viremia and cytokine patterns on TFS of HBV-ALF patients.
We identified 48 acute and 20 history of HBV infection ALF patients from the US ALF Study Group registry (> 3400 patients). The inclusion criteria were age > 18 years, diagnosis of HBV-ALF with hepatic encephalopathy and INR ≥ 1.5. Data were collected from ICU admission through day 21. Serum collected at admission and at days 3-5 were used for cytokine quantification by Luminex and novel HBV biomarkers, genotypes and variants.
In 48 acute (50% F, median age 40 years) and 20 history/reactivation (40% F, median age 53 years) HBV-ALF patients, there were 26 (54%) and 5 (25%) TFS, respectively. Detectable HBV DNA by clinical PCR assay (median 3.39 logIU/mL, aOR 5.308; 95% CI: 1.217-23.155, p = 0.026) and qAHBc levels (median 4.5 logIU/mL, aOR 4.466, 95% CI: 0.968-20.608, p = 0.050) were associated with TFS in acute HBV-ALF patients. HBV variants associated with anti-viral immune escape were more frequently detected in acute HBV-ALF TFS patients compared to non-TFS (p < 0.05). TFS with acute HBV-ALF had higher angiogenic factors (PDGF-AA, p = 0.008; PDGF-BB, p = 0.0006; VEGF-A, p = 0.014) and lower pro-inflammatory cytokine levels (IL-1α, p = 0.031; IL-2, p = 0.014; IL-6, p = 0.039). Significant differences in HBV viremia were not observed in history/reactivation of HBV-ALF patients.
Acute HBV-ALF patients with TFS were often viremic with immune escape variants, increased angiogenic factors and decreased pro-inflammatory cytokines.
ClinicalTrials.gov identifier: NCT00518440.
仅25%的乙型肝炎相关急性肝衰竭（HBV-ALF）患者在未进行肝移植的情况下存活（无移植生存，TFS）。对这些患者的免疫和病毒学特征的研究有限。我们分析了HBV-ALF患者的乙肝病毒血症与细胞因子模式对TFS的关联。
我们从美国急性肝衰竭研究组登记处（>3400例患者）中确定了48例急性和20例有HBV感染史的ALF患者。纳入标准为年龄>18岁，诊断为伴有肝性脑病的HBV-ALF且INR≥1.5。数据从重症监护病房入院时收集至第21天。入院时及第3 - 5天收集的血清用于通过Luminex进行细胞因子定量以及检测新型HBV生物标志物、基因型和变异体。
在48例急性（50%为女性，中位年龄40岁）和20例有病史/再激活（40%为女性，中位年龄53岁）的HBV-ALF患者中，分别有26例（54%）和5例（25%）实现了TFS。临床PCR检测可检测到的HBV DNA（中位值3.39 logIU/mL，调整后比值比5.308；95%置信区间：1.217 - 23.155，p = 0.026）和qAHBc水平（中位值4.5 logIU/mL，调整后比值比4.466，95%置信区间：0.968 - 20.608，p = 0.050）与急性HBV-ALF患者的TFS相关。与非TFS患者相比，在急性HBV-ALF TFS患者中更频繁地检测到与抗病毒免疫逃逸相关的HBV变异体（p < 0.05）。急性HBV-ALF实现TFS的患者具有更高的血管生成因子（PDGF-AA，p = 0.008；PDGF-BB，p = 0.0006；VEGF-A，p = 0.014）和更低的促炎细胞因子水平（IL-1α，p = 0.031；IL-2，p = 0.014；IL-6，p = 0.039）。在有HBV-ALF病史/再激活的患者中未观察到HBV病毒血症的显著差异。
实现TFS的急性HBV-ALF患者常伴有病毒血症，携带免疫逃逸变异体，血管生成因子增加且促炎细胞因子减少。
ClinicalTrials.gov标识符：NCT00518440。
