Lefere Sander, Mosca Antonella, Hudert Christian, Dupont Ellen, Fitzpatrick Emer, Kyrana Eirini, Dhawan Anil, Kalveram Laura, Pietrobattista Andrea, Geerts Anja, De Bruyne Ruth
Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium.
Hepatology. 2025 Apr 1;81(4):1276-1287. doi: 10.1097/HEP.0000000000001016. Epub 2024 Jul 19.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent pediatric liver disease, yet accurate risk scores for referral of children/adolescents with suspected clinically significant liver fibrosis are currently lacking.
Clinical and biochemical variables were collected in a prospective cohort of 327 children and adolescents with severe obesity, in whom liver fibrosis was evaluated by transient elastography. Logistic regression was performed to establish continuous (pFIB-c) and simplified (pFIB-6) diagnostic scores that accurately exclude significant (≥F2) fibrosis. Performance for each was compared to established noninvve fibrosis scores. These scores were validated in elastography (n=504) and multiple biopsy-proven MASLD (n=261) cohorts. Patient sex, ethnicity, weight z-score, homeostatic model assessment of insulin resistance index, ALT, and presence of hypertension were included in the scores. The pFIB-c and pFIB-6 exhibited good discriminatory capacity (c-statistic of 0.839 and 0.826), outperforming existing indices. Negative predictive values were >90% for both scores in the derivation and elastography validation cohorts. Performance in the histological cohorts varied (AUROCs for the pFIB-c between 0.710 and 0.770), as the scores were less accurate when applied to populations in tertiary referral centers characterized by a high prevalence of significant fibrosis and high ALT levels.
Analyzing several cohorts totaling approximately 1100 children and adolescents, we developed novel risk scores incorporating readily available clinical variables. In accordance with the aim of excluding pediatric MASLD-associated fibrosis, the scores performed better in nonselected cohorts of children and adolescents living with obesity than in patients referred to tertiary liver units.
代谢功能障碍相关脂肪性肝病（MASLD）是最常见的儿童肝病，但目前缺乏用于转诊疑似具有临床显著肝纤维化的儿童/青少年的准确风险评分。
前瞻性收集了327例严重肥胖儿童和青少年的临床及生化变量，通过瞬时弹性成像评估其肝纤维化情况。进行逻辑回归分析以建立能够准确排除显著（≥F2）纤维化的连续（pFIB-c）和简化（pFIB-6）诊断评分。将每个评分的性能与已建立的非侵入性纤维化评分进行比较。这些评分在弹性成像队列（n = 504）和多个经活检证实的MASLD队列（n = 261）中进行了验证。评分纳入了患者的性别、种族、体重z评分、胰岛素抵抗指数的稳态模型评估、ALT以及是否存在高血压。pFIB-c和pFIB-6表现出良好的鉴别能力（c统计量分别为0.839和0.826），优于现有指标。在推导队列和弹性成像验证队列中，两个评分的阴性预测值均>90%。在组织学队列中的性能有所不同（pFIB-c的曲线下面积在0.710至0.770之间），因为当应用于以显著纤维化高患病率和高ALT水平为特征的三级转诊中心人群时，评分的准确性较低。
通过分析总计约1100例儿童和青少年的多个队列，我们开发了包含易于获得的临床变量的新型风险评分。根据排除儿童MASLD相关纤维化的目标，这些评分在未选择的肥胖儿童和青少年队列中比在转诊至三级肝病科的患者中表现更好。
