Department of Gastroenterology & Hepatology, Fiona Stanley Fremantle Hospital Group, Murdoch, Western Australia, Australia.
Faculty of Medicine, University of Queensland, Herston, Brisbane, Queensland, Australia.
Clin Gastroenterol Hepatol. 2021 Jul;19(7):1459-1468.e5. doi: 10.1016/j.cgh.2020.07.052. Epub 2020 Aug 1.
BACKGROUND & AIMS: Hemochromatosis that is associated with variants in the homeostatic iron regulator gene (HFE) is characterized by intestinal absorption of iron and excessive body and hepatic iron stores; it can lead to hepatic fibrosis and cirrhosis. Fibrosis has been staged by analysis of liver biopsies, but non-invasive staging methods are available. We evaluated the ability of aspartate aminotransferase:platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and gamma-glutamyl transferase:platelet ratio (GPR) to assess hepatic fibrosis staging in subjects with HFE-associated hemochromatosis, using liver biopsy-staged fibrosis as the reference standard.
We performed a retrospective, cross-sectional analysis of 181 subjects with HFE-associated hemochromatosis and hepatic fibrosis staged by biopsy analysis and available serum samples. We calculated APRI, FIB-4, and GPR at diagnosis for all 181 subjects and following venesection therapy in 64 of these subjects (7 subjects had follow-up biopsy analysis). We used area under the receiver operating characteristic curve (AUROC) analysis to assess the relationships between APRI score, FIB-4 score, and GPR and advanced (F3-F4) fibrosis and to select cut-off values.
Hepatic fibrosis stage correlated with APRI score (r = 0.54; P < .0001), FIB-4 score (r = 0.35; P < .0001), and GPR (r = 0.36, P < .0001). An APRI score above 0.44 identified patients with advanced fibrosis with an AUROC of 0.88, 79.4% sensitivity, 79.4% specificity, and 81% accuracy. A FIB-4 score above 1.1 identified patients with advanced fibrosis with an AUROC of 0.86, 80% sensitivity, 80.3% specificity, and 81% accuracy. A GPR above 0.27 identified patients with advanced fibrosis with an AUROC of 0.76, 67.7% sensitivity, 70.3% specificity, and 69% accuracy. APRI score was significantly more accurate than GPR (P = .05) in detecting advanced fibrosis; there was no difference between APRI and FIB-4. Venesection treatment was associated with significant reductions in APRI (P < .0001) and GPR (P < .001), paralleling fibrosis regression observed in available liver biopsies. Post-venesection APRI identified 87% of subjects with advanced fibrosis that decreased to levels that indicate stage F1-F2 fibrosis.
In a retrospective study of 181 subjects with HFE-associated hemochromatosis, we found that APRI and FIB-4 scores identified patients with advanced hepatic fibrosis with 81% accuracy. APRI scores might also be used to monitor fibrosis regression following venesection.
与稳态铁调节基因（HFE）变异相关的血色病的特征是肠道铁吸收和体内及肝脏铁储存过多；它可导致肝纤维化和肝硬化。纤维化已通过肝活检进行分期，但也有非侵入性分期方法。我们评估了天门冬氨酸氨基转移酶：血小板比值指数（APRI）、纤维化-4 指数（FIB-4）和γ-谷氨酰转肽酶：血小板比值（GPR）在 HFE 相关血色病患者中评估肝纤维化分期的能力，使用肝活检分期纤维化作为参考标准。
我们对 181 例 HFE 相关血色病患者进行了回顾性、横断面分析，这些患者均进行了肝纤维化分期的肝活检分析和可用的血清样本检测。我们计算了所有 181 例患者的 APRI、FIB-4 和 GPR 值，并在其中 64 例患者（7 例患者有随访肝活检分析）进行静脉切开术治疗后进行了评估。我们使用接受者操作特征曲线（AUROC）分析来评估 APRI 评分、FIB-4 评分和 GPR 与晚期（F3-F4）纤维化之间的关系，并选择截断值。
肝纤维化分期与 APRI 评分（r = 0.54；P <.0001）、FIB-4 评分（r = 0.35；P <.0001）和 GPR（r = 0.36，P <.0001）相关。APRI 评分>0.44 可识别出患有晚期纤维化的患者，AUROC 为 0.88，灵敏度为 79.4%，特异性为 79.4%，准确性为 81%。FIB-4 评分>1.1 可识别出患有晚期纤维化的患者，AUROC 为 0.86，灵敏度为 80%，特异性为 80.3%，准确性为 81%。GPR>0.27 可识别出患有晚期纤维化的患者，AUROC 为 0.76，灵敏度为 67.7%，特异性为 70.3%，准确性为 69%。APRI 评分在检测晚期纤维化方面明显优于 GPR（P =.05）；APRI 和 FIB-4 之间没有差异。静脉切开术治疗与 APRI（P <.0001）和 GPR（P <.001）显著降低相关，这与可获得的肝活检中观察到的纤维化消退相平行。静脉切开术后 APRI 识别出 87%的晚期纤维化患者，其水平降低至指示 F1-F2 纤维化阶段的水平。
在对 181 例 HFE 相关血色病患者的回顾性研究中，我们发现 APRI 和 FIB-4 评分可准确识别出患有晚期肝纤维化的患者，准确率为 81%。APRI 评分也可用于监测静脉切开术后纤维化的消退情况。
