Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba.
Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indiana, USA.
Liver Int. 2017 Dec;37(12):1887-1896. doi: 10.1111/liv.13480. Epub 2017 Jun 14.
BACKGROUND & AIMS: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI.
Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis.
Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively.
Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.
生活方式干预（LI）后血清纤维化生物标志物对肝脏组织学变化的动态反应尚不清楚。我们探讨了接受 LI 的 NASH 患者血清生物标志物变化与肝纤维化之间的关系。
对 261 例 NASH 患者进行了配对肝活检，以评估 LI 后 1 年的纤维化变化。我们探讨了血清纤维化标志物预测肝纤维化变化的效用，并为基线纤维化患者建立并内部验证了一种预测纤维化改善的模型。
51 例（20%）、165 例（63%）和 45 例（17%）患者的纤维化分别出现缓解、稳定和进展。多变量分析显示，HbA1c（OR，0.39，P<.01）、血小板（OR，1.22，P<.01）和 NFS（OR，0.27，P<.01）的变化以及 ALT 正常化（OR，9.7，P<.01）与纤维化改善独立相关，而血小板（OR，0.96，P<.01）和 NFS（OR，1.8，P<.01）以及 ALT 正常化（OR，0.21，P<.01）的变化与纤维化进展相关。包括 HbA1c、血小板和 ALT 正常化变化的模型对预测纤维化改善的准确性明显高于 NFS、FIB-4 和 APRI（AUC 为 0.96，95%CI，0.94-0.99）。使用阈值≥0.497，阳性预测值和阴性预测值分别为 94%（95%CI，84-98）和 91%（95%CI，81-96）。
NFS、血小板和 ALT 正常化的变化与 LI 后 1 年的肝纤维化变化相关。包括 HbA1c、血小板和 ALT 正常化变化的模型比其他生物标志物更好地鉴别出纤维化改善的患者。
