Shteyer Eyal, Ramm Grant A, Xu Chunxia, White Frances V, Shepherd Ross W
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Pediatr Gastroenterol Nutr. 2006 Jan;42(1):93-9. doi: 10.1097/01.mpg.0000189324.80323.a6.
Biliary atresia (BA), a congenital idiopathic obliterative cholangiopathy, rapidly leads to liver cirrhosis and liver failure if untreated. A timely Kasai portoenterostomy (KP) variably alters this natural history. We evaluated liver fibrogenesis by the intensity of alpha-smooth-muscle actin (SMA) expression, which is a marker for hepatic stellate cell activation. We hypothesized that liver fibrogenesis as determined by intensity of alpha-SMA is already progressing at the time of KP, is related to age and degree of fibrosis at KP, and predicts outcome after KP.
BA patients at KP (n = 22, age 22-84 days, median 59) had wedge liver biopsies assessed by quantitative morphometry of immunohistochemistry for alpha-SMA expression. Fibrosis was scored by blinded pathologists. Outcome, reflected by conjugated bilirubin concentration 3 months after KP (CBili3m), survival of the native liver, need for liver transplant, or death, were assessed for 2 to 10 years after KP.
At KP, age, fibrosis score, and alpha-SMA expression were significantly correlated. Moderate-severe fibrosis and intense alpha-SMA expression was observed in 15 of 22 (68%) patients. Severe fibrosis and high alpha-SMA expression were significantly associated with CBili3m greater than 2 g/dL and unfavorable liver survival (>90% of these ultimately underwent liver transplantation or died). Conversely, those with mild fibrosis and low alpha-SMA expression had normal CBili3m and favorable liver survival.
Intense liver fibrogenesis is already established in many cases of BA at the time of KP. Fibrosis scores and intensity of alpha-SMA expression may be predictors of outcome after KP and may indicate those patients who might benefit from trials of potential antifibrotic agents early in the course of BA.
胆道闭锁（BA）是一种先天性特发性闭塞性胆管病，若不治疗会迅速导致肝硬化和肝衰竭。及时进行肝门空肠吻合术（KP）可不同程度地改变其自然病程。我们通过α-平滑肌肌动蛋白（SMA）表达强度评估肝纤维化形成，α-SMA是肝星状细胞激活的标志物。我们假设，KP时由α-SMA强度所确定的肝纤维化形成已经在进展，与KP时的年龄和纤维化程度相关，并可预测KP后的结局。
接受KP的BA患者（n = 22，年龄22 - 84天，中位数59天）接受楔形肝活检，通过免疫组织化学定量形态学评估α-SMA表达。由不知情的病理学家对纤维化进行评分。评估KP后2至10年的结局，以KP后3个月的结合胆红素浓度（CBili3m）、自体肝存活情况、肝移植需求或死亡情况来反映。
在KP时，年龄、纤维化评分和α-SMA表达显著相关。22例患者中有15例（68%）观察到中度至重度纤维化和强烈的α-SMA表达。严重纤维化和高α-SMA表达与CBili3m大于2 g/dL以及不良的肝脏存活情况（这些患者中超过90%最终接受了肝移植或死亡）显著相关。相反，那些纤维化程度轻且α-SMA表达低的患者CBili3m正常，肝脏存活情况良好。
在许多BA病例中，KP时强烈的肝纤维化形成已经存在。纤维化评分和α-SMA表达强度可能是KP后结局的预测指标，并可能提示那些在BA病程早期可能从潜在抗纤维化药物试验中获益的患者。
