Abstract 1

AUTOIMMUNE ACUTE LIVER FAILURE IN CHILDREN: CLINICAL CLUES AND A NEW DIAGNOSTIC SCORE

儿童自身免疫性急性肝功能衰竭：临床线索和新诊断评分

Background: Autoimmune hepatitis (AIH) is considered an underdiagnosed cause of acute liver failure (ALF) both in adults and children. If treatment is initiated promptly, patients with autoimmune acute liver failure (AI-ALF) may survive without transplantation (OLT). There are no reported series of children with AI-ALF. We aimed to review our experience and propose a score to recognise AI-ALF in this setting. 

Patients and Methods: We retrospectively reviewed all cases of ALF referred to our Hospital in the last 16 years. ALF was defined by high transaminases, INR ≥ 2.0 regardless of encephalopathy, no previously recognised liver disease. AI-ALF was diagnosed in presence of positive autoantibodies (ANA, SMA, LKM, LC1) and a compatible histology obtained during the course of the disease or at hepatectomy. Features of children with AI-ALF were compared to non AI-ALF patients and a diagnostic score was built on the basis of statistically significant differences between the two groups.

Results: We identified 46 children with ALF; 10/46 (21.7%, M/F=6/4,median age of 6.4 years, range 1.3–15.1, Group 1), had AIALF(AIH1=4; AIH2=6); 36/46 (78.3%, M/F=20/16, median age 2.4 years, range 0.2–13.7, Group 2), had ALF due to acetaminophen overdose (6), metabolic disorders (3), Wilson’s disease (3),mushroom poisoning (3), viral infection (1) and indeterminate (20). Histological evaluation was available in 93% of patients. In Group 1 median age at diagnosis was greater (6.4 y vs 2.4 y in Group 2, p < 0.05), alanine aminotrasferase (ALT) was lower (1020 U/L vs 3229 U/L, p < 0.05), IgG was greater (1845 mg/dl vs 971 mg/dl, p < 0.001). Based on these results we defined a scoring system including autoantibody positivity, ALT levels, Immunoglobulin levels and age at onset to diagnose children with AI-ALF (range −2 to +6). The optimal cutoff point on the ROC curve was 3 (sensibility 100%, specificity 97.2%, area under the curve 0.994).

Conclusion: In our experience AI-ALF accounts for 22% of all paediatric cases of ALF which is higher than previously described. A simple diagnostic score may be utilized to identify children with such aetiology, allow prompt treatment and probably avoid OLT in a proportion of cases.

背景：自身免疫性肝炎（AIH）在成人和儿童急性肝功能衰竭（ALF）中均诊断不足。自身免疫性急性肝功能衰竭（AI-ALF）患者如果治疗及时有可能存活，而不需要进行肝移植（OLT）。目前还没有关于儿童AI-ALF的系列报道。本研究的目的是总结既往经验并提出在这种情况下识别AI-ALF的新诊断评分。

患者和方法：本研究回顾性分析了过去16年中所有来院的ALF病例。ALF定义为转氨酶高，INR≥2.0，而无论是否伴随脑病，并且先前未诊断为肝病。存在自身抗体（ANA，SMA，LKM，LC1）阳性时诊断为AI-ALF，并且和疾病过程或肝切除组织的组织学变化一致。对AI-ALF儿童与非AI-ALF儿童的特点进行比较，诊断评分建立在两组间统计学上显著差异的基础上。

结果：共确定了46例ALF儿童；10/46（21.7％，男/女=6/4，年龄中位数为6.4年，范围1.3~～15.1，为第1组）为AI-ALF（AIH1=4；AIH2=6），36/46（78.3％，男/女=20/16，中位数年龄2.4岁，范围为0.2~～13.7，为第2组）ALF的原因分别为乙酰氨基酚过量（6），代谢障碍（3），威尔逊氏病（3），蘑菇中毒（3），病毒感染（1）和不确定（20）。93％患者有组织学评估结果。第1组平均诊断年龄较大（6.4年比2.4年（第2组），P<0.05），谷丙转氨酶（ALT）较低（1020 U/L比3229 U/L，P<0.05），IgG滴度较高（1845 mg/dL和971 mg/dL，P<0.001）。基于上述结果，本研究定义了一个新评分系统，包括自身抗体阳性、ALT水平、免疫球蛋白水平和诊断儿童AI-ALF的发病年龄（范围为-2至+6）。在ROC曲线上的最佳临界点为3（敏感度为100％，特异度为97.2％，曲线下面积0.994）。

结论：本研究结果显示AI-ALF占所有ALF儿科病例的22％，高于先前报道。一个简单的诊断评分可以用来识别这种病因儿童，进而给予及时治疗，从而可使一部分病例避免OLT。