Background

Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. As therapies for hyperammonemia associated with urea cycle dysfunction have improved, chronic complications, such as liver disease, have become increasingly apparent in individuals with UCDs. Liver disease in UCDs may be associated with hepatic inflammation, hepatic fibrosis, portal hypertension, liver cancer and even liver failure. However, except for monitoring serum aminotransferases, there are no clear guidelines for screening and/or monitoring individuals with UCDs for liver disease. Thus, we systematically evaluated the potential utility of several non-invasive biomarkers for liver fibrosis in UCDs.

Methods

We evaluated grey-scale ultrasonography, liver stiffness obtained from shear wave elastography (SWE), and various serum biomarkers for hepatic fibrosis and necroinflammation, in a cohort of 28 children and adults with various UCDs.

Results

Overall, we demonstrate a high burden of liver disease in our participants with 46% of participants having abnormal grey-scale ultrasound pattern of the liver parenchyma, and 52% of individuals having increased liver stiffness. The analysis of serum biomarkers revealed that 32% of participants had elevated FibroTest™ score, a marker for hepatic fibrosis, and 25% of participants had increased ActiTest™ score, a marker for necroinflammation. Interestingly, liver stiffness did not correlate with ultrasound appearance or FibroTest™.

Conclusion

Overall, our results demonstrate the high overall burden of liver disease in UCDs and highlights the need for further studies exploring new tools for identifying and monitoring individuals with UCDs who are at risk for this complication.

Trial registration

This study has been registered in ClinicalTrials.gov (NCT03721367).

中文翻译：

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尿素循环障碍中肝病的生物标志物

背景

尿素循环障碍 (UCD) 是肝脏代谢最常见的先天性错误之一。随着与尿素循环功能障碍相关的高氨血症的治疗得到改善，慢性并发症（如肝病）在 UCD 患者中变得越来越明显。UCDs中的肝病可能与肝脏炎症、肝纤维化、门静脉高压症、肝癌甚至肝功能衰竭有关。然而，除了监测血清转氨酶外，没有明确的指南来筛查和/或监测 UCD 患者的肝病。因此，我们系统地评估了几种非侵入性生物标志物在 UCD 中肝纤维化的潜在效用。

方法

我们在一组 28 名患有各种 UCD 的儿童和成人中评估了灰度超声检查、从剪切波弹性成像 (SWE) 获得的肝脏硬度以及肝纤维化和坏死性炎症的各种血清生物标志物。

结果

总体而言，我们证明参与者的肝病负担很高，46% 的参与者肝实质灰度超声模式异常，52% 的参与者肝硬度增加。血清生物标志物分析显示，32% 的参与者的 FibroTest™ 评分升高，这是肝纤维化的标志，25% 的参与者的 ActiTest™ 评分升高，这是坏死性炎症的标志。有趣的是，肝脏硬度与超声外观或 FibroTest™ 无关。

结论

总体而言，我们的研究结果表明 UCD 中肝病的总体负担较高，并强调需要进一步研究探索新的工具来识别和监测有这种并发症风险的 UCD 患者。

试用注册

该研究已在 ClinicalTrials.gov (NCT03721367) 上注册。