Department of Hepatology, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, 350025, Fujian, China.
Department of Hepatobiliary Medicine, 900th Hospital of PLA, Fuzhou, 350025, Fujian, China.
BMC Pregnancy Childbirth. 2021 Sep 8;21(1):617. doi: 10.1186/s12884-021-04095-8.
Acute fatty liver of pregnancy (AFLP) is an acute, rare and potentially lethal disease typically occurring in the third trimester of pregnancy. So far, there is no effective means of prevention. Therefore, in this study, we retrospectively analyzed the clinical features of AFLP patients for a better understanding. Meanwhile, for the first time, the genetic background associated with the onset of AFLP was discussed by high-throughput sequencing, hoping to provide evidence for genetic counseling and prenatal diagnosis of AFLP.
Thirteen AFLP patients admitted to our hospital and other hospital from March 2012 to February 2020 were selected. Clinical data about general condition, laboratory test, liver biopsy and the prognosis of mother and fetus were collected for retrospective analysis. In addition, the peripheral blood of five patients with AFLP and one newborn infant of his mother with AFLP was sequenced with whole-exome sequencing and gene mutation was analyzed by bioinformatics methods.
The initial symptoms of AFLP varied differently, with jaundice (9/13, 69%), fatigue (8/13, 62%) and nausea and vomiting (6/13, 46%) being the most common. Moreover, the main maternal complications were coagulopathy (13/13, 100%), followed by acute renal dysfunction (10/13, 77%). Raised serum bilirubin, transaminases and uric acid were found in all patients (100%), hypoglycemia was found in six patients (46%) and fatty liver on ultrasound was seen in five patients (5/12, 42%). One (7%) maternal death occurred and all neonates survived delivery. In addition, to our surprise, whole-exome sequencing showed that no gene mutation in related enzymes involved in fatty acid metabolism was noted in the pregnant women and children receiving genetic testing.
Early visit, early detection, early termination of pregnancy and multidisciplinary comprehensive treatment are the key factors to improve the prognosis of AFLP patients and their newborn infants. Furthermore, although limited size of study, to our knowledge, this report is the first to present the lack of common mutation involved in fatty acid oxidation in Chinese patients with AFLP via whole-exome sequencing. Thus, further studies are needed with larger and more varied samples to validate the conclusion.
妊娠急性脂肪肝（AFLP）是一种罕见的急性、潜在致命疾病，通常发生在妊娠晚期。到目前为止，还没有有效的预防措施。因此，在本研究中，我们回顾性分析了 AFLP 患者的临床特征，以便更好地了解。同时，我们首次通过高通量测序探讨了与 AFLP 发病相关的遗传背景，希望为 AFLP 的遗传咨询和产前诊断提供依据。
选择 2012 年 3 月至 2020 年 2 月我院及其他医院收治的 13 例 AFLP 患者，收集一般情况、实验室检查、肝活检及母婴预后等临床资料进行回顾性分析。此外，对 5 例 AFLP 患者及 1 例 AFLP 产妇新生儿的外周血进行全外显子测序，采用生物信息学方法分析基因突变。
AFLP 的首发症状各不相同，以黄疸（9/13，69%）、乏力（8/13，62%）和恶心呕吐（6/13，46%）最常见。此外，主要的母体并发症是凝血功能障碍（13/13，100%），其次是急性肾功能不全（10/13，77%）。所有患者均出现血清胆红素、转氨酶和尿酸升高（100%），6 例（46%）出现低血糖，5 例（5/12，42%）超声提示脂肪肝。1 例（7%）产妇死亡，所有新生儿均存活分娩。此外，令我们惊讶的是，全外显子测序显示接受基因检测的孕妇和儿童未发现与脂肪酸代谢相关的酶的基因突变。
早期就诊、早期发现、早期终止妊娠及多学科综合治疗是改善 AFLP 患者及其新生儿预后的关键因素。此外，尽管本研究样本量较小，但据我们所知，这是首次通过全外显子测序报告中国 AFLP 患者缺乏常见的脂肪酸氧化相关突变。因此，需要进一步研究更大、更多样化的样本以验证这一结论。
