Objective: To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods: Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results: Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion: The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.
目的： 探讨成人ABCB4基因变异相关的胆汁淤积性肝病患者的临床表现、病理特征及其基因突变特点。 方法： 将2010年5月至2022年12月在解放军总医院第五医学中心肝病医学部住院的8例成人ABCB4基因变异相关的胆汁淤积性肝病患者纳入研究，分析其临床表现、病理特征、基因突变特点及其预后情况，应用全外显子二代测序对患者进行基因检测并进行生物学信息分析。采用SPSS 19.0软件进行描述性分析。 结果： 8例成人ABCB4基因变异患者中男3例，女5例，发病中位年龄24（20，37）岁。ABCB4复合杂合突变3例，临床表型包括进行性家族性肝内胆汁淤积症3型2例，妊娠肝内胆汁淤积症重叠低磷脂相关胆石综合征1例；ABCB4单杂合突变5例，临床表型包括妊娠肝内胆汁淤积症重叠药物性肝损伤2例，低磷脂相关胆石综合征3例。8例患者影像学均提示肝纤维化，6例已达肝硬化。所有患者均进行肝组织病理学检查，主要表现为胆汁淤积8例、汇管区纤维化8例、小胆管增生7例、铜沉积3例，肝硬化5例。ABCB4筛查发现了11种不同的突变，包括新突变8种，经致病性评估，c.2394+82C>T（intron）为良性突变，其余为有害突变。所有患者均用熊去氧胆酸治疗，随访中位时间7.5（0.5，12.7）年。1例因终末期肝病死亡，2例胆汁淤积肝硬化进展，5例病情稳定。 结论： 成人ABCB4基因变异相关的胆汁淤积性肝病以单杂合突变为主，临床表型多样，多有重叠，携带无功能突变者病情偏重。.