进行性家族性肝内胆汁淤积症3型合并AIH-PBC重叠综合征1例

Type 3 progressive familial intrahepatic cholestasis combined with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome:A case report

背景自身免疫性肝炎(autoimmune hepatitis,AIH)和原发性胆汁性胆管炎(primary biliary cholangitis,PBC)的AIH-PBC重叠综合征在肝病中并非少见,同时合并进行性家族性肝内胆汁淤积症则较为罕见,通常容易造成漏诊.病例简介本例患者因为肝功能异常伴黄疸11年均未能明确诊断.在本院住院期间,AIH-PBC重叠综合征获得确诊.在接受正规治疗后,效果欠佳.给与遗传性肝病基因检测,发现ABCB4基因突变,提示患者同时合并进行性家族性肝内胆汁淤积症3型(progressive familial intrahepatic cholestasis type 3,PFIC3).2020年和2021年,患者先后因为“上消化道出血”又2次入住我院,病情呈现不断加重的趋势.结论对于1例久未获得确诊的肝病患者,通过生化学、血清学、影像学、组织学等检查,明确了AIH-PBC重叠综合征的诊断.但本病例由于脾脏明显肿大,似不能完全以AIH-PBC重叠综合征加以解释,因此对患者进行了遗传性肝病相关的基因检测,发现了ABCB4基因突变,避免了PFIC3的漏诊.

BACKGROUND Autoimmune hepatitis-primary biliary cholangitis(AIH-PBC)overlap syndrome is not uncommon in autoimmune liver disease,but autoimmune liver disease combined with progressive familial intrahepatic cholestasis is relatively rare,which usually makes the diagnosis more complicated and difficult,and thus easily leads to a missed diagnosis and misdiagnosis.CASE SUMMARY A 32-year-old woman complained of“abnormal liver function and jaundice for 11 years”,and was first admitted to our hospital in 2019.She visited different hospitals previously and could not achieve a clear diagnosis.During her first hospitalization in our hospital,a diagnosis of AIH-PBC overlap syndrome was made by the indicators of liver function enzymology,levels of IgG and IgM,autoantibodies related to liver disease,and the pathology of liver biopsy.The patient received the treatment of ursodeoxycholic acid plus glucocorticoid,and her liver function improved but the overall effects were suboptimal.Due to the patient’s significantly enlarged spleen unexplained by AIH-PBC overlap syndrome,she was advised to undergo gene sequencing for the detection of potential genetic liver diseases.The findings showed heterozygous deletion mutations in the ABCB4 gene,suggesting that the patient had type 3 progressive familial intrahepatic cholestasis(PFIC3).In 2020 and 2021,the patient was twice admitted to our hospital because of upper gastrointestinal bleeding.CONCLUSION A clear diagnosis of AIH-PBC overlap syndrome was first made for the patient whose liver disease could not be clearly diagnosed for a long time.Due to the apparent splenomegaly not explained satisfactorily by AIH-PBC overlap syndrome,gene sequencing was permormed,which revealed the presence of ABCB4 gene mutations,resulting in a final diagnosis of PFIC3.