Etiological spectrum and clinical features of patients with unexplained liver disease manifesting as isolated jaundice: An analysis of 91 cases

Yufeng ZHENG; Xulei ZHANG; Yuhang WENG; Yongfeng YANG

doi:10.3969/j.issn.1001-5256.2023.05.016

Volume 39 Issue 5

May 2023

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2023 > 39(5): 1105-1109

PDF( 1926 KB)

Etiological spectrum and clinical features of patients with unexplained liver disease manifesting as isolated jaundice: An analysis of 91 cases

DOI: 10.3969/j.issn.1001-5256.2023.05.016

Department of Hepatology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine & Nanjing Second Hospital, Nanjing 210003, China

Research funding:

General Project of National Natural Science Foundation of China (81970454);

Jiangsu Provincial Commission of Health Key Scientific Research Project (ZD2021061)

More Information

Corresponding author: YANG Yongfeng, yangyongfeng@njucm.edu.cn (ORCID: 0000-0002-0942-4833)
Received Date: 2022-11-15
Accepted Date: 2022-12-15
Published Date: 2023-05-20

Abstract

Abstract

Objective To investigate the etiological and clinical features of patients with unexplained liver disease manifesting as isolated jaundice and the value of whole-exome sequencing in the diagnosis of such diseases. Methods A retrospective analysis was performed for the clinical data of the patients who attended Nanjing Second Hospital due to unexplained liver disease and underwent whole-exome sequencing from February 2017 to December 2021, and according to liver function parameters and imaging data, all cases were classified based on clinical phenotype and were diagnosed based on the whole-exome sequencing report. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. Results A total of 519 patients underwent whole-exome sequencing, among whom 102 patients with missing or incomplete clinical data were excluded, and finally 417 patients were included in analysis, among whom 91(91/417, 21.82%) had the manifestation of isolated jaundice. The etiology of jaundice was not determined by whole-exome sequencing in 8 patients (8/91, 8.79%). With reference to genetic testing results, 83 patients (83/91, 91.21%) had a confirmed diagnosis, among whom there were 68 patients with hereditary hyperbilirubinemia (68/91, 74.72%), 3 patients with hereditary spherocytosis (3/91, 3.30%), 2 patients with pyruvate kinase deficiency (2/91, 2.20%), and 10 patients with UGT1A1 gene disease combined with other diseases (10/91, 10.99%). Hereditary hyperbilirubinemia was the main etiology, and there were 61 patients with UGT1A1 gene disease (61/91, 67.03%), 5 patients with Dubin-Johnson syndrome (5/91, 5.49%) and 2 patients with Rotor syndrome (2/91, 2.20%). There was a significant difference in indirect bilirubin/total bilirubin ratio between the patients with the different diagnoses above (H=22.835, P < 0.05), and the patients with UGT1A1 gene disease and other diseases had a significantly higher level of total bilirubin than those with UGT1A1 gene disease alone [95.8 (37.5-187.1) μmol/L vs 51.4 (34.8-267.1) μmol/L, Z=-2.372, P=0.018]. Conclusion Whole-exome sequencing can help with the diagnosis of most cases of unexplained liver disease manifesting as isolated jaundice. Hereditary hyperbilirubinemia is the main etiology, and UGT1A1 gene disease is the most common disease. Whole-exome sequencing can assist the clinical diagnosis of unexplained liver disease manifesting as isolated jaundice.
- Liver Diseases,
- Jaundice,
- Diagnosis,
- Exome

FullText(HTML)

References(11)

References

[1]	YANG YF. Road map of diagnosis in patients with unknown causes[J]. J Prac Hepatol, 2018, 21(1): 1-3. DOI: 10.3969/j.issn.1672-5069.2018.01.001. 杨永峰. 不明原因肝病诊断思路[J]. 实用肝脏病杂志, 2018, 21(1): 1-3. DOI: 10.3969/j.issn.1672-5069.2018.01.001.
[2]	MEMON N, WEINBERGER BI, HEGYI T, et al. Inherited disorders of bilirubin clearance[J]. Pediatr Res, 2016, 79(3): 378-386. DOI: 10.1038/pr.2015.247.
[3]	STRASSBURG CP. Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome)[J]. Best Pract Res Clin Gastroenterol, 2010, 24(5): 555-571. DOI: 10.1016/j.bpg.2010.07.007.
[4]	MARUO Y, BEHNAM M, IKUSHIRO S, et al. Two different UGT1A1 mutations causing Crigler-Najjar syndrome types I and Ⅱ in an Iranian family[J]. J Gastrointestin Liver Dis, 2015, 24(4): 523-526. DOI: 10.15403/jgld.2014.1121.244.ugt.
[5]	BAI J, ZHENG SJ, DUAN ZP. Clinical features and diagnosis of four common types of congenital hyperbilirubinemia[J]. J Clin Hepatol, 2019, 35(8): 1680-1683. DOI: 10.3969/j.issn.1001-5256.2019.08.005. 白洁, 郑素军, 段钟平. 4种常见先天性高胆红素血症的临床特征及诊断思路[J]. 临床肝胆病杂志, 2019, 35(8): 1680-1683. DOI: 10.3969/j.issn.1001-5256.2019.08.005.
[6]	DHAWAN A, LAWLOR MW, MAZARIEGOS GV, et al. Disease burden of Crigler-Najjar syndrome: Systematic review and future perspectives[J]. J Gastroenterol Hepatol, 2020, 35(4): 530-543. DOI: 10.1111/jgh.14853.
[7]	KRINGEN MK, PIEHLER AP, GRIMHOLT RM, et al. Serum bilirubin concentration in healthy adult North-Europeans is strictly controlled by the UGT1A1 TA-repeat variants[J]. PLoS One, 2014, 9(2): e90248. DOI: 10.1371/journal.pone.0090248.
[8]	ERLINGER S, ARIAS IM, DHUMEAUX D. Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences[J]. Gastroenterology, 2014, 146(7): 1625-1638. DOI: 10.1053/j.gastro.2014.03.047.
[9]	CHRISTOFORIDOU A, FASOULAKIS Z, KONTOMANOLIS EN. Diagnosis and management of congenital dyserythropoietic anaemia Type Ⅱ in a secundigravida[J]. Cureus, 2017, 9(10): e1811. DOI: 10.7759/cureus.1811.
[10]	BERGMANN C, GUAY-WOODFORD LM, HARRIS PC, et al. Polycystic kidney disease[J]. Nat Rev Dis Primers, 2018, 4(1): 50. DOI: 10.1038/s41572-018-0047-y.
[11]	BOTSTEIN D, RISCH N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease[J]. Nat Genet, 2003, 33 Suppl: 228-237. DOI: 10.1038/ng1090.

Relative Articles

[1]	Branch of Gastrointestinal Diseases， China Association of Chinese Medicine. Expert consensus on Traditional Chinese Medicine diagnosis and treatment of jaundice（2023）[J]. Journal of Clinical Hepatology, 2024, 40(10): 1959-1966. doi: 10.12449/JCH241006
[2]	Yangqing MA, Haina FAN, Xin SUN, Chenghai LIU. Role of Golgi protein 73(GP73) in diagnosis of chronic liver diseases[J]. Journal of Clinical Hepatology, 2023, 39(8): 1999-2004. doi: 10.3969/j.issn.1001-5256.2023.08.035
[3]	Zeshan CHEN, Bin WEN, Peirong QIU, Hongni LAN, Baote HUANG, Xin DENG. Role of microRNA-122 in the development, progression, and diagnosis of liver disease[J]. Journal of Clinical Hepatology, 2021, 37(7): 1724-1728. doi: 10.3969/j.issn.1001-5256.2021.07.052
[4]	Xiaoqin ZHENG, Li LI, Hua JIN, Chunyan GOU, Xiaojun WANG. Clinical features of hyperthyroidism with severe jaundice: An analysis of seven cases[J]. Journal of Clinical Hepatology, 2021, 37(6): 1409-1412. doi: 10.3969/j.issn.1001-5256.2021.06.036
[5]	Wang JiangBin. Association between inflammatory bowel disease and chronic liver diseases and related management strategies[J]. Journal of Clinical Hepatology, 2020, 36(7): 1444-1449. doi: 10.3969/j.issn.1001-5256.2020.07.002
[6]	Xu Shuai, Zhang LiPing. Research advances in the role of exosomes in non-neoplastic liver diseases[J]. Journal of Clinical Hepatology, 2020, 36(4): 940-943. doi: 10.3969/j.issn.1001-5256.2020.04.052
[7]	Zhang Jie, Zheng SuJun. Clinical features and differential diagnosis of hemolytic jaundice[J]. Journal of Clinical Hepatology, 2020, 36(6): 1423-1427. doi: 10.3969/j.issn.1001-5256.2020.06.052
[8]	Chen ShuRu, Chong YuTian, Li XinHua. Pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism[J]. Journal of Clinical Hepatology, 2019, 35(8): 1667-1672. doi: 10.3969/j.issn.1001-5256.2019.08.003
[9]	Gao LuHua, Nie QingHe, Zhao XiTai. A case of jaundice of unknown origin[J]. Journal of Clinical Hepatology, 2019, 35(4): 854-857. doi: 10.3969/j.issn.1001-5256.2019.04.029
[10]	Zheng YiShan. Early diagnosis of liver disease during pregnancy should be taken seriously[J]. Journal of Clinical Hepatology, 2019, 35(7): 1435-1438. doi: 10.3969/j.issn.1001-5256.2019.07.005
[11]	Wu DongBo, Chen EnQiang, Bai Lang, Tang Hong. Liver biopsy and related techniques in pathological diagnosis[J]. Journal of Clinical Hepatology, 2018, 34(11): 2295-2299. doi: 10.3969/j.issn.1001-5256.2018.11.006
[12]	Yang YuYing, Wang XinHui, Wan Gang, Meng PeiPei, Zhou Yang, Wu Tong, Hou YiXin, Yu Hao, Jiang TingTing, Jiang YuYong. Clinical features of liver injury associated with acute Epstein-Barr virus infection in adults: an analysis of 115 cases[J]. Journal of Clinical Hepatology, 2017, 33(6): 1141-1144. doi: 10.3969/j.issn.1001-5256.2017.06.025
[13]	Zhang XiaoTong, Guo LiPing. Value of ultrasonic elastography in diagnosis of liver diseases[J]. Journal of Clinical Hepatology, 2016, 32(11): 2210-2213. doi: 10.3969/j.issn.1001-5256.2016.11.048
[14]	Chen Juan, Yin HuaBin. Main applications of diffusion-weighted magnetic resonance imaging in liver diseases[J]. Journal of Clinical Hepatology, 2015, 31(1): 139-142. doi: 10.3969/j.issn.1001-5256.2015.01.032
[15]	Zhang Kai, Chen Hong, Lu MingXia, Wang FeiFei, Wan Hui, Zhang LiTing. One case of adult Still's disease with fever and jaundice as main clinical manifestations[J]. Journal of Clinical Hepatology, 2014, 30(6): 567-568. doi: 10.3969/j.issn.1001-5256.2014.06.023
[16]	Peng XiaoFang, Liu HaiYing. Research advances in circulating miRNAs for diagnosis of hepatobiliary diseases[J]. Journal of Clinical Hepatology, 2014, 30(9): 965-968. doi: 10.3969/j.issn.1001-5256.2014.09.032
[17]	Chen Qian, Wen XiaoYu, Pan Yu. Jaundice due to hepatic syphilis: A case report[J]. Journal of Clinical Hepatology, 2013, 29(4): 303-304.
[18]	Bao XuLi, Tian Zhou, Chen QingFeng, Li Li, Zhang Lei, Lu: Jun. One case of primary hepatic amyloidosis characterized by jaundice[J]. Journal of Clinical Hepatology, 2013, 29(12): 943-944. doi: 10.3969/j.issn.1001-5256.2013.12.018

Supplements(0)

Cited By

Cited by

Periodical cited type(3)

1.	贺世超，王瑜，朱斌. 急性病毒性肝炎患者心电图异常相关因素及其对预后的预测价值. 临床误诊误治. 2024(04): 24-28+41 .
2.	李纾绮，陈美娅，宋阳，周飞，陈二妹，陈立刚，周静平. 94例不明原因肝损伤患者肝穿刺病理诊断与临床特征分析. 临床肝胆病杂志. 2024(05): 997-1002 . 本站查看
3.	蒯钰，朱会，唐笠，黄宇，朱道娟，朱书瑶，罗泽民，陈艾，熊复. 婴儿期Dubin-Johnson综合征：1例报道并文献复习. 胃肠病学和肝病学杂志. 2024(06): 789-792 .

Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(1) / Tables(4)

Get Citation

PDF

XML

Article Metrics

Article views (602) PDF downloads(84)

Etiological spectrum and clinical features of patients with unexplained liver disease manifesting as isolated jaundice: An analysis of 91 cases

DOI: 10.3969/j.issn.1001-5256.2023.05.016