良性肝功能异常的临床意义

韩旭; 李嘉; 熊清芳; 杨永峰

doi:10.12449/JCH240231

良性肝功能异常的临床意义

DOI: 10.12449/JCH240231

韩旭^{1, 2, 3},
李嘉^{1, 3},
熊清芳²,
杨永峰^2, , ,

1.
天津市第二人民医院消化内科，天津 300192
2.
南京中医药大学附属南京医院（南京市第二医院）肝病科，南京 210003
3.
天津肝病研究所，天津 300192

基金项目:

国家自然科学基金 (81970454);

江苏省卫生健康委员会重点科研项目 (ZD2021061)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：韩旭负责资料分析，撰写论文；李嘉、熊清芳参与收集资料，修改论文；杨永峰负责课题设计，拟定写作思路，指导撰写并最后定稿。

详细信息

通信作者:
杨永峰， yangyongfeng@njucm.edu.cn （ORCID： 0000-0002-3214-0038）

计量
- 文章访问数: 340
- HTML全文浏览量: 67
- PDF下载量: 134
- 被引次数: 0
出版历程
- 收稿日期: 2023-06-11
- 录用日期: 2023-07-26
- 出版日期: 2024-02-19

Clinical significance of benign liver function abnormality

Xu HAN^{1, 2, 3},
Jia LI^{1, 3},
Qingfang XIONG²,
Yongfeng YANG^{2
, ,
,}

1.
Department of Gastroenterology，Tianjin Second People’s Hospital，Tianjin 300192，China
2.
Department of Hepatology，Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine/Nanjing Second Hospital，Nanjing 210003，China
3.
Tianjin Institute of Hepatology，Tianjin 300192，China

Research funding:

National Natural Science Foundation of China (81970454);

Key Project of Jiangsu Provincial Health Commission (ZD2021061)

More Information

Corresponding author: YANG Yongfeng， yangyongfeng@njucm.edu.cn （ORCID： 0000-0002-3214-0038）

摘要

摘要: 肝生化指标检测是临床上判断肝功能的重要方法，但肝生化指标异常不完全等同于肝损伤。一些遗传、免疫因素也可引起肝生化指标异常，但预后大多良好。本文归纳了一些良性肝生化指标异常的原因及检测方法，以提醒临床医生拓宽诊治思路，考虑到遗传、免疫等因素，避免误诊误治。
- 肝疾病 /
- 诊断 /
- 肝功能试验
Abstract: Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.
- Liver Diseases /
- Diagnosis /
- Liver Function Tests

HTML全文

参考文献(53)

[1]	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.
[2]	WAGNER KH, SHIELS RG, LANG CA, et al. Diagnostic criteria and contributors to Gilbert’s syndrome[J]. Crit Rev Clin Lab Sci, 2018, 55( 2): 129- 139. DOI: 10.1080/10408363.2018.1428526.
[3]	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.
[4]	KAMAL S, ABDELHAKAM S, GHORABA D, et al. The frequency, clinical course, and health related quality of life in adults with Gilbert’s syndrome: A longitudinal study[J]. BMC Gastroenterol, 2019, 19( 1): 22. DOI: 10.1186/s12876-019-0931-2.
[5]	KING D, ARMSTRONG MJ. Overview of Gilbert’s syndrome[J]. Drug Ther Bull, 2019, 57( 2): 27- 31. DOI: 10.1136/dtb.2018.000028.
[6]	HUANG MJ, CHEN YC, HUANG YY, et al. Effect of UDP-glucuronosyltransferase 1A1 activity on risk for developing Gilbert’s syndrome[J]. Kaohsiung J Med Sci, 2019, 35( 7): 432- 439. DOI: 10.1002/kjm2.12077.
[7]	HAMOUD AR, WEAVER L, STEC DE, et al. Bilirubin in the liver-gut signaling axis[J]. Trends Endocrinol Metab, 2018, 29( 3): 140- 150. DOI: 10.1016/j.tem.2018.01.002.
[8]	INOGUCHI T, SASAKI S, KOBAYASHI K, et al. Relationship between Gilbert syndrome and prevalence of vascular complications in patients with diabetes[J]. JAMA, 2007, 298( 12): 1398- 1400. DOI: 10.1001/jama.298.12.1398-b.
[9]	NANO J, MUKA T, CEPEDA M, et al. Association of circulating total bilirubin with the metabolic syndrome and type 2 diabetes: A systematic review and meta-analysis of observational evidence[J]. Diabetes Metab, 2016, 42( 6): 389- 397. DOI: 10.1016/j.diabet.2016.06.002.
[10]	NOVOTNÝ L, VÍTEK L. Inverse relationship between serum bilirubin and atherosclerosis in men: A meta-analysis of published studies[J]. Exp Biol Med(Maywood), 2003, 228( 5): 568- 571. DOI: 10.1177/15353702-0322805-29.
[11]	RUBINO A, BARBIERI A, PIERRO M. Therapeutic use of Luminal in Crigler-Najjar type icterus[J]. Pediatria(Napoli), 1968, 76( 3): 358- 365.
[12]	KUMAR P, SASMAL G, GUPTA S, et al. Crigler najjar syndrome type 2(CNS type 2): An unwonted cause of jaundice in adults[J]. J Clin Diagn Res, 2017, 11( 7): OD05-OD 06. DOI: 10.7860/JCDR/2017/28195.10221.
[13]	FERNANDES SR, MOURA CM, RODRIGUES B, et al. Acute cholangitis in an old patient with Crigler-Najjar syndrome type II- a case report[J]. BMC Gastroenterol, 2016, 16: 33. DOI: 10.1186/s12876-016-0449-9.
[14]	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.
[15]	GAILITE L, ROTS D, PUKITE I, et al. Case report: Multiple UGT1A1 gene variants in a patient with Crigler-Najjar syndrome[J]. BMC Pediatr, 2018, 18( 1): 317. DOI: 10.1186/s12887-018-1285-6.
[16]	ZHENG BX, HU GR, YU J, et al. Crigler-Najjar syndrome type II in a Chinese boy resulting from three mutations in the bilirubin uridine 5′-diphosphate-glucuronosyltransferase(UGT1A1) gene and a family genetic analysis[J]. BMC Pediatr, 2014, 14: 267. DOI: 10.1186/1471-2431-14-267.
[17]	WU JX, CHENG GY, HUANG J. A homozygous mutation in a Chinese man with Crigler-Najjar syndrome type II and a family genetic analysis[J]. J Dig Dis, 2008, 9( 2): 89- 94. DOI: 10.1111/j.1751-2980.2008.00328.x.
[18]	MARUO Y, OZGENC F, MIMURA Y, et al. Compound heterozygote of a novel missense mutation(p.K402T) and a double missense mutation(p.[G71R;Y486D]) in type II crigler-najjar syndrome[J]. J Pediatr Gastroenterol Nutr, 2011, 52( 3): 362- 365. DOI: 10.1097/MPG.0b013e3181fcafb8.
[19]	YAMAMOTO K, SATO H, FUJIYAMA Y, et al. Contribution of two missense mutations(G71R and Y486D) of the bilirubin UDP glycosyltransferase(UGT1A1) gene to phenotypes of Gilbert’s syndrome and Crigler-Najjar syndrome type II[J]. Biochim Biophys Acta, 1998, 1406( 3): 267- 273. DOI: 10.1016/s0925-4439(98)00013-1.
[20]	CHAUBAL AN, PATEL R, CHOKSI D, et al. Management of pregnancy in Crigler Najjar syndrome type 2[J]. World J Hepatol, 2016, 8( 11): 530- 532. DOI: 10.4254/wjh.v8.i11.530.
[21]	TOH S, WADA M, UCHIUMI T, et al. Genomic structure of the canalicular multispecific organic anion-transporter gene(MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome[J]. Am J Hum Genet, 1999, 64( 3): 739- 746. DOI: 10.1086/302292.
[22]	WU LN, LI YM, SONG Y, et al. A recurrent ABCC2 p.693R mutation resulting in loss of function of MRP2 and hyperbilirubinemia in Dubin-Johnson syndrome in China[J]. Orphanet J Rare Dis, 2020, 15( 1): 74. DOI: 10.1186/s13023-020-1346-4.
[23]	van de STEEG E, STRÁNECKÝ V, HARTMANNOVÁ H, et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver[J]. J Clin Invest, 2012, 122( 2): 519- 528. DOI: 10.1172/JCI59526.
[24]	CORPECHOT C, BARBU V, CHAZOUILLÈRES O, et al. Genetic contribution of ABCC2 to Dubin-Johnson syndrome and inherited cholestatic disorders[J]. Liver Int, 2020, 40( 1): 163- 174. DOI: 10.1111/liv.14260.
[25]	ZHOU DH, QI SP, ZHANG W, et al. Insertion of LINE-1 retrotransposon inducing exon inversion causes a rotor syndrome phenotype[J]. Front Genet, 2019, 10: 1399. DOI: 10.3389/fgene.2019.01399.
[26]	KAGAWA T, OKA A, KOBAYASHI Y, et al. Recessive inheritance of population-specific intronic LINE-1 insertion causes a rotor syndrome phenotype[J]. Hum Mutat, 2015, 36( 3): 327- 332. DOI: 10.1002/humu.22745.
[27]	VITEK L, BELLAROSA C, TIRIBELLI C. Induction of mild hyperbilirubinemia: Hype or real therapeutic opportunity?[J]. Clin Pharmacol Ther, 2019, 106( 3): 568- 575. DOI: 10.1002/cpt.1341.
[28]	DANIELSON ML, SAWADA GA, RAUB TJ, et al. In silico and in vitro assessment of OATP1B1 inhibition in drug discovery[J]. Mol Pharm, 2018, 15( 8): 3060- 3068. DOI: 10.1021/acs.molpharmaceut.8b00168.
[29]	FORTUNATO G, IORIO R, ESPOSITO P, et al. Macroenzyme investigation and monitoring in children with persistent increase of aspartate aminotransferase of unexplained origin[J]. J Pediatr, 1998, 133( 2): 286- 289. DOI: 10.1016/s0022-3476(98)70238-0.
[30]	CHTIOUI H, MAUERHOFER O, GÜNTHER B, et al. Macro-AST in an asymptomatic young patient[J]. Ann Hepatol, 2010, 9( 1): 93- 95. DOI: 10.1016/s1665-2681(19)31687-4.
[31]	LORD R, FAHIE-WILSON M, SURI S. A paediatric case of macro aspartate aminotransferase[J]. Ann Clin Biochem, 2008, 45( 3): 323- 324. DOI: 10.1258/acb.2007.007094.
[32]	KONTTINEN A, MURROS J, OJALA K, et al. A new cause of increased serum aspartate aminotransferase activity[J]. Clin Chim Acta, 1978, 84( 1-2): 145- 147. DOI: 10.1016/0009-8981(78)90487-4.
[33]	TRIESTER SL, DOUGLAS DD. Development of macro-aspartate aminotransferase in a patient undergoing specific allergen injection immunotherapy[J]. Am J Gastroenterol, 2005, 100( 1): 243- 245. DOI: 10.1111/j.1572-0241.2005.41284.x.
[34]	KULECKA M, WIERZBICKA A, PAZIEWSKA A, et al. A heterozygous mutation in GOT1 is associated with familial macro-aspartate aminotransferase[J]. J Hepatol, 2017, 67( 5): 1026- 1030. DOI: 10.1016/j.jhep.2017.07.003.
[35]	CASTIELLA A, AGUAYO FJ, RUEDA M, et al. Macroaspartate aminotransferase(Macro-AST) a rare cause of hipertransaminasemia: Another way to diagnosis?[J]. J Clin Gastroenterol, 2006, 40( 7): 655. DOI: 10.1097/00004836-200608000-00024.
[36]	CAROPRESO M, FORTUNATO G, LENTA S, et al. Prevalence and long-term course of macro-aspartate aminotransferase in children[J]. J Pediatr, 2009, 154( 5): 744- 748. DOI: 10.1016/j.jpeds.2008.11.010.
[37]	WERNER T, VARGAS HE, CHALASANI N. Macro-aspartate aminotransferase and monoclonal gammopathy: A review of two cases[J]. Dig Dis Sci, 2007, 52( 5): 1197- 1198. DOI: 10.1007/s10620-006-9555-9.
[38]	CABRERA-ABREU J, JAIN R, ROBINSON P, et al. A case of aspartate aminotransferase macroenzyme[J]. Ann Clin Biochem, 2008, 45( Pt 3): 320- 322. DOI: 10.1258/acb.2007.007063.
[39]	SHAH-KHAN SM, HSUEH W, REYNOLDS GJ. An 8-year history of increased level of aspartate aminotransferase[J]. Gastroenterology, 2019, 157( 2): 318- 319. DOI: 10.1053/j.gastro.2018.11.079.
[40]	MCTAGGART MP, RAWSON C, LAWRENCE D, et al. Identification of a macro-alkaline phosphatase complex in a patient with inflammatory bowel disease[J]. Ann Clin Biochem, 2012, 49( Pt 4): 405- 407. DOI: 10.1258/acb.2011.011224.
[41]	KLONOFF DC. Macroamylasemia and other immunoglobulin-complexed enzyme disorders[J]. West J Med, 1980, 133( 5): 392- 407.
[42]	CERVINSKI MA, LEE HK, MARTIN IW, et al. A macro-enzyme cause of an isolated increase of alkaline phosphatase[J]. Clin Chim Acta, 2015, 440: 169- 171. DOI: 10.1016/j.cca.2014.11.017.
[43]	WATANABE M, KITAHORA T, AISO S, et al. A case of ulcerative colitis associated with alkaline phosphatase(ALP)-and lactate dehydrogenase(LDH)-binding immunoglobulins[J]. Nihon Shokakibyo Gakkai Zasshi, 1984, 81( 6): 1468- 1473.
[44]	KUNUTSOR SK. Gamma-glutamyltransferase-friend or foe within?[J]. Liver Int, 2016, 36( 12): 1723- 1734. DOI: 10.1111/liv.13221.
[45]	de GRANDI A, FRANZINI M, ROSIPAL Š, et al. Highly elevated plasma γ-glutamyltransferase elevations: A trait caused by γ-glutamyltransferase 1 transmembrane mutations[J]. Hepatology, 2020, 71( 3): 1124- 1127. DOI: 10.1002/hep.30944.
[46]	FRANZINI M, FORNACIARI I, FIERABRACCI V, et al. Accuracy of b-GGT fraction for the diagnosis of non-alcoholic fatty liver disease[J]. Liver Int, 2012, 32( 4): 629- 634. DOI: 10.1111/j.1478-3231.2011.02673.x.
[47]	FORNACIARI I, FIERABRACCI V, CORTI A, et al. Gamma-glutamyltransferase fractions in human plasma and bile: Characteristic and biogenesis[J]. PLoS One, 2014, 9( 2): e88532. DOI: 10.1371/journal.pone.0088532.
[48]	VAZ FM, PAULUSMA CC, HUIDEKOPER H, et al. Sodium taurocholate cotransporting polypeptide(SLC10A1) deficiency: Conjugated hypercholanemia without a clear clinical phenotype[J]. Hepatology, 2015, 61( 1): 260- 267. DOI: 10.1002/hep.27240.
[49]	ERLINGER S. NTCP deficiency: A new inherited disease of bile acid transport[J]. Clin Res Hepatol Gastroenterol, 2015, 39( 1): 7- 8. DOI: 10.1016/j.clinre.2014.07.011.
[50]	GÄLMAN C, ANGELIN B, RUDLING M. Pronounced variation in bile acid synthesis in humans is related to gender, hypertriglyceridaemia and circulating levels of fibroblast growth factor 19[J]. J Intern Med, 2011, 270( 6): 580- 588. DOI: 10.1111/j.1365-2796.2011.02466.x.
[51]	DENG LJ, OUYANG WX, LIU R, et al. Clinical characterization of NTCP deficiency in paediatric patients: A case-control study based on SLC10A1 genotyping analysis[J]. Liver Int, 2021, 41( 11): 2720- 2728. DOI: 10.1111/liv.15031.
[52]	ROSENMAN KD, GUSS PS. Prevalence of congenital deficiency in serum cholinesterase[J]. Arch Environ Health, 1997, 52( 1): 42- 44. DOI: 10.1080/00039899709603798.
[53]	BRAZZOLOTTO X, COURCELLE S, SAUVANET C, et al. Characterization of four BCHE mutations associated with prolonged effect of suxamethonium[J]. Pharmacogenomics J, 2021, 21( 2): 165- 173. DOI: 10.1038/s41397-020-00192-7.