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学龄期儿童胆汁淤积性肝病的病因研究进展
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Abstract:
胆汁淤积性肝病(Cholestatic Liver Disease, CLD)在中国儿童群体中是导致肝病住院的主要原因之一,其复杂的病因学特征使得准确区分不同病因颇具挑战。鉴于不同病因引发的CLD具有迥异的临床进程和预后效果,早期识别病因对于制定临床诊断策略和预测疾病进展至关重要。本文针对学龄期儿童胆汁淤积性肝病的致病因素进行了全面梳理,同时引入现阶段相关研究的新动向,以期为临床实践提供科学依据,从而制定出更具针对性的干预策略,进而优化患儿的预后管理。
Cholestatic liver disease (CLD) is one of the main causes of liver disease hospitalization in Chinese children. Its complex etiological characteristics make it challenging to accurately distinguish different causes. Given that CLD caused by different etiologies has distinct clinical courses and prognoses, early identification of the cause is crucial for formulating clinical diagnostic strategies and predicting disease progression. This article comprehensively reviews the pathogenic factors of CLD in school-aged children and introduces the latest research trends in this field to provide a scientific basis for clinical practice, thereby formulating more targeted intervention strategies and optimizing the prognosis management of affected children.
[1] | 中华医学会肝病学分会. 胆汁淤积性肝病管理指南(2021) [J]. 中华肝脏病杂志, 2022, 30(3): 253-263. |
[2] | European Association for the Study of the Liver (2009) EASL Clinical Practice Guidelines: Management of Cholestatic Liver Diseases. Journal of Hepatology, 51, 237-267. https://doi.org/10.1016/j.jhep.2009.04.009 |
[3] | Björnsson, E.S., Bergmann, O.M., Björnsson, H.K., Kvaran, R.B. and Olafsson, S. (2013) Incidence, Presentation, and Outcomes in Patients with Drug-Induced Liver Injury in the General Population of Iceland. Gastroenterology, 144, 1419-1425.e3. https://doi.org/10.1053/j.gastro.2013.02.006 |
[4] | Fontana, R.J., Watkins, P.B., Bonkovsky, H.L., Chalasani, N., Davern, T., Serrano, J., et al. (2009) Drug-Induced Liver Injury Network (DILIN) Prospective Study. Drug Safety, 32, 55-68. https://doi.org/10.2165/00002018-200932010-00005 |
[5] | Chalasani, N.P., Hayashi, P.H., Bonkovsky, H.L., Navarro, V.J., Lee, W.M. and Fontana, R.J. (2014) ACG Clinical Guideline: The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. American Journal of Gastroenterology, 109, 950-966. https://doi.org/10.1038/ajg.2014.131 |
[6] | Devarbhavi, H. (2012) An Update on Drug-Induced Liver Injury. Journal of Clinical and Experimental Hepatology, 2, 247-259. https://doi.org/10.1016/j.jceh.2012.05.002 |
[7] | Hunt, C.M., Yuen, N.A., Stirnadel-Farrant, H.A. and Suzuki, A. (2014) Age-Related Differences in Reporting of Drug-Associated Liver Injury: Data-Mining of WHO Safety Report Database. Regulatory Toxicology and Pharmacology, 70, 519-526. https://doi.org/10.1016/j.yrtph.2014.09.007 |
[8] | 朱世殊, 董漪, 徐志强, 等. 2001-2010年儿童非病毒性肝病谱分析[J]. 传染病信息, 2011, 24(5): 279-281, 285. |
[9] | 甘雨, 张敏, 朱世殊, 等. 2011-2017年单中心儿童非病毒性肝病谱分析[J]. 传染病信息, 2019, 32(2): 109-112, 135. |
[10] | Andrade, R.J., Aithal, G.P., Björnsson, E.S., Kaplowitz, N., Kullak-Ublick, G.A., Larrey, D., et al. (2019) EASL Clinical Practice Guidelines: Drug-Induced Liver Injury. Journal of Hepatology, 70, 1222-1261. https://doi.org/10.1016/j.jhep.2019.02.014 |
[11] | Chalasani, N.P., Maddur, H., Russo, M.W., Wong, R.J. and Reddy, K.R. (2021) ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. American Journal of Gastroenterology, 116, 878-898. https://doi.org/10.14309/ajg.0000000000001259 |
[12] | Devarbhavi, H., Aithal, G., Treeprasertsuk, S., Takikawa, H., Mao, Y., Shasthry, S.M., et al. (2021) Drug-Induced Liver Injury: Asia Pacific Association of Study of Liver Consensus Guidelines. Hepatology International, 15, 258-282. https://doi.org/10.1007/s12072-021-10144-3 |
[13] | 中华医学会肝病学分会药物性肝病学组. 药物性肝损伤诊治指南[J]. 中华肝脏病杂志, 2015, 23(11): 810-820. |
[14] | Hoofnagle, J.H. and Björnsson, E.S. (2019) Drug-Induced Liver Injury—Types and Phenotypes. New England Journal of Medicine, 381, 264-273. https://doi.org/10.1056/nejmra1816149 |
[15] | 李学娟, 陈泽彬, 邱宝明, 等. 388例儿童药品不良反应回顾性分析[J]. 中国医院药学杂志, 2016, 36(8): 662-666. |
[16] | DiPaola, F., Molleston, J.P., Gu, J., Cirulli, E.T., Chalasani, N., Barnhart, H., et al. (2019) Antimicrobials and Antiepileptics Are the Leading Causes of Idiosyncratic Drug-Induced Liver Injury in American Children. Journal of Pediatric Gastroenterology and Nutrition, 69, 152-159. https://doi.org/10.1097/mpg.0000000000002383 |
[17] | 郑新, 卢雄才, 秦小莲, 等. 我国2007-2016年儿童药物性肝损伤文献分析[J]. 中国药房, 2017, 28(32): 4507-4510. |
[18] | Ibrahim, S., Dayoub, R., Krautbauer, S., Liebisch, G., Wege, A.K., Melter, M., et al. (2019) Bile Acid-Induced Apoptosis and Bile Acid Synthesis Are Reduced by Over-Expression of Augmenter of Liver Regeneration (ALR) in a STAT3-Dependent Mechanism. Experimental Cell Research, 374, 189-197. https://doi.org/10.1016/j.yexcr.2018.11.023 |
[19] | Norman, B.H. (2020) Drug Induced Liver Injury (DILI). Mechanisms and Medicinal Chemistry Avoidance/Mitigation Strategies. Journal of Medicinal Chemistry, 63, 11397-11419. https://doi.org/10.1021/acs.jmedchem.0c00524 |
[20] | 耿文静, 刘晖, 丁惠国. 药物性肝损伤的潜在机制、病理特点及生物标志物[J]. 临床肝胆病杂志, 2019, 35(4): 925-929. |
[21] | DiPaola, F. and Molleston, J.P. (2018) Drug-Induced Liver Injury in Children. Current Hepatology Reports, 17, 283-291. https://doi.org/10.1007/s11901-018-0413-y |
[22] | Devarbhavi, H. and Andrade, R. (2014) Drug-Induced Liver Injury Due to Antimicrobials, Central Nervous System Agents, and Nonsteroidal Anti-Inflammatory Drugs. Seminars in Liver Disease, 34, 145-161. https://doi.org/10.1055/s-0034-1375956 |
[23] | Nakaharai, K., Sakamoto, Y., Yaita, K., Yoshimura, Y., Igarashi, S. and Tachikawa, N. (2016) Drug-Induced Liver Injury Associated with High-Dose Ceftriaxone: A Retrospective Cohort Study Adjusted for the Propensity Score. European Journal of Clinical Pharmacology, 72, 1003-1011. https://doi.org/10.1007/s00228-016-2064-7 |
[24] | Crerar-Gilbert, A., Boots, R., Fraenkel, D. and Macdonald, G.A. (1999) Survival Following Fulminant Hepatic Failure from Fluconazole Induced Hepatitis. Anaesthesia and Intensive Care, 27, 650-653. https://doi.org/10.1177/0310057x9902700616 |
[25] | Gayam, V., Khalid, M., Dahal, S., Garlapati, P. and Gill, A. (2018) Hyperacute Liver Injury Following Intravenous Fluconazole: A Rare Case of Dose-Independent Hepatotoxicity. Journal of Family Medicine and Primary Care, 7, 451-454. https://doi.org/10.4103/jfmpc.jfmpc_330_17 |
[26] | Wen, Y., Guo, J., Lv, L. and Qi, X. (2018) A Case of Acute Liver Failure Caused by Fluconazole. China Pharmacist, 21, 882-883. |
[27] | Wang, P., Pradhan, K., Zhong, X. and Ma, X. (2016) Isoniazid Metabolism and Hepatotoxicity. Acta Pharmaceutica Sinica B, 6, 384-392. https://doi.org/10.1016/j.apsb.2016.07.014 |
[28] | Centers for Disease Control and Prevention (2010) Severe Isoniazid-Associated Liver Injuries among Persons Being Treated for Latent Tuberculosis Infection—United States, 2004-2008. Morbidity and Mortality Weekly Report, 59, 224-229. |
[29] | Devarbhavi, H., Karanth, D., Prasanna, K.S., Adarsh, C.K. and Mallikarjun, P. (2011) Drug-Induced Liver Injury with Hypersensitivity Features Has a Better Outcome: A Single-Center Experience of 39 Children and Adolescents. Hepatology, 54, 1344-1350. https://doi.org/10.1002/hep.24527 |
[30] | Metushi, I.G., Cai, P., Zhu, X., Nakagawa, T. and Uetrecht, J.P. (2011) A Fresh Look at the Mechanism of Isoniazid-Induced Hepatotoxicity. Clinical Pharmacology & Therapeutics, 89, 911-914. https://doi.org/10.1038/clpt.2010.355 |
[31] | Wang, Y. and Bao, J. (2019) Research Progress on the Pathogenesis of Isoniazid Induced Liver Injury. Journal of Pharmacy Practice, 37, 289-293. |
[32] | Thatishetty, A.V., Agresti, N. and O’Brien, C.B. (2013) Chemotherapy-Induced Hepatotoxicity. Clinics in Liver Disease, 17, 671-686. https://doi.org/10.1016/j.cld.2013.07.010 |
[33] | (2012) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. |
[34] | Stewart, J.D., Horvath, R., Baruffini, E., Ferrero, I., Bulst, S., Watkins, P.B., et al. (2010) Polymerase γ GenePOLGDetermines the Risk of Sodium Valproate-Induced Liver Toxicity. Hepatology, 52, 1791-1796. https://doi.org/10.1002/hep.23891 |
[35] | Bűdi, T., Tóth, K., Nagy, A., Szever, Z., Kiss, Á., Temesvári, M., et al. (2015) Clinical Significance of CYP2C9-Status Guided Valproic Acid Therapy in Children. Epilepsia, 56, 849-855. https://doi.org/10.1111/epi.13011 |
[36] | Zhu, M., Li, H., Shi, L., Chen, X., Luo, J. and Zhang, Z. (2017) The Pharmacogenomics of Valproic Acid. Journal of Human Genetics, 62, 1009-1014. https://doi.org/10.1038/jhg.2017.91 |
[37] | Russell, S. (2007) Carnitine as an Antidote for Acute Valproate Toxicity in Children. Current Opinion in Pediatrics, 19, 206-210. https://doi.org/10.1097/mop.0b013e32805e879a |
[38] | Lheureux, P.E.R. and Hantson, P. (2009) Carnitine in the Treatment of Valproic Acid-Induced Toxicity. Clinical Toxicology, 47, 101-111. https://doi.org/10.1080/15563650902752376 |
[39] | Price, K.E., Pearce, R.E., Garg, U.C., Heese, B.A., Smith, L.D., Sullivan, J.E., et al. (2011) Effects of Valproic Acid on Organic Acid Metabolism in Children: A Metabolic Profiling Study. Clinical Pharmacology & Therapeutics, 89, 867-874. https://doi.org/10.1038/clpt.2011.47 |
[40] | 侯鹏鹏. 药物性肝炎研究进展[J]. 医学理论与实践, 2008, 21(8): 899-900. |
[41] | Chidiac, A.S., Buckley, N.A., Noghrehchi, F. and Cairns, R. (2023) Paracetamol (Acetaminophen) Overdose and Hepatotoxicity: Mechanism, Treatment, Prevention Measures, and Estimates of Burden of Disease. Expert Opinion on Drug Metabolism & Toxicology, 19, 297-317. https://doi.org/10.1080/17425255.2023.2223959 |
[42] | 吴宇宇. 485例药物性肝损伤的临床特征分析[D]: [硕士学位论文]. 沈阳: 中国医科大学, 2019. |
[43] | 沈丽霞, 吴婧, 王新敏, 等. 某院2016年至2020年保肝药临床应用分析[J]. 中国药业, 2023, 32(4): 19-22. |
[44] | 黄影, 邓秋云, 蒋俊俊. 广西1-14岁儿童乙型肝炎病毒感染状况和影响因素分析[J]. 内科, 2023, 18(2): 121-126. |
[45] | Tseng, Y., Wu, J., Kong, M., Hu, F., Yang, Y., Yeung, C., et al. (2014) Infantile Hepatitis B in Immunized Children: Risk for Fulminant Hepatitis and Long-Term Outcomes. PLOS ONE, 9, e111825. https://doi.org/10.1371/journal.pone.0111825 |
[46] | McMahon, B.J. (2009) The Natural History of Chronic Hepatitis B Virus Infection. Hepatology, 49, S45-S55. https://doi.org/10.1002/hep.22898 |
[47] | Nguyen, V.T.T., Law, M.G. and Dore, G.J. (2009) Hepatitis B‐Related Hepatocellular Carcinoma: Epidemiological Characteristics and Disease Burden. Journal of Viral Hepatitis, 16, 453-463. https://doi.org/10.1111/j.1365-2893.2009.01117.x |
[48] | Sun, Y., Lei, X., Sai, Y., Chen, J., Sun, Y. and Gao, X. (2016) Relationship between Genotypes and Clinical Manifestation, Pathology, and cccDNA in Chinese Children with Hepatitis B Virus-Associated Glomerulonephritis. World Journal of Pediatrics, 12, 347-352. https://doi.org/10.1007/s12519-016-0015-0 |
[49] | Arnone, O.C., Serranti, D., Bartolini, E., Mastrangelo, G., Stinco, M., Trapani, S., et al. (2020) Chronic Hepatitis B in Children, Report of a Single-Centre Longitudinal Study on 152 Children. Journal of Viral Hepatitis, 27, 1344-1351. https://doi.org/10.1111/jvh.13382 |
[50] | Lampertico, P., Agarwal, K., Berg, T., Buti, M., Janssen, H.L.A., Papatheodoridis, G., et al. (2017) EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection. Journal of Hepatology, 67, 370-398. https://doi.org/10.1016/j.jhep.2017.03.021 |
[51] | World Health Organization (2015) Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. |
[52] | Indolfi, G., Easterbrook, P., Dusheiko, G., Siberry, G., Chang, M., Thorne, C., et al. (2019) Hepatitis B Virus Infection in Children and Adolescents. The Lancet Gastroenterology & Hepatology, 4, 466-476. https://doi.org/10.1016/s2468-1253(19)30042-1 |
[53] | Jonas, M.M., Lok, A.S.F., McMahon, B.J., Brown, R.S., Wong, J.B., Ahmed, A.T., et al. (2016) Antiviral Therapy in Management of Chronic Hepatitis B Viral Infection in Children: A Systematic Review and Meta-Analysis. Hepatology, 63, 307-318. https://doi.org/10.1002/hep.28278 |
[54] | Sokal, E.M., Paganelli, M., Wirth, S., Socha, P., Vajro, P., Lacaille, F., et al. (2013) Management of Chronic Hepatitis B in Childhood: ESPGHAN Clinical Practice Guidelines. Journal of Hepatology, 59, 814-829. https://doi.org/10.1016/j.jhep.2013.05.016 |
[55] | Terrault, N.A., Lok, A.S.F., McMahon, B.J., Chang, K.M., Hwang, J.P., Jonas, M.M., Brown Jr., R.S., Bzowej, N.H., Wong, J.B. (2018) Up-Date on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Hepatology, 67, 1560-1599. |
[56] | Sarin, S.K., Kumar, M., Lau, G.K., Abbas, Z., Chan, H.L.Y., Chen, C.J., et al. (2016) Asian-Pacific Clinical Practice Guidelines on the Management of Hepatitis B: A 2015 Update. Hepatology International, 10, 1-98. https://doi.org/10.1007/s12072-015-9675-4 |
[57] | 葛均波, 徐永健. 内科学[M]. 第8版. 北京: 人民卫生出版社, 2013: 693-736. |
[58] | World Health Organization (2017) Global Hepatitis Report. |
[59] | Indolfi, G., Guido, M., Azzari, C., et al. (2015) Histopathology of Hepatitis C in Children, a Systematic Review: Implications for Treatment. Expert Review of Anti-Infective Therapy, 13, 1225-1235. https://doi.org/10.1586/14787210.2015.1070668 |
[60] | Di Marco, V. (2011) Chronic Hepatitis C in Children Is a Mild and Curable Liver Disease. Digestive and Liver Disease, 43, 266-267. https://doi.org/10.1016/j.dld.2011.02.005 |
[61] | Squires, J.E. and Balistreri, W.F. (2017) Hepatitis C Virus Infection in Children and Adolescents. Hepatology Communications, 1, 87-98. https://doi.org/10.1002/hep4.1028 |
[62] | Jonas, M.M. (2002) Children with Hepatitis C. Hepatology, 36, s173-s178. https://doi.org/10.1053/jhep.2002.36799 |
[63] | Sarwari, N.M., Khoury, J.D. and Hernandez, C.M.R. (2016) Chronic Epstein Barr Virus Infection Leading to Classical Hodgkin Lymphoma. BMC Hematology, 16, Article No. 19. https://doi.org/10.1186/s12878-016-0059-3 |
[64] | Kimberlin, D.W., Barnett, E.D. and Lynfield, R. (2021) Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd edition, American Academy of Pediatrics, 318-322. |
[65] | Fafi‐Kremer, S., Morand, P., Brion, J., Pavese, P., Baccard, M., Germi, R., et al. (2005) Long-Term Shedding of Infectious Epstein-Barr Virus after Infectious Mononucleosis. The Journal of Infectious Diseases, 191, 985-989. https://doi.org/10.1086/428097 |
[66] | Noor, A., Panwala, A., Forouhar, F. and Wu, G.Y. (2018) Hepatitis Caused by Herpes Viruses: A Review. Journal of Digestive Diseases, 19, 446-455. https://doi.org/10.1111/1751-2980.12640 |
[67] | Dan, R. and Chang, R.S. (1990) A Prospective Study of Primary Epstein-Barr Virus Infections among University Students in Hong Kong. The American Journal of Tropical Medicine and Hygiene, 42, 380-385. https://doi.org/10.4269/ajtmh.1990.42.380 |
[68] | Balfour, H.H., Odumade, O.A., Schmeling, D.O., Mullan, B.D., Ed, J.A., Knight, J.A., et al. (2013) Behavioral, Virologic, and Immunologic Factors Associated with Acquisition and Severity of Primary Epstein-Barr Virus Infection in University Students. The Journal of Infectious Diseases, 207, 80-88. https://doi.org/10.1093/infdis/jis646 |
[69] | 陈坤, 王晶, 刘艳云. 儿童传染性单核细胞增多症合并肺炎支原体感染25例分析[J]. 贵州医药, 2018, 42(10): 1198-1200. |
[70] | 中华医学会儿科学分会感染消化学组. 巨细胞病毒感染诊断方案[J]. 中华儿科杂志, 1999(7): 48. |
[71] | 王晓红, 郭红梅, 朱启锫, 等. 婴儿巨细胞病毒感染与胆道闭锁的关系[J]. 实用儿科临床杂志, 2005, 20(3): 274-275. |
[72] | 龚四堂, 董永绥, 方峰. 婴儿肝组织巨细胞病毒抗原和病理检测[J]. 中国误诊学杂志, 2004, 4(9): 1361-1363. |
[73] | 王宝香, 朱润庆. 婴儿肝炎综合征、胆道闭锁、胆总管囊肿与巨细胞病毒感染的关系[J]. 世界华人消化杂志, 2006, 14(17): 1745-1747. |
[74] | 李宇泽. 牛津传染病学[M]. 北京: 人民卫生出版社, 2011: 70-74. |
[75] | 刘军连, 徐志凯, 王德堂, 王红英, 许东亮. 西安市两医院育龄妇女和儿童中人疱疹病毒6型血清流行病学调查[J]. 第四军医大学学报, 2004, 25(1): 92-93. |
[76] | Whitehead, M.W. (2001) The Causes of Obvious Jaundice in South West Wales: Perceptions versus Reality. Gut, 48, 409-413. https://doi.org/10.1136/gut.48.3.409 |
[77] | Baker, A., Kerkar, N., Todorova, L., et al. (2019) Systematic Review of Progressive Familial Intrahepatic Cholestasis. Clinics and Research in Hepatology and Gastroenterology, 43, 20-36. |
[78] | 宁慧娟, 宫幼喆, 廖伟伟, 刘文雯, 钟雪梅. 以肝内胆汁淤积为主要表现的MYO5B基因缺陷1例并文献复习[J]. 中国医学前沿杂志(电子版), 2022, 14(4): 34-39. |
[79] | European Association for the Study of the Liver (2012) EASL Clinical Practice Guidelines: Wilson’s Disease. Journal of Hepatology, 56, 671-685. https://doi.org/10.1016/j.jhep.2011.11.007 |
[80] | Zhang, X. and Jain, D. (2023) The Many Faces and Pathologic Diagnostic Challenges of Autoimmune Hepatitis. Human Pathology, 132, 114-125. https://doi.org/10.1016/j.humpath.2022.06.019 |
[81] | Mack, C.L., Adams, D., Assis, D.N., Kerkar, N., Manns, M.P., Mayo, M.J., et al. (2020) Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines from the American Association for the Study of Liver Diseases. Hepatology, 72, 671-722. https://doi.org/10.1002/hep.31065 |
[82] | Sciveres, M., Nastasio, S. and Maggiore, G. (2019) Novel Diagnostic and Therapeutic Strategies in Juvenile Autoimmune Hepatitis. Frontiers in Pediatrics, 7, Article 382. https://doi.org/10.3389/fped.2019.00382 |
[83] | Nastasio, S., Mosca, A., Alterio, T., Sciveres, M. and Maggiore, G. (2023) Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome. Diagnostics, 13, Article 2753. https://doi.org/10.3390/diagnostics13172753 |
[84] | Deneau, M.R., El-Matary, W., Valentino, P.L., et al. (2017) The Natural History of Primary Sclerosing Cholangitis in 78 Children: A Muticenter, International Collaboration. Hepatology, 66, 518-527. |
[85] | Weismüller, T.J., Trivedi, P.J., Bergquist, A., et al. (2017) Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate with Course of Primary Sclerosing Cholangitis. Gastroenterology, 152, 1975-1984. e8. |
[86] | 曹建国, 索成云, 郝艳爽. 以胆汁淤积性肝病为首发的急性淋巴细胞性白血病1例[C]//中华医学会感染病学分会, 中华医学会肝病学分会. 中华医学会第十六次全国病毒性肝炎及肝病学术会议论文集. 邯郸: 峰峰集团总医院消化内科, 2013: 296-297. |
[87] | Allen, C.E., Merad, M. and McClain, K.L. (2018) Langerhans-Cell Histiocytosis. New England Journal of Medicine, 379, 856-868. https://doi.org/10.1056/nejmra1607548 |
[88] | Fu, Z., Li, H., Arslan, M.E., Ells, P.F. and Lee, H. (2021) Hepatic Langerhans Cell Histiocytosis: A Review. World Journal of Clinical Oncology, 12, 335-341. https://doi.org/10.5306/wjco.v12.i5.335 |
[89] | Braier, J., Ciocca, M., Latella, A., de Davila, M.G., Drajer, M. and Imventarza, O. (2002) Cholestasis, Sclerosing Cholangitis, and Liver Transplantation in Langerhans Cell Histiocytosis. Medical and Pediatric Oncology, 38, 178-182. https://doi.org/10.1002/mpo.1306 |