肉芽肿性肝炎的临床-病理特点及预后分析

摘要/Abstract

摘要： 目的探讨肉芽肿性肝炎的临床-病理特征。方法回顾性分析2016年1月至2024年3月于首都医科大学附属北京友谊医院经肝脏活检确诊的36例肉芽肿性肝炎患者临床、病理数据,并根据不同病因、是否自发缓解、预后及复发与否进行分析。结果 36例患者中位发病年龄为51.0岁,女性20例(55.6%),略多于男性。患者中肝细胞损伤型14例(38.8%),胆汁淤积型17例(47.2%),混合型5例(13.8%)。ALT为137.5(30.7,235.3)U/L,ALP为132.6(98.6,198.5)U/L。在病因分析中,药物性占47.2%和特发性占19.4%。药物相关性肉芽肿性肝炎患者基线ALT、AST水平均显著高于特发性肉芽肿性肝炎和结节病患者(P<0.05)。肉芽肿分布于肝汇管区占41.7%,小叶内占38.9%,汇管区及小叶内均可见肉芽肿占19.4%。非坏死性上皮样肉芽肿是最常见的类型,占83.3%。所有患者均有小叶内炎症,且大多数(83.3%)伴有不同程度的汇管区炎症,多数患者(61.1%)无纤维化特征。绝大多数患者(91.7%)存在胆管损伤,其中仅1例出现胆管缺失。糖皮质激素治疗者的基线ALP水平显著高于自发缓解者(P=0.003)。ALP水平对自发缓解有较好的预测能力,AUC为0.796(95%CI: 0.649~0.943)。结论肉芽肿性肝炎是一种少见的慢性肝脏炎性疾病,临床表现非特异性,病因多样,肝活检可明确诊断。糖皮质激素为常用治疗药物,多数预后良好。

关键词: 肉芽肿性肝炎, 糖皮质激素, 治疗, 自发缓解

Abstract: Objective To summarize the clinical characteristics of Granulomatous Hepatitis (GH) to improve the awareness, diagnosis and management of the disease. Methods We retrospectively collected clinical data of 36 GH patients treated from January 2016 to March 2024 at Beijing Friendship Hospital, Capital Medical University. Subgroup analyses were conducted based on etiologies, spontaneous remission, prognosis, and relapse. Methods The median age of 36 GH patients was 51.0 years old, with a higher prevalence in females (Female∶Male, 1.25∶1). All patients had liver enzyme abnormalities; there are 14 cases of hepatocellular injury type (38.8%), 17 cases of cholestasis type (47.2%), and 5 cases of mixed type (13.8%). The median ALT is 137.50 (range 30.7-235.3) U/L, and the median ALP is 132.6(range 98.6-198.5) U/L. In subgroup analyses, drug-related(47.2%)and idiopathic(19.4%) etiologies were the most common causes of GH. Patients with drug-related GH had significantly higher ALT and AST levels compared to those with idiopathic GH and sarcoidosis (P<0.05). Granulomas were found in the portal areas (41.7%) or within the lobules (38.9%), with a minority (19.4%) of patients having granulomas present in both the portal areas and within the lobules. The predominant type of granuloma was non-necrotizing epithelioid granuloma (83.3%). All patients exhibited inflammation within the lobules, with the majority (83.3%) having varying degrees of inflammation in the portal areas. Most patients (61.1%) showed no signs of fibrosis, and the vast majority of patients (91.7%) had bile duct injury, with only one case showing bile duct loss. Patients treated with corticosteroids showed significantly higher ALP level compared to those with spontaneous remission (P=0.003). The ALP level demonstrated good predictive performance for spontaneous remission (AUC 0.796(95%CI 0.649-0.943). Conclusion GH is a rare chronic inflammatory liver disease, characterized by non-specific clinical manifestations and a variety of causes. Liver biopsy can help the diagnosis. Corticosteroid therapy is commonly used in patients with GH and results in a favorable prognosis for most patients.

Key words: Granulomatous Hepatitis, Corticosteroids, Treatment, Spontaneous Remission

何萌, 韩笑, 赵新颜. 肉芽肿性肝炎的临床-病理特点及预后分析[J]. 肝脏, 2025, 30(1): 101-106.

HE Meng, HAN Xiao, ZHAO Xin-yan. Clinical characteristics of 36 cases of Granulomatous Hepatitis[J]. Chinese Hepatolgy, 2025, 30(1): 101-106.

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参考文献

[1] LaganaSM, Moreira RK, Lefkowitch JH. Hepatic granulomas: pathogenesis and differential diagnosis[J]. Clin Liver Dis, 2010,14(4):605-617.
[2] LewisJ. Histopathology of granulomatous liver disease[J]. Clin Liver Dis (Hoboken),2018, 11(3):77-80.
[3] DrebberU, Kasper HU, Ratering J, et al. Hepatic granulomas: histological and molecular pathological approach to differential diagnosis-a study of 442 cases[J]. Liver Int, 2008, 28(6):828-834.
[4] IordacheA, Fuursted K, Rift CV, et al. Hepatic granulomas following liver transplantation: a retrospective survey, and analysis of possible microbiological etiology[J]. Pathol Res Pract, 2024, 3(255):155-201.
[5] MironovaM, Gopalakrishna H, Rodriguez Franco G, et al. Granulomatous liver diseases[J]. Hepatol Commun, 2024,8(4):e0392.
[6] LampsLW. Hepatic granulomas: a review with emphasis on infectious causes[J]. Arch Pathol Lab Med, 2015,139(7):867-875.
[7] TahanV, Ozaras R, Lacevic N, et al. Prevalence of hepatic granulomas in chronic hepatitis B[J]. Dig Dis Sci, 2004,49(10):1575-1577.
[8] OzarasR, Tahan V, Mert A, et al. The prevalence of hepatic granulomas in chronic hepatitis C[J]. J Clin Gastroenterol, 2004,38(5):449-452.
[9] Kocabaş E, Özgür Gündeşlioğlu Ö, Kılıç Çil M,et al. A rare cause of granulomatous hepatitis: Tularemia[J]. J Infect Public Health, 2020,13(7):1003-1005.
[10] 刘红丽,熊清芳,杨永峰.以肝损害为主要表现的肉芽肿性疾病[J].中华肝脏病杂志,2023,31(9):897-900.
[11] GrafC, Arncken J, Lange CM, et al. Hepatic sarcoidosis: Clinical characteristics and outcome[J]. JHEP Rep, 2021, 3(6):100360.
[12] KumarM, Herrera JL. Sarcoidosis and the Liver[J]. Clin Liver Dis, 2019,23(2):331-343.
[13] SartinJS, Walker RC. Granulomatous hepatitis: a retrospective review of 88 cases at the Mayo Clinic[J]. Mayo Clin Proc, 1991, 66(9):914-918.
[14] ZoutmanDE, Ralph ED, Frei JV. Granulomatous hepatitis and fever of unknown origin. An 11-year experience of 23 cases with three years' follow-up[J]. J Clin Gastroenterol, 1991, 13(1):69-75.
[15] PenchasS, Ligumski M, Eliakim M. Idiopathic granulomatous hepatitis with a prolonged course: effect of corticosteroid therapy[J]. Digestion, 1978,17(1):46-55.
[16] WilsonPA, Gan L, King S. Granulomatous hepatitis with hepatic mass lesions and a response to infliximab[J]. Intern Med J, 2015,45(7):783-785.
[17] 倪倍倍,赵俊,曹战起,郭切,徐文,冷萍.卡介苗膀胱灌注相关肉芽肿性肝炎的临床特点分析[J].药物不良反应杂志,2022,24(5):252-257.
[18] AggarwalA, Jaswal N, Jain R, et al. Amoxicillin-clavulanate-induced granulomatous hepatitis: case report and review of the literature[J]. J Clin Transl Hepatol, 2019, 7(3):280-283.
[19] SpenglerEK, Kleiner DE, Fontana RJ. Vemurafenib-induced granulomatous hepatitis[J]. Hepatology, 2017,65(2):745-748.