Yi Wei, Yan Suqi, Tang Jianqiao, Ma Xiang, Su Mengjie, Li Hong
Department of Integrated Traditional Chinese and Western Medicine, Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430016, Hubei, China.
Department of Clinical Laboratory, Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430016, Hubei, China.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Jul;35(7):741-745. doi: 10.3760/cma.j.cn121430-20230316-00186.
To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis.
Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups.
During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05).
The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.
探讨利胆合剂治疗小儿胆汁淤积性肝纤维化的临床疗效。
采用前瞻性随机对照试验,选取2021年1月至12月在华中科技大学同济医学院附属武汉儿童医院中西医结合科及消化内科符合小儿胆汁淤积性肝纤维化诊断标准的患者纳入研究。根据随机数字表将其分为常规治疗组和利胆合剂组。常规治疗组患者按照指南给予常规治疗。利胆合剂组在常规治疗基础上给予自制中药复方利胆合剂(方剂:茵陈、连翘、熟大黄、制何首乌、赤芍、桂枝、枳壳、白术、五味子、鳖甲、甘草),通过口服、灌肠或鼻饲给药,每日60 mL,分2或3次服用,共28天。门诊随访4周。记录两组患者治疗前后血清肝纤维化4项指标[IV型胶原(IV-C)、透明质酸酶(HA)、III型前胶原(PC III)、层粘连蛋白(LN)]、肝功能及胆汁淤积相关指标[总胆红素(TBil)、直接胆红素(DBil)、总胆汁酸(TBA)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(γ-GGT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)]、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)]、经瞬时弹性成像(TE)检测的肝脏硬度值(LSM)、天冬氨酸氨基转移酶与血小板比值指数(APRI)以及肝脾回缩时间。
观察期间,共治疗胆汁淤积性肝纤维化患者40例,其中常规治疗组21例,利胆合剂组19例。治疗前,两组患者血清肝纤维化4项指标、血清肝功能及胆汁淤积相关指标、氧化应激指标、LSM及APRI差异均无统计学意义。治疗后,两组患者肝纤维化4项指标、肝功能及胆汁淤积相关指标、LSM及APRI均显著降低,且利胆合剂组各项指标均显著低于常规治疗组[HA(ng/L):165.81±21.57比203.87±25.88,PC III(μg/L):69.86±9.32比81.82±7.39,IV-C(μg/L):204.14±38.97比239.08±24.93,LN(μg/L):162.40±17.39比190.86±15.97,TBil(μmol/L):37.58±27.63比53.06±45.09,DBil(μmol/L):20.55±19.34比30.08±27.39,ALP(U/L):436.50±217.58比469.60±291.69,γ-GGT(U/L):66.78±35.84比87.00±32.82,ALT(U/L):64.75±50.53比75.20±50.19,AST(U/L):77.25±54.23比96.80±59.77,TBA(μmol/L):74.35±44.44比85.45±39.50,LSM(kPa):5.24±0.39比7.53±3.16,APRI:0.52±0.39比0.98±0.29,均P<0.05]。治疗后,两组患者MDA均显著低于治疗前,SOD及GSH均显著高于治疗前。利胆合剂组SOD水平显著高于常规治疗组(kU/L:64.56±6.69比51.58±5.98,P<0.05)。此外,利胆合剂组肝回缩时间(天:20.13±10.97比24.33±13.46)及脾回缩时间(天:25.93±13.01比29.14±14.52)均显著短于常规治疗组(均P<0.05)。
利胆合剂治疗小儿胆汁淤积性肝纤维化可有效改善患儿胆汁淤积、肝纤维化、氧化应激指标及临床症状。