药物性胆汁淤积型肝损伤患者的临床表现、影像学特征以及转归

摘要/Abstract

摘要： 目的分析药物性胆汁淤积型肝损伤患者临床表现、影像学特征以及转归。方法纳入2020年3月至2022年3月在我院确诊为药物性胆汁淤积型肝损伤的患者47例。分析纳入病例的年龄阶段、用药情况、临床表现、致病药物及影像学表现,比较不同预后结局并分析预后的影响因素。结果 47例患者中,年龄＜40岁、40~60岁、＞60岁分别为3例(6.4%)、23例(48.9%)、21例(44.7%)。用药时间为3~150 d,潜伏时间2~180 d。42例(89.4%)存在1种及以上临床症状,5例(10.6%)仅有肝功能异常而无自觉症状。致病药物共计74种,其中31例(65.9%)服用1种以上致病药物,排名前5种药物包括服用中草药21例(44.7%)、服用抗菌类药物16例(34.0%)、服用抗结核药物14例(29.8%)、服用消化系统药物13例(27.6%)及服用抗肿瘤药物7例(14.9%)。病情严重程度1级、2级、3级、4级分别为19例(50.0%)、17例(44.7%)、6例(15.8%)、5例(13.1%)。有30例(63.8%)行磁共振胰胆管成像,其余患者均行B超或腹部CT检查。10例(21.3%)影像学上存在硬化性胆管炎样改变,其中5例(10.6%)为肝外狭窄,3例(6.4%)肝内外胆管均有狭窄,2例(4.2%)为肝门部胆管狭窄。随访至2023年10月,治愈27例(62.5%),好转11例(20.0%),预后不良7例(12.5%),死亡2例(5.0%),总有效率为82.5%。定义治愈、好转病例为有效组(n=38),预后不良、死亡病例为无效组(n=9)。有效组年龄、RUCAM评分、WBC、PLT、初始ALP、初始TBil、峰值ALP、峰值TBil、硬化性胆管炎样改变分别为(53.5±7.0)岁、 8(7,9)分、5.0(3.9,7.5)×10⁹/L、227(170,278)×10⁹/L、(401.6±37.2)U/L、(126.5±21.3)μmol/L、(436.0±37.2)U/L、(146.3±35.6)μmol/L、4例(10.5%),无效组分别为(62.4±11.3)岁、 6(6,7)分、7.4(5.0,9.3)×10⁹/L、130(98,155)×10⁹/L、(503.4±54.0)U/L、(150.2±47.0)μmol/L、(634.5±82.6)U/L、(181.2±64.5)μmol/L、6例(66.7%),差异均有统计学意义(P<0.05)。有效组1、2、3、4级为17例(44.7%)、16例(42.1%)、 3例(7.9%)、2例(5.3%),无效组1、2、3、4级为2例(22.2%)、1例(11.1%)、3例(33.3%)、3例(33.3%),差异有统计学意义(P<0.05)。RUCAM评分、峰值ALP、峰值TBil及病情严重程度是药物性胆汁淤积型肝损伤患者预后独立影响因素(P<0.05)。结论多数药物性胆汁淤积性肝损伤预后良好,临床应对RUCAM评分低、峰值ALP、峰值TBil高及病情严重患者密切关注。

关键词: 药物性, 胆汁淤积型, 肝损伤, 临床表现, 影像学特征, 转归

Abstract: Objective To analyze the clinical manifestations, imaging features and prognosis of patients with drug-induced cholestatic liver injury. Methods Between March 2020 and March 2022, our hospital diagnosed 47 patients with drug-induced cholestatic liver injury, comprising 29 males and 18 females, with an average age of 55.5±7.1 years. We analyzed the patients age, medication history, clinical manifestations, causative drugs, and imaging findings. Additionally, we compared clinical data based on different prognostic outcomes and identified factors influencing prognosis. Results Among 47 patients diagnosed with pharmacological cholestatic liver injury, age distribution was aas follows: 3 patients(6.4%) were under 40 years old, 23 patients(48.9%) were between 40-60 years old, and 21 patients(44.7%) were over 60 years old. The duration of medication ranged from 3 to 150 days, with a median of 13 days(IQR 3, 25days).Tthe latency period varied from 2 to 180 days, with a median of 21 days(IQR 10, 32days). 42 patients (89.4%) exhibted one or more clinical symptoms, while 5 patients (10.6%) displayed only liver function abnormalities without conscious symptoms. Among the causative agents, a total of 74 drugs were identified, with 31 patients (65.9%) being exposed to more than one causative drug. The top five categories of drugs included Chinese herbs(21 cases, 44.7%), antimicrobials(16 cases, 34.0%), anti-tuberculosis drugs(14 cases, 29.8%), digestive system drugs(13 cases, 27.6%), and antitumor drugs(7 cases, 14.9%). Disease severity was categorized into four levels: level 1 (19 cases, 50.0%), level 2(17 case, 44.7%), level 3 (6 cases, 15.8%), and level 4(5 cases, 13.1%). 30 patients (63.8%) underwent magnetic resonance cholangiopancreatography(MRCP), while the remaining patients underwent B-ultrasound or abdominal CT examination. Imaging revealed sclerosing cholangitis-like changes in 10 patients (21.3%), including extrahepatic strictures (5 cases, 10.6%), strictures of both intrahepatic and extrahepatic bile ducts(3 cases, 6.4%), and hilar bile duct strictures(2 cases, 4.2%). By October 2023, of the 47 patients, 27 were cured (62.5%), 11 showed improvedment (20.0%), 7 had poor outcomes(12.5%) and 2 died (5.0%), resulting in a total effective rate of 82.5%. Patients were divided into an effective group (cured and improved, n=38) and an ineffective group( poor and deceased, n=9). The clinical and laboratory parameters showed significant differences between the effective and ineffective groups. In the effective group, the age, RUCAM score, WBC, PLT, initial ALP, initial TBil, peak ALP, peak TBil and presnece of sclerosing cholangitis-like changes were 53.5±7.0 years, 8 (IQR 7, 9) points, 5.0 (IQR 3.9, 7.5) × 10⁹/L, 227 (IQR 170, 278) ×10⁹/L, 401.6±37.2 U/L, 126.5±21.3 μmol/L, 436.0±37.2 U/L, 146.3±35.6 μmol/L, and 4 cases (10.5%), respectively. In the ineffective group, these parameters were 62.4±11.3 years old, 6 (IQR 6, 7) points, 7.4 (IQR 5.0, 9.3) × 10⁹/L, 130 (IQR 98, 155) × 10⁹/L, 503.4±54.0 U/L, 150.2±47.0 μmol/L, 634.5±82.6 U/L, 181.2±64.5 μmol/L, and 6 cases (66.7%), respectively, with all the differences being statistically significant (P<0.05). In terms of disease severity, the distribution in the effective group was as follows: level 1, 17 cases (44.7%); level 2, 16 cases (42.1%); level 3, 3 cases (7.9%); and level 4, 2 cases (5.3%). In the ineffective group, the distribution was: level 1, 2 cases (22.2%); level 2, 1 case (11.1%); level 3, 3 cases (33.3%); and level 4, 3 cases (33.3%), with statistically significant differences(P<0.05). Conclusion Most patients with drug-induced cholestatic liver injury have a good prognosis; however, close attention should be paid to those with a low RUCAM score, high peak ALP, high peak TBil, and severe disease.

Key words: Pharmacologic, cholestatic, Liver injury, Clinical presentation, Imaging features, Regression

高硕玉, 张秦, 张帅, 姚博悰. 药物性胆汁淤积型肝损伤患者的临床表现、影像学特征以及转归[J]. 肝脏, 2024, 29(8): 971-974.

GAO Shuo-yu, ZHANG Qin, ZHANG Shuai, YAO Bo-yang. Clinical manifestations, imaging features, and recovery in pharmacological cholestatic liver injury: an analytical approach[J]. Chinese Hepatolgy, 2024, 29(8): 971-974.

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