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胆汁淤积性肝病“上升”病理生理学模式及用药合理性探讨

顾天翊 陆伦根

引用本文:
Citation:

胆汁淤积性肝病“上升”病理生理学模式及用药合理性探讨

DOI: 10.3969/j.issn.1001-5256.2019.02.006
详细信息
  • 中图分类号: R575

Rationality of medication based on the “ascending” pathophysiology of cholestatic liver disease

  • 摘要:

    近年来,有学者提出胆汁淤积性肝病具有"上升"病理生理学模式,尤其是在原发性胆汁性胆管炎和原发性硬化性胆管炎中。该理论认为,胆汁淤积性肝病在病变过程中随时间推延,在解剖结构上呈自下而上发展。原发或早期病灶通常位于"下游"的胆管,主要病因可能为免疫介导的胆管坏死性炎症损伤;当发生胆汁淤积时,胆盐介导的毒性作用将导致"上游"的肝实质损伤,因此胆汁毒性在疾病进展期间显得更为重要。基于其"上升"病理生理学模式,可以看到不同阶段的发病部位及病因均不同,因此有必要对胆汁淤积性肝病进行分期,并根据不同疾病阶段选取不同治疗药物,以更有效的方式利用现有药物,并为新药开发指明方向。然而,目前尚缺乏胆汁淤积性肝病早期生化标志物,寻找特异性强、敏感度高的生化标志物是目前临床的主要工作。

     

  • [1]POLLHEIMER MJ, FICKERT P, STIEGER B.Chronic cholestatic liver diseases:Clues from histopathology for pathogenesis[J].Mol Aspects Med, 2014, 37 (2) :35-56.
    [2]ALVAREZ F.Is biliary atresia an immune mediated disease?[J].J Hepatol, 2013, 59 (4) :648-650.
    [3]ZHAO SX, ZHANG YG, ZHOU GD, et al.Clinicopathological features of early-and late-stage primary biliary cirrhosis:Acomparative study[J].Chin J Hepatol, 2016, 24 (6) :412-416. (in Chinese) 赵素贤, 张玉果, 周光德, 等.原发性胆汁性肝硬化早晚期临床病理学对比研究[J].中华肝脏病杂志, 2016, 24 (6) :412-416.
    [4]de VRIES EM, WANG J, LEEFLANG MM, et al.Alkaline phosphatase at diagnosis of primary sclerosing cholangitis and 1year later:Evaluation of prognostic value[J].Liver Int, 2016, 36 (12) :1867-1875.
    [5] ZWEERS SJ, SHIRYAEV A, KOMUTA M, et al.Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis[J].Liver Int, 2016, 36 (9) :1370-1377.
    [6]FRIEDRICH K, SMIT M, BRUNE M, et al.CD14 is associated with biliary stricture formation[J].Hepatology, 2016, 64 (3) :843-852.
    [7]LI T, HUANG Y, LIU P, et al.Lower plasma levels of IL-35 in patients with primary biliary cirrhosis[J].Tohoku J Exp Med, 2018, 244 (2) :123-131.
    [8]DOORENSPLEET ME, HUBERS LM, CULVER EL, et al.Immunoglobulin G4 (+) B-cell receptor clones distinguish immunoglobulin G4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies[J].Hepatology, 2016, 64 (2) :501-507.
    [9]DINANI AM, FISCHER SE, MOSKO J, et al.Patients with autoimmune hepatitis who have antimitochondrial antibodies need long-term follow-up to detect late development of primary biliary cirrhosis[J].Clin Gastroenterol Hepatol, 2012, 10 (6) :682-684.
    [10]VIJAYVARGIYA P, CAMILLERI M, SHIN A, et al.Methods for diagnosis of bile acid malabsorption in clinical practice[J].Clin Gastroenterol Hepatol, 2013, 11 (10) :1232-1239.
    [11]CAMILLERI M, NADEAU A, TREMAINE WJ, et al.Measurement of serum 7alpha-hydroxy-4-cholesten-3-one (or7alphaC4) , a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry[J].Neurogastroenterol Motil, 2009, 21 (7) :734-e43.
    [12]LIM AG, JAZRAWI RP, AHMED HA, et al.Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis:Relationship with disease stage, immune activity and cholestasis[J].Hepatology, 1994, 20 (4 Pt 1) :882-888.
    [13]TAKEYAMA Y, UEHARA Y, INOMATA S, et al.Alternative transporter pathways in patients with untreated early-stage and latestage primary biliary cirrhosis[J].Liver Int, 2009, 29 (3) :406-414.
    [14]MASUBUCHI N, SUGIHARA M, SUGITA T, et al.Oxidative stress markers, secondary bile acids and sulfated bile acids classify the clinical liver injury type:Promising diagnostic biomarkers for cholestasis[J].Chem Biol Interact, 2016, 255:83-91.
    [15]GROVER VP, SOUTHERN L, DYSON JK, et al.Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging[J].Aliment Pharmacol Ther, 2016, 44 (9) :936-945.
    [16]MENDES FD, KIM WR, PEDERSEN R, et al.Mortality attributable to cholestatic liver disease in the United States[J].Hepatology, 2008, 47 (4) :1241-1247.
    [17]LEE J, BELANGER A, DOUCETTE JT, et al.Transplantation trends in primary biliary cirrhosis[J].Clin Gastroenterol Hepatol, 2007, 5 (11) :1313-1315.
    [18]IMAM MH, LINDOR KD.The natural history of primary biliary cirrhosis[J].Semin Liver Dis, 2014, 34 (3) :329-333.
    [19]BEUERS U, TRAUNER M, JANSEN P, et al.New paradigms in the treatment of hepatic cholestasis:From UDCA to FXR, PXRand beyond[J].J Hepatol, 2015, 62 (1 Suppl) :s25-s37.
    [20]LINDOR KD, KOWDLEY KV, LUKETIC VA, et al.High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis[J].Hepatology, 2009, 50 (3) :808-814.
    [21]KOBAYASHI A, UTSUNOMIYA T, OHBE Y, et al.Ascending cholangitis after successful surgical repair of biliary atresia[J].Arch Dis Child, 1973, 48 (9) :697-703.
    [22]DUAN WJ, ZHANG FK, OU XJ, et al.The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid[J].Chin J Hepatol, 2011, 19 (2) :118-120. (in Chinese) 段维佳, 张福奎, 欧晓娟, 等.原发性胆汁性肝硬化患者对熊去氧胆酸应答欠佳的影响因素[J].中华肝脏病杂志, 2011, 19 (2) :118-120.
    [23]ZHANG LN, SHI TY, SHI XH, et al.Early biochemical response to ursodeoxycholic acid and long-term prognosis of primary biliary cirrhosis:Results of a 14-year cohort study[J].Hepatology, 2013, 58 (1) :264-272.
    [24]ZHAO J, LI W, YAO DK.Role of farnesoid X receptor in treatment of primary biliary cholangitis[J].Chin J Gastroenterol, 2017, 22 (2) :109-111. (in Chinese) 赵健, 李伟, 姚定康.法尼醇X受体在原发性胆汁性胆管炎治疗中的作用[J].胃肠病学, 2017, 22 (2) :109-111.
    [25]WUNSCH E, MILKIEWICZ M, WASIK U, et al.Expression of hepatic fibroblast growth factor 19 is enhanced in primary biliary cirrhosis and correlates with severity of the disease[J].Sci Rep, 2015, 5:13462.
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  • 出版日期:  2019-02-20
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