原发性胆汁性肝硬化(PBC)是以肝内小胆管进行性、非化脓性炎症为特征的慢性胆汁淤积性疾病,可发展至肝纤维化及肝硬化。该病的临床表现不一,包括无症状、肝脏生化功能异常、明显的肝硬化等。诊断PBC主要依据包括提示胆汁淤积的肝脏生化指标、抗线粒体抗体阳性以及肝脏组织病理表现为非化脓性胆管炎。但是本病容易因患者无症状或者医师认识不足而漏诊。目前一致推荐的治疗方法为使用熊去氧胆酸(UDCA,剂量为13~15 mg·kg^-1),并认为可以改善本病的预后。但是仍有1/3的患者对UDCA应答欠佳,可能需要进行肝脏移植治疗。我们仍需要在诊断早期PBC、研发新的治疗药物等方面继续作出努力。作者对近年来有关PBC的诊断和治疗方面的进展做一综述。

[1] KIM K A,JEONG S H.The diagnosis and treatment of primary biliary cirrhosis[J].Korean J Hepatol,2011,17:173-179.
[2] ADDISON T,GULL W.On a certain affection of the skin-vitiligoidea-α-plana,β-tuberosa[J].Guys Hosp Rep,1851,7:265-276.
[3] KAPLAN M M,GERSHWIN M E.Primary biliary cirrhosis[J].N Engl J Med,2005,353:1261-1273.
[4] PRINCE M I,JAMES O F.The epidemiology of primary biliary cirrhosis[J].Clin Liver Dis,2003,7:795-819.
[5] PRINCE M I,CHETWYND A,CRAIG W L,et al.Asymptomatic primary biliary cirrhosis:clinical features,prognosis,and symptom progression in a large population based cohort[J].Gut,2004,53:865-870.
[6] KIM W R,LINDOR K D,LOCKE G R,et al.Epidemiology and natural history of primary biliary cirrhosis in a US community[J].Gastroenterology,2000,119:1631-1636.
[7] FORTON D M,PATEL N,PRINCE M,et al.Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels[J].Gut,2004,53:587-592.
[8] POUPON R E,CHRÉTIEN Y,CHAZOUILLÈRES O,et al.Quality of life in patients with primary biliary cirrhosis[J].Hepatology,2004,40:489-494.
[9] NEWTON J L,GIBSON G J,TOMLINSON M,et al.Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence[J].Hepatology,2006,44:91-98.
[10] TALWALKAR J A,SOUTO E,JORGENSEN R A,et al.Natural history of pruritus in primary biliary cirrhosis[J].Clin Gastroenterol Hepatol,2003,1:297-302.
[11] LAURIN J M,DeSOTEL C K,JORGENSEN R A,et al.The natural history of abdominal pain associated with primary biliary cirrhosis[J].Am J Gastroenterol,1994,89:1840-1843.
[12] NAKANUMA Y.Are esophagogastric varices a late manifestation in primary biliary cirrhosis?[J].J Gastroenterol,2003,38:1110-1112.
[13] NIJHAWAN P K,THERNEAU T M,DICKSON E R,et al.Incidence of cancer in primary biliary cirrhosis: the Mayo experience[J].Hepatology,1999,29:1396-1398.
[14] LINDOR K D,GERSHWIN M E,POUPON R,et al.Primary biliary cirrhosis[J].Hepatology,2009,50:291-308.
[15] CORPECHOT C,POUJOL-ROBERT A,WENDUM D,et al.Biochemical markers of liver fibrosis and lymphocytic piecemeal necrosis in UDCA-treated patients with primary biliary cirrhosis[J].Liver Int,2004,24:187-193.
[16] KUIPER E M,HANSEN B E,de VRIES R A,et al.Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid[J].Gastroenterology,2009,136:1281-1287.
[17] WALKER J G,DONIACH D,ROITT I M,et al.Serological tests in diagnosis of primary biliary cirrhosis[J].Lancet,1965,1:827-831.
[18] SPRINGER J,CAUCH-DUDEK K,O'ROURKE K,et al.Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis[J].Am J Gastroenterol,1999,94:47-53.
[19] PRINCE M,CHETWYND A,NEWMAN W,et al.Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years[J].Gastroenterology,2002,123:1044-1051.
[20] FUSSEY S P,GUEST J R,JAMES O F,et al.Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis[J].Proc Natl Acad Sci USA,1988,85:8654-8658.
[21] Van NORSTRAND M D,MALINCHOC M,LINDOR K D,et al.Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: relationship of levels of autoantibodies to disease progression[J].Hepatology,1997,25:6-11.
[22] HU C Y,ZHANG F C,LI Y Z,et al.Primary biliary cirrhosis:what do autoantibodies tell us?[J].World J Gastroenterol,2010,16: 3616-3629.
[23] TANAKA A,NEZU S,UEGAKI S,et al.The clinical significance of IgA antimitochondrial antibodies in sera and saliva in primary biliary cirrhosis[J].Ann NY Acad Sci,2007,1107: 259-270.
[24] KUMAGI T,ONJI M.Presentation and diagnosis of primary biliary cirrhosis in the 21st century[J].Clin Liver Dis,2008,12:243-259.
[25] POUPON R E,LINDOR K D,CAUCH-DUDEK K,et al.Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis[J].Gastroenterology,1997,113:884-890.
[26] POUPON R.Primary biliary cirrhosis: a 2010 update[J].J Hepatol,2010,52:745-758.
[27] CORPECHOT C,ABENAVOLI L,RABAHI N,et al.Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis[J].Hepatology,2008,48:871-877.
[28] LEE J,BELANGER A,DOUCETTE J T,et al.Transplantation trends in primary biliary cirrhosis[J].Clin Gastroenterol Hepatol,2007,5:1313-1315.
[29] CORPECHOT C,POUPON R.Geotherapeutics of primary biliary cirrhosis: bright and sunny around the Mediterranean but still cloudy and foggy in the United Kingdom[J].Hepatology,2007,46:963-965.
[30] EASL Clinical Practice Guidelines: management of cholestatic liver diseases[J].J Hepatol,2009,51:237-267.
[31] LINDOR K D,GERSHWIN M E,POUPON R,et al.Primary biliary cirrhosis[J].Hepatology,2009,50:291-308.
[32] THOMAS C,AUWERX J,SCHOONJANS K.Bile acids and the membrane bile acid receptor TGR5 - connecting nutrition and metabolism[J].Thyroid,2008,18:167-174.
[33] PARES A,CABALLERIA L,RODES J.Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid[J].Gastroenterology,2006,130:715-720.
[34] ANGULO P,JORGENSEN R A,KEACH J C,et al.Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid[J].Hepatology,2000,31:318-323.
[35] BATTEZZATI P M,ZUIN M,CROSIGNANI A,et al.Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind,placebo-controlled trial on symptomatic patients[J].Aliment Pharmacol Ther,2001,15: 427-1434.
[36] COMBES B,EMERSON S S,FLYE N L,et al.Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis[J].Hepatology,2005,42:1184-1193.
[37] ANGULO P,PATEL T,JORGENSEN R A,et al.Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid[J].Hepatology,2000,32: 897-900.
[38] NAKAI S,MASAKI T,KUROKOHCHI K,et al.Combination therapy of bezafibrate and ursodeoxycholic acid in primary biliary cirrhosis: a preliminary study[J].Am J Gastroenterol,2000,95:326-327.
[39] LEVY C,PETER J A,NELSON D R,et al.Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid[J].Aliment Pharmacol Ther,2011,33:235-242.
[40] LINDOR K D.Farnesoid X receptor agonists for primary biliary cirrhosis[J].Curr Opin Gastroenterol,2011,27:285-288.
[41] FICKERT P,Wagner M,MARSCHALL H U,et al.24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice[J].Gastroenterology,2006,130:465-481.
[42] REDDY A,PRINCE M,JAMES O F,et al.Tamoxifen:a novel treatment for primary biliary cirrhosis?[J].Liver Int,2004,24:194-197.
[43] STOJAKOVIC T,PUTZ-BANKUTI C,FAULER G,et al.Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid[J].Hepatology,2007,46:776-784.
[44] SYLVESTRE P B,BATTS K P,BURGART L J,et al.Recurrence of primary biliary cirrhosis after liver transplantation: Histologic estimate of incidence and natural history[J].Liver Transpl,2003,9:1086-1093.
[45] 杨华,郑勤.肝癌放射治疗进展[J].东南大学学报:医学版,2012,31(4):488-491.
[46] 邱少敏,陈刚,李宏波.肝动脉化疗栓塞联合经皮微波凝固疗法治疗中晚期肝癌的临床观察[J].现代医学,2011,39(5):526-529.