Current understanding of primary biliary cholangitis

Abstract

Primary biliary cholangitis (PBC) causes chronic and persistent cholestasis in the liver, eventually resulting in cirrhosis and hepatic failure without appropriate treatment. PBC mainly develops in middle-aged women, but it is also common in young women and men. PBC is considered a model of autoimmune disease because of the presence of diseasespecific autoantibodies, that is, antimitochondrial antibodies (AMAs), intense infiltration of mononuclear cells into the bile ducts, and a high prevalence of autoimmune diseases such as comorbidities. Histologically, PBC is characterized by degeneration and necrosis of intrahepatic biliary epithelial cells surrounded by a dense infiltration of mononuclear cells, coined as chronic non-suppurative destructive cholangitis, which leads to destructive changes and the disappearance of small- or medium-sized bile ducts. Since 1990, early diagnosis with the detection of AMAs and introduction of ursodeoxycholic acid as first-line treatment has greatly altered the clinical course of PBC, and liver transplantation-free survival of patients with PBC is now comparable to that of the general population.

Keywords: Anti-mitochondrial antibody; Bezafibrate; Epidemiology.

Figure 1.

Epidemiological data of PBC over time and in different geographical regions. (A) The prevalence (per 100,000 population) and (B) incidence (per 100,000 population) of PBC. PBC, primary biliary cholangitis.

Figure 2.

A diagnostic flowchart of patients with PBC. ALP, alkaline phosphatase; GGT, gamma glutamyl transferase; US, ultrasonography; CT, computed tomography; PSC, primary sclerosing cholangitis; AMA, anti-mitochondrial antibody; CNSDC, chronic non-suppurative destructive cholangitis; PBC, primary biliary cholangitis.

Figure 3.

Histopathological findings in PBC characterizing stage 1, 2, 3, and 4 of the Scheruer’s classification. (A) Chronic non-suppurative destructive cholangitis (arrow, hematoxylin, and eosin staining). Black bar indicates 400 mm. (B) Ductular proliferation (hematoxylin and eosin staining). Black bar, 400 mm. (C) Scarring (silver impregnation staining). Black bar, 100 mm. (D) Nodular cirrhosis (hematoxylin and eosin staining). Black bar, 200 mm. All these figures were kindly provided by Professor Kenichi Harada (Kanazawa University, Kanazawa, Japan).

Figure 4.

A change of treatment and outcome over time in Japan. (A) The proportion of patients treated with UDCA (light gray bars) and bezafibrate (dark gray bars) in Japan stratified by the diagnosis year. (B) The LT-free survival rate of patients with PBC in Japan, stratified by the diagnosis year. LT, liver transplantation; UDCA, ursodeoxycholic acid; PBC, primary biliary cholangitis.

Figure 5.

A treatment flowchart of patients with PBC. UDCA, ursodeoxycholic acid; PBC, primary biliary cholangitis.