Patterns of disease progression and incidence of complications in primary biliary cholangitis (PBC)

Abstract

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Clinical Updates in Primary Biliary Cholangitis: Trends, Epidemiology, Diagnostics, and New Therapeutic Approaches

“…Cholestasis contributes to chronic granulomatous inflammation, which eventually leads to fibrosis and the subsequent development of cirrhosis and portal hypertension, along with its associated complications, including a predisposition to hepatocellular carcinoma (HCC). 43 With increasing awareness and understanding of the natural history of the disease, as well as earlier diagnosis and prompt treatment initiation, the progression to fibrosis and cirrhosis among PBC patients is becoming increasingly rarer, as demonstrated by the decrease in the indications of liver transplantation for PBC patients. 19,41,44 The introduction and use of UDCA for treating PBC has impacted the natural history of the disease.…”

“…Patients with PBC are at an increased risk of developing HCC, though at a lower rate compared to those with other chronic liver diseases. 37,43 In a multicenter study involving over 4,500 patients over a 40-year period, Trivedi et al 57 showed that the incidence of HCC among PBC patients was 3.4 cases per 1,000 person-years. In particular, PBC patients with advanced age at diagnosis, advanced disease, male sex, and suboptimal response to UDCA are at higher risk for development of HCC.…”

“…57 Development of HCC in patients with PBC is associated with notably worse transplant-free and overall survival. 43 Given this, PBC patients with known or suspected cirrhosis should receive screening ultrasounds for HCC with or without alpha fetoprotein at regular 6 month intervals. Development of portal hypertension can also occur in these patients with cirrhosis or in some patients before full-blown cirrhosis, given granulomatous inflammation leading to presinusoidal portal hypertension.…”

“…Baseline bone mineral density scans should be done at diagnosis and then subsequent screening should be continued on the basis of risk. 23,43 General management includes calcium and vitamin D supplementation, encouraged weight-bearing exercises, and bisphosphonates to improve bone mineral density, though their effectiveness in PBC is not clear. 23 Because of chronic cholestasis, hyperlipidemia is common but rarely of clinical significance; lipid-lowering therapies should be considered in patients with other coexisting cardiovascular risk factors.…”

Interplay between Mast Cells and Regulatory T Cells in Immune-Mediated Cholangiopathies

“…PBC is characterised by T-lymphocyte-mediated destruction of the intrahepatic small bile ducts [ 6 ], cholestatic liver biochemistries, and the presence of antimitochondrial antibodies (AMAs) [ 7 ]. These highly disease-specific autoantibodies are directed against the E2 subunit of the pyruvate dehydrogenase complex and are present in 90–95% of PBC patients and less than 1% of healthy controls [ 8 , 9 ]. In PSC, circulating autoantibodies are not as frequent, but rather auto-inflammation is a more typical characteristic of the condition [ 10 ].…”