The association of histological progression with biochemical response to ursodeoxycholic acid in primary biliary cholangitis

Abstract

Primary biliary cholangitis (PBC) is currently diagnosed at an early stage; therefore, the number of patients with PBC without symptoms at the time of diagnosis is increasing. However, up to 30% of patients with PBC exhibit the suboptimal response to ursodeoxycholic acid (UDCA) and are at high risk of end-stage liver disease. Obeticholic acid is an approved second-line therapy for patients with PBC that are refractory to UDCA. Novel surrogate endpoints are required to identify individuals eligible for second-line therapies. An inadequate biochemical response to UDCA is a useful predictor of poor outcomes in patients with PBC. In addition to UDCA effects on biochemical parameters, histological outcomes could be considered as candidate surrogate endpoints. Alterations in liver histology are used as surrogate endpoints in clinical studies. However, current staging systems are insufficient to determine PBC disease severity and progression because of the pathological heterogeneity of the disease. Histological features at baseline and biochemical response to UDCA treatment can affect the disease course of PBC. Therefore, novel surrogate endpoints must be represented by parameters characterized by histological outcomes and treatment responses in PBC. In this review, we discuss the existing histological parameters and newly created factors to identify patients with PBC who are at a high risk of developing end-stage liver disease and, consequently, the potential need for additional treatments.

Enhanced liver fibrosis score as a surrogate of liver-related complications and mortality in primary biliary cholangitis

“…The Ishak system is based entirely on the extent of fibrosis and provides prognostic information in PBC, a condition characterized by the presence of typical histological features such as non-suppurative destructive cholangitis and ductopenia in its early stages. These data reinforce the fact that ELF score reflects liver fibrosis progression associated with bile duct damage [3] …”

“…These data reinforce the fact that ELF score reflects liver fibrosis progression associated with bile duct damage. [3] The ELF score of ≥10.0 was highly significantly associated with significant fibrosis in PBC and reliably identifies those highly at risk of experiencing these complications and death. The 2016 United Kingdom's National Institute for Health and Care Excellence (NICE) guidelines have shown that ELF of ≥10.51 could successfully diagnose advanced fibrosis in nonalcoholic fatty liver disease.…”

“…These data reinforce the fact that ELF score reflects liver fibrosis progression associated with bile duct damage. [ 3 ]…”

“…Primary biliary cholangitis (PBC) is histologically characterized by chronic non-suppurative destructive cholangitis and intrahepatic bile duct destruction, leading to an unfavorable biochemical response and progress to end-stage liver disease that may ultimately require liver transplantation. [ 1 , 2 ] Liver fibrosis is a major independent prognostic factor in patients with chronic liver disease (CLD), including PBC [ 3 ] and nonalcoholic steatohepatitis. [ 4 ] Repeat liver biopsy helps assess liver fibrosis progression or regression over a period of time and evaluate the effects of drug treatment.…”

Macrophage Activation Markers Predict Liver-Related Complications in Primary Biliary Cholangitis

“…Data were collected at baseline and upon treatment with UDCA at a daily dose of 13–15 mg/kg of body weight. The complications of PBC include pruritus, jaundice, ascites, esophageal varices, and hepatocellular carcinoma [ 16 , 17 ]. In this study, patients with PBC were treated with UDCA at a daily dose of 13–15 mg/kg at baseline.…”