Pharmacological interventions for primary biliary cholangitis: an attempted network meta-analysis

Area of Science:

• Hepatology
• Clinical Pharmacology
• Evidence Synthesis

Background:

• Primary biliary cholangitis (PBC) is a chronic liver disease characterized by bile duct destruction, leading to cholestasis, fibrosis, and cirrhosis.
• The optimal pharmacological treatment for PBC remains uncertain, necessitating a comprehensive review of available interventions.

Purpose of the Study:

• To conduct a network meta-analysis comparing the benefits and harms of pharmacological interventions for PBC.
• To rank interventions based on safety and efficacy, aiming to clarify optimal treatment strategies.

Main Methods:

• A systematic search of multiple databases (CENTRAL, MEDLINE, Embase, etc.) identified randomized clinical trials up to February 2017.
• Standard Cochrane methodology was employed for data collection and analysis, including risk of bias assessment and GRADE quality evaluation.
• Due to heterogeneity, a network meta-analysis was not performed; instead, standard comparative methods were used.

Main Results:

• 74 trials (5902 participants) were identified; 46 provided outcome data. All trials had a high risk of bias, with evidence quality rated as low or very low.
• Methotrexate showed a potential increase in mortality (low quality evidence), while azathioprine showed a potential decrease (low quality evidence, but with unreliable results).
• D-penicillamine and obeticholic acid plus UDCA showed increased serious adverse events compared to no intervention or UDCA alone, respectively (low quality evidence).

Conclusions:

• Current evidence, of very low quality, suggests no definitive benefit from any pharmacological intervention for PBC.
• Significant uncertainty exists due to short follow-up periods and high risk of bias in included trials.
• Further well-designed, adequately powered randomized clinical trials with longer follow-up and clinically relevant outcomes are essential for establishing effective PBC treatments.