The Treatment of Primary Biliary Cholangitis: Time for Personalized Medicine

Primary Biliary Cholangitis is an autoimmune liver disease distinguished by Anti-mitochondrial Antibodies and chronic non-suppurative lymphocytic microcholangitis. UDCA remains the exclusively recommended initial therapy for PBC. However, 40% of patients experience either incomplete biochemical response or intolerance to UDCA, which represents poorer outcomes and increased mortality. Therefore, early identification of high-risk patients and timely intensive treatments are necessary to delay the progression of PBC and better improve the prognosis. Intensive therapeutic strategies based on more stringent treatment goals and early efficacy assessment criteria are elaborated in this review. To exclude AIH-PBC overlap syndrome, liver biopsy is required for cholestasis patients with negative AMAs or PBC patients who respond inadequately to UDCA, especially those with elevated ALT and IgG. Combined immunosuppressants are considered for patients with moderate-to-severe hepatitis. ALP normalization is considered the improved therapeutic goal for high-risk patients, which has been verified achievable in multiple treatment attempts. The control of pruritus and fatigue constitutes the key therapeutic targets in the symptom management of PBC. Bezafibrate, Seladelpar, and IBAT inhibitors have demonstrated significant therapeutic potential in pruritus. Last but not least, Liver Stiffness Measurement is substantiated as efficient in the fibrotic monitoring of PBC patients. OCA and fibrates are respectively useful for compensated and decompensated fibrotic patients. Moreover, the conventional efficacy assessment procedure, which is the "wait-to-fail" strategy, exhibits suboptimal sensitivity in the timely detection of treatment-responsive patients. Therefore, early prediction and evaluation criteria at baseline and 1-month treatment will help in timely interventions for patients with insufficient efficacy. This improved identification strategy is expected to provide precise and personalized treatment for PBC patients.