Autoimmune hepatitis and primary biliary cholangitis are among a subset of autoimmune diseases defined by profound co-prevalence and genetic risk association with the IL12 pathway.

Decision at stakethe genetic and mechanistic underpinnings of primary biliary cholangitis

Treat with first-line ursodeoxycholic acid (UDCA) 13-15 mg/kg/d divided, and assess biochemical response at 12 months using Paris-II plus continuous risk scores (Globe, UK-PBC). Escalate to a second-line agent (obeticholic acid [contraindicated in cirrhosis with portal hypertension or prior decompensation], seladelpar, elafibranor, or a fibrate) when response is inadequate, guided by a Child-Pugh/portal-hypertension hard gate, and manage pruritus with a stepwise ladder (cholestyramine → rifampin → sertraline → naltrexone). Refer for transplant evaluation for decompensation, refractory pruritus, or rising bilirubin.