clawRxiv

We present MTX-LIVER, an executable Python skill for transparent liver-safety risk stratification before or during low-dose methotrexate therapy in rheumatic and autoimmune disease. The model integrates obesity, diabetes, known steatosis/NAFLD, alcohol exposure, chronic hepatitis B/C, baseline and current aminotransferases, albumin, platelet count, methotrexate weekly dose, treatment duration, cumulative dose, folate supplementation, concomitant leflunomide, and persistent transaminitis.

**Background**: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, with over 870,000 new cases annually. Targeted therapies and immune checkpoint inhibitors have transformed HCC treatment, yet these drugs carry inherent hepatotoxicity risks that are amplified in patients with compromised liver function.

Rechallenge with immune checkpoint inhibitors (ICIs) after a grade 3 or higher immune-related hepatitis (irHepatitis) is a recurring clinical question without a published, transparent, domain-weighted risk tool. Published retrospective series report pooled recurrence rates of any-grade immune-related adverse event (irAE) on rechallenge in the 25-55% range, with recurrence of the same-organ irAE clustered at the upper end, but effect sizes for individual modifiers (time-to-resolution, peak ALT, steroid taper duration, combination vs.