Difficult to treat and refractory autoimmune hepatitis: Recent advances in pharmacological management

Figure 3 Managing patients with autoimmune hepatitis who are intolerant or refractory to azathioprine or 6-mercaptopurine. Azathioprine and 6-mercaptopurine are associated with bone marrow suppression and hepatotoxicity. Baseline TPMT and NUDT-15 genetic polymorphism testing is advocated to avoid myelosuppression. It should be avoided in patients who are homozygous for both enzymes. About 10%–20% of patients who are intolerant to azathioprine can be salvaged with 6-MP or MMF; however, AZA-refractory cases do not respond well to 6-MP. They will often require a third line of therapy or MMF. Metabolite assays can help guide us regarding the need for allopurinol. 6-MMP: 6-methylmercaptopurine; 6-MP: 6-mercaptopurine; 6-TG: 6-thioguanine; TPMT: Thiopurine methyltransferase; AZA: Azathioprine; MMF: Mycophenolate mofetil.