2 Thiopurine

methyltransferase (TPMT) level was normal (53 nmol/g, range 35-79). Subsequently she started azathioprine (AZA) 75 mg daily (1 mg/kg). Her ALT and IgG normalized 6 weeks later. Following prednisolone reduction to 10 mg, her ALT increased to 147 IU/L despite AZA compliance. Forty milligrams prednisolone was reinstituted. On tapering to 10 mg she developed persistently fluctuating ALT (40-80 IU/L) despite increased AZA to 150 mg (2 mg/kg). A rise of ALT to 133 IU/L required 40 mg prednisolone again. Repeat liver biopsy revealed steatosis but much reduced interface hepatitis. Thiopurine metabolite levels (Lennard method) revealed a 6-thioguanine (6-TGN-the active moiety) level of 100 pmol/8 × 108 red blood cells (RBC) (normal range 250-450) and a 6-methyl mercaptopurine (6-MMP) level of 5800 pmol/8 × 108 RBC, consistent with hypermethylation this website and preferential shunting to 6-MMP. Allopurinol 100 mg once daily was added and her AZA dose reduced by 75%. Subsequently, her ALT normalized within 4 weeks (Fig. 1). This combination corrected her metabolite levels (6-TGN 202 pmol/8 × 108 RBC and 6-MMP 196 pmol/8 × 108 RBC). Prednisolone was withdrawn after 3 months; her ALT remains 10-15 IU/L 12 months later. AZA is essential in managing AIH, often obviating the need for long-term prednisolone. Between 3%-13% of inflammatory bowel disease (IBD) and AIH patients will develop AZA-induced

hepatotoxicity,3-5 which may be difficult to distinguish from AIH nonresponse or relapse without liver APO866 research buy biopsy. In this setting, measuring thiopurine metabolites can provide diagnostic guidance. The finding of increased 6-MMP >5700 pmol/8 × 108 RBC with low or normal 6-TGN (“shunting”) is associated with hepatotoxicity and other side effects including nausea, anorexia, and influenza-like symptoms in IBD patients.5 Our patient’s persistently elevated ALT was consistent with AZA-induced hepatotoxicity (raised ALT secondary to high 6-MMP.) Repeat liver biopsy revealed prednisolone-induced

MCE公司 steatosis with only mildly active AIH. High 6-MMP levels do not always cause hepatotoxicity, however. Allopurinol acts through inhibition of xanthine oxidase, producing preferential AZA breakdown by the TPMT enzymatic pathway resulting in higher 6-TGN and lower 6-MMP (Fig. 2), although the exact mechanism is not fully understood. The combination requires AZA dose reduction to prevent excess 6-TGN production. This is the first reported adult case of allopurinol co-therapy in AIH for the management of AZA-induced hepatotoxicity. This strategy allowed our patient to discontinue prednisolone and avoid alternative immunosuppression. A study into the utility of measuring thiopurine metabolites identified AZA-induced hepatotoxicity, although the investigators found no role for measuring levels to monitor treatment response.