Abstract: Objective To investigate the clinical phenotype characteristics and prognostic differences of drug-induced liver injury (DILI) caused by Tripterygium wilfordii in patients with rheumatoid arthritis (RA), and to provide evidence for early identification and risk stratification management of Tripterygium wilfordii-related liver injury. Methods Patients with RA who developed DILI after treatment with Tripterygium wilfordii were enrolled. Based on liver biochemical parameters at onset, the R ratio was calculated and patients were classified into hepatocellular, cholestatic, and mixed DILI phenotypes. Onset characteristics, baseline clinical data, laboratory findings, treatment course, and prognostic outcomes were compared among the different phenotypes. Results A total of 96 patients with Tripterygium wilfordii–associated drug-induced liver injury (DILI) were included, comprising 45 cases of hepatocellular type, 35 cases of cholestatic type, and 16 cases of mixed type. Patients with hepatocellular DILI had the shortest time to onset[28 (18, 41) days] and the highest proportion of acute onset (62.2%), whereas those with cholestatic and mixed DILI showed significantly delayed onset[56 (38, 82) days and 43 (29, 65) days, respectively] and markedly higher rates of concomitant jaundice (60.0% and 56.3%, respectively; all P<0.05). Laboratory findings revealed markedly elevated ALT levels in the hepatocellular group[612 (388, 945) U/L], while ALp[386 (291, 524) U/L and 312 (236, 418) U/L] and total bilirubin (TBil)[68.4 (45.2, 103.7) μmol/L and 52.1 (34.6, 78.9) μmol/L] levels were significantly higher in the cholestatic and mixed groups than in the hepatocellular group (all P<0.05). During treatment, the rates of ursodeoxycholic acid use (62.9% and 50.0%), glucocorticoid use(42.9% and 43.8%), hospitalization (60.0% and 50.0%), and length of hospital stay[14 (10, 19) days and 12 (9, 16) days] were all significantly higher in the cholestatic and mixed groups compared with the hepatocellular group (P<0.05). In terms of prognosis, the hepatocellular group showed the highest rate of complete liver function recovery (91.1%) and the shortest ALT normalization time[46 (32, 68) days], whereas delayed recovery occurred in 51.4% and 43.8% of patients in the cholestatic and mixed groups, respectively, and chronic DILI developed in 20.0% and 18.8% of patients, respectively (P<0.05 or a trend toward difference). Conclusion DILI caused by Tripterygium wilfordii in patients with RA exhibits marked heterogeneity across clinical phenotypes. Significant differences exist among DILI phenotypes in onset patterns, clinical course, and prognostic outcomes, with cholestatic and mixed phenotypes associated with slower recovery and poorer prognosis. Clinical phenotyping of DILI is helpful for early risk assessment and individualized management of Tripterygium wilfordii-related liver injury.

Key words: Rheumatoid arthritis, Drug-induced liver injury, Tripterygium wilfordii, Clinical phenotype