What factors affect time to recovery in patients with drug-induced liver injury?

Serum bilirubin and alkaline phosphatase (ALP) levels, along with the extent of drug metabolism, all affect the time to recover from drug-induced liver injury (DILI), a recent study has found.

Using data from 294 cases of DILI from the International Drug-Induced Liver Network Consortium, the researchers applied an accelerated failure time model. Findings were externally validated using the Spanish DILI Registry (n=257) and the LiverTox database (n=191).

Multivariate analysis identified the log of serum ALP (time ratio [TR], 1.25, 95 percent confidence interval [CI], 1.06–1.48; p=0.008), of serum bilirubin (TR, 1.32, 95 percent CI, 1.19–1.47; p<0.001), and of time to onset (TR, 1.17, 95 percent CI, 1.07–1.29; p=0.001) as significant correlates of longer recovery. The same was true for the extent of drug metabolism, though with an inverse association (TR, 0.64, 95 percent CI, 0.50–0.83; p<0.001).

Taking the above factors into consideration, the researchers then defined high- and low-risk groups. Those with high-risk had an estimated probability of recovery by 6 months of 0.46 (95 percent CI, 0.26–0.61). On the other hand, the respective probability estimate for the low-risk group was 0.93 (95 percent CI, 0.58–0.99).

Validation in both external cohorts returned similar results, with the high-risk groups, as defined by the above factors, taking longer to recover from DILI.

“The model we developed is robust, maintaining significance in drug-specific subgroups, as well as in a separate cohort which included a number of different drugs,” the researchers said.