Prolonged interval of total bilirubin decline is an early independent predictive factor of chronic persistent drug‐induced liver injury

Abstract

Aim Chronic drug‐induced liver injury (DILI) with persistent abnormal liver function tests (LFTs) >6 months after cessation of the insulting drugs could progress to cirrhosis. The aim of the present study was to identify the risk factors of chronic DILI for early recognition and better management. Methods History of drug intake and results of LFTs were retrospectively retrieved for patients with a discharge diagnosis of DILI for at least 1‐year follow up. The risk factors independently associated with chronic DILI were analyzed by multiple logistic regression analyses. Results A total of 33 of the 140 DILI patients had persistent abnormal LFTs >6 months, which were considered as chronic DILI. It was found that the time intervals of alanine aminotransferase and total bilirubin decline from the peak to their half peak (T0.5ALT, T0.5TBIL) were significantly longer in the chronic DILI group than that in the recovered group (P = 0.001 and P < 0.001). The risk factors associated with chronic DILI independently were T0.5TBIL (OR 1.315, 95% CI 1.038–1.668), longer period of insulting drug(s) intake (OR 1.018, 95% CI 1.003–1.033), mixed/cholestatic pattern (OR 97.159, 95% CI 1.866–5005.994). More importantly, receiver operating characteristic curve analysis showed that the prognostic value of T0.5TBIL for chronic DILI had a sensitivity of 60.0% at a specificity of 90.7% with the threshold of 16 days. Conclusions The time intervals of total bilirubin decline from its peak to half of its peak (T0.5TBIL) was an early independent predictive factor of chronic DILI, suggesting that T0.5TBIL might serve as an indicator for chronicity.

Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI

“…A recent retrospective study found that prolonged bilirubin decline from the peak value to its half of the peak value was an independent risk factor for chronic DILI. 27 Some studies defined chronic DILI as 6 months or 1 year from onset; 3,5,28,29 whereas our study relied on an AFT model rather than a binary cut-off, giving us more statistical power with which to identify influential factors (i.e., total bilirubin at onset). Of note, our extended analysis showed that the initial bilirubin value remained significant when tested in all injury type subgroups: hepatocellular (time ratio 1.63; 95% CI 1.35-1.97; p <0.0001), mixed (time ratio 1.43; 95% CI 1.20-1.69; p <0.0001), and cholestatic (time ratio 1.24; 95% CI 1.04-1.47, p = 0.019).…”

Analysis of Clinical Characteristics and Chronic Factors of Drug-induced Liver Injury in Chronic Hepatitis B Infection: A Retrospective Study

“…The serum microRNA-122 level has been proposed to predict adverse outcomes such as subsequent development of DILI to liver failure (22). Zhu et al (23) have reported that prolonger T0.5TBil (total bilirubin decreased from peak to half of the peak), an index of cholestasis, is an early and independent predictor of chronic DILI. These findings need to be further validated by larger prospective studies.…”