DILI Is an Important Cause of Hepatocellular and Mixed Liver Injury—A Nationwide Prospective Study on Elevated Liver Enzymes

Background and Aims: Very few prospective studies have investigated the most common causes of concomitant elevation of ALT and ALP. We aimed to investigate the most common aetiologies of hepatocellular or cholestatic liver injury, and to study the proportion of patients with DILI. Methods: A 2-year prospective study, in Landspitali Hospital, Iceland on patients with (A) ALT > 500 and (B) ALT > 250 U/L and ALP > 210 U/L. Appropriate diagnostic work-up was undertaken. Causality assessment in suspected DILI was with RECAM and expert opinion. Results: A total of 835 patients were identified with: ALT > 500 U/L (n = 500) or ALT > 250 and ALP > 210 (n = 318), 17 were excluded due to a lack of information or elevations of non-liver related causes. Among 818 patients: 451 females (55%), median age 58 (IQR 40–72). The most common causes were choledocholithiasis 42%, ischaemic hepatitis (IH) 17%, hepato-biliary cancer (HBC) 8.4%, DILI 8.2%, viral hepatitis 6.2%, other aetiologies 11% and unknown aetiologies in 7.8%. IH was significantly more common in Group A but HBC in Group B. DILI was similar in both groups. Amoxicillin-clavulanate, checkpoint inhibitors, herbal-dietary supplements (HDS) and paracetamol were the major causative agents in DILI patients. IH and HBC patients had the highest mortality. Two DILI patients died of liver failure and one patient needed emergency liver transplantation associated with HDS. Conclusions: The most common cause in both groups was choledocholithiasis. IH was associated with hepatocellular injury whereas HBC was associated with cholestatic injury. DILI was an important aetiology with 8% prevalence in the cohort and was similar in the two groups.