A new framework for advancing in drug‐induced liver injury research. The Prospective European DILI Registry

Expert judgement is the approach used to assess causality in large prospective DILI registries such as the Spanish, Latin American, European, and DILIN registries.

“Expert judgement is the approach used to assess causality in large prospective DILI registries such as the Spanish, the Latin American, the European, or the DILIN.”

In response to limitations of expert judgement, the Spanish, LATINDILI and Pro-Euro DILI networks combined evaluation of suspected DILI cases by three experts with further assessment using causality scales, while DILIN developed a structured expert opinion process.

“In response to these limitations, the Spanish, LATINDILI and Pro‐Euro DILI networks have combined the evaluation of suspected DILI cases by three experts and further assessment using causality scales, while the DILIN has developed a structured expert opinion process.”

The pharmacological groups most frequently involved in DILI are antimicrobials, cardiovascular system drugs, and musculoskeletal system drugs, although this varies according to country and areas of the world.

“The pharmacological groups most frequently involved in DILI are antimicrobials, cardiovascular system drugs, and musculoskeletal system drugs, although this varies according to country and areas of the world [3][4][5][6].”

ChILI is accounting for an increasing proportion of recent DILI cohort studies.

“Checkpoint inhibitor-induced liver injury (ChILI) is accounting for an increasing proportion of recent DILI cohort studies.”

There are differences between the main agents responsible in the three registries analysed.

“It is important to note that there are differences between the main agents responsible in the three registries analysed (Table 1; Fig. 1) [3][4][5].”

In the more recent European registry, there is a notable increase in the presence of flucoxacillin (11%), atorvastatin (8%), and nivolumab-ipilimumab, a combination with 16 cases (8%).

“In contrast, in the more recent European registry, there is a notable increase in the presence of flucoxacillin (11%), atorvastatin (8%), and nivolumab-ipilimumab, a combination with 16 cases (8%) [5].”

In the Spanish register there is a predominance of males, compared to the other two where females predominate (48% in Spanish, 57% in European and 59% in American).

“Furthermore, in the Spanish register there is a predominance of males, compared to the other two where females predominate (48% in Spanish, 57% in European and 59% in American) [3][4][5].”

Data on liver transplantation are higher in the American DILI cohort (4%) than in the European (2.5%) and Spanish (1.5%) cohorts.

“Data on liver transplantation are also higher in the American DILI cohort (4%) than in the European (2.5%) and Spanish (1.5%) cohorts [3][4][5].”

In all three registries, the predominant pattern was hepatocellular, with jaundice rates of between 60 and 70%.

“In all three registries, the predominant pattern was hepatocellular, with jaundice rates of between 60 and 70% [3][4][5].”

The average age was around 55 years in both the European and Spanish hepatotoxicity registries, being slightly lower (49 years on average) in the North American registry.

“Regarding to demographic data, it should be noted that the average age was around 55 years in both the European and Spanish hepatotoxicity registries, being slightly lower (49 years on average) in the North American registry.”

In terms of severity of liver injury, percentages are fairly homogeneous between the Spanish and European registries, with a higher frequency of severe and fatal outcomes in the American registry, at 19% and 7% respectively.

“In terms of severity of liver injury, percentages are fairly homogeneous between the Spanish and European registries, with a higher frequency of severe and fatal outcomes in the American registry, at 19% and 7% respectively.”

Amoxicillin-clavulanic acid is the most common xenobiotic, accounting for 10.1%, 22.9% and 12% in American, Spanish and European registries, respectively.

“Evaluating only the responsible agents separately, amoxicillin-clavulanic acid is the most common xenobiotic, accounting for 10.1%, 22.9% and 12% in American, Spanish and European registries, respectively [3][4][5].”

Regarding herbal products, the percentage is much higher in the American registry (145 cases, 16%) than in the Spanish and European registries (6% in both, including cases of anabolic steroids).

“Regarding to herbal products, the percentage is much higher in the American registry (145 cases, 16%) than in the Spanish and European registries (6% in both, including cases of anabolic steroids) [3][4][5]”