In Idiosyncratic drug-induced liver injury (DILI), the adverse effect is unexpected from
the known pharmacological action of the agent. The incidence of DILI is estimated as
between 14-19 per 100,000 inhabitants; a population-based study in Europe reported the
annual incidence as 19.1 per 100,000. Despite its rarity, idiosyncratic DILI accounts for
7-15% of the cases of acute liver failure in Europe, although many cases resolve quickly.
DILI is the most frequent reason for the market withdrawal of an approved drug. In
addition, DILI occurs in association with many drugs and shows heterogeneity. There are
no markers that can effectively pre-empt and prevent DILI or monitor the severity and
course of the adverse event. It is also emerging that immunotherapy regimens devised for
cancer treatment are associated with increased risk of DILI development.
Further characterisation and understanding of this is urgently needed to distinguish from
other causes and develop more effective treatments. Age, smoking, metabolic syndrome,
co-morbidity and other yet unidentified factors may generate an environment of oxidative
stress that contributes to DILI. Therefore, 'in-depth phenotyping' is needed to develop a
refined understanding of drug-related factors, host genetic and environmental risk
factors linked to disease characteristics that would enable us to pre-empt and treat
DILI. Further work is also needed to identify patients who may benefit from new
treatments becoming available, so identification and analysis of certain sub-groups is of
value.
Based on the pattern of liver biochemistry at the time of initial presentation, DILI is
classified as cholestatic, hepatocellular or mixed type. Pruritus (itching) occurs in a
proportion of patients with cholestatic and mixed pattern of DILI. Most DILI
manifestations resolve within 3 months following the prompt withdrawal of the causative
medication, but symptoms persist for 6 months in 18.8% and for 1 year in 12.4%;
persistence of symptoms are more common in cholestatic pattern of DILI. Those with
persistent DILI have significantly lower SF-36 quality of life scores at baseline and
during follow-up.
Research is needed to identify patients who may benefit from new treatments becoming
available, so identification and analysis of certain sub-groups is of value. DILI is the
second most common cause of itching in adult Hepatology, after biliary obstruction.
Cholestatic or mixed pattern of DILI is associated with chronicity as well as reduced
quality of life.
There is currently limited data available on the incidence and impact of pruritus in
DILI. Although therapeutics targeting bile acid pathways have been deployed to tackle
cholestatic pruritus in primary biliary cholangitis (PBC), their application in
cholestatic DILI requires investigation. Further, there is now also effective treatment
that have been licensed to improve quality of life of patients with itching as well as
potentially improving natural history of cholestatic conditions.