Checkpoint Inhibitor-induced Liver Injury
Checkpoint Inhibitor-induced Liver Injury
In this multi-center prospective observational study, the investigators plan to identify the
 incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize
 biochemical, genetic, immunological, and histological features associated with it.
Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category
 of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such
 as direct or idiosyncratic DILI. The data regarding the incidence and risk factors is
 lacking. Therefore, 'in-depth phenotyping' together with data from the control group exposed
 to checkpoint inhibitors (CPI) is necessary to develop refined algorithms incorporating
 CPI-related factors, host genetic and environmental risk factors that would enable
 pre-empting ChILI.

 The aim of the study is to enroll two deeply phenotyped cohorts (patients who developed ChILI
 and patients who are starting checkpoint inhibitors) and obtain biological samples at
 multiple time points.
Inclusion Criteria:

 Both patient groups and control group:

 • Able to give written informed consent OR Potential participants who have developed
 encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the
 capacity to give written informed consent and have a consultee (personal or nominated) -
 for ChILI patient group only

 ChILI group:

 Patients who developed checkpoint inhibitor-induced liver injury and meet the following
 criteria:

 1. Meets one of the following analytical thresholds at enrolment (visit 1)

 -  Alanine transaminase (ALT) exceeding 5 times the upper limit of normal (ULN) OR

 -  ALT exceeding 3 times ULN plus bilirubin exceeding 2 times ULN OR

 -  Alkaline phosphatase (ALP) exceeding 2 times ULN with accompanying elevations of
 gamma-glutamyl transferase in the absence of known bone metastases driving the
 rise in ALP level

 2. Absence of other known causes of liver injury after detailed investigations

 Patients who developed ChILI but did not meet the above criteria at enrolment or who were
 found to have a different cause for their liver injury after further investigations will be
 excluded from the analysis

 Control group:

 Consecutive patients with cancer who have a clinical indication to start checkpoint
 inhibitors. A small proportion of patients will develop ChILI following their checkpoint
 inhibitor treatment and will be classified as cases.

 Exclusion Criteria:

 -  Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint
 inhibitors.

 -  On the judgment of chief investigator that the person has certain alternative
 explanations to the acute event (rather than ChILI).