Drug-induced Liver Injury: Itching Study

April 24, 2026 updated by: University of Nottingham

Understanding the Natural History and Impact of Itching (Pruritus) in Patients With Drug-induced Liver Injury (DILI)

Idiosyncratic drug-induced liver injury (DILI) is an unpredictable adverse hepatic reaction to a medication used in its therapeutic dose. DILI is the second most common cause of itching in adult Hepatology after biliary obstruction. In particular cholestatic or mixed pattern types of DILI (in which bile flow from the liver is impaired) are associated with long-lasting effects as well as reduced quality of life. There is therefore an urgent need to determine the incidence and natural history of itching in DILI and establish a network of centres that will form a basis for a clinical trial to investigate a novel intervention to treat these.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospitals NHS Trust
        • Contact:
          • Sophie Cusick

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients recruited are those who meet the criteria for DILI, as defined by Aithal et al. (2011) and endorsed by the EASL DILI Guidelines.

Description

Inclusion Criteria:

  • Age ≥18 (no upper age limit) and able to give informed written consent

  • Exposure to potential causal agent and diagnosed with suspected acute DILI defined as meeting one of the following analytical thresholds at enrolment (visit 1):

    • alanine transaminase (ALT) ≥5 times upper limit of normal (ULN) or
    • alkaline phosphatase ≥2 times ULN or
    • ALT ≥3 times ULN plus total bilirubin >2 times ULN

Results from clinical test samples collected within 36h of visit will be acceptable (as DILI is an acute event, patients are expected to recover or deteriorate quickly so enrolment aligned with diagnostic tests is necessary).

Exclusion Criteria:

  • Patients with comorbidities of eczema and urticaria associated with pruritus
  • Patients with existing diagnosis of blood-borne viral hepatitis infection (Hepatitis B/C/E)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of pruritus (itching) in patients with DILI
Time Frame: 2 years
To determine the number of participants who have diagnosis of DILI who report pruritus (itching) compared to the number with other acute non-DILI conditions (e.g. autoimmune hepatitis/viral hepatitis) who report itching within a cohort of patients presenting with acute liver injury.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of itching (pruritus) in patients who present with acute liver injury
Time Frame: 4 years
To determine the duration and re-occurrence of pruritus (itching) symptoms in patients who are diagnosed with DILI and in those with other acute non-DILI conditions. This will entail a repeated questionnaire at study visits and assessment of medical records to report a timescale of symptoms (weeks).
4 years
Severity of itching (pruritus) in patients who present with acute liver injury
Time Frame: 4 years
To determine the severity of pruritus (itching) symptoms in patients who are diagnosed with DILI and in those with other acute non-DILI conditions. This will entail a repeated questionnaire at study visits to establish the level of itching.
4 years
Genetic variants associated with itching (pruritus) in patients who present with acute liver injury
Time Frame: 2.5 years
To determine whether any genetic variants of a 77 gene liver cholestasis panel (including causal variants of progressive familial intrahepatic cholestasis (PFIC)) are associated with pruritus in acute liver injury patients. The study will report presence or absence of genetic markers
2.5 years
Health status reported by patients who present with acute liver injury
Time Frame: 4 years
To determine the health status reported by patients who are diagnosed with DILI and in those with other acute non-DILI conditions. This will entail a repeated Short Form 36 Health Survey Questionnaire (SF-36) questionnaire at study visits giving a score ranging from 0 to 100. Higher scores indicate better health status.
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nottingham

Collaborators

Nottingham University Hospitals NHS Trust
Ipsen
National Institute for Health Research, United Kingdom

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2025

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

May 15, 2024

First Submitted That Met QC Criteria

June 4, 2024

First Posted (Actual)

June 6, 2024

Study Record Updates

Last Update Posted (Actual)

April 30, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

June 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23056

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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