ClinicalTrials.gg
RecruitingNCT06446609Updated Jul 27, 2026

Drug-induced Liver Injury: Itching Study

An observational study in Drug Induced Liver Injury and Pruritus, sponsored by University of Nottingham. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-27.

Sponsored by University of Nottingham · Observational

From the registry’s dates

  • Started Jun 2025; still recruiting 1 year 4 months later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
50
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

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Conditions studied

  • Drug Induced Liver Injury
  • Pruritus
03

In context

Chemical and Drug Induced Liver Injury

80 studies on the registry are indexed under Chemical and Drug Induced Liver Injury; 21 are open to participants now.

This study's planned enrollment of 50 is below the median of 407 across 39 observational studies indexed under Chemical and Drug Induced Liver Injury.

Browse Chemical and Drug Induced Liver Injury studies →

Lead sponsor

University of Nottingham is the lead sponsor of 465 studies on the registry; 80 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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):

    • (ALT) ≥5 times (ULN) or
    • alkaline phosphatase ≥2 times ULN or
    • ALT ≥3 times ULN plus total >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

Exclusion Criteria:

  • Patients with comorbidities of eczema and urticaria associated with pruritus
  • Patients with existing diagnosis of blood-borne viral hepatitis infection (/C/E)
Terms in these criteria, in plain language(4)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
50 participants (estimated)
Patient registry
No
06

What researchers measure

Primary outcomes

  1. Incidence of pruritus (itching) in patients with DILI

    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.

    Time frame: 2 years

Secondary outcomes

  1. Duration of itching (pruritus) in patients who present with acute liver injury

    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).

    Time frame: 4 years

  2. Severity of itching (pruritus) in patients who present with acute liver injury

    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.

    Time frame: 4 years

  3. Genetic variants associated with itching (pruritus) in patients who present with acute liver injury

    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

    Time frame: 2.5 years

  4. Health status reported by patients who present with acute liver injury

    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.

    Time frame: 4 years

07

Study locations

1 of 1 sites recruiting
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References and documents

Publications

  • Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011 Jun;89(6):806-15. doi: 10.1038/clpt.2011.58. Epub 2011 May 4. PubMed 21544079 ↗
  • Andrade RJ, Chalasani N, Bjornsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, Devarbhavi H, Merz M, Lucena MI, Kaplowitz N, Aithal GP. Drug-induced liver injury. Nat Rev Dis Primers. 2019 Aug 22;5(1):58. doi: 10.1038/s41572-019-0105-0. PubMed 31439850 ↗
  • Bjornsson ES, Bergmann OM, Bjornsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013 Jun;144(7):1419-25, 1425.e1-3; quiz e19-20. doi: 10.1053/j.gastro.2013.02.006. Epub 2013 Feb 16. PubMed 23419359 ↗
  • Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, Weber S, Stirnimann G, Kullak-Ublick G, Cortez-Pinto H, Grove JI, Lucena MI, Andrade RJ, Aithal GP. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023 Jan;43(1):115-126. doi: 10.1111/liv.15378. Epub 2022 Aug 15. PubMed 35899490 ↗
  • Chen HL, Li HY, Wu JF, Wu SH, Chen HL, Yang YH, Hsu YH, Liou BY, Chang MH, Ni YH. Panel-Based Next-Generation Sequencing for the Diagnosis of Cholestatic Genetic Liver Diseases: Clinical Utility and Challenges. J Pediatr. 2019 Feb;205:153-159.e6. doi: 10.1016/j.jpeds.2018.09.028. Epub 2018 Oct 23. PubMed 30366773 ↗
  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019 Jun;70(6):1222-1261. doi: 10.1016/j.jhep.2019.02.014. Epub 2019 Mar 27. PubMed 30926241 ↗
  • Fontana RJ, Hayashi PH, Barnhart H, Kleiner DE, Reddy KR, Chalasani N, Lee WM, Stolz A, Phillips T, Serrano J, Watkins PB; DILIN Investigators. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol. 2015 Oct;110(10):1450-9. doi: 10.1038/ajg.2015.283. Epub 2015 Sep 8. PubMed 26346867 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 27, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT06446609
Collaborators
Ipsen, National Institute for Health Research, United Kingdom, Nottingham University Hospitals NHS Trust
Responsible party
Sponsor
First posted
Jun 6, 2024
Start date
Jun 30, 2025
Primary completion
May 2027 (estimated)
Completion
May 2028 (estimated)
Last update
Jul 27, 2026

Study contacts

Elinor Study Coordinator
Contact
Elinor.Cross@nottingham.ac.uk
0115 7484390

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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