Idiosyncratic Liver Injury Associated with Drugs (ILIAD)

The goal of the ILIAD protocol is to create a database and bank of biological specimens (DNA, plasma, lymphocytes) from individuals with severe drug-induced liver injury (DILI) due to isoniazid (INH), phenytoin (Dilantin), amoxicillin/clavulanate (Augmentin), or valproic acid (Depakote) after January 1, 1994. This study is funded by the NIH/NIDDK.

Inclusion Criteria

• The suspect medication is isoniazid, phenytoin, amoxicillin/clavulanate, or valproic acid

• For INH, phenytoin, or amoxicillin/clavulanate, peak total serum bilirubin >2.5 mg/dL

• For valproic acid, clinical presentation severe enough to prompt hospitalization with evidence of liver injury (INR >1.5, serum ALT >3 x ULN, or characteristic liver biopsy)

• DILI episode after January 1, 1994

Exclusion Criteria

• Age <2 years at enrollment

Study Design

• Telephone or personal interview of medical history surrounding DILI event
• Single blood draw
• Participant receives $75

Please contact Suzanne Welch at (734) 936-4886, toll free 1-866-UM-LIVER, pager # 4742, or swelc@umich.edu or Robert Fontana rfontana@umich.edu or pager # 4820 for referrals or questions.

For more information, see the following web sites:
Drug-Induced Liver Injury Network http://dilin.dcri.duke.edu/index.html
NIH funds network to study drug-induced liver injury http://www.nih.gov/news/pr/nov2004/niddk-19.htm
Press Release: U-M helps lead national study of liver damage http://www.med.umich.edu/opm/newspage/2004/liverstudy.htm

1-866-UM-LIVER
swelc@umich.edu

A Multicenter, Longitudinal Study of Drug- and CAM-Induced Liver Injury

The goal of this NIH study is to prospectively identify bona fide cases of liver injury due to drugs and complementary and alternative medications (CAM) within 6 months of onset. Clinical data, blood, DNA, and urine will be collected from affected patients and matched controls for mechanistic and genetic studies.

Inclusion criteria

• Age >2 years
• Liver injury known or suspected to be related to a drug or CAM product in the 6-months prior to enrollment
• Clinically important DILI, defined as:
  —ALT or AST > 5 x ULN or Alk Phos > 2 x ULN confirmed on at least 2 consecutive blood draws in patients with previously normal values
  —If baseline (BL) ALT, AST, or Alk Phos are elevated, ALT or AST >5 x BL or Alk Phos > 2 x BL on at least 2 consecutive blood draws
  —Any elevation in ALT, Alk Phos, or AST associated with total bilirubin > 2.5 mg/dL in absence of liver disease, Gilbert’s, hemolysis
• For liver disease cases, established chronic hepatitis B or C infections for > 6 months prior to DILI onset.

Exclusion Criteria

• Competing cause of acute liver injury such as hepatic ischemia or acetaminophen overdose or pre-existing autoimmune hepatitis, PBC, or PSC which may confound the ability to diagnose DILI.
• Liver transplant prior to DILI onset.

Study Design

• All subjects have a baseline and 6-month follow-up visit at the GCRC which includes surveys, medical history, blood and urine collection.
• Patients with liver injury at 6 months return for 12- and 24-month visits.

Costs

• Costs of study lab tests provided by sponsor (NIDDK).
• Subjects receive $50 for each completed study visit.

Please contact Suzanne Welch at (734) 936-4886, toll free 1-866-UM-LIVER, pager # 4742, or swelc@umich.edu or Robert Fontana rfontana@umich.edu or pager # 4820 for referrals or questions.

For more information, see the following web sites:
Drug-Induced Liver Injury Network http://dilin.dcri.duke.edu/index.html
NIH funds network to study drug-induced liver injury http://www.nih.gov/news/pr/nov2004/niddk-19.htm
Press Release: U-M helps lead national study of liver damage http://www.med.umich.edu/opm/newspage/2004/liverstudy.htm

1-866-UM-LIVER
swelc@umich.edu