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Acetaminophen

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Cysteine

Subjects will take extra strength acetaminophen (4g/day) for the three days prior to the embolization procedure.

Subjects will take no acetaminophen containing products prior to the embolization procedure.

1 gram acetaminophen 4 times a day with at least 6 hour intervals between doses for the 3 days prior to the embolization procedure.

Kennon Heard, MD, PhD

The objective of this study is to provide preliminary data to describe serum acetaminophen-cysteine protein adduct (APAP-CYS) concentrations following therapeutic doses of acetaminophen in the setting of non-acetaminophen induced liver injury. This study will utilize hepatic embolization as a model of hepatic injury.

Acetaminophen-cysteine protein adducts (APAP-CYS) are formed when acetaminophen is oxidized by CYP 2E-1. When hepatocytes die, these proteins are released into the serum and can be detected. APAP-CYS can therefore be an experimental biomarker of acetaminophen exposure. It is possible that massive necrosis of hepatocytes that contain APAP-CYS from therapeutic doses of acetaminophen can be misinterpreted as acetaminophen overdose as the cause of liver injury. This study aims to describe serum APAP-CYS concentrations in patients taking a therapeutic dose of acetaminophen who develop a liver injury from a cause other than acetaminophen. This study will seek to enroll subjects undergoing a hepatic embolization procedure to treat a secondary liver tumor. This procedure is a reproducible model of non-acetaminophen induced hepatic injury. A small number of subjects who are otherwise eligible to participate but are unwilling to take acetaminophen will be offered participation in the observational arm of the study. They will undergo the same assessments with the exception of acetaminophen dosing. Subjects willing to take acetaminophen will be asked to take extra strength acetaminophen (4g/day) for the 3 days prior to their embolization procedure. All subjects will be asked to keep a detailed medication diary for the three days prior and up to their embolization procedure. Blood samples for the measurement of APAP-CYS concentrations and markers of liver function will be collected prior to acetaminophen dosing, prior to the embolization procedure, and at several time points after the procedure.

APAP-CYS Protein Adduct Concentrations in Patients With Liver-Directed Therapy Intended to Treat Hepatic Tumors

Serum Acetaminophen-Cysteine (APAP-CYS) Adduct Concentrations in Subjects Expected to Develop Aminotransferase Elevations With Liver-Directed Therapy Intended to Treat Hepatic Tumors

To describe the course of APAP-CYS concentrations following hepatic embolization in subjects who receive 4 grams/day of acetaminophen for three days prior to the procedure

To determine if subjects who report no exposure to acetaminophen prior to the procedure have detectable APAP-CYS concentrations

To evaluate the relationship between APAP-CYS concentrations with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and miRNA activity

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
APAP-CYS Protein Adduct Concentrations in Patients With Liver-Directed Therapy Intended to Treat Hepatic Tumors	NCT02911961	Acetaminophen E...	Acetaminophen	21 Years - 80 Years	Denver Health and Hospital Authority
APAP-CYS Protein Adduct Concentrations in Patients With Liver-Directed Therapy Intended to Treat Hepatic Tumors	NCT02911961	Acetaminophen E...	Acetaminophen	21 Years - 80 Years	Denver Health and Hospital Authority

Spots Global Cancer Trial Database for acetaminophen exposure