Hy's law is a
rule of thumb
In English language, English, the phrase ''rule of thumb'' refers to an approximate method for doing something, based on practical experience rather than theory. This usage of the phrase can be traced back to the 17th century and has been associat ...
that a
patient
A patient is any recipient of health care services that are performed by Health professional, healthcare professionals. The patient is most often Disease, ill or Major trauma, injured and in need of therapy, treatment by a physician, nurse, op ...
is at high risk of a fatal
drug-induced liver injury if given a medication that causes hepatocellular injury (not
Hepatobiliary injury) with
jaundice
Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
.
The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury.
United States Department of Health and Human Services
The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the US federal government created to protect the health of the US people and providing essential human services. Its motto is ...
, Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
, Center for Drug Evaluation and Research
The Center for Drug Evaluation and Research (CDER, pronounced "see'-der") is a division of the Food and Drug Administration (United States), U.S. Food and Drug Administration (FDA) that monitors most drugs as defined in the Food, Drug, and Cosmet ...
(CDER) Center for Biologics Evaluation and Research
The Center for Biologics Evaluation and Research (CBER) is one of six main centers for the U.S. Food and Drug Administration (FDA), which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Vinay Pras ...
(CBER)
Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation, Final, July 2009
/ref> Some have suggested the principle be called a hypothesis or observation.
Hy's Law cases have three components:
* The drug causes hepatocellular injury, generally defined as an elevated ALT or AST by 3-fold or greater above the upper limit of normal. Often with aminotransferases much greater (5-10x) than the upper limit of normal.
* Among subjects showing such aminotransferase elevations, they also have elevation of their serum total bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase
The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryo ...
activity less than 2× the upper limit of normal).
* No other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
, preexisting liver disease, or another drug capable of causing the observed injury.
In Zimmerman's analysis of 116 patients with hepatocellular injury and jaundice due to drug exposure, 76% went on to either require a liver transplant or died. Other studies have reported a lower but still significant mortality of 10%.
References
Diseases of liver
Hepatology
Rules of thumb
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