Hy's law is a

rule of thumb In 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 associated with various t ...

that a

patient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health c ...

is at high risk of a fatal

drug-induced liver injury Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

if given a medication that causes hepatocellular injury (not Hepatobiliary injury) with

jaundice Jaundice, also known as icterus, is a yellowish or 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 abnormal heme meta ...

. The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury.

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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 respon ...

Center for Drug Evaluation and Research The Center for Drug Evaluation and Research (CDER, pronounced "see'-der") is a division of the U.S. Food and Drug Administration (FDA) that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also leg ...

(CDER)

Center for Biologics Evaluation and Research The Center for Biologics Evaluation and Research (CBER) is one of six main centers for the Food and Drug Administration, U.S. Food and Drug Administration (FDA), which is a part of the U.S. Department of Health and Human Services. The current Dir ...

(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 Alt or ALT may refer to: Abbreviations for words * Alt account, an alternative online identity also known as a sock puppet account * Alternate character, in online gaming * Alternate route, type of highway designation * Alternating group, mathema ...

or AST by 3-fold or greater above the upper limit of normal. Often with

aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...

s much greater (5-10x) 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 (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...

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 wi ...

, 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 {{treatment-stub