Hy's law
Encyclopedia
Hy's law is a prognostic indicator
that a pure drug-induced liver injury
(DILI) leading to jaundice
, without a hepatic transplant
, has a case fatality rate of 10% to 50%. The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury.
As defined by The U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) in their final document of 2009 Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation.
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
that a pure drug-induced liver injury
Hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
(DILI) leading to jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, without a hepatic transplant
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...
, has a case fatality rate of 10% to 50%. The law is based on observations by Hy Zimmerman, a major scholar of drug-induced liver injury.
Hy’s Law cases have the following three components
- The drug causes hepatocellular injury, generally shown by more frequent 3-fold or greater elevations above the ULN of ALTAlanine transaminaseAlanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
or ASTAspartate transaminaseAspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...
than the (nonhepatotoxic) control agent or placebo. - Among subjects showing such AT elevations, often with ATs much greater than 3xULN, some subjects also show elevation of serum TBL to >2xULN, without initial findings of cholestasis (serum alkaline phosphatase (ALP) activity >2xULN).
- No other reason can be found to explain the combination of increased AT and TBL, such as viral hepatitis A, B, or C, preexisting or acute liver disease, or another drug capable of causing the observed injury.
As defined by The U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) in their final document of 2009 Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation.