Drug-Induced liver Injury Network (DILIN)
rugs cause a variety of forms of liver injury that range in severity from transient, asymptomatic elevations in serum aminotransferase levels to acute hepatic failure. Drug-induced liver disease can be cholestatic or hepatitic or, more typically, a combination of both. But it can also manifest as alcoholic hepatitis-like fatty liver disease, severe microvesicular steatosis with lactic acidosis, acute cholangitis, chronic sclerosing cholangitis, hyperbilirubinemia, acute or subacute veno-occlusive disease, chronic hepatitis, cryptogenic cirrhosis, and liver cancer. For these and other reasons, druginduced liver disease is a complex and difficult area for research. Most drugs that are hepatotoxic in humans do not produce liver injury in experimental animals. For the drugs that do cause human liver disease, attribution of injury is frequently difficult: Patients often have other risk factors for liver disease, may be on many hepatotoxic drugs, and may not present until the injury has resolved. Nevertheless, drug-induced liver disease is important, and further research is critically needed. Hepatotoxicity is one of the major reasons why new medications fail during development, and it is the single major reason for withdrawal of approved medications.
Research on drug-induced liver injury has not been particularly successful in identifying why certain medications cause liver injury and why certain persons are affected and others are not. The mechanism(s) by which specific drugs cause damage to the liver are known for only a few drugs. Susceptibility factors for hepatotoxicity are not well defined. For most causes of druginduced liver disease, there are no specific means of prevention or treatment except for early identification and rapid withdrawal. At the same time, drug-induced liver disease is now the major cause of death from acute liver failure in the United States. Many of the drugs currently implicated in cases of acute liver failure have been used and have been known to cause liver injury for more than 50 years.
For these reasons, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has created the "Drug-Induced Liver Injury Network" (DILIN) made up of five Clinical Centers with expertise in hepatotoxicity, and a Data Coordinating Center responsible for data collection and analysis. The primary objective of the Network is to advance understanding and research on drug-induced liver disease. The Network has been charged specifically with developing standardized definitions and instruments to identify and characterize cases of drug-induced liver injury and to validate these instruments in a prospective manner. The Network is also charged with identifying a large number of well-defined cases of drug-induced liver disease prospectively that will allow for collection of epidemiological data and biological samples that can be used for the study of pathogenesis. The Network will collaborate with other investigators in the areas of hepatocyte biology