Charles S. Lieber, Pioneer in Alcohol-Induced Liver Disease

Article Outline

• Copyright

Charles Saul Lieber, MD, Specialty Chief of Liver Disease at the James J. Peters VA Medical Center in The Bronx, New York, and Professor of Medicine in the Division of Gastroenterology and Pathology at The Mount Sinai School of Medicine in New York City died on March 1, 2009. He was 78 years old and had been battling gastric cancer.

Dr Lieber was internationally renowned for his investigations into the pathogenesis and treatment of alcoholic liver disease and was the first scientist to show that alcohol itself is toxic to the liver. Lieber reported in 1974 that baboons developed cirrhosis of the liver, even though their diet was carefully controlled and very healthful. In published reports from 1959, while a Fellow in Medicine at Harvard University and the Thorndike Memorial Laboratory and into the 1970s, Lieber was able to correct the prevailing dogma in the United States that liver disease caused by alcohol was due to malnutrition and not to any toxicity of the alcohol.

Lieber conducted clinical and experimental studies for more than 4 decades with an emphasis on liver, nutrition, and gastrointestinal pathophysiology. His elucidation of the pathogenesis of alcoholic liver disease was achieved through judicious clinical studies and newly developed rodent and primate models with the administration of ethanol in liquid diets. The mechanisms of various pathologic and metabolic effects of ethanol were clarified, including hyperlipemia (with the rise in high-density lipoprotein cholesterol), hyperuricemia, the role of acetaldehyde toxicity, and alcohol-induced oxidative stress.

• 
  • View Large Image
  • Download to PowerPoint

• Reprinted with permission; credit: Institute of Alcohol Studies, www.ias.org.uk

Lieber also discovered a new, microsomal, pathway of ethanol metabolism responsible for the tolerance to ethanol and for several clinically important toxic interactions with other drugs (eg, acetaminophen), anesthetics, industrial solvents, and carcinogens, as well as retinol and β-carotene, thereby narrowing their therapeutic window. His work defined the role of the stomach in ethanol metabolism, description of corresponding gender differences, cloning (for the first time) of the gene for sigma alcohol dehydrogenase (a newly recognized gastric alcohol dehydrogenase isozyme) with its chromosomal localization, and the discovery of the effects of commonly used medications (eg, H₂ blockers and aspirin) on the activities of the enzyme and on blood alcohol levels in social drinkers.

Lieber was among the first to use antibiotics for the elimination of gastric bacterial urease and its ammonia production in humans, thereby alleviating chronic gastritis and hypoacidity, with an ensuing attenuation of hepatic encephalopathy in cirrhotics. He promoted early detection and treatment of heavy drinkers before their social or medical disintegration, by defining precirrhotic lesions and markers of alcohol consumption.

Lieber took his medical degree in 1955 from the University of Brussels. During his career, Lieber published nearly 1000 research papers and 15 books, trained more than 200 researchers, and received numerous awards.

Stephen Schenker, MD, Clinical Professor of Medicine in the Division of Gastroenterology and Nutrition at the University of Texas Health Science Center at San Antonio knew Lieber at the Thorndike laboratory while also a postdoctoral Fellow. “Charles Lieber was probably the most important person in the world in alcohol-induced liver disease,” Schenker said.

Charles Lieber is survived by his wife and co-worker, Dr Maria Leo–Lieber, 3 daughters, 2 sons, and 6 grandchildren.