fecal contamination of water sources. It accounts for more than 55,000 deaths annually with approximately 20 million people worldwide thought to be infected with the virus. It affects predominantly young adults, causing acute hepatitis. In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Those with weakened immune systems, such as organ transplant recipients, are also susceptible. Infection is rare in the United States but rates are high in the developing world (Africa, Asia, Central America, Middle East). Many genotypes exist and are differentially distributed around the world. There is some evidence of hepatitis E infection of animals, serving as a reservoir for human infection. Alcoholic hepatitis Alcoholic hepatitis (AH) in its severe form has a one-month mortality as high as 50%. Most people who develop AH are men but women are at higher risk of developing AH and its complications likely secondary to high body fat and differences in alcohol metabolism. Other contributing factors include younger age <60, binge pattern drinking, poor nutritional status, obesity and hepatitis C co-infection. It is estimated that as much as 20% of people with AH are also infected with hepatitis C. In this population, the presence of hepatitis C virus leads to more severe disease with faster progression to cirrhosis, hepatocellular carcinoma and increased mortality. Obesity increases the likelihood of progression to cirrhosis in cases of alcoholic hepatitis. It is estimated that 70% of people who have AH will progress to cirrhosis. Non-alcoholic steatohepatitis Non-alcoholic steatohepatitis (NASH) is projected to become the top reason for liver transplantation in the United States by 2020, supplanting chronic liver disease due to hepatitis C. About 20–45% of the U.S. population have NAFLD and 6% have NASH. The estimated prevalence of NASH in the world is 3–5%. Of NASH patients who develop cirrhosis, about 2% per year will likely progress to hepatocellular carcinoma. Worldwide, the estimated prevalence of hepatocellular carcinoma related to NAFLD is 15–30%. NASH is thought to be the primary cause of cirrhosis in approximately 25% of patients in the United States, representing 1–2% of the general population. History Early observations Initial accounts of a syndrome that we now think is likely to be hepatitis begin to occur around 3000 B.C. Clay tablets that served as medical handbooks for the ancient Sumerians described the first observations of jaundice. The Sumerians believed that the liver