The liver is a large, complex organ that processes nutrients and other materials absorbed from the digestive tract. The liver plays a central role in metabolism. In cooperation with the spleen the liver destroys old red blood cells and reclaims their constituents. The liver is also a digestive organ that secretes digestive factors such as bile. The liver synthesizes molecular components of blood such as lipoproteins and plasma proteins, including clotting factors. The liver processes sugars and maintains a stable blood glucose level by absorbing and storing glucose as glycogen, by forming glucose from noncarbohydrate sources such as amino acids and by converting glycogen to glucose when more glucose is needed.
Food-derived molecules go directly from the digestive track to the liver through the hepatic portal vein. The food processing unit of the liver is the acinus where liver cells are arranged in plates that radiate out from the portal vein. Liver disease causes metabolic and bile flow abnormalities. When liver cells are sick or die, liver enzymes are released into the blood. Increases in serum concentrations of the aminotransferases, AST and ALT, are used as diagnostic tests.
AST and ALT are enzymes that catalyze the transfer of -amino groups from aspartate and alanine to the -keto group of ketoglutaric acid to generate oxalacetic and pyruvic acids respectively, which are important contributors to the citric acid cycle. Both aminotransferases are concentrated in the liver.
Patients with acute viral or ischemic or toxic liver injury have the highest serum aminotransferase levels, but there is a confusing range in aminotransferase values between patients with acute alcoholic hepatitis and autoimmune hepatitis as well as between patients with chronic hepatitis and liver cirrhosis. Checking the level of these enzymes is often part of routine “checkup” blood tests. A minimal or mild increase in aminotransferase level is the most common biochemical alteration encountered in medical practice. Patients who are taking drugs known to cause liver injury or who drink alcohol should stop and a second reading of aminotransferase levels are required. Further investigations are usually undertaken at the discretion of the physician.
Glutamyl transpeptidase (GGT) is an enzyme that is present in the liver, kidneys, pancreas and small intestine. Elevated GGT levels are found in liver disease, chronic obstructive pulmonary disease, renal failure, and acute myocardial infarction. GGT levels may be elevated 2–3 times with nonalcoholic fatty liver disease and chronic hepatitis C infection. Nonalcoholic fatty liver disease is the most common cause of mild alteration of liver enzyme levels. According to the National Health and Nutritional Survey, prevalence is about 23% among American adults. Aminotransferase and GGT levels can be elevated up to 3 times the upper reference value in the absence of ethanol consumption. Non-alcoholic fatty liver disease is linked to the metabolic syndrome and insulin resistance (increased body mass index, diabetes, hyperlipemia, hypertension).
Ioannou et al proposed that dietary composition affects the development or progression of hepatic steatosis and contributes to 3 prevalent liver diseases: nonalcoholic fatty liver disease (diabetes), hepatitis C virus infection, and alcoholic liver disease. A high-cholesterol diet in rabbits and mice induces steatosis, inflammation, and centrilobular fibrosis, whereas a diet low in animal protein in mice was associated with decreased liver injury and decreased incidence of hepatocellular carcinoma. They examined data from the first National Health and Nutrition Examination Survey (NHANES I), a cross-sectional study of 14,407 participants conducted between 1971 and 1975 and evaluated followup data on 9221 adults (aged 25 – 74 years) using data from NHANES III from 1988 to 1994 that included measurements of viral hepatitis serologies. During an average follow-up of 13.3 years, 118 of the 9221 participants had a new diagnosis of cirrhosis and 5 had a new diagnosis of liver cancer. Patients who reported a diet high in protein were at higher risk for hospitalization or death because of cirrhosis or liver cancer whereas those reporting a diet high in carbohydrates were at a significantly lower risk. Cholesterol consumption was associated with a higher risk for cirrhosis or liver cancer. Caloric intake, total quantity of fat consumed, and serum cholesterol level were not associated.
Yu-Jui Yvonne Wan, who studies liver disease at the University of California, Davis stated: “It makes intuitive sense that the gut microbiome would be implicated in liver cancer. Whatever comes from the gut enters the liver,” she says. As blood leaves the intestines it passes through the liver, carrying nutrients extracted from our food. It also carries our own digestive chemicals as well as fragments of the bacteria that live in the digestive system (such as bits of DNA and cell walls) and their metabolic by-products. Some of these by-products help us to access energy and nutrients in food, but some are toxic. And a few might provoke an inflammatory immune response in the liver — if the inflammation becomes chronic, cancer can be the consequence. "