Elevated serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has similar pathologic findings of alcoholic fatty liver but occurs in patients who drink little or no alcohol. Accumulation of excess fat in the liver is regarded as a clinical feature of insulin resistance and is known to be associated with metabolic syndrome components such as abdominal obesity, hypertension, type 2 diabetes and dyslipidemia. For this reason, NAFLD is currently considered as a form of metabolic syndrome occurring in the liver. NAFLD can progress from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis which are accompanied with hepatic cellular destruction. It can even develop to hepatocellular carcinoma. As a result, patients with liver cirrhosis often have concomitant metabolic diseases such as diabetes and coronary heart disease and the major causes of their mortality are reported to be coronary vascular disease (CVD), extrahepatic malignancy and cirrhosis related events. Bilirubin is the end product of heme catabolism. Heme is degraded to biliverdin, cabon monoxide and ferrous iron by heme oxygenase (HMOX) and biliverdin is reduced to bilirubin by biliverdin reductase. Bilirubin is bound to albumin in the plasma and is delivered to the liver in the form of albumin-bound bilirubin. Albumin-bound bilirubin is conjugated with glucuronic acid by UDP-glucuronosyltransferase (UGT1A1) and is excreted to biliary duct in the form of bisglucuronosyl bilirubin. Bilirubin used to be regarded as a toxic metabolite in the central nerve system. However, in recent years, cytoprotective effects of bilirubin have been reported in a few studies. Frei et al reported that serum bilirubin significantly contributes to total antioxidant capacity. It was discovered that bilirubin had anti-inflammatory effects as well as acts as scavengers of reactive oxygen species, as it was mentioned above. In addition to bilirubin, experimental studies have found that enzymes involved in bilirubin metabolism also have several effects. In an experiment conducted with an animal model, it was shown that HMOX1 stimulated insulin products and reduced insulin resistance. It was also reported that biliverdin reductase has multiple functions affecting cell signaling and modulating immune system response In clinical practice, it has been reported that the level of serum bilirubin is related to several diseases. There have been a number of studies reporting a negative relation between serum bilirubin and CVD since Schwertner et al reported a negative relationship Elevated serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease