Liver Fatty Acid-binding Protein as a Sensitive Serum Marker of Acute Hepatocellular Damage in Liver Transplant Recipients

Abstract

Serum tests of acute hepatocellular injury are commonly used to investigate the presence and monitor the progress of liver disease (1)(2). The release of cytoplasmic proteins from damaged hepatocytes into the vascular system follows tissue necrosis caused by, e.g., acetaminophen intoxication, ischemia and reperfusion injury, or rejection after liver transplantation. Although the hepatocytes are in direct contact with the vasculature and no interstitial barrier is between the two, smaller proteins appear earlier in the circulation than do larger ones (1) and would therefore increase earlier in serum above their upper reference value after an acute hepatocellular injury. α-Glutathione S -transferase (α-GST; 26 kDa) is a more sensitive and specific marker of hepatocellular damage (3)(4) than either alanine transaminase (ALT; 96 kDa) or aspartate transaminase. α-GST is present in liver, kidney, and intestine; is released rapidly from damaged hepatocytes; and has a relatively short in vivo plasma half-life (3)(4). The use of α-GST for the detection of hepatocellular injury secondary to acute rejection after liver transplantation improved the biochemical monitoring of patients and decreased mortality and morbidity (3). In search of even smaller and more specific cytoplasmic proteins for the detection of liver injury, we have studied the liver-type fatty acid-binding protein (L-FABP). FABPs are a family of 15-kDa proteins that are involved in the intracellular transport of long-chain fatty acids (5). To date, nine different FABPs have been identified and named according to the tissues in which they were first identified (5). L-FABP occurs mainly in the liver but, in small quantities, also in kidney and small intestine. In the hepatic lobule, L-FABP is expressed in hepatocytes in a declining portal-to-central gradient (5)(6). Extensive studies …