Blood tests remain a mainstay for the diagnosis of a patient with suspected liver disease or to stage patients with known liver disease. In general, the goal of such tests is to detect the release of products that are characteristic of the liver into the bloodstream, thereby indicating liver cell injury. Similarly, accumulation of molecules normally excreted via the biliary system is indicative of a failure in liver function, although further tests are necessary to assess the site at which the defect is occurring.
Two enzymes referred to as transaminases are easily measured in the serum, and are sensitive markers of liver cell injury. Alanine aminotransferease (ALT) is produced by hepatocytes, and when these cells are injured, its circulating levels are increased. Aspartate aminotransferase (AST) is similarly increased in the setting of hepatocellular injury, although it is less specific for liver disease because it is also produced by other tissues. For example, AST levels are increased following cardiac injury, such as a myocardial infarction. Nevertheless, measurement of AST remains useful in the setting of clinical symptoms consistent with liver disease, particularly because it appears to be disproportionately elevated in patients whose liver injury is related to alcohol abuse. Measurements of ALT and AST over time are also used to assess the progress of established liver disease. It is important to remember, however, that elevations in transaminases can only occur if these is ongoing hepatocellular death. In cirrhosis, where large portions of the liver may be replaced by fibrous tissue, little new cell injury may be occurring and thus ALT and AST levels may not be elevated.
Two other enzymes are useful markers of injury to the biliary system. Alkaline phosphatase, while not specific to the liver (being produced also by bone, the intestine and placenta), is expressed as a membrane protein in the canaliculus. In the setting of localized obstruction to the biliary tree, alkaline phosphatase levels in the serum are increased. Similarly, gamma glutamyltranspeptidase (GGT) is localized predominantly to the apical membrane of cholangiocytes, although some is also expressed in the bile canaliculi. Serum elevations in GGT are therefore largely reflective of cholangiocyte injury.
The foregoing tests, while often referred to as “liver function” tests, are not strictly measures of actual hepatic function. To assess whether liver function is impaired, other tests are needed. One such test that is very important clinically is the measurement of bilirubin. Accumulation of bilirubin in the circulation indicates cholestasis, which can result from injury to either hepatocytes or cholangiocytes, or obstruction within the biliary system. Based on the discussion of the synthetic functions of the liver, it should be easy to understand that liver function can also be assessed by measuring levels of its various products in the circulation. The most useful tests are to measure serum albumin, and a blood clotting parameter, the prothrombin time. Tests of coagulation are not specific for liver disease and thus must be interpreted in the context of other findings. Patients with suspected liver disease are also often evaluated for serum glucose and ammonia levels, since hypoglycemia and hyperammonemia are major problems in the setting of liver failure.
Biopsies and imaging tests also play a major role in the evaluation of liver disease. Liver biopsies, which are usually obtained by inserting a needle into the liver percutaneously, can be used to evaluate the extent of liver fibrosis, or to search for evidence of rejection in a previously transplanted liver. A widely applied imaging technique is referred to as ERCP, which stands for endoscopic retrograde cholangiopancreatography. In this procedure, a special endoscope is introduced into the duodenum via the mouth, and used to insert a small tube through the sphincter of Oddi, through which contrast medium is injected. Subsequent X-rays can then visualize the drainage routes from the biliary system and pancreas, which permits the diagnosis of obstructions or strictures. Other imaging modalities, such as magnetic resonance imaging, are also assuming an increasing role in assessing liver disease and the architecture of the biliary system.
The prognosis of end-stage liver disease, and by extension the urgency of transplantation, has commonly been assessed by calculating the so-called Child-Pugh score, which takes into account 5 measures of hepatic function. The Child-Pugh score was originally designed as a predictor of surgical mortality in liver disease patients. More recently, the Child-Pugh score has been supplemented by the Model for End-Stage Liver Disease (MELD) score, which weights serum bilirubin, creatinine, and prothrombin time to predict survival. Patients awaiting liver transplantation in the United States are now prioritized on the basis of their MELD score, which results in the allocation of organs first to those who are sickest. This has reduced waiting-list mortality without impairing post-transplant outcomes.