Tests for liver disease can be subdivided according to the subpopulation of liver cells we are trying to test: serum enzymes estimate the population of damaged but still viable liver cells; tests of liver function estimate the remaining population of healthy and effective liver cells; and tests of liver fibrosis test the functionally ineffective tissue which has replaced dead liver cells (see figure).
1) Serum enzymes – serum concentrations of alkaline phosphatase (AP), aspartate aminotransferase (AST), gamma glutamyltranferase (GGT), glutamate dehydrogenase (GLDH), iditol dehydrogenase (IDH), lactate dehydrogenase (LDH) are all known to increase in response to various forms of liver disease. Generally speaking these various enzymes are released from damaged, but still viable, liver cells. A certain amount of information may be gleaned from comparative elevations of the different enzymes with GGT and AP being primarily derived from biliary epithelial cells due to biliary disease or secondary biliary hyperplasia whereas other enzymes are primarily derived from hepatocytes per se. GLDH and IDH are very ‘time-sensitive’ with rapid rises and falls in association with active liver disease. Other enzymes are less ‘time sensitive’ with persistently raised serum concentrations are often seen for some time following resolution of a primary hepatic insult – especially with GGT. Prognostic value has been attributed to certain enzymes by some previous studies including a recent large investigation performed at Liphook in conjunction with the Animal Health Trust, The Royal Veterinary College and Bristol University Veterinary School. However, the association between raised liver enzymes and prognosis is often weak except when marked elevations are seen. In other words, in most cases enzymes are helpful in establishing the presence of liver disease but not necessarily the severity.
2) Tests of liver function – simple serum tests including albumin, various amino acids, ammonia, bile acids, bilirubin, fibrinogen, globulins, glucose, and urea may give a reflection of the remaining functional capacity of the liver and therefore help quantify the remaining mass of healthy liver cells (see figure) which is clearly more relevant to the degree of liver failure. It is therefore not surprising that the prognostic value of these tests is superior to that of serum enzyme analysis. Further tests of liver function that are also often performed include blood clotting times (PT and APTT) and BSP half-life. In our experience the simple tests that have proved most predictive of a poor prognosis in cases of liver disease have been raised globulins (no additional benefit from electrophoresis), raised bile acids, low albumin, low urea and high fibrinogen (low fibrinogen has been reported as useful in some previous publications!). Anecdotally prolonged clotting times and BSP half-life also seem very helpful but we have not generated adequate numbers for meaningful statistical analysis.
3) Tests for liver fibrosis – serum indicators of hepatic fibrosis have not been reported in horses but are often used in human hepatology. Fibrosis is a common pathologic feature detected in biopsy samples from various equine hepatopathies and has important prognostic relevance. Several tests can be used including serum hyaluronate – a substance which has been analysed in equine blood samples in experimental studies of joint and respiratory disease and normal ranges are established. This test is not currently commercially available but may become of interest in the future.
Apart from blood testing, other diagnostic techniques have also been proven to help assess the prognosis of hepatopathy cases including severity of clinical signs and ultrasonographic examination. However, the single most helpful and important diagnostic and prognostic test is liver biopsy which remains the ‘gold standard’ in both human and equine hepatopathies.
Ultrasound-guided liver biopsy is a quick, simple, inexpensive and highly safe procedure frequently performed on an outpatient basis (see Hospital facilities). Only liver biopsy can help answer all 4 of the central issues of most concern to the owner: How bad is the liver disease?; What might have caused the liver disease?; How should we treat it?; Is the horse likely to recover? A liver biopsy scoring system developed by Liphook Equine Hospital and the Animal Health Trust shows great promise in more precisely quantifying the likely outcome of liver disease cases subjected to liver biopsy – details available for those who are interested.
© The Liphook Equine Hospital 2009
