Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are intracellular enzymes. I am not sure if these enzymes are secreted by the cell like prothrombin. In my opinion ALT and AST may be predictive of liver cell damage but not the functional capability (If function and damage are not considered synonyms) whereas prothombin may be predictive of liver function.
Look at the brief summary of liver functions:
1. Synthetic: albumin, coagulation proteins, some binding proteins etc.
2. Metabolic/homeostatis: glucose, lipids etc.
3. Storage: glycogen, iron, copper, lipid etc.
4. Catabolic: ammonia/urea, hormones, detoxification of drugs, chemicals etc.
5. Excretory: bile excretion
Why you are focusing on AST and ALT? You should define what exactly you want to know/study and further build very accurately your questions.
Generally speaking – you should read classical hepatology textbooks.
Dear friend;
Organopathies could effect on the functional activities of the organ. For instance, in drug-induced generalized toxicities, marked disturbances in cellular secretions could be observed. In my opinion this classification is not logical. Best Regards.
The enzymes are released because of liver damage, so I think they are not liver function tests. See Wikipedia for an answer about how to do liver function tests and what high ALT and AST vslues mean. But I also think that if your liver is not functioning properly, then it is more susceptible to being damaged when insults are present and then enzymes like ALT and AST are released. So it seems that it is a matter of which came first, the chicken or the egg. But there are definitely solely liver function tests. Most liver function test panels also measure albumin, bilirubin etc. I don't think liver function and damage are synonymous, especially to a doctor who specializes in the area.
Liver function and liver damage are not the same things, but increased ALT/AST levels surely indicate ongoing liver damage with following or causative impaired liver function, whereas to assess a real functional activity of the liver without obvious pathology or to evaluate disease severity, more wide range of tests is used in addition to transferases - albumin, bilirubin, GGT levels, coagulation test. Also, breath tests with metabolic substances labeled with a non-radioactive carbon isotope measured in breath after getting metabolized in the liver looks quite promising, but not sure it's widely used in the clinic yet as may be a bit expensive.
ALT/AST 've usually used for liver damage for my opinion. But at the same time AST is not only specific for liver damage. It also have been in red blood cells. And ALT/AST have been in liver cells. When cells damaged, they going out cells and pass serum.
If we are trying to document liver damage ALT and AST are appropriate, both are increased in necroinflammation of liver cells whatever, its etiology. In severe fulminant hepatitis, the level of both enzymes might decrease after their initial marked rise despite the presence of decompensation. The same occurs in cirrhosis, both enzymes could be within normal and this continues when the condition progressed to decompensation. However, in severe chronic hepatitis leading to marked fibrosis, the rise in AST is usually higher compared to ALT so AST/ALT is usually more than one and this is also noticed in cirrhosis. Indeed this pattern is considered as a marker of fibrosis of the liver and is seen in CLD complicationg HCV which is common in Egypt
ALT and AST are typical liver enzyme. They are liver function markers when intracellular ALT or AST enzyme activity is meaured. They are liver damage markers, when intracellular ALT or AST enzyme activity is low. In addition, such as Lactate dehydrogenase assays, you can measure the release into the cell culture supernatant or into blood. This occurs, when the liver cell is damaged and cell membrane is getting leaky. A high release of ALT, or AST means hepatotoxicity.
ALT and AST can be used to determine liver damage. ALT is more specific to the liver, since AST can come from other organs and tissue as well. Coagulation factors (especially the Vitamin K dependant factors), bilirubin and albumin (especial pre-albumin) determine the synthetic and metabolic function of the liver. If there is severe damage to the liver the ALT and functional factors can both be elevated at the same time (indicating ongoing cellular injury and enough mass has been injured to affect liver function). If we use liver transplantation as an example of liver injury, it is not uncommon to see an elevated ALT, indicating ischemia/reperfusion injury with a normal or near normal INR.
AST and ALT levels are not expression of reduced liver function.The parameters that we used for evaluating liver function are the INR, the level of albumin and the bilirubin ( from a clinical point of we we evaluate also the presence of ascites and of signs of encefalopahy).
As you know these are the parameters considered for CHILD PUGH classification.
I agree with comments above. ALT and AST are enzymes in the hepatocytes which are released in the serum, when hepatocyte dies. Therefore normally their level in the serum is very low and indicates about physiological replenishment of hepatocytes. Although it increases drastically durign liver injury, when lots of hepatocytes die by necrosis. That is a reason why ALT and AST serve as a markers to evaluate liver damage and not the function of live hepatocytes.
For the evaluation of live hepatocyte function you can look article in wiki:
http://en.wikipedia.org/wiki/Liver_function_tests
AST and ALT levels are markers of cytolisis since these two enzymes are released in the blood by dead hepatocytes. However, there is only a situation when they can be considered "predictive" of liver function: in case of persistent very high levels of aminotransferases. This situation corresponds to a serius episode of acute hepatitis that can lead to liver failure. However, you have to monitor other liver function parameters, in particular coagulation parameters such as Factor V, that are more specific and highly predictive of liver function deterioration.
The response is negative, but we should consider that the ASL/ALT can give us more information and our experiences after progression of liver disease to cirrhosis, the level of ALT will decrease to normal range and normal ALT can not exclude the severe liver disease. we need to liver function tests evaluation such PT , Albumin and...
Look at the brief summary of liver functions:
1. Synthetic: albumin, coagulation proteins, some binding proteins etc.
2. Metabolic/homeostatis: glucose, lipids etc.
3. Storage: glycogen, iron, copper, lipid etc.
4. Catabolic: ammonia/urea, hormones, detoxification of drugs, chemicals etc.
5. Excretory: bile excretion
Why you are focusing on AST and ALT? You should define what exactly you want to know/study and further build very accurately your questions.
Generally speaking – you should read classical hepatology textbooks.
I agree with many answers above.
I would like to add a few comments. Increase in serum AST and ALT indicates different extent of hepatocytes damaga (AST and ALT are leaking into serum when hepatocytes are not intact). We only need one fourth to one third of liver to survive. In other words, liver function may not be compromised when the amount of damaged hapetocytes doesn't exceed the limit. So, only when serum AST and ALT level is very high, you might think that it is possible that this patient's liver function might also be compromised. On the other hand, when someone's liver function is compromised, his or her serum AST and ALT could be normal or close to normal sine this patient's hepatocytes could be intact but not function apropriately. Therefore, Child-Pugh score system which used to evaluate someone's liver disease severity does not include AST and ALT, instead it include PT/INR, bilirubin, albumin, ascites and encephalopathy.
Chi
AST and ALT are liver damage markers. These enzymes are released into the blood in large amounts when there is damage to the hepatocyte membrane.
The term Anicteric Hepatitis is used , When AST & ALT are elevated , but serum Bilirubin is normal . It is significant if the rise is more than four fold . If bilirubin is elevated , it is considered as Icteric Hepatitis , which is a severe form of hepatitis . Anicteric Hepatitis warns the physician to be careful about hepatotoxic drugs . For eg. Rifampicin , Isoniazid & Pyrazinamide should be discontinued to prevent severe liver injury in the management of Tuberculosis . It is essential to monitor AST & ALT in acute Febrile Illness . In Malaria , Leptospirosis & Sepsis , Bilirubin is grossly elevated compared to AST & ALT suggesting cholestasis , compared to Viral Hepatitis , where AST & ALT are grossly elevated compared to bilirubin due to parenchymal injury . Therefore , it is essential to screen for Bilirubin , AST & ALT to assess liver function for therapeutic decisions .
Liver function reserve is very difficult to be established because, in contrast with kidney, liver has normally som many function that ti so difficult to explore all of them. So I believe a good way to have a common and practical index of liver reserve function could be to examine some volatile marker in the exhaled breathe air. Could we consider liver as a car engine and could we focalise aour attention to the way the engine is working ?? How it is bursting food components coming from the portal vein.... for example.
Transaminases are markers of lhepotocyte damage and do not predictie or inform ius about THE actual liver synthesis function
As always, do not look at labs (or images) without clinical examination: ALT and AST are in every tissue and can be elevated when there is a cell damage, whatever is the cell, not only liver cells. Hepatology stays in Internal Medicine and the referral to your clinic is not necessarily right. I can quote a patient of mine, a middle-aged woman referred to my outpatient clinic of Gatroenterology and Liver Diseases for ALT/AST x 5 (approximately). Briefly, I had to refer her to the neurologist for a muscle disease! So I cannot agree with the opinions that limit ALT/AST to liver damage: actually these enzymes point, more generally, to cell damage.
Not the best tests, although often used. Real liver function tests should include BUN, INR (or prothrombin time) and serum protein levels., especially albumin.
Dear Atta
I think they are liver cell damage markers as:
AST/ALT elevations instead of ALP elevations favor liver cell necrosis as a mechanism over cholestasis. When AST and ALT are both over 1000 IU/L, the differential can include acetaminophen toxicity, shock, or fulminant liver failure. When AST and ALT are >3X of normal but not > 1000 IU/L, the differential can include alcohol toxicity, viral hepatitis, drug induced, liver cancer, sepsis, Wilson disease, post-transplant rejection of liver, autoimmune hepatitis, and steatohepatitis (non-alcoholic). When AST/ALT elevations are minor it may be due to rhabdomyolysis among many possibilities.
I agree with the above comments as liver is a big central factory in the body with large reserves.Albumin and prothrobin time are simple informative tests for liver function and very practical,We should not forget liver biobsy as it will give a vey objective tool of assessment for the state of the liver and with the LFTs and some serological tests (if indicated) one can reach reasonable diagnostic information.
ALT is a marker of cytosolic damage, AST is a marker of cytosolic damage and necrosis. Most useful liver function test are albumin synthesis and prothrombin time. Gamma glutamyl transferase is a marker of cholestasis. LPX, a lipoprotein with cholesterol charge and inverse electrophoretic mobility, is also a marker of cholestasis. ALT , Gamma GT and AST are markers , among other pathologies, of non alcoholic liver steatosis (NALF). Liver punction is also a marker of NALF and is the complement of ecographic studies.
In my 6 months chronic toxicity in mice study of herbal medicine for analgesic & anti-inflammation found both AST & ALT reduced / reduction as compare to control normal value (taken from control animal given only saline). Does it indicate the live function is better as the hepatocytes are more healthy then release both AST & ALT less??
ALT is present in liver but AST is found in brain, pancreas, heart, kidney and lung.
if there is any damage in these organs then AST level will incresae in the blood. AST/ALT ratio is not good method to detect hepatic damage. So AST/ALT ratio can used to detect cell damage. Recently I read a paper "AST/ALT ratio is not an index of liver fibrosis in chronic hepatitis C when aminotransferase activities are determinate according to the international recommendations".
Hi find below an attached article, may give you some ideas
The aminotransferases are usually markers of cell necrosis and death and are not secreted. Some of the comments here on intracellular location of AST and ALT giving rise to different profiles in the peripheral circulation, while found in text books and some literature, must be tempered by the fact that although AST is largely in the mitochondria (80%) very little of that isoenzyme appears in the serum after acute or chronic liver damage.
See: https://www.researchgate.net/publication/20469142_Aminotransferases_in_disease?ev=prf_pub
Article Aminotransferase in disease
It may not be easy to say just no. I would like to add that these liver enzymes are very useful in follow up of chronic hepatitis and in following the toxic effect of some drug treatments e.g, in treatment of rheumatoid arthritis
Please remember: AST (SGOT) was originally developed as a test for Acute Myocardial Infarction
“Glutamic Oxaloacetic Transaminase is…most concentrated in heart muscle. This...led us to study its concentration in human serum following acute myocardial infarction.” From: Ladue JS, Wroblewski F, Karmen A. Serum Glutamic Oxalacetic Transaminase activity in human acute transmural myocardial infarction. Science 1954
It is also rich in muscle. AST (also ALT) may reflect myositis and rhabdomyolysis !
I totally agree, but it has to be interpretated taking into cosideration the clinical picture
AST and ALT are not markers of liver function, they are very non-specific markers of hepatocye injury, i.e., necrosis and cell death. Functionally liver assays would more than likely be measuring phase I and II metabolizing enzymes. One must remember that AST and ALT levels measured in the serum can be arbitrarily high, for instance due to medications and that some patients with for example hepatitis C, had normal serum AST and ALT levels. The bottom line is that this measurement should be verified by another method.
The term "liver function test" is possibly the single biggest misnomer is Medicine. LFTs are poor predictors of actual synthetic function of the liver with INR, amongst a few others, being the most useful marker of function. I personally prefer and use the term "liver chemistry profile" as it provides one with a pattern of injury. ALT/AST are largely markers of hepatocellular injury but as is known are not enzymes unique to hepatocytes.
I agree. It is a clinical term that roughly asks "what's going on in the liver?" Not always "function". Not really specific. Semantically weak.
I would say albumin in terms of function, ALT does mark for liver damage though.
I agree with the participants of this discussion: ALT/AST are not function markers, they are markers of injury (and not very liver specific). If liver damage is the cause for ALT/AST elevations, it is important to know, that the grade of elevation (xULN) is not predictive for the prognosis and is not reflecting the actual severity of injury (i.e. ALT 5XULN can be severe injury, whereas ALT 10XULN can be less severe injury in terms of outcome).
Severity of liver injury is only roughly estimated from parameters that reflect parts of the synthesis capacity (INR, albumin, factor V, ammonia) and excretion capacity (bilirubin in absence of posthepatic cholestasis).
There is a decent slide summarizing liver "biomarkers" here (4th slide): http://www.aasld.org/meetings/Documents/Hepatotoxicity%20STC/3A-3_Lawrence.pdf
ALT/AST are not markers of liver function, but only of damage, which may not be directly proportional to function given the liver's impressive reserve of functionality.
one point is important in case of liver cirrhosis, damage is there but enzymes are normal, so ALT/AST are markers mostly for acute injury rather than an established damage
Prothrombin, albumin and bilirubin are considred liver function tests ALT compared to AST is liver specific test for hepatocyte damage.
ALT AST are marker of liver injury but not he function. It does not define the extent of liver injury. Though there are many reports where there are marked liver injury without elevation of Transaminases.
ALT and AST in most of cases reflect the acute hepatic damage; acute hepatitis, liver ischemia....But in the chronic conditions it may not reflect the underlying hepatic damage e.g one third of patients with chronic HCV who have normal liver enzymes had significant fibrosis in the liver biopsy and also patients with immune liver diseases liver enzymes tends to wan ups and downs also the progression of liver fibrosis toward liver cirrhosis goes on irrespective of liver enzymes. also in cirrhosis of any cause the levels of liver enzymes is not correlated with cirrhosis. ALT and AST are not measures of synthetic liver function.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are intracellular enzymes. In very general words, a living differentiated cell is considered to be committed to perform all its function as is clearly displayed in Alexander Julianov´s response. Life was dependent upon the integrity of cell membrane and therefore it was considered that fully differentiated liver cells were alive if it was shown that the liver do not release in the blood more intracellular enzymes than the amount that could be considered the product of normal cell renew of the liver. By this line of reasoning, to measure the amount of intracellular enzymes released in the blood was considered as an indirect form of evaluation of all liver function without measuring each function one by one...
Yes. they are the primary indicators, that are easily performed. these parameters can also be used for the purpose of prognosis.
Imapired liver function tests may be indicated by: hypoalbuminemia, low prothrombin activity, low serum cholesterol, low cholinesterase, high ammoniemia, mixed hyperbilirubunemia and some other marker. Often they do not parallel among themselves and are not related to imaging investigations or fibrosis detected by fibroscan. This makes impossible a suitable short term prognosis for liver advanced disorders. Transaminases indicate a hepatocellular damage, which may reflect a bad prognosis if associated to impaired liver function indicators.
Alcoholism, HIV-1 infections and other causes result in liver disease and those patients on HAART must be carefully monitored for possible hepatic destruction by measuring serum GGT, ALT and AST, all non invasive methods which are cost effective and easily performed
Deshpande, Neelesh, et al. "Effect of Alcohol Consumption on Oxidative Stress Markers and its Role in the Pathogenesis and Progression of Liver Cirrhosis." American Journal of Medical and Biological Research 1.4 (2013): 99-102
Ramana KV, Ratna Rao, Sabitha Abnormal Levels of γ-Glutamyl Transpeptidase (GGTP), ALT, AST in Human Immunodeficiency Virus-1(HIV-1) Infection. Biochem Physiol 2012; 1:101.
Obviously ALT and AST are enzymes released from the liver cells as markers of liver damage but not necessarily indicative of its function in the long term because this occurs in cases of acute viral hepatitis infection and acute stages of any infection tend to be transcient but the reocurrence or not largely depends on the general health of the liver , taking into consideration that the liver performs over 500 functions in the body and as the largest internal organ it regenerates its dead cells as well. High levels of ALT and AST in acute viral hepatitis are due to the fact when theses viruses enter the hepatocyte , the immune system would naturally react by releasing virus specific cytokines which contain T lymphocytes to combat these viruses. In this process the T lymphocytes would destroy the virus but since they are cytotoxic they would also cause hepatocellular damage leading to inflamation and therefore high levels of ALT and AST from the hepatocytes. The liver obviously will repair this damage and its function will not easily be affected. The frequency and intensity of this acute infection is very important in analysing the function of the liver but high levels of ALT and AST are not the sole indicators of a malfunctioning liver but direct indicators of hepatocellular damage which might lead to malfunctioning when alowed to go repeatedly.
ALT is a liver marker. A 3 fold increase in ALT in blood is considered to indicate liver injury. There are other markers as well and depends on the nature of injury to liver.
ALT and AST are markers of acute liver injury, rather than reflection of the hepatocellular function. Meanwhile, the data can indicate the extent of liver injury, such as in the conditions of acute liver failure, liver transplantation.
I agree with your view mostly. Partly this depends on how you view these liver enzymes in a clinical scenario. In a septic or critically ill patient a cholestatic picture with raised ALT and AST would suggest hepatocellular failure and possibly MODS if other organs are involved (thus liver is one of the organs). However in a patient with significantly raised transaminases in the setting of drug toxicity would indicate acute hepatocellular failure primarily involving this organ which may involve other organs if the patient develops MODS. In a transplantation setting a significantly raised transaminases may indicate early transplant failure. This assessment becomes tricky in gall bladder and CBD pathology, however a significantly raised transaminase over some days along with raise in bilirubin should suggest CBD pathology. Organ assessment in critical illness is through function, in the case of liver its secretory function. Thus prothrombin and albumin and other easily recognisable substances are used for its assessment (SOFA or MODS score, Childs etc). However acute and significant raise in just the transaminases may be a indicator of primary hepatocellular damage and with passage of time the secretory function would be affected.
As everyone here has unanimously said that aminotransferases are liver injury marker in strict sense. The so called liver function tests basically rely on measurement of cellular injury marker/non functional plasma enzymes (ALT; AST) or actual metabolic competency marker of the liver (Urea, albumin and fibrinogen synthesis). The presence of these intracellular enzyme in serum indicates damage to the membranes of hepatocytes and depending on the extent need medical attention. The non functional enzymes might vary to a greater extent when compared to the metabolic marker such as Urea. A 2-3 fold change in urea levels is considered more serious problem when compare to similar changes with ALT and AST. Furthermore failure to NH3 detoxification leads to increase NH3 levels in a compromised liver. The NH3 can crosS the Blood brain barrier and lead to hepatic encephalopathy.
It depends on the clinical senario, so liver enzymes are part of the work up. Of course albumin level and prothrombin time are more sensetive prameters of liver function. So we have to take all these into consideration + others together with the clinical state.
Liver function cannot be indicated by a single test. This is an ancient rule that cannot be forgotten! The patient is a person with a complex pathophysiological mechanism and cannot be reduced to a mathematical model.
So again Leradi Enzo answer emphasizes that each case should be taken on its own merits and has its own work-up mainly dedicated by the clinical senario.
They can be called neither because both ALT and AST can be normal in case abnormal liver function or in case of liver damage as in chronic liver disease. Similarly the degree of abnormality is not commensurate with the degree of liver damage and cannot predict recovery or progress of failure in case of acute liver damage. Prothrombin time and bilirubin are better markers of liver damage considered together in proper perspecive
It is evident from the whole discussion that the final answer is that the increase in AST and ALT are not predictive of liver damage. However, I should mention that in clinical practice, their increase is often the first indicator of a silent liver disease that would otherwise not be diagnosed at an early stage.
Please refer to a new publication..how useful are clinical liver function tests in vitro?
The item of liver function tests is very old. A very recent example of open questions is: Borlak J, Chougule A, Singh PK: How useful are clinical liver function tests in vitro in human hepatotoxicity assays? Toxicol In Vitro. 2014 Mar 28;28(5):784-795. doi: 10.1016/j.tiv.2014.03.006. [Epub ahead of print]. You know better than me this paper. I think, however, that it is possible we are not discussing about the same topic. May I ask some question to you? How many patients with increased levels of AST and ALT have you seen in your clinical practice? And how many different diagnosis did you perform? What investigations other than transaminases did help your diagnosis? How did you ascertain the entity of liver damage? How many patients did need liver transplantation? Thank you for your patience.
ALT and AST are markers of acute liver injury. Liver function can not be judged by a single test.
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