Editing Liver function tests (section)

==Standard liver panel==
Standard liver tests for assessing liver damage include alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Bilirubin may be used to estimate the excretory function of the liver and coagulation tests and albumin can be used to evaluate the metabolic activity of the liver.<ref name="Shivaraj 2009"/>

Although example reference ranges are given, these will vary depending on method of analysis used at the administering laboratory, as well as age, gender, ethnicity, and potentially unrelated health factors. Individual results should always be interpreted using the reference range provided by the laboratory that performed the test.<ref>{{cite |url=https://www.testing.com/articles/laboratory-test-reference-ranges/#:~:text=A%20normal%20result%20in%20one,this%20website%2C%20Testing.com. |title=Laboratory Test Reference Ranges |website=Testing.com |access-date=15 December 2024}}</ref>

===Total bilirubin===
{{Main|Bilirubin}}
{| class="wikitable"
|+ Reference range in adults
! Parameters/units
! Total bilirubin
! Unconjugated bilirubin
! Conjugated bilirubin
|-
! mg/dL
| 0.1–1.0<ref name="Lisa B 2015"/> ||0.2–0.7<ref name="Lisa B 2015"/> || 0.1–0.4<ref name="Lisa B 2015">{{cite journal|last1=Lisa B|first1=VanWagner|title=Evaluating Elevated Bilirubin Levels in Asymptomatic Adults|journal=Journal of the American Medical Association|date=3 February 2015|volume=313|issue=5|pages=516–517|doi=10.1001/jama.2014.12835|pmid=25647209|pmc=4424929}}</ref>
|-
! μmol/L
| 2.0–21<ref name="Shivaraj 2009"/>
| < 12<ref name="Shivaraj 2009"/>
| < 8<ref name="Shivaraj 2009"/>
|}

Measurement of total [[bilirubin]] includes both unconjugated (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of [[heme]] (a part of [[hemoglobin]] in red blood cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it (modified to make it water-soluble) through an enzyme named [[UDP-glucuronyl-transferase]]. When the total bilirubin level exceeds 17 μmol/L, it indicates liver disease. When total bilirubin levels exceed 40 μmol/L, bilirubin deposition at the sclera, skin, and mucous membranes will give these areas a yellow colour, thus it is called [[jaundice]].<ref name="Shivaraj 2009">{{cite journal|display-authors=3|last1=Shivaraj|first1=Gowda|last2=Prakash|first2=B Desai|last3=Vinayak|first3=V Hull|last4=Avinash|first4=AK Math|last5=Sonal N|first5=Venekar|last6=Shruthi S|first6=Kulkarni|title=A review on laboratory liver function tests|journal=The Pan African Medical Journal|date=22 November 2009|volume=3|issue=17|pages=17|pmid=21532726|pmc=2984286}}</ref>

The increase in predominantly unconjugated bilirubin is due to overproduction, reduced hepatic uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due to the reabsorption of a [[haematoma]] and ineffective [[erythropoiesis]] leading to increased red blood cell destruction. [[Gilbert's syndrome]] and [[Crigler–Najjar syndrome]] have defects in the [[UDP-glucuronyl-transferase]] enzyme, affecting bilirubin conjugation.<ref name="Shivaraj 2009"/>

The degree of rise in conjugated bilirubin is directly proportional to the degree of hepatocyte injury. Viral [[hepatitis]] can also cause the rise in conjugated bilirubin. In parenchymal liver disease and incomplete extrahepatic obstruction, the rise in conjugated bilirubin is less than the complete [[common bile duct]] obstruction due to malignant causes. In [[Dubin–Johnson syndrome]], a mutation in [[Multidrug resistance-associated protein 2|multiple drug-resistance protein 2 (MRP2)]] causes a rise in conjugated bilirubin.<ref name="Shivaraj 2009"/>

In [[acute appendicitis]], total bilirubin can rise from 20.52 μmol/L to 143 μmol/L. In pregnant women, the total bilirubin level is low in all three trimesters.<ref name="Shivaraj 2009"/>

The measurement of bilirubin levels in the newborns is done through the use of bilimeter or transcutanoeus bilirubinometer instead of performing LFTs. When the total serum bilirubin increases over 95th percentile for age during the first week of life for high risk babies, it is known as hyperbilirubinemia of the newborn ([[neonatal jaundice]]) and requires [[light therapy]] to reduce the amount of bilirubin in the blood. Pathological jaundice in newborns should be suspected when the serum bilirubin level rises by more than 5&nbsp;mg/dL per day, serum bilirubin more than the physiological range, clinical jaundice more than 2 weeks, and conjugated bilirubin (dark urine staining clothes). [[Hemolytic disease of the newborn|Haemolytic jaundice]] is the commonest cause of pathological jaundice. Those babies with Rh hemolytic disease, ABO incompatibility with the mother, [[Glucose-6-phosphate dehydrogenase]] (G-6-PD) deficiency and minor blood group incompatibility are at increased risk of getting haemolytic jaundice.<ref>{{cite journal|last1=Sana|first1=Ullah|last2=Khaista|first2=Rahman|last3=Mehdi|first3=Hedayati|title=Hyperbilirubinemia in Neonates: Types, Causes, Clinical Examinations, Preventive Measures and Treatments: A Narrative Review Article|journal=Iranian Journal of Public Health|date=May 2016|volume=45|issue=5|pages=558–568|pmid=27398328|pmc=4935699}}</ref>

===Alanine transaminase (ALT)===
{{Main|Alanine transaminase|Elevated transaminases}}
{| class="wikitable" align="right"
| Reference range
|-
| 7-56 IU/L<ref name="Shivaraj 2009"/>
|}
Apart from being found in high concentrations in the liver, ALT is found in the kidneys, heart, and muscles. It catalyses the [[transamination]] reaction, and only exists in a cytoplasmic form. Any kind of liver injury can cause a rise in ALT. A rise of up to 300 IU/L is not specific to the liver, but can be due to the damage of other organs such as the kidneys or muscles. When ALT rises to more than 500 IU/L, causes are usually from the liver. It can be due to hepatitis, ischemic liver injury, and toxins that causes liver damage. The ALT levels in [[hepatitis C]] rises more than in hepatitis A and B. Persistent ALT elevation more than 6 months is known as [[chronic hepatitis]]. [[Alcoholic liver disease]], [[non-alcoholic fatty liver disease]] (NAFLD), fat accumulation in liver during childhood obesity, [[steatohepatitis]] (inflammation of fatty liver disease) are associated with a rise in ALT. Rise in ALT is also associated with reduced insulin response, reduced glucose tolerance, and increased free [[fatty acid]]s and [[triglyceride]]s. Bright liver syndrome (bright liver on ultrasound suggestive of fatty liver) with raised ALT is suggestive of [[metabolic syndrome]].<ref name="Shivaraj 2009"/>

In pregnancy, ALT levels would rise during the second trimester. In one of the studies, measured ALT levels in pregnancy-related conditions such as [[hyperemesis gravidarum]] was 103.5 IU/L, [[pre-eclampsia]] was 115, [[HELLP syndrome]] was 149. ALT levels would reduce by greater than 50% in three days after child delivery. Another study also shows that [[caffeine]] consumption can reduce the risk of ALT elevation in those who consume alcohol, overweight people, impaired glucose metabolism, and viral hepatitis.<ref name="Shivaraj 2009"/>

===Aspartate transaminase (AST)===
{{Main|Aspartate transaminase|Elevated transaminases}}
{| class="wikitable" align="right"
| Reference range
|-
| 0-35 IU/L<ref name="Shivaraj 2009"/>
|}

AST exists in two [[isoenzymes]] namely mitochondrial form and cytoplasmic form. It is found in highest concentration in the liver, followed by heart, muscle, kidney, brain, pancreas, and lungs.<ref name=":0">{{Cite book|title=Harrison's principles of internal medicine |isbn=9781259644047|edition= Twentieth|publisher=McGraw Hill LLC|location=New York|oclc=990065894|last1 = Kasper|first1 = Dennis L.|last2=Fauci|first2=Anthony S.|last3=Hauser|first3=Stephen L.|last4=Longo|first4=Dan L.|last5=Larry Jameson|first5=J.|last6=Loscalzo|first6=Joseph|date=2018-02-06}}</ref> This wide range of AST containing organs makes it a relatively less specific indicator of liver damage compared to ALT. An increase of mitochondrial AST in bloods is highly suggestive of tissue [[necrosis]] in [[myocardial infarction]] and chronic liver disease. More than 80% of the liver AST activity are contributed by mitochondrial form of the isoenzymes, while the circulating AST in blood are contributed by cytoplasmic form of AST. AST is especially markedly raised in those with [[liver cirrhosis]].<ref name="Shivaraj 2009"/> AST can be released from a variety of other tissues and if the elevation is less than two times the normal AST, no further workup needs to be performed if a patient is proceeding to surgery.{{citation needed|date=November 2021}}

In certain pregnancy related conditions such as hyperemesis gravidarum, AST can reach as high as 73 IU/L, 66 IU/L in pre-eclampsia, and 81 IU/L in HELLP syndrome.<ref name="Shivaraj 2009"/>

===AST/ALT ratio===
{{Main|AST/ALT ratio}}
The AST/ALT ratio increases in liver functional impairment. In alcoholic liver disease, the mean ratio is 1.45, and mean ratio is 1.33 in post necrotic liver cirrhosis. Ratio is greater than 1.17 in viral cirrhosis, greater than 2.0 in alcoholic hepatitis, and 0.9 in non-alcoholic hepatitis. Ratio is greater than 4.5 in [[Wilson disease]] or [[hyperthyroidism]].<ref name="Shivaraj 2009"/>

===Alkaline phosphatase (ALP)===
{| class="wikitable" align="right"
| Reference range
|-
| 41 to 133 IU/L<ref name="Shivaraj 2009"/>
|}
{{Main|Elevated alkaline phosphatase}}

[[Alkaline phosphatase]] (ALP) is an enzyme in the cells lining the [[biliary tract|biliary ducts]] of the liver.  It can also be found on the mucosal epithelium of the small intestine, [[proximal convoluted tubule]] of the kidneys, bone, liver, and placenta. It plays an important role in lipid transposition in small intestines and calcification of bones. 50% of all the serum ALP activities in blood are contributed by bone. Acute viral hepatitis usually has normal or increased ALP. For example, hepatitis A has increased ALP due to [[cholestasis]] (impaired bile formation or bile flow obstruction) and would have the feature of prolonged itching. Other causes include: infiltrative liver diseases, granulomatous liver disease, abscess, [[amyloidosis]] of the liver and [[peripheral arterial disease]]. Mild elevation of ALP can be seen in liver cirrhosis, hepatitis, and [[congestive cardiac failure]]. Transient [[hyperphosphataemia]] is a benign condition in [[infant]]s, and can reach normal level in 4 months. In contrast, low levels of ALP is found in [[hypothyroidism]], [[pernicious anemia]], [[zinc deficiency]], and [[hypophosphatasia]].<ref name="Shivaraj 2009"/>

ALP activity is significantly increased in the third trimester of [[pregnancy]].<ref name="Gronowski2004" /> This is due to increased synthesis from the [[placenta]] as well as increased synthesis in the [[liver]] induced by large amounts of estrogens.<ref name="Gronowski2004" /><ref name="McCombBowersPosen1979">{{cite book | title = Alkaline Phosphatase | last1 = McComb | first1 = Robert B. | last2 = Bowers | first2 = George N. | last3 = Posen | first3 = Solomon | chapter = Clinical Utilization of Alkaline Phosphatase Measurements | date = 1979 | pages = 525–786 | publisher = Springer US | doi = 10.1007/978-1-4613-2970-1_9 | isbn = 978-1-4613-2972-5 | url = }}</ref><ref name="pmid14236214">{{cite journal | vauthors = Mueller MN, Kappas A | title = Estrogen pharmacology. I. The influence of estradiol and estriol on hepatic disposal of sulfobromophthalein (BSP) in man | journal = J Clin Invest | volume = 43 | issue = 10| pages = 1905–14 | date = October 1964 | pmid = 14236214 | pmc = 289635 | doi = 10.1172/JCI105064 | url = }}</ref> Levels in the third trimester can be as much as 2-fold greater than in non-pregnant women.<ref name="Gronowski2004">{{cite book | title = Handbook of Clinical Laboratory Testing During Pregnancy | last1 = Gronowski | first1 = Ann M. | chapter = Human Pregnancy | date = 2004 | pages = 1–13 | publisher = Humana Press | doi = 10.1007/978-1-59259-787-1_1 | isbn = 978-1-4684-9862-2 | url = }}</ref> As a result, ALP is not a reliable marker of hepatic function in pregnant women.<ref name="Gronowski2004" /> In contrast to ALP, levels of ALT, AST, GGT, and [[lactate dehydrogenase]] are only slightly changed or largely unchanged during pregnancy.<ref name="Gronowski2004" /> [[Bilirubin]] levels are significantly decreased in pregnancy.<ref name="Gronowski2004" />

In pregnancy conditions such as hyperemesis gravdirum, ALP levels can reach 215 IU/L, meanwhile, in pre-eclampsia, ALP can reach 14 IU/L, and in HELLP syndrome ALP levels can reach 15 IU/L.<ref name="Shivaraj 2009"/>

===Gamma-glutamyltransferase (GGT)===
{| class="wikitable" align="right"
| Reference range
|-
| 9 to 85 IU/L<ref name="Shivaraj 2009"/>
|}
{{Main|Gamma-glutamyltransferase}}
GGT is a microsomal enzyme found in hepatocytes, biliary epithelial cells, renal tubules, pancreas, and intestines. It helps in [[glutathione]] metabolism by transporting peptides across the cell membrane. Much like ALP, GGT measurements are usually elevated if cholestasis is present.<ref name=":0" /> In acute viral hepatitis, the GGT levels can peak at 2nd and 3rd week of illness, and remained elevated at 6 weeks of illness. GGT is also elevated in 30% of the hepatitis C patients. GGT can increase by 10 times in alcoholism. GGT can increase by 2 to 3 times in 50% of the patients with non-alcoholic liver disease. When GGT levels is elevated, the [[triglyceride]] level is elevated also. With insulin treatment, the GGT level can reduce. Other causes of elevated GGT are: diabetes mellitus, [[acute pancreatitis]], myocardial infarction, [[anorexia nervosa]], [[Guillain–Barré syndrome]], hyperthyroidism, obesity and [[myotonic dystrophy]].<ref name="Shivaraj 2009"/>

In pregnancy conditions GGT activity is reduced in 2nd and 3rd trimesters. In hyperemesis gravidarum, GGT level value can reach 45 IU/L, 17 IU/L in pre-eclampsia, and 35 IU/L in HELPP syndrome.<ref name="Shivaraj 2009"/>

===Albumin===
{| class="wikitable" align="right"
| [[Reference ranges for common blood tests|Reference range]]
|-
| 3.5 to 5.3 g/dL
|}
[[Albumin]] is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein (the remaining constituents are primarily [[globulins]]). Albumin levels are decreased in chronic liver disease, such as [[cirrhosis]]. It is also decreased in [[nephrotic syndrome]], where it is lost through the urine.  The consequence of low albumin can be edema since the intravascular [[oncotic pressure]] becomes lower than the extravascular space. An alternative to albumin measurement is prealbumin, which is better at detecting acute changes (half-life of albumin and prealbumin is about 2 weeks and about 2 days, respectively).<ref>{{Cite journal|last=Smith|first=Susan H.|date=April 2017|title=Using albumin and prealbumin to assess nutritional status|url=https://dx.doi.org/10.1097%2F01.NURSE.0000511805.83334.df|journal=Nursing2021|language=en-US|volume=47|issue=4|pages=65–66|doi=10.1097/01.NURSE.0000511805.83334.df|pmid=28328780|s2cid=45694428 |issn=0360-4039|url-access=subscription}}</ref><ref>{{Cite web|title=Prealbumin Blood Test: MedlinePlus Medical Test|url=https://medlineplus.gov/lab-tests/prealbumin-blood-test/|access-date=2021-02-25|website=medlineplus.gov|language=en}}</ref>