Evaluation of aberrant liver part tests

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  1. J One thousand Limdi1,
  2. G M Hydetwo
  1. 1Tameside General Hospital, Ashton-nether-Lyne, Manchester
  2. 2Wythenshawe Hospital, South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester
  1. Correspondence to:
 Dr Jimmy K Limdi, Tameside General Hospital, Fountain Street, Ashton-nether-Lyne OL6 9RW, Uk; limdi{at}aol.com

Abstruse

Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more than common with the introduction of automated routine laboratory testing. Not all persons with 1 or more abnormalities in these tests actually take liver illness. The diverse biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review.

  • liver function tests
  • ALP, element of group i phosphatase
  • ALT, alanine transaminase
  • AST, aspartate transaminase
  • ELISA, enzyne linked immunosorbent assay
  • HbsAg, hepatitis B surface antigen
  • HFE, haemochromatosis gene
  • NASH, not-alcoholic steatohepatitis

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  • liver function tests
  • ALP, alkaline phosphatase
  • ALT, alanine transaminase
  • AST, aspartate transaminase
  • ELISA, enzyne linked immunosorbent assay
  • HbsAg, hepatitis B surface antigen
  • HFE, haemochromatosis gene
  • NASH, non-alcoholic steatohepatitis

Commonly available tests include alanine transaminase (ALT) and aspartate transaminase (AST), alkaline phosphatase (ALP), gammaglutamyl transferase, serum bilirubin, prothrombin time, or international normalised ratio and serum albumin (box 1). They reflect different functions of the liver—that is, to excrete anions (bilirubin), hepatocellular integrity (transaminases), formation and the subsequent complimentary menstruation of bile (bilirubin and ALP), and protein synthesis (albumin).

Box 1: Normal values

  • Alanine transaminase: 0–45 IU/l.

  • Aspartate transaminase: 0–35 IU/l.

  • Alkaline phosphatase: 30–120 IU/l.

  • Gammaglutamyl transferase: 0–thirty IU/fifty.

  • Bilirubin: 2–17 μmol/l.

  • Prothrombin fourth dimension: 10.9–12.5 sec.

  • Albumin: 40–sixty g/50.

Other tests are ofttimes performed past a specialist and include hepatitis serology, fe and copper studies, α1-antitrypsin levels, and autoantibodies. These relate to the possible aetiology of the abnormality.

The enzymes tested are most usually raised in liver disease just some enzymes are too present in other tissues and consequently may exist raised in other conditions.

When faced with an aberration in an asymptomatic patient it is imperative to found that there is an abnormality in the first place, that is statistically meaning (the normal value is the mean value in a group of good for you individuals ±2SD). The tests should be repeated and when confirmed appropriate steps be taken.

CLINICAL Cess

A detailed history should be taken and full concrete test performed with a particular accent on alcohol consumption, risk factors for viral hepatitis (intravenous drug use, sexual promiscuity, homosexual relations, tattoos, non-sterile ear or trunk piercing, blood or claret product transfusions), medications used currently or previously, herbal or alternative remedies, and occupational exposure to toxins (box 2).

Box ii: Clinical cess

  1. Alcohol consumption.

  2. Risk factors for viral hepatitis:

    • Intravenous drug use.

    • Sexual promiscuity.

    • Homosexual relations.

    • Tattoos.

    • Non-sterile ear or torso piercing.

    • Blood or claret product transfusions.

    • Residence in developing nations.

  3. Medications.

  4. Occupational exposure to toxins.

Other factors such as diabetes, obesity and hyperlipidaemia in non-alcoholic fatty liver affliction, and family history (for Wilson's affliction, haemochromatosis, autoimmune disease) may be significant.

BILIRUBIN

Bilirubin is formed from the lysis of reddish cells (the haem component) within the reticuloendothelial system. Unconjugated bilirubin is transported to the liver loosely bound to albumin. It is water insoluble and therefore cannot be excreted in urine. Conjugated bilirubin is water soluble and appears in urine.

Within the liver information technology is conjugated to bilirubin glucoronide and subsequently secreted into bile and the gut respectively. Intestinal flora breaks it down into urobilinogen, some of which is reabsorbed and either excreted via the kidney into urine or excreted past the liver into the gastrointestinal tract. The residual is excreted in the stool equally stercobilinogen giving stool its brownish colour.

Serum bilirubin is commonly mainly in an unconjugated form reflecting a remainder between production and hepatobiliary excretion. Bilirubin product increases in haemolysis, ineffective erythropoiesis, resorption of a haematoma, and rarely in muscle injury. In all these cases the bilirubin is mainly in an unconjugated form. Conjugated hyperbilirubinaemia characteristically occurs in parenchymal liver disease and biliary obstacle.

UNCONJUGATED HYPERBILIRUBINAEMIA

Unconjugated hyperbilirubinaemia (indirect bilirubin fraction >85% of total bilirubin) occurs with increased bilirubin production or in defects in hepatic uptake or conjugation, which in turn may exist inherited or caused (box iii).

Box 3: Causes of isolated hyperbilirubinaemia

  • Unconjugated

    1. Increased bilirubin product.

      • Haemolysis.

      • Ineffective erythropoiesis.

      • Claret transfusion.

      • Resorption of haematomas.

    2. Decreased hepatic uptake.

      • Gilbert's syndrome.

      • Drugs—for example, rifampicin.

    3. Decreased conjugation.

      • Gilbert'south syndrome.

      • Criggler-Najjar syndrome.

      • Physiological jaundice of the newborn.

  • Conjugated

    1. Dubin-Johnson syndrome.

    2. Rotor's syndrome.

    • Gilbert'south syndrome deserves particular mention. This is a common, beneficial disorder characterised by unconjugated hyperbilirubinaemia, which is exacerbated by fasting. It does non require whatever specific treatment and the patient should be reassured.

    Disproportionate isolated unconjugated hyperbilirubinaemia may as well be seen in fulminant Wilson'due south disease. It is interesting that the ALP is low in such situations. Haemolysis is believed to result from copper release in the claret stream with resulting red jail cell lysis.

    It is worth mentioning here that bilirubin levels of more than 85 μmol/fifty in the presence of normal hepatic function cannot be explained by chronic haemolysis alone.ane, two

    CONJUGATED HYPERBILIRUBINAEMIA (DIRECT BILIRUBIN >l% OF TOTAL BILIRUBIN)

    This occurs in inherited or caused defects in hepatic excretion. Bilirubin levels have prognostic significance in alcoholic hepatitis, principal biliary cirrhosis, and in acute liver failure. However a disproportionate rise in conjugated bilirubin has express diagnostic value. As conjugated bilirubin is excreted in urine, bilirubin levels rarely exceed 510 μmol/l in the absence of renal failure or haemolysis.three

    AMINOTRANSFERASES

    These include AST and ALT. They are an splendid marking of hepatocellular injury. They participate in gluconeogenesis by catalysing the transfer of amino groups from aspartic acid or alanine to ketoglutaric acid to produce oxaloacetic acid and pyruvic acid respectively.

    AST is present in cytosolic and mitochondrial isoenzymes and is found in the liver, cardiac muscle skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and cerise cells.4 Information technology is less sensitive and specific for the liver.

    ALT, a cytosolic enzyme is found in its highest concentrations in the liver and is more specific to the liver.4

    Hepatocellular injury and not necessarily cell death is the trigger for release of these enzymes into the circulation.

    When faced with an aberration, the first step should be to assess the degree of aberration. The tests should probably be repeated if the abnormality is mild. Further investigation is warranted if repeated tests ostend abnormality. Very high levels should prompt further evaluation without delay.

    Mutual causes are non-alcoholic fatty liver affliction, alcoholic liver disease, chronic hepatitis B and C, autoimmune liver disease, haemochromatosis, Wilson's disease, αi- antitrypsin deficiency, and coeliac disease.

    CAUSES OF RAISED AMINOTRANSFERASES

    Alcohol

    A reliable history is helpful; in reality this tin be difficult. A biochemical clue is the ratio of AST to ALT (2:1 at to the lowest degree), reflecting the low level of activity of ALT in people with alcoholic liver disease.

    A gammaglutamyl transferase level of twice the normal with an AST/ALT ratio of 2:1 or more is highly suggestive of alcohol corruption.5 Gammaglutamyl transferase is not specific to alcohol and hence cannot be used equally an isolated test.4

    Notably, AST levels of more than 8 times normal and ALT levels more than fives times normal are exceptionally rare in alcoholic liver illness.5 Conversely ALT may be normal fifty-fifty in the face of severe alcoholic liver illness. Typically aminotransferase levels are less than 300 U/l in alcohol induced liver injury unless of class other insults such as viral or Paracetamol induced liver injury are superimposed on alcoholic liver disease, when serum aminotransferase levels may exceed thou U/l. Very high aminotransferase levels are characteristically seen in ischaemic liver injury, acute viral hepatitis, and drug or toxin induced liver injury and occasionally in astute obstructing choledocholithiasis.

    Medication

    Several drugs may crusade raised liver enzymes, commonly non-steroidal anti-inflammatory drugs, antibiotics, statins, antiepileptics, and antituberculosis drugs (box 4). A specific inquiry should be fabricated well-nigh herbal remedies, alternative medications, and substance abuse. The commonest drug induced cause of a massive aminotransferase rise is paracetamol overdose, typically at doses of ten g or more than but likewise at lower doses particularly in the context of other insults such as alcohol.

    Box iv: Common causes of raised transaminases

    • Alcohol.

    • Medications: non-steroidal anti-inflammatory drugs, antibiotics, HMG Co-A-reductase inhibitors, antiepileptic drugs, antituberculous drugs, herbal medications, illicit drug utilize.

    • Non-alcoholic steatohepatosis.

    • Chronic hepatitis B and C.

    • Autoimmune diseases.

    • Haemochromatosis.

    • Wilson'due south disease.

    • Congestive cardiac failure and ischaemic hepatitis.

    • α1-Antitrypsin deficiency.

    • Coeliac illness.

    • Endocrine disease: hypothyroidism, Addison'due south disease.

    • Diseases of striate muscle.

    • Glycogen storage diseases.

    Drug induced liver enzyme ascension may present as an enzyme ascent soon later starting a drug. A logical step is to stop the drug and see if the results normalise. If the drug is essential for the patient a risk benefit cess volition be required. A liver biopsy may exist necessary to assess the severity of the injury or confirm a drug induced reaction.

    Viral hepatitis

    Hepatitis B and/or C are common causes and hepatitis serology should thus be requested. Nosotros volition consider the diagnostic laboratory features in turn.

    If hepatitis B surface antigen (HbsAg) is positive then HBeAg and HBe antibody results are normally available automatically. A positive HbsAg may stand for an acute or chronic infection. HbsAg becomes positive 2–8 weeks before biochemical evidence of jaundice or liver damage. In one case HbsAg has appeared other markers of viral replication—namely, hepatitis B virus Deoxyribonucleic acid and HbeAg—will as well announced. IgM anti-HBc, the best serological test for acute hepatitis B, is detectable within 2–four weeks of the advent of the surface antigen. If positive, information technology suggests acute hepatitis B infection and HbsAg and anti-HBs should exist obtained in 6 months.

    The infection may have resolved (HbsAg negative, anti-HBs positive) or may have get chronic (HbsAg positive, anti-HBs negative). If IgM anti-HBc is negative suggesting a chronic hepatitis B virus infection, the HbeAg and anti-HBe will help make up one's mind whether the infection in the carrier is actively replicating or is quiescent.vi Patients with a positive HBe Ag and hepatitis B virus Deoxyribonucleic acid may be considered for a liver biopsy.four Family members and intimate contacts of HbsAg positive individuals should be screened for exposure to hepatitis B by checking HbsAg and anti-HBc. If anti-HBc negative, family unit members/intimate contacts would be candidates for immunoprophylaxis if not previously vaccinated.6

    A positive hepatitis C antibody in a patient with risk factors would reflect previous contact with the virus. Antibodies to hepatitis C virus are not protective. The presence of antihepatitis C in a patient with an aberrant ALT, and risk factors for hepatitis C infection would strongly suggest current hepatitis C infection. The initial test for antihepatitis C is the enzyne linked immunosorbent assay (ELISA) test. The exam is very sensitive just faux positive tests are not infrequent even with 3rd generation ELISAs as seen in hypergammaglobulinaemia of autoimmune hepatitis. If antihepatitis C is negative information technology is unlikely that the patient has hepatitis C. The specificity of ELISA testing may be improved past addition of the recombinant immunoblot analysis for antihepatitis C.3 No methods of culturing the virus are bachelor. Consequently detection of the virus in serum is used as a mark of the virus itself. Hepatitis C RNA detected by polymerase chain reaction is the current gilded standard.7 A positive test would suggest agile viral infection and replication. Polymerase chain reaction testing may be done by quantitative or qualitative methods. The sensitivity of quantitative testing varies between 2000–200 000 viral copies/ml whereas qualitative tests will observe as few as 100 viral copies/ml usually within i week of exposure.3 Quantitative tests should therefore not exist used for diagnosis equally these tin miss patients with a low level viraemia. Due consideration would be given for antiviral therapy past a specialist. If the polymerase concatenation reaction is negative despite a positive antibody test, it should be retested in three months to ensure that it was not a false negative.

    AUTOIMMUNE HEPATITIS

    Autoimmune hepatitis is an unresolving inflammation of the liver of unknown cause that is associated with interface hepatitis on histological examination, hypergammaglobulinaemia, and autoantibodies. The typical clinical case is that of a young to eye aged woman (a ratio of female to male of 4:1) with raised transaminases in the absence of any other apparent cause. On serum protein electrophoresis around 80% or more patients demonstrate hypergammaglobulinaemia.8 Polyclonal immunoglobulins more than than twice normal are highly suggestive.4

    Appropriate tests would include immunoglobulins, antinuclear antibodies, antibodies to smooth muscle, antiliver-kidney microsomal antibodies and antibodies to the soluble liver antigen, which typify type one, two, and 3 autoimmune liver disease. Routine use of all three tests is not required. Liver biopsy is useful.

    Blazon 1 autoimmune hepatitis is characterised by the presence of antinuclear antibody and/or polish muscle (actin) antibodies. It is the near common form of the disease worldwide. Seventy percent are women less than 40 years old and over 30% accept concurrent immune diseases, especially autoimmune thyroiditis, synovitis, or ulcerative colitis.

    Type 2 autoimmune hepatitis is characterised by the presence of anti-LKM1 and is predominantly a disease of children anile 2–fourteen years. Patients with this form of hepatitis commonly have other concurrent autoimmune disorders such every bit type 1 diabetes, vitiligo, and autoimmune thyroiditis. Other organ specific autoimmune antibodies such as antibodies to parietal cells, islets of Langerhans, and thyroid may be found. These patients may have low serum levels of immunoglobulin A. Both type ane and ii autoimmune hepatitis mostly respond well to steroids.

    Type 3 autoimmune hepatitis is the least established form of the illness and is characterised by the presence of antibodies to soluble liver antigen/liver pancreas. Patients with these antibodies are indistinguishable from patients with classical blazon 1 autoimmune hepatitis past age, gender distribution, frequency and nature of other autoantibodies, and responsiveness to steroids.

    HEPATIC STEATOSIS AND Non-ALCOHOLIC STEATOHEPATITIS

    Not-alcoholic steatohepatitis (NASH) has emerged in contempo years equally a chronic hepatic disease of clinical importance. NASH in fact represents a phase within a spectrum of histological illness known as non-alcoholic fatty liver disease. The diagnosis of NASH is unremarkably suspected among individuals with asymptomatic increases in serum liver biochemistries; the presence of a raised body mass index, type ii diabetes mellitus, or hyperlipidaemia; and no testify of clinically relevant alcohol use. Mild increases in transaminases (less than four times normal) may exist the only clinical clue and in fact information technology is fair to say that not-alcoholic fat liver affliction is probably the commonest cause of mild aminotransferase increases.9, 10 The AST to ALT ratio is usually less than one:i.10, 11 Full bilirubin and albumin are usually normal. Leucopenia and thrombocytopenia should raise concerns for the beingness of cirrhosis and occult portal hypertension. Ultrasonography, which should form part of the assessment of chronically raised transaminases, may show fatty infiltration. NASH can be proved past liver biopsy4 if felt advisable in the clinical context.

    Steatosis tends to follow a beneficial course whereas NASH may progress to cirrhosis,12 though liver failure is uncommon. Programmed weight loss and addressing underlying factors form the basis of treatment.13

    HAEMOCHROMATOSIS

    This is a common autosomal recessive condition amidst white people associated with increased intestinal absorption of iron and degradation of excessive amounts of iron in the liver, pancreas, and other organs. Many patients are asymptomatic at diagnosis just clinical manifestations include cutaneous hyperpigmentation, diabetes mellitus, and chronic liver illness which may manifest as fatigue, intestinal pain, hepatomegaly, aberrant liver tests, cirrhosis, and hepatocellular carcinoma. Other clinical features include cardiomyopathy, cardiac conduction disorders, hypothyroidism, hypogonadism, impotence, and arthropathy.

    A diagnosis of haemochromatosis is based upon a combination of clinical, laboratory, and pathological criteria. A raised serum ferritin raises suspicion of underlying haemochromatosis but a more reliable test is transferrin saturation. Measuring serum fe and total fe bounden capacity gives a transferrin saturation index. A value more 45% is suggestive.14 Serum ferritin being an acute phase reactant may also exist raised in a number of other inflammatory states and as such is not a useful screening examination.

    Iron overload may exist confirmed by liver biopsy to assess hepatic atomic number 26 index (hepatic iron level in μmol/chiliad of dry weight divided by the patient's historic period). A ratio of more than ane.9 is consequent with homozygous hereditary haemochromatosis.xiv

    The discovery of the haemochromatosis cistron (HFE) in 1996 has revolutionised the diagnosis of haemochromatosis. The mutation in HFE, located on the short arm of chromosome 6 responsible for the majority of cases is now available by genetic testing. Two point mutations take been designated C282Y and H63D. The greatest gamble of atomic number 26 overload exists in those who are homozygous for the C282Y mutation. Iron overload also occurs in a minority of those with other HFE mutations, especially compound heterozygotes who have one copy of C282Y and i copy of H63D and occasionally H63D homozygotes. It must be remembered that clinically significant iron overload can occur in the absence of HFE mutations. A negative gene test therefore does not exclude haemochromatosis. The HFE test is a polymerase chain reaction that is usually performed on a whole blood sample. The gene test is most useful in screening developed family members of an identified proband. It is often likewise useful in helping resolve ambiguous cases, such every bit fe overload associated with hepatitis C, alcoholic liver disease, or other causes of finish phase liver disease. Earlier obtaining the HFE test an private should be counselled about the risks, benefits, and alternatives of genetic testing by a qualified professional. There is concern about the possibility of insurance or employment based on the results of these tests. For this reason gene testing usually is non recommended for anyone younger than 18 years of age.

    The need for liver biopsy has decreased with genetic testing becoming available. Liver biopsy notwithstanding remains the gilded standard for assessing the degree of fibrosis. Information technology is of import to exclude cirrhosis because of the increased hazard of developing hepatocellular carcinoma. In such patients screening with an ultrasound and α-fetoprotein every six months may exist advisable. A recent written report15 confirmed that certain not-invasive predictors were accurate in excluding cirrhosis in C282Y homozygotes. In this study, there were no cases of cirrhosis in 96 C282Y homozygotes who had serum ferritin levels lower than 1000 μg/l, normal AST values, and no bear witness of hepatomegaly. These results have been confirmed in other studies. A serum ferritin of <one thousand μg/l therefore seems to exist the best predictor of the absence of cirrhosis in C282Y homozygotes. The positive predictive value of a serum ferritin >1000 μg/l is poor, notwithstanding, every bit but about 50% of those with values of >1000 μg/fifty have cirrhosis. A liver biopsy is advisable in this group of patients to definitely assess for the presence of cirrhosis. Similar data is non available for non-C282Y homozygotes.

    Liver biopsy is non essential in patients with hereditary haemochromatosis less than 40 years with normal liver role.4

    WILSON'South DISEASE

    This is a genetic disorder of biliary copper excretion. Usually detected between the ages of v and 25, it should too exist considered in patients up to 40 years of age.

    Serum caeruloplasmin, the usual screening examination is reduced in approximately 85% of cases.4 Kayser-Fleischer rings may be a useful clinical clue. Caeruloplasmin may be normal and Kayser-Fleischer rings absent, in which case a 24 60 minutes urinary copper excretion should exist checked. Excretion of more than 100 μg suggests Wilson's disease.

    Liver biopsy will confirm the diagnosis if hepatic copper concentrations are more than than 250 μg/thou dry liver weight. The genetic defect has been identified but due to the large number of mutations involved molecular diagnosis is not yet possible.

    ALPHAone-ANTITRYPSIN DEFICIENCY

    This is an uncommon cause of chronic liver illness in adults. Low levels of α1-antitrypsin may be detected by direct measurement of serum levels or by the lack of a rise in α-globulin bands on serum protein electrophoresis.iv

    NON-HEPATIC CAUSES OF ABNORMALITY

    Hepatic infiltration such as metastatic or fifty-fifty primary hepatocellular carcinoma, tuberculosis, sarcoidosis, and amyloidosis may crusade a modest (upwardly to threefold) rises in aminotransferases, and an up to xx-fold rising in ALP depending upon the extent of involvement. Bilirubin levels are usually normal but up to fivefold increases are recognised.3

    Occult coeliac sprue is recognised as a cause of raised transaminases.16 Antiendomyseal antibodies and antigliadin antibodies are useful confirmatory tests. Box 4 lists common and rare but recognised non-hepatic causes of transaminase abnormalities.

    If despite comprehensive testing the cause is not apparent a liver biopsy may be required. Figure 1 suggests an algorithm for the investigation of abnormal transaminases.

    CAUSES OF RAISED ALKALINE PHOSPHATASE

    ALP originates mainly from two sources: liver and bone.2 The enzymes may exist present in a diverseness of other tissues namely intestine, kidney placenta, and leucocytes. The elevation may be physiological or pathological. The physiological office of these enzymes is not entirely clear but production increases in tissues undergoing metabolic stimulation. Elevations are seen in the third trimester of pregnancy, a outcome of an influx of placental ALP. Adolescents may prove increases that are twice normal for adults as a upshot of bone ALP into the blood, respective with growth.

    Conspicuously the showtime step in determining the crusade is to identify the source of the raised ALP. The nigh sensitive and indeed specific method is electrophoretic separation simply it is not freely available. A good discriminator is testing for 5′ nucleotidase or gammaglutamyl transferase, which rising in liver just non os disease. If ALP is of liver origin, imaging by ultrasound should be bundled.

    Box five lists mutual causes of raised ALP. Extrahepatic biliary obstruction, infiltrative diseases, and metastasis may crusade balmy to striking elevations in ALP

    Box 5: Mutual causes of raised ALP

  • Physiological

    • Women in the third trimester of pregnancy.

    • Adolescents.

    • Benign, familial (due to increased intestinal ALP).

  • Pathological

    • Bile duct obstruction.

    • Primary biliary cirrhosis.

    • Primary sclerosing cholangitis.

    • Drug induced cholestasis—for case, anabolic steroids.

    • Adult bile ductopenia.

    • Metastatic liver disease.

    • Bone disease.

    • Hepatic ALP is present on the canalicular and luminal domain of the bile duct epithelium and levels rise as a result of increased synthesis and consequent release into the apportionment. Equally a result levels may not ascent until i or two days after biliary obstruction. Farther the enzyme has a one-half life of a week and so even after resolution of biliary obstacle, information technology may take several days for levels to normalise.

    It is also worth noting that ALP may be raised in malignancies without liver or bone involvement. This isoenzyme is called the "Regan isoenzyme" and occurs in diverse neoplasms for example lung cancers.3

    Figure ii suggests an algorithm for evaluating patients with a raised ALP.

    Figure 2

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    Effigy ii

    Suggested algorithm for evaluating a raised ALP (ALP, alkaline phosphatase; ERCP, endoscopic retrograde cholangiopancreatography; GGT, gammaglutamyl transferase; PT, prothrombin time; MRCP, magnetic resonance cholangiopancreatography).

    GAMMAGLUTAMYL TRANSFERASE

    This enzyme is constitute in hepatocytes and biliary epithelial cells. Though a sensitive test of hepatobiliary illness its usefulness is limited by lack of specificity. Raised levels may be seen in pancreatic disease, myocardial infarction, renal failure, chronic obstructive pulmonary disease, diabetes, and alcoholism.17

    Medications like phenytoin, carbamazepine, and barbiturates may besides cause a mild ascension in gammaglutamyl transferase (box vi).18

    Box half dozen: Causes of raised gammaglutamyl transferase

    • Hepatobiliary disease (oft with other liver enzyme abnormalities).

    • Pancreatic disease.

    • Alcoholism.

    • Chronic obstructive pulmonary disease.

    • Renal failure.

    • Diabetes.

    • Myocardial infarction.

    • Drugs—for example, carbamazepine, phenytoin, and barbiturates.

    With other enzyme abnormalities, a raised gammaglutamyl transferase would support a hepatobiliary source. For example information technology would confirm hepatic source for a raised ALP. A raised gammaglutamyl transferase with raised transaminases and a ratio of AST to ALT of 2:1 or more would propose booze related liver affliction.

    A sensible approach is to follow patients with isolated gammaglutamyl transferase elevations at few monthly intervals. If other enzymes become abnormal or gammaglutamyl transferase increases farther an intestinal ultrasound, computed tomography, or both should exist requested to exclude a space occupying lesion and a liver biopsy examination considered.nineteen

    ALBUMIN

    Albumin synthesis is an of import office of the liver. Approximately ten g is synthesised and secreted daily. With progressive liver disease serum albumin levels autumn, reflecting decreased synthesis. Albumin levels are dependant on a number of other factors such every bit the nutritional status, catabolism, hormonal factors, and urinary and gastrointestinal losses. These should be taken into account when interpreting low albumin levels. Having said that, albumin concentration does correlate with the prognosis in chronic liver disease.

    PROTHROMBIN TIME

    The synthesis of coagulation factors (except gene Eight) is an important function of the liver. The prothrombin fourth dimension measures the rate of conversion of prothrombin to thrombin (requiring factors 2, 5, Vii, and X) and thus reflects a vital synthetic office of the liver. Vitamin K is required for the gamma carboxylation of the above named factors.

    Prothrombin fourth dimension may therefore be prolonged in vitamin K deficiency, warfarin therapy, liver illness, and consumptive coagulopathy.

    Information technology is of import to distinguish a prolonged prothrombin time due to hepatocellular illness from that due to chronic cholestasis with fatty malabsorption. In practice a useful mode of differentiating the two is the administration of vitamin Grand, which volition reduce a prolonged prothrombin time due to fat malabsorption but not due to intrinsic liver disease.

    INTERNATIONAL NORMALISED RATIO

    This is more than oft tested now instead of or along with prothrombin time, in order to standardise the reporting of prothrombin time (PT) results. Information technology is calculated according to a formula as follows:

    International normalised ratio = [patient PT/mean control PT] ISI

    (ISI = international sensitivity index).

    This is helpful considering it avoids the interlaboratory variability in prothrombin time. Its estimation is otherwise similar to prothrombin time.

    QUANTITATIVE TESTS OF LIVER Role

    Limitations of the diverse biochemical tests have prompted the search for more sensitive and quantitative tests of liver role. Though these tests are currently limited to research centres they deserve mention and includethree:

    • Indocyanine green clearance.

    • 14C-aminopyrine jiff test.

    • Antipyrine clearance.

    • Galactose elimination capacity.

    • 13C-caffeine breath test.

    The tests are expensive and more labour intensive. Well designed clinical trials are needed comparing them to biochemical tests before they gain wider acceptance.

    WHEN TO REFER FOR A SPECIALIST Opinion?

    This would commonly include6 patients with:

    (1) Unexplained liver abnormalities more ane.5 times normal on two occasions, a minimum of half-dozen months autonomously.

    (2) Unexplained liver disease with evidence of hepatic dysfunction (hypoalbuminaemia, hyperbilirubinaemia, prolonged prothrombin time, or international normalised ratio)

    (3) Known liver disease where treatment across the withdrawal of the implicating amanuensis is required.

    WHAT TESTS TO DO Earlier REFERRAL6

    Consider the following:

    (1) Screen for viral hepatitis: IgM antihepatitis A virus, HbsAg, antihepatitis C virus.

    (2) Antinuclear antibodies.

    (iii) Caeruloplasmin in patients younger than forty years.

    (iv) Iron studies (iron, total iron binding capacity, and ferritin).

    (5) Ultrasound of the liver especially where fatty infiltration is suspected (obese individuals, diabetics and/or hyperlipidaemic patients).

    Key points

    • Abnormal liver tests may present in an asymptomatic patient.

    • A practiced clinical history and concrete test are ofttimes rewarding.

    • Liver tests often become aberrant in non-hepatic diseases.

    • If a systematic approach is adopted the cause is often apparent.

    • A specialist opinion should be sought when appropriate.

    An ultrasound should as well exist performed in symptomatic patients with liver enzyme abnormalities or those with evidence of hepatic dysfunction (increased bilirubin or prothrombin time, or decreased albumin) and in those with biochemical evidence of cholestasis.

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