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Abnormal Transaminases

Evaluation of chronic (>6 months), mild (<250 U/L) isolated elevations of ALT/AST

Isolated elevated ALT/AST results are a common finding, the following causes should be considered:

False positive results relate to the way normal test reference values are defined and cut-off values chosen to define an abnormal test. There is some debate that cut-off values should be adjusted for gender and body mass index.

Single elevated AST/ALT results should be repeated over 6 months to define chronicity, consistency of abnormality and the peak levels.

Non hepatic disease: muscle disease (in the case of isolated raised AST), thyroid disease, adrenal insufficiency and Coeliac disease.

Hepatic disease: Drugs and Alcohol, Non Alcoholic Fatty Liver disease, Viral hepatitis, Hereditary Haemachromatosis, Autoimmune hepatitis, Wilson’s disease, Alpha 1 Anti-trypsin deficiency. Malignancy: hepatoma and secondary deposits. Liver abscess.

A diagnosis can be established in most patients with abnormal LFT’s non-invasively by a careful history, examination and further blood tests/radiology.

1. History

This is the single most important part of the evaluation, ask about:

Alcohol intake

Medications: NSAIDS, antibiotics, lipid lowering drugs, anti-epileptics, Paracetamol especially if combined with hepatic enzymes inducers like alcohol and Dilantin

Natural and alternative remedies

Note symptoms of;

arthalgias/myalgias/rash/fever; suggests viral (Hep A/B/C, CMV, EBV, Dengue and Ross River); drug causes and auto-immune hepatitis

abdominal pain: choledocholithiasis and cholangitis

malignancy in any organ system, especially in elderly patients

Family history liver disease, haemachromatosis in particular

Risk of exposure to HIV, Hep B and C: sexual history, IDU, blood transfusion and country of birth

2. Examination

Stigmata Chronic liver disease: Palmar Erythema, Dupuytren’s contractures, spiders, gynaecomastia, testicular atrophy, bruising, wasting, portal hypertension (ascites, encephalopathy, caput medusae) and an enlarged or shrunken liver

Right heart failure can cause liver congestion, peripheral oedema and ascites. The JVP will be raised and there may also be signs of left heart failure.

Signs of malignancy; pleural effusion, nodes, abdominal mass, melanoma, breast lumps

Fever may indicate; liver abscess and cholangitis

Calculate BMI; Weight in kg, divided by Height in meters squared. Normal 20-25, overweight 25-30, obese >30. These ranges may be too high for Asians.

3. Laboratory tests

Severe liver dysfunction as seen in cirrhosis is suggested by; thrombocytopenia, rising bilirubin levels, low albumin, prolonged PT not corrected by Vit K

Viral hepatitis is associated with ALT levels higher than AST levels. In alcoholic liver disease this pattern is reversed, ie. AST is higher than ALT, also GGT is raised.

If non hepatic causes are suspected; CK, TSH/thyroxine, tissue transglutaminase antibody and IgA level for Coeliac disease and basal cortisol for Addison’s disease

Hepatitis B sAg, HCV ab, Hep A Ig M, other viral serology if clinically indicated- CMV, EBV, Dengue, Ross River, Leptospiral, HIV antibody

Iron saturation and ferritin: Haemochromatosis gene test if Hereditary Haemochromatosis suspected

ANA, ASmA, Protein electrophoresis to detect polyclonal hypergammaglobulinaemia, associated with autoimmune hepatitis

Serum Copper and Ceruloplasmin for Wilson’s disease in patients aged less than 40 yrs

Alpha 1 anti-trypsin level, phenotyping if alpha 1 anti-trypsin level is low and/or there is a history of emphysema at a young age

Serum Cholesterol and glucose as risk factors for fatty liver

Alpha feto-protein if Hepatoma is a concern

4. Radiology

Upper abdominal ultrasound and or CT scan are mainly used to look for; portal hypertension, choledocholithiasis and biliary dilatation, liver abscess and malignant disease- hepatoma or metastases

5. Liver biopsy

In most patients with raised AST/ALT a liver biopsy does not lead to a significant diagnosis that requires therapy, but can be reassuring that no serious disease is present. Non alcoholic fatty liver and alcoholic liver disease are the main diagnoses when is biopsy is done.

Perhaps observation with 6 monthly LFT’s is best when AST/ALT levels are less than 2-fold elevated and referral for biopsy is made when above this.

In summary, elevated AST/ALT levels are not an uncommon finding, a diagnosis can be established in most patients non invasively with a thorough history, examination, specific bloods tests and radiology. Those patients who come to liver biopsy are usually diagnosed with steatosis, steato-hepatitis (non-alcoholic fatty liver disease) or alcoholic liver disease.