Approach to
transaminitis
Siti Maryam
Definition
Refers to having high levels of transaminases (liver enzymes)
Transaminases:
1) Serum aminotransferases:
a) aspartate aminotransferase (AST)
b) alanine aminotransferase (ALT)
2) Alkaline phosphatases (ALP)
AST and ALT
Hepatic enzymes that are usually intracellular but are released from hepatocytes when there is
hepatocellular injury.
AST : Found in hepatocytes, skeletal muscles and erythrocytes.
ALT : Found primarily in the liver. (low concentrations in other tissues)
AST/ALT ratio :
● Normal ratio: less than 1
● Greater than 2 suggests alcoholic liver disease
● Lesser than 1 suggest non-alcoholic fatty liver disease
● Greater than 4 may suggests Wilson’s disease
ALP
Primarily found in the liver, bones, intestine, and kidneys.
ALP is present in the epithelial cells of bile ducts, and its elevation is typically seen in cholestatic liver
disease.
Cholestatic liver disease can be categorized as either mechanical obstruction to bile flow (extrahepatic
cholestasis) or impairments of bile formation by the hepatocytes (intrahepatic cholestasis).
Biliary dilatation suggests an extrahepatic cause, while a normal biliary system on abdominal ultrasound
suggests that the cause of elevated ALP is intrahepatic.
Extrahepatic causes of cholestasis include choledocholithiasis and obstruction of the biliary tract due to
malignancy.
Other Causes: Cirrhosis, Primary or metastatic liver tumour
Concomitant rising of GGT confirms liver origin.
DIFFERENTIAL DIAGNOSIS
Alcoholic liver disease
Non-Alcoholic Fatty liver disease (NAFLD)
Drug induced liver injury
Viral hepatitis (hepatitis B and C)
Hemochromatosis.
Autoimmune hepatitis
Biliary obstruction
Alcoholic liver disease
AST/ALT ratio: >2
History: Excessive alcohol consumption.A daily alcohol consumption of 30 g for men and
20 g for women indicates ALD
Blood investigation: LFT
Patients with ARLD should be encouraged to cease alcohol consumption and be referred
to a multidisciplinary team
Non-alcoholic fatty liver disease
NAFLD is present in 17–46% of adults in Western countries and between 42 and 70% in
individuals with (T2DM)
History: Patients with obesity, evidence of metabolic risk factors, including BMI >25,
arterial hypertension, dyslipidemia, insulin resistance, or T2DM, should be further
assessed for NAFLD
Blood investigation : LFT (AST/ALT ratio: <1), FLP (high TG, Low HDL), FBS (raised)
Abdominal ultrasound: to look for fatty infiltration of liver. However, abdominal ultrasound
is sensitive for the detection of liver steatosis only when hepatocytes are more than 30%
steatotic, while patients with milder steatosis might have a normal ultrasound.
Drug induced
liver disease
Hemochromatosis
A dysregulation of iron absorption causing iron overload.
Classic Triad: Cirrhosis (hepatic damage), Diabetes (type II) (pancreatic damage),
Bronzing of skin (hyperpigmentation)
History: Family history of hemochromatosis. Autosomal recessive inheritance ( C282Y
mutation )
Investigation: Transferrin > 45%, serum iron and ferritin elevated, and TIBC normal or
slightly elevated. Liver biopsy if ferritin >1000 mcg/L to assess damage. Can also
consider genetic testing for confirmation.
Treatment: Phlebotomy weekly or twice weekly, iron chelating therapy.
Autoimmune hepatitis
Self perpetuating hepatocellular inflammation of unknown cause.
Clinical criteria: Presence of characteristic clinical features, Liver histology, Exclusion of other
diseases
Clinical features: jaundice, fever, fatigue, pruritus, abdominal pain, anorexia, hepatomegaly,
jaundice, ascites, concurrent immune disease.
Investigations: elevated transaminases and ggt, presence of autoantibodies to liver/kidney,
anti ANA, anti sma. anti-LKM1, histology findings (periportal hepatitis, bridging necrosis,
cirrhosis)
Treatment: prednisolone and azathioprine regiment.
Biliary obstruction
Intrahepatic: Hepatitis, Cirrhosis, Drugs.
Extrahepatic: Carcinoma of head of pancreas, Stones in biliary track, Inflammation of
common bile duct, Cysts of bile duct, Pancreatitis.
Management
Alcoholic liver disease: alcohol abstinence, lifestyle modifications
Non-alcoholic fatty liver disease: lifestyle modifications
Drug induced liver disease: stop medication/alternatives
Viral hepatitis: antiviral, regular lft and viral load monitoring,
Conclusion
Transaminitis is a common finding in clinical practice.
It's important to perform a thorough evaluation and identify the underlying cause.
Treatment depends on the etiology, and monitoring and follow-up are essential to
evaluate treatment effectiveness and prevent complications.
References
https://www.aafp.org/pubs/afp/issues/2011/1101/p1003.html
- American Gastroenterological Association. (2017). American Gastroenterological Association Institute
guideline on the evaluation of abnormal liver chemistries. Gastroenterology, 152(4), 1-15.
- Terrault, N. A., Lok, A. S., & McMahon, B. J. (2018). Chronic hepatitis B: update 2009. Hepatology, 50(3),
661-662.
- Younossi, Z., Anstee, Q. M., Marietti, M., Hardy, T., Henry, L., & Eslam, M. (2018). Global burden of NAFLD
and NASH: trends, predictions, risk factors and prevention. Nature Reviews Gastroenterology & Hepatology,
15(1), 11-20.
