Liver Function Test (LFT)

About liver function tests

Liver function test is a term usually used to refer to the blood tests that measure different enzymes, proteins, and other substances made by the liver (such as albumin, bilirubin, AST or ALT).

The main purposes of LFTs are:

• Screening for liver infections, such as hepatitis;
• Monitoring progression of hepatic disease and reaction to treatment;
• Measuring severity of hepatic damage (particularly scarring of the liver in cirrhosis);
• Monitoring possible side effects of medication (due to liver clearance).

LFTs may be required following symptoms such as jaundice, nausea and vomiting, abdominal pain, diarrhoea, dark-coloured urine, light-coloured stool or persistent unexplained fatigue.

The table below summarizes the main liver function enzymes and proteins that are tested:

This data can then be used, along with others such as serum sodium or platelet count and subject age, gender, height and weight, to compute several hepatic parameters and scores that evaluate liver function, signs of liver disease or even differentiate between different manifestations of liver conditions.

MELD Score

The MELD score assesses the severity of the chronic liver disease and is used in the liver transplant waiting list prioritization by the United Network for Organ Sharing (UNOS).

• Original MELD Score (rounded) = 10 x [(0.957 x ln(Creatinine)) + (0.378 x ln(Bilirubin)) + (1.12 x ln(INR))] + 6.43

In January 2016, OPTN changed Policy 9.1 in regard to the calculation of the MELD score to include serum sodium. Therefore, the new formula where original MELD score is MELD(i) is:

• MELD Score (2016) = MELD(i) + 1.32 x (137-Na) – [0.033 x MELD(i) x (137-Na)]

Please note the calculator also accounts for the following adjustments:

• Values less than 1 are automatically adjusted to the lower limit value of 1 to prevent obtaining a negative score.
• The upper limit for serum creatinine is 4 mg/dL, therefore for those patients that have had 2 rounds of dialysis in the past week, the value is automatically adjusted to 4 mg/dL.
• Sodium values less than 125 mmol/L will be set to 125, and values greater than 137 mmol/L will be set to 137.

The range of results is presented with its corresponding 3-month mortality percentage (based on original MELD).

MELD-Na Score

The MELD Na Score adds the sodium determination to the variables of the original Model of End Stage Liver Disease. The two equations used are the following:

• MELD Score = 10 x [(0.957 x ln(Creatinine)) + (0.378 x ln(Bilirubin)) + (1.12 x ln(INR))] + 6.43
• MELD Na = MELD − Na − [0.025 × MELD × (140 − Na)] + 140

Same adjustments apply as at MELD Score with the difference that serum sodium values greater than 140 mmol/L are reduced to 140mmol/L not to 137 mmol/L/

Child-Turcotte-Pugh Score

The Child-Turcotte-Pugh score (shortened name: Child Pugh Score) determines the prognosis of hepatic disease. The five items in the score are awarded points, from 1 to 3, depending on their weight on liver disease.

Three classes of diseases severity have been defined, as follows:

Serum Ascites Albumin Gradient (SAAG)

Serum Ascites Albumin Gradient (SAAG) determines the gradient between the serum and ascites fluid albumin to find if is caused by portal hypertension.

• SAAG = Serum Albumin – Ascites Fluid Albumin

Due to oncotic pressure, SAAG is usually below 1.7 g/dL. SAAG values above 1.1 g/dL are consistent with portal hypertension as the etiology of ascites, with 97% accuracy. The increase in hydrostatic pressure determines fluid to leave circulation and enter in the peritoneal space, creating the ascites fluid, while albumin molecules remain in the circulatory system.

SAAG values below 1.1 g/dL rule out increased portal pressure as ascites cause. Some conditions manifesting with low SAAG are tuberculosis, infections, serositis, some peritoneal carcinomas, pulmonary infarcts or the nephrotic syndrome.

AST to ALT Ratio

The ratio between Aspartate transaminase (AST) and Alanine transaminase (ALT) may be used as a diagnostic indicator.

• AST to ALT ratio = AST (IU/L) / ALT (IU/L)

A raised AST level out of proportion to the ALT level may be caused by a differential reduction in hepatic ALT (deficiency of the cofactor pyridoxine-5-phosphate).

AST/ALT ratios are greater than 2.0 are indicative of alcoholic liver disease, especially when accompanied by ALT levels below 500 IU/L and raised levels of serum Gamma-glutamyltransferase (GGT).

Discriminant Function (Maddrey Score)

The Maddrey Score (known as discriminant function) can be used to predict short term prognosis in patients with alcoholic hepatitis (AH) and helps prioritize corticosteroid therapy. The discriminant function applied in stratifying AH patients is:

• DF = 4.6 x (Prothrombin time - Control time) + Bilirubin in mg/dL

The bilirubin value reflects the metabolic function of the liver and is usually higher than normal in cases of alcoholic liver disease.

All Maddrey score results above 32 are indicative of a poor prognosis with 35-45% mortality risk within first month. The patient may benefit from corticosteroid therapy and should undergo a liver biopsy.

AST to Platelet Ratio Index (APRI)

The AST to Platelet Ratio Index is a non-invasive method that can offer information about risk of hepatic fibrosis and cirrhosis, based on platelet count and aspartate aminotransferase level.

• APRI = AST (IU/L) / AST upper normal limit (IU/L) /Platelet count (10⁹/L) x 100

The aspartate aminotransferase to platelet ratio index suggests the level of hepatic fibrosis and possible liver disease:

Fatty Liver Index (FLI)

The Fatty Liver Index supports the diagnosis of fatty liver and the referral of suspected patients to ultrasonography.

• FLI = (^e0.953*log_e ^{(triglycerides) + 0.139*BMI + 0.718*log}_e ^{(ggt) + 0.053*waist circumference - 15.745}) / (1 + ^e0.953*log_e ^{(triglycerides) + 0.139*BMI + 0.718*log}_e ^{(ggt) + 0.053*waist circumference - 15.745}) x 100

The FLI scores vary between 1 and 100, with cut-off points at 30 and 60:

• FLI scores below 30 indicate that FL should be ruled out (with a negative likelihood ratio of up to 0.2);
• FLI scores between 30 and below 60 remain inconclusive;
• FLI scores of 60 and above indicate that FL is present (with a positive likelihood ratio starting from 4.3).

Fibrosis 4 Score (FIB 4)

The FIB 4 score evaluates the degree of fibrosis in patients suspected of or already diagnosed with hepatic fibrosis. The score contributes to assessment of NASH (non-alcoholic steatohepatitis), HCV (hepatic C virus) or cholestatic and metabolic liver diseases.

• FIB 4 = (Age x AST) / (Platelet count x √ALT)

The result is interpreted according to two cut off values:

• FIB 4 <1.45 indicates absence of cirrhosis (with a negative predictive value of 90% for advanced fibrosis);
• FIB 4 between 1.45 - 3.25 are deemed inconclusive;
• FIB 4 >3.25 indicates cirrhosis (with a positive predictive value of 65% for advanced fibrosis).

Hepatic Steatosis Index (HSI)

The Hepatic Steatosis Index is a simple to use screening tool that reflects non-alcoholic fatty liver disease. It can help clinicians identify candidates for liver ultrasonography and those in need of lifestyle and dietary modifications.

• HSI = 8 x ALT/AST + BMI (+ 2 if type 2 diabetes yes, + 2 if female)

Where the body mass index (BMI) is calculated using: body weight (kg)/height squared (m²).

The result is interpreted by comparison to the two cut-off points:

• HSI values below 30 indicate that NAFLD can be ruled out (with a negative likelihood ratio of up to 0.186).
• HSI values of 36 and above indicate that NAFLD positive diagnosis is highly likely (with a positive likelihood ratio starting from 6.069).

References

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2. OPTN's announcement about Sodium Inclusion

3. Biggins SW, Kim WR, Terrault NA, Saab S, Balan V, Schiano T, Benson J, Therneau T, Kremers W, Wiesner R, Kamath P, Klintmalm G. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology. 2006; 130(6):1652-60.

4. Child CG, Turcotte JG. Surgery and portal hypertension. In: The liver and portal hypertension. Edited by CG Child. Philadelphia: Saunders 1964:50-64.

5. Uddin MS, Hoque MI, Islam MB, Uddin MK, Haq I, Mondol G, Tariquzzaman M. Serum-ascites albumin gradient in differential diagnosis of ascites. Mymensingh Med J. 2013; 22(4):748-54.

6. Maddrey WC, Boitnott JK, Bedine MS, Weber FL Jr, Mezey E, White RI Jr. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978; 75(2):193-9.

7. Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011; 53:726-36.

8. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006; 6:33.

9. Sterling RK, Lissen E, Clumeck N, et. al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology 2006; 43:1317-1325.

10. Lee JH, Kim D, Kim HJ, et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 2010; 42: 503–8.