Portal hypertension laboratory findings

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

There are no diagnostic laboratory findings exclusively associated with portal hypertension. Laboratory findings related with the diagnosis of cirrhosis, as the most common underlying disease for portal hypertension, include indirect serum markers and direct fibrosis markers. Indirect serum markers are platelet count, AST/ALT index, AST/platelet ratio index, and Lok score. Direct fibrosis markers are fibrotest, fibrometer, hepascore, hyaluronic acid, and enhanced liver fibrosis.

• There are no diagnostic laboratory findings exclusively associated with portal hypertension.
• Laboratory findings related with the diagnosis of cirrhosis, as the most common underlying disease for portal hypertension, include indirect serum markers and direct fibrosis markers.

• Reduced platelet count is the most frequent test used to diagnose portal hypertension in chronic liver disease.^[1]
• 78% of the patients with cirrhosis have thrombocytopenia.^[2]
• The probability of esophageal varices are low when the platelet count is normal.^[3]

• The AST/ALT ratio was first described by De Ritis, known also as De Ritis ratio.^[4]
• Elevated levels of AST/ALT index reflects the hepatocellular damage or death.^[5]
• The AST/ALT ratio of more than 1 in chronic hepatitis is suggestive of cirrhosis.^[6]

• Since both AST and platelet count are predictors of cirrhosis and fibrosis in liver, AST to platelet ratio index (APRI) is postulated to multiply the diagnostic value.
• The APRI is significantly correlated with the stage of fibrosis in liver, more than AST or platelet count separately.

<math display=”block”>APRI = [(AST/ULN)/platelet count(10^{9}/L)] \times 100</math>ULN= Upper limit of normal

• APRI ≤ 0.50 is suggestive of absence of fibrosis and APRI > 1.50 is suggestive of presence of the significant fibrosis.^[7]

• The best serologic test for portal hypertension and esophageal varices is Lok score.
• The score is calculated through following formula: ^[8]

<math display=”block”>\log_{Predicting Cirrhosis}= -5.56 -0.0089 \times platelet (\times10^{3}/mm^3) + 1.26\times AST/ALT ratio + 5.27 \times INR</math>

• The Lok score of more than 0.73 is suggesting fibrosis and cirrhosis of the liver.^[9]

• Fibrosis-4 (FIB-4) index is a simple non-invasive serologic method for diagnosing the fibrosis and cirrhosis in liver.
• The FIB-4 index is calculated through following formula:

<math display=”block”>FIB-4 = Age \times AST [U/L]/ \sqrt{platelet [10^9]\times ALT[U/L]}</math>

• FIB-4 index of less than 1.6 excludes the cirrhosis, while FIB-4 more than 3.6 is diagnostic of cirrhosis.^[10]

• The Forns score is designated for diagnosing mild fibrosis in cirrhotic patients.
• Forns fibrosis score is calculated using 4 factors of platelet count, gamma glutamyl transferase (GGT), age, and cholesterol level.

<math display=”block”>Forns = 7.8111 – 3.131 \times\ln (platelet) + 0.781 \times \ln (GTT)+3.467\times \ln (age) – 0.014 \times (cholesterol)</math>

• Forns score of less than 4.2 excludes severe fibrosis in cirrhotic patients, with a reliable negative predictive value (NPV).^[11]

• Fibrotest is a simple non-invasive test which is exclusively for liver fibrosis measurement, suggested by WHO.^[12]
• Calculation of fibrotest is through 5 factors including GGT, total bilirubin (bili), alpha-2-macroglobulin (A2MG), apolipoprotein A1 (ApoA1), and haptoglobin (HG).

<math display=”block”>FibroTest = 4.467\times\log_{10} [A2MG(g/L)] – 1.357 \times log_{10} [HG(g/L)] + 1.017 \times log_{10}[GMT(IU/L)] + 0.0281 \times[age(years)] + 1.737 \times log_{10} [Bili( \mu mol/L)] -1.184 \times[ApoA1(g/L)] + 0.301 \times sex – 5.54 </math>Sex: (female= 0, male= 1)

• Fibrotest score of less than 0.1 suggests very mild or absence of fibrosis and score of more than 0.6 strongly revealed moderate to severe fibrosis.^[13]

• Fibrometer score is a non-invasive test for diagnosing severe stages of fibrosis among patients with cirrhosis and portal hypertension.^[14]
• Calculating fibrometer is by means of seven factors, including glucose (Glc), ferritin, platelet count, ALT, body weight (BW), and age.

<math display=”block”>FibroMeter = 0.4184 \times Glc [mmol/L] + 0.0701 \times AST [U/L] + 0.00008 \times ferritin [\mu g/L] – 0.0102 \times platelet [g/L] – 0.0260 \times ALT [U/L] + 0.0459 \times BW [kg] + 0.0842 \times age [years] + 11.6226 </math>

• FibroMeter score of less than 0.36 reveals absence of significant fibrosis, and score of more than 0.36 is suggestive of dramatic fibrosis.^[13]

• Hepascore is a scale for determining the level of fibrosis in liver.
• The hepascore calculation is consisted of multiple factors, such as A2MG, hyaluronic acid, GGT, total bilirubin, along with age and sex.^[15]

<math display=”block”>Logistic regression = y = \exp [-4.185818-(0.0249 \times age) + (0.7464 \times sex) + (1.0039\times A2MG) + (0.032 \times hyaluronic acid) + (0.0691 \times bilirubin) -(0.0012 \times GGT)]</math>

<math display=”block”>HepaScore= \tfrac{y}{y+1} </math>

• The cut-off point of 0.84 is set for diagnosis of cirrhosis in patients with portal hypertension.^[13]

• Hyaluronic acid is a non-routine test for diagnosis of cirrhosis (sensitivity 78%, specificity 88%).
• In a patient with cirrhotic liver the plasma level of hyaluronic acid is increased up to 2 to 10-fold.^[13]
• The cut-off point for hyaluronic acid is 60 μg/L.

• Enhanced liver fibrosis (ELF) score is shows a reasonable correlation with the stage of fibrosis in chronic liver disease.
• ELF score is calculated by means of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP), and hyaluronic acid (HA).

<math display=”block”>ELF score = 2.494+ 0.846 \times \ln (HA) + 0.735 \times \ln (PIIINP) + 0.391\times\ln (TIMP-1) </math>

• The reference point for ELF score is 6.72 and the variable of ‘age‘ found to be the most effective factor on the score.^[16]

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