Portal hypertension laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
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.
Laboratory Findings
- 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
Platelet count
- 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]
AST/ALT index
- 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]
AST/platelet ratio index
- 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]
Lok
- 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>
FIB-4
- 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]
Forns
- 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]
Direct fibrosis markers
Fibrotest
- 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
- 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
- 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
- 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
- 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]
References
- ↑ Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, García-Pagán JC, Pinzani M, Bosch J (2013). "Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis". Gastroenterology. 144 (1): 102–111.e1. doi:10.1053/j.gastro.2012.10.001. PMID 23058320.
- ↑ Qamar AA, Grace ND, Groszmann RJ, Garcia-Tsao G, Bosch J, Burroughs AK, Ripoll C, Maurer R, Planas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Makuch R, Rendon G (2009). "Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis". Clin. Gastroenterol. Hepatol. 7 (6): 689–95. doi:10.1016/j.cgh.2009.02.021. PMC 4545534. PMID 19281860.
- ↑ de Franchis R (2015). "Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension". J. Hepatol. 63 (3): 743–52. doi:10.1016/j.jhep.2015.05.022. PMID 26047908.
- ↑ DE RITIS F, COLTORTI M, GIUSTI G (1957). "An enzymic test for the diagnosis of viral hepatitis; the transaminase serum activities". Clin. Chim. Acta. 2 (1): 70–4. PMID 13447217.
- ↑ Botros M, Sikaris KA (2013). "The de ritis ratio: the test of time". Clin Biochem Rev. 34 (3): 117–30. PMC 3866949. PMID 24353357.
- ↑ Williams AL, Hoofnagle JH (1988). "Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis". Gastroenterology. 95 (3): 734–9. PMID 3135226.
- ↑ Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS (2003). "A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C". Hepatology. 38 (2): 518–26. doi:10.1053/jhep.2003.50346. PMID 12883497.
- ↑ Lok AS, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK, Everhart JE, Lindsay KL, Bonkovsky HL, Di Bisceglie AM, Lee WM, Morgan TR, Dienstag JL, Morishima C (2005). "Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort". Hepatology. 42 (2): 282–92. doi:10.1002/hep.20772. PMID 15986415.
- ↑ Procopet B, Cristea VM, Robic MA, Grigorescu M, Agachi PS, Metivier S, Peron JM, Selves J, Stefanescu H, Berzigotti A, Vinel JP, Bureau C (2015). "Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension". Dig Liver Dis. 47 (5): 411–6. doi:10.1016/j.dld.2015.02.001. PMID 25732434.
- ↑ Kim, Beom Kyung; Kim, Do Young; Park, Jun Yong; Ahn, Sang Hoon; Chon, Chae Yoon; Kim, Ja Kyung; Paik, Yong Han; Lee, Kwan Sik; Park, Young Nyun; Han, Kwang Hyub (2010). "Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients". Liver International. 30 (4): 546–553. doi:10.1111/j.1478-3231.2009.02192.x. ISSN 1478-3223.
- ↑ Forns, X (2002). "Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model". Hepatology. 36 (4): 986–992. doi:10.1053/jhep.2002.36128. ISSN 0270-9139.
- ↑ "BioPredictive Library - FibroTest Publications".
- ↑ 13.0 13.1 13.2 13.3 "cdn.intechopen.com" (PDF).
- ↑ Castera, Laurent; Vilgrain, Valérie; Angulo, Paul (2013). "Noninvasive evaluation of NAFLD". Nature Reviews Gastroenterology & Hepatology. 10 (11): 666–675. doi:10.1038/nrgastro.2013.175. ISSN 1759-5045.
- ↑ Pereira HG, Tumova B, Webster RG (1967). "Antigenic relationship between influenza A viruses of human and avian origins". Nature. 215 (5104): 982–3. PMID 6055434.
- ↑ Lichtinghagen, Ralf; Pietsch, Daniel; Bantel, Heike; Manns, Michael P.; Brand, Korbinian; Bahr, Matthias J. (2013). "The Enhanced Liver Fibrosis (ELF) score: Normal values, influence factors and proposed cut-off values". Journal of Hepatology. 59 (2): 236–242. doi:10.1016/j.jhep.2013.03.016. ISSN 0168-8278.