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* The probability of esophageal varices are low when the platelet count is normal.<ref name="pmid26047908">{{cite journal |vauthors=de Franchis R |title=Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension |journal=J. Hepatol. |volume=63 |issue=3 |pages=743–52 |year=2015 |pmid=26047908 |doi=10.1016/j.jhep.2015.05.022 |url=}}</ref>
* The probability of esophageal varices are low when the platelet count is normal.<ref name="pmid26047908">{{cite journal |vauthors=de Franchis R |title=Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension |journal=J. Hepatol. |volume=63 |issue=3 |pages=743–52 |year=2015 |pmid=26047908 |doi=10.1016/j.jhep.2015.05.022 |url=}}</ref>


==== ALT/AST index ====
==== AST/ALT index ====
* The AST/ALT ratio was first described by De Ritis, known also as De Ritis ratio.<ref name="pmid13447217">{{cite journal |vauthors=DE RITIS F, COLTORTI M, GIUSTI G |title=An enzymic test for the diagnosis of viral hepatitis; the transaminase serum activities |journal=Clin. Chim. Acta |volume=2 |issue=1 |pages=70–4 |year=1957 |pmid=13447217 |doi= |url=}}</ref>
* Elevated levels of AST/ALT index reflects the hepatocellular damage or death.<ref name="pmid24353357">{{cite journal| author=Botros M, Sikaris KA| title=The de ritis ratio: the test of time. | journal=Clin Biochem Rev | year= 2013 | volume= 34 | issue= 3 | pages= 117-30 | pmid=24353357 | doi= | pmc=3866949 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353357  }}</ref>
* The AST/ALT ratio of more than 1 in chronic hepatitis is suggestive of cirrhosis.<ref name="pmid3135226">{{cite journal |vauthors=Williams AL, Hoofnagle JH |title=Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis |journal=Gastroenterology |volume=95 |issue=3 |pages=734–9 |year=1988 |pmid=3135226 |doi= |url=}}</ref>


==== AST/platelet ratio index ====
==== 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><small>ULN= Upper limit of normal</small>
* APRI ≤ 0.50 is suggestive of absence and APRI > 1.50 is suggestive of presence of the significant fibrosis.<ref name="pmid12883497">{{cite journal |vauthors=Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS |title=A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C |journal=Hepatology |volume=38 |issue=2 |pages=518–26 |year=2003 |pmid=12883497 |doi=10.1053/jhep.2003.50346 |url=}}</ref>


==== Lok ====
==== Lok ====
* The best serologic test for portal hypertension and esophageal varices is Lok score.
* The score is calculated through following formula: <ref name="pmid15986415">{{cite journal |vauthors=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 |title=Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort |journal=Hepatology |volume=42 |issue=2 |pages=282–92 |year=2005 |pmid=15986415 |doi=10.1002/hep.20772 |url=}}</ref>
<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.<ref name="pmid25732434">{{cite journal |vauthors=Procopet B, Cristea VM, Robic MA, Grigorescu M, Agachi PS, Metivier S, Peron JM, Selves J, Stefanescu H, Berzigotti A, Vinel JP, Bureau C |title=Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension |journal=Dig Liver Dis |volume=47 |issue=5 |pages=411–6 |year=2015 |pmid=25732434 |doi=10.1016/j.dld.2015.02.001 |url=}}</ref>


==== FIB-4 ====
==== 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.<ref name="KimKim2010">{{cite journal|last1=Kim|first1=Beom Kyung|last2=Kim|first2=Do Young|last3=Park|first3=Jun Yong|last4=Ahn|first4=Sang Hoon|last5=Chon|first5=Chae Yoon|last6=Kim|first6=Ja Kyung|last7=Paik|first7=Yong Han|last8=Lee|first8=Kwan Sik|last9=Park|first9=Young Nyun|last10=Han|first10=Kwang Hyub|title=Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients|journal=Liver International|volume=30|issue=4|year=2010|pages=546–553|issn=14783223|doi=10.1111/j.1478-3231.2009.02192.x}}</ref>


==== Forns ====
==== 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).<ref name="Forns2002">{{cite journal|last1=Forns|first1=X|title=Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model|journal=Hepatology|volume=36|issue=4|year=2002|pages=986–992|issn=02709139|doi=10.1053/jhep.2002.36128}}</ref>


=== Direct fibrosis markers ===
=== Direct fibrosis markers ===


==== Fibrotest ====
==== Fibrotest ====
* Fibrotest is a simple non-invasive test which is exclusively for liver fibrosis measurement, suggested by WHO.<ref name="urlBioPredictive Library - FibroTest Publications">{{cite web |url=http://library.biopredictive.com/article/325/ |title=BioPredictive Library - FibroTest Publications |format= |work= |accessdate=}}</ref>
* Calculation of Fibrotest is through 5 factors of GGT, total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, and haptoglobin.
<math display="block">FibroTest = 4.467\times\log_{10} [alpha2macroglobulin(g/L)] - 1.357 \times log_{10} [haptoglobin(g/L)] + 1.017 \times log_{10}[GMT(IU/L)] + 0.0281 \times[age(years)] + 1.737 \times log_{10} [bilirubin( \mu mol/L)] -1.184 \times[apolipoprotein A1(g/L)] + 0.301 \times sex (female= 0,male= 1) - 5.54 </math>
* 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.<ref name="urlcdn.intechopen.com">{{cite web |url=http://cdn.intechopen.com/pdfs-wm/18776.pdf |title=cdn.intechopen.com |format= |work= |accessdate=}}</ref>


==== Fibrometer ====
==== Fibrometer ====

Revision as of 16:59, 3 November 2017

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

Overview

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 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>

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

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 of GGT, total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, and haptoglobin.

<math display="block">FibroTest = 4.467\times\log_{10} [alpha2macroglobulin(g/L)] - 1.357 \times log_{10} [haptoglobin(g/L)] + 1.017 \times log_{10}[GMT(IU/L)] + 0.0281 \times[age(years)] + 1.737 \times log_{10} [bilirubin( \mu mol/L)] -1.184 \times[apolipoprotein A1(g/L)] + 0.301 \times sex (female= 0,male= 1) - 5.54 </math>

  • 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

Hepascore

Hyaluronic acid

Enhanced liver fibrosis

  • An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
  • Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Botros M, Sikaris KA (2013). "The de ritis ratio: the test of time". Clin Biochem Rev. 34 (3): 117–30. PMC 3866949. PMID 24353357.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. "BioPredictive Library - FibroTest Publications".
  13. "cdn.intechopen.com" (PDF).

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