Hepatocellular carcinoma laboratory tests
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]
Overview
Some patients with hepatocellular carcinoma may have elevated concentration of alpha-fetoprotein, which is usually suggestive of progression of HCC. In order to determine disease severity and causation. Liver function tests, complete blood count, basic metabolic panel and coagulation factors are standard in the evaluation of HCC. More specific testing for markers and serum enzymes may be performed when certain etiologies are suspected.
Laboratory Findings
- Common abnormalities include:[1][2][3][4][5][6][7][8][8][9][5][10][11][12][13][14][15][16][17][18]
- Elevated serum alpha-fetoprotein
- Elevated anti-polyclonal carcinoembryonic antigen (anti-CEAp)
- Increased serum bilirubin levels
- Abnormal aminotransferase levels
- Elevated alkaline phosphatase
- Elevated gamma-glutamyl transpeptidase
- Prolonged prothrombin time/INR
- Thrombocytopenia
- Hyponatremia
Liver function tests:
- Aminotransferases:[19][20][21][22][23][24][25]
- LFTs may be normal in cirrhosis patients
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are usually moderately elevated
- AST is more often elevated than ALT
- Alcoholic liver disease - AST and ALT are both elevated but less than 300 IU/L with a AST: ALT ratio > 2.0
- Alkaline phosphatase: [26]
- Alkaline phosphatase is usually elevated
- Usually less than two to three times the upper limit
- High levels may be seen in patients with underlying cholestatic liver disease such as:[27][28]
- Gamma-glutamyl transpeptidase:[26][29][30]
- Non specific
- Correlates with ALP levels
- Higher in chronic liver disease (CLD) due to alcohol use:
- Mechanism of raised GGT in alcoholic liver disease:
- Alcohol induces microsomal GGT in liver
- Alcohol causes GGT release from hepatocytes
- Albumin:[31]
- Albumin levels reflect synthetic function of the liver
- Serum albumin levels are widely used in most of the staging systems for hepatocellular carcinoma
- Hypoalbuminemia is non specific for liver disease and may be seen in:
- Bilirubin:
- Bilirubin levels may be normal or raised
- Prothrombin time: [32]
- Prothrombin time reflects the degree of hepatic synthetic function.
- Worsening coagulopathy correlates with the severity of hepatic dysfunction.
- Metabolic panel:
- Hyponatremia[33]
- Progressive rise in serum creatinine: may be indicative of hepatorenal syndrome
Hematologic abnormalities: [34]
- Thrombocytopenia: most common hematologic abnormality in the patients of hepatocellular carcinoma with underlyingcirrhosis
- Rarely results in a platelet count < 50,000/mL
- Mechanism of thrombocytopenia:
- caused by portal hypertension with congestive splenomegaly: sequesters circulating platelets
- decreased thrombopoietin levels
- Anemia
- Mechanism of anemia:
- Acute and chronic gastrointestinal blood loss
- Folate deficiency
- Hemolysis
- Anemia of chronic disease
- Direct toxicity due to alcohol
- Hypersplenism
- Bone marrow suppression ( hepatitis-associated aplastic anemia)
- Leukopenia/neutropenia: due to hypersplenism with splenic margination
- Coagulation defects - the liver produces most of the coagulation factors and coagulopathy correlates with worsening liver disease
- Other abnormalities :
- Globulins: increase due to shunting of bacterial antigens away from the liver to lymphoid tissue which induces immunoglobulin production[35]
- Disseminated intravascular coagulation
- Vitamin K deficiency
- Diabetes: seen in patients with hemochromatosis [36][37]
- Insulin resistance: seen in nonalcoholic fatty liver disease
- Dysfibrinogenemia
- Fibrinolysis
- Ascitic fluid analysis:
- A diagnostic paracentesis may be performed if the ascites is new or if the patient with ascites is being admitted to the hospital.
- The fluid is analysed for the following:
- Serum-ascites albumin gradient (SAAG) is probably a better discriminant than older measures (transudate versus exudate) for the causes of ascites[39]
- A high gradient (> 1.1 g/dL) indicates the ascites is due to portal hypertension
- A low gradient (< 1.1 g/dL) indicates ascites of non-portal hypertensive etiology
- Ascites is broadly classified as two types based on the Serum-ascites albumin gradient (SAAG):
- Transudate - SAAG > 1.1 g/dL (indicates the ascites is due to portal hypertension)
- Exudate - SAAG < 1.1 g/dL (indicates the ascites is due to non-portal hypertension etiology)
FibroTest
- A validated and patented combination of six serum markers as non-invasive biomarkers of fibrosis are included in the FibroTest[40]
- The FibroTest score is correlated with the degree of liver damage in people with a variety of liver diseases
- FibroTest score is calculated combining the following six serum markers with the age and gender of the patient:
- Alpha-2-macroglobulin
- Haptoglobin
- Apolipoprotein A1
- Gamma-glutamyl transpeptidase (GGT)
- Total bilirubin
- Alanine transaminase (ALT)
Other laboratory studies performed in newly diagnosed hepatocellular carcinoma may include:
- Serology for hepatitis viruses.
- Autoantibodies
- ANA - present in underlying autoimmune hepatitis
- Anti-smooth muscle antibody - present in underlying autoimmune hepatitis
- Anti-mitochondrial antibody - present in underlying primary biliary cirrhosis
- Anti-LKM
- Total iron, TIBC, transferrin saturation, and ferritin - elevated totat iron, reduced TIBC, elevated transferrin saturation, and elevated ferritin in hemochromatosis
- Serum ceruloplasmin- low in Wilson's disease
- Immunoglobulin levels (IgG, IgM, IgA) - these are non-specific but may assist in distinguishing various causes
- Chronic hepatitis B - Chronic hepatitis B can be diagnosed with detection of HBsAg > 6 months after initial infection
- HBeAg and HBV DNA are determined to assess whether or not patients will need antiviral therapy
- Serum protein electrophoresis - alpha-1 band absent in alpha-1 antitrypsin deficiency
- Cholesterol and glucose
- Alpha 1-antitrypsin - reduced in alpha-1 antitrypsin deficiency
References
- ↑ Gyllensten UB, Sundvall M, Erlich HA (1991). "Allelic diversity is generated by intraexon sequence exchange at the DRB1 locus of primates". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3686–90. PMC 51517. PMID 2023919.
- ↑ Di Tommaso L, Roncalli M (2017). "Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How". Front Med (Lausanne). 4: 10. doi:10.3389/fmed.2017.00010. PMC 5322593. PMID 28280721.
- ↑ Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012). "The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology". Gastroenterology. 142 (7): 1592–609. doi:10.1053/j.gastro.2012.04.001. PMID 22656328.
- ↑ Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM (2012). "Does this patient with liver disease have cirrhosis?". JAMA. 307 (8): 832–42. doi:10.1001/jama.2012.186. PMID 22357834.
- ↑ 5.0 5.1 Kwo PY, Cohen SM, Lim JK (2017). "ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries". Am. J. Gastroenterol. 112 (1): 18–35. doi:10.1038/ajg.2016.517. PMID 27995906.
- ↑ Cabrera-Abreu JC, Green A (2002). "Gamma-glutamyltransferase: value of its measurement in paediatrics". Ann. Clin. Biochem. 39 (Pt 1): 22–5. doi:10.1258/0004563021901685. PMID 11853185.
- ↑ Moussavian SN, Becker RC, Piepmeyer JL, Mezey E, Bozian RC (1985). "Serum gamma-glutamyl transpeptidase and chronic alcoholism. Influence of alcohol ingestion and liver disease". Dig. Dis. Sci. 30 (3): 211–4. PMID 2857631.
- ↑ 8.0 8.1 Krzeski P, Zych W, Kraszewska E, Milewski B, Butruk E, Habior A (1999). "Is serum bilirubin concentration the only valid prognostic marker in primary biliary cirrhosis?". Hepatology. 30 (4): 865–9. doi:10.1002/hep.510300415. PMID 10498635.
- ↑ Pratt DS, Kaplan MM (2000). "Evaluation of abnormal liver-enzyme results in asymptomatic patients". N. Engl. J. Med. 342 (17): 1266–71. doi:10.1056/NEJM200004273421707. PMID 10781624.
- ↑ Ruhl CE, Everhart JE (2010). "Trunk fat is associated with increased serum levels of alanine aminotransferase in the United States". Gastroenterology. 138 (4): 1346–56, 1356.e1–3. doi:10.1053/j.gastro.2009.12.053. PMC 2847039. PMID 20060831.
- ↑ Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G (2002). "Updated definitions of healthy ranges for serum alanine aminotransferase levels". Ann. Intern. Med. 137 (1): 1–10. PMID 12093239.
- ↑ Piton A, Poynard T, Imbert-Bismut F, Khalil L, Delattre J, Pelissier E, Sansonetti N, Opolon P (1998). "Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group". Hepatology. 27 (5): 1213–9. doi:10.1002/hep.510270505. PMID 9581673.
- ↑ Kaplan MM (2002). "Alanine aminotransferase levels: what's normal?". Ann. Intern. Med. 137 (1): 49–51. PMID 12093245.
- ↑ Nannipieri M, Gonzales C, Baldi S, Posadas R, Williams K, Haffner SM, Stern MP, Ferrannini E (2005). "Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study". Diabetes Care. 28 (7): 1757–62. PMID 15983331.
- ↑ Liangpunsakul S, Chalasani N (2012). "What should we recommend to our patients with NAFLD regarding alcohol use?". Am. J. Gastroenterol. 107 (7): 976–8. doi:10.1038/ajg.2012.20. PMC 3766378. PMID 22764020.
- ↑ Cohen JA, Kaplan MM (1979). "The SGOT/SGPT ratio--an indicator of alcoholic liver disease". Dig. Dis. Sci. 24 (11): 835–8. PMID 520102.
- ↑ Schuppan D, Afdhal NH (2008). "Liver cirrhosis". Lancet. 371 (9615): 838–51. doi:10.1016/S0140-6736(08)60383-9. PMC 2271178. PMID 18328931.
- ↑ "EASL Clinical Practice Guidelines: management of cholestatic liver diseases". J. Hepatol. 51 (2): 237–67. 2009. doi:10.1016/j.jhep.2009.04.009. PMID 19501929.
- ↑ Sheth SG, Flamm SL, Gordon FD, Chopra S (1998). "AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection". Am. J. Gastroenterol. 93 (1): 44–8. doi:10.1111/j.1572-0241.1998.044_c.x. PMID 9448172.
- ↑ 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.
- ↑ Forns X, Ampurdanès S, Llovet JM, Aponte J, Quintó L, Martínez-Bauer E, Bruguera M, Sánchez-Tapias JM, Rodés J (2002). "Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model". Hepatology. 36 (4 Pt 1): 986–92. doi:10.1053/jhep.2002.36128. PMID 12297848.
- ↑ Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S (2007). "FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest". Hepatology. 46 (1): 32–6. doi:10.1002/hep.21669. PMID 17567829.
- ↑ Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T (2001). "Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study". Lancet. 357 (9262): 1069–75. doi:10.1016/S0140-6736(00)04258-6. PMID 11297957.
- ↑ Rosenberg WM, Voelker M, Thiel R, Becka M, Burt A, Schuppan D, Hubscher S, Roskams T, Pinzani M, Arthur MJ (2004). "Serum markers detect the presence of liver fibrosis: a cohort study". Gastroenterology. 127 (6): 1704–13. PMID 15578508.
- ↑ 26.0 26.1 Ellis G, Goldberg DM, Spooner RJ, Ward AM (1978). "Serum enzyme tests in diseases of the liver and biliary tree". Am. J. Clin. Pathol. 70 (2): 248–58. PMID 696683.
- ↑ Rong G, Wang H, Bowlus CL, Wang C, Lu Y, Zeng Z, Qu J, Lou M, Chen Y, An L, Yang Y, Gershwin ME (2015). "Incidence and risk factors for hepatocellular carcinoma in primary biliary cirrhosis". Clin Rev Allergy Immunol. 48 (2–3): 132–41. doi:10.1007/s12016-015-8483-x. PMID 25762349.
- ↑ Carr BI, Guerra V, Giannini EG, Farinati F, Ciccarese F, Ludovico Rapaccini G, Di Marco M, Benvegnù L, Zoli M, Borzio F, Caturelli E, Chiaramonte M, Trevisani F (2014). "Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype". Semin. Oncol. 41 (2): 252–8. doi:10.1053/j.seminoncol.2014.03.006. PMC 4009489. PMID 24787296.
- ↑ Goldberg DM (1980). "Structural, functional, and clinical aspects of gamma-glutamyltransferase". CRC Crit Rev Clin Lab Sci. 12 (1): 1–58. PMID 6104563.
- ↑ Barouki R, Chobert MN, Finidori J, Aggerbeck M, Nalpas B, Hanoune J (1983). "Ethanol effects in a rat hepatoma cell line: induction of gamma-glutamyltransferase". Hepatology. 3 (3): 323–9. PMID 6132864.
- ↑ Tanriverdi O (2014). "A discussion of serum albumin level in advanced-stage hepatocellular carcinoma: a medical oncologist's perspective". Med. Oncol. 31 (11): 282. doi:10.1007/s12032-014-0282-3. PMID 25316265.
- ↑ Chrostek L, Panasiuk A (2014). "Liver fibrosis markers in alcoholic liver disease". World J. Gastroenterol. 20 (25): 8018–23. doi:10.3748/wjg.v20.i25.8018. PMC 4081671. PMID 25009372.
- ↑ Papadakis MA, Fraser CL, Arieff AI (1990). "Hyponatraemia in patients with cirrhosis". Q. J. Med. 76 (279): 675–88. PMID 2217672.
- ↑ 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.
- ↑ Triger DR, Wright R (1973). "Hyperglobulinaemia in liver disease". Lancet. 1 (7818): 1494–6. PMID 4123153.
- ↑ Bianchi G, Marchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E (1994). "Prognostic significance of diabetes in patients with cirrhosis". Hepatology. 20 (1 Pt 1): 119–25. PMID 8020880.
- ↑ Petrides AS, Vogt C, Schulze-Berge D, Matthews D, Strohmeyer G (1994). "Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis". Hepatology. 19 (3): 616–27. PMID 8119686.
- ↑ Warrell DA, Cox TN, Firth JD, Benz ED. Oxford textbook of medicine. Oxford: Oxford University Press, 2003. ISBN 0-19-262922-0.
- ↑ Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med 1992;117:215-20. PMID 1616215.
- ↑ Halfon P, Munteanu M, Poynard T (2008). "FibroTest-ActiTest as a non-invasive marker of liver fibrosis". Gastroenterol Clin Biol. 32 (6): 22–39. doi:10.1016/S0399-8320(08)73991-5. PMID 18973844.