Clinical Background
Chronic liver disease is a common entity worldwide.
Epidemiology
- Prevalence
- Chronic viral hepatitis, a leading cause of chronic liver disease, affects >4 million people in the U.S.
- Alcohol related liver disease results in >12,000 deaths annually in U.S.
Etiology
- Infectious
- Viral, parasitic, bacterial
- Chemical/toxin
- Alcohol, drugs (acetaminophen)
- Autoimmune disorders
- Autoimmune hepatitis (AIH)
- Genetic
- Wilson disease, hemochromatosis, alpha-1-antitrypsin deficiency
Pathophysiology
- Chronic liver inflammation leads to an increase in interstitial fibrous tissue
- Widespread disruption and secondary attempts at repair by the liver cause irreversible histologic changes leading to cirrhosis
- Hyaluronic Acid
- Unsulfated highly polymerized glycosaminoglycan
- Endogenous ligand for toll like receptor of Kupffer cells
- Synthesized by activated hepatic stellate cells
Clinical Presentation
- May be asymptomatic until late in the disease
- Hepatocellular dysfunction - jaundice, hepatomegaly
- Portal hypertension - varices, splenomegaly, ascites, palmar erythema, spider angiomata
See Also
Diagnosis
Diagnosis
- Invasive - liver biopsy (histology)
- Considered the gold standard
- Limitations - painful, subject to sampling error (identifies hepatic disease in only 65-75%), definite morbidity (0.3%) and mortality (0.01%) and costly
- Noninvasive - (serum testing)
- Serum markers
- Albumin, prothrombin time, bilirubin and platelets may be abnormal
- Amino transferase levels do not correlate with fibrosis
- Biomarkers
- Multiple biomarkers exist - most have relatively low specificity and sensitivity if used alone
- Hyaluronic acid
- Most useful in nonalcoholic liver fibrosis
- Negative predictive value is 93-99%
- Excludes patients unlikely to have extensive fibrosis or cirrhosis
- May avoid or postpone need for liver biopsy
- Has been combined in panel testing with other markers in attempts to improve sensitivity (Fibrospect, Fibrotest, Fibrometer, Hepascore)
Tests generally appear in the order most useful for common clinical situations
| Test name: Hyaluronic Acid, Serum
|
| ARUP #: 0081138 |
| Methodology: Protein Binding
|
| Use: Use as noninvasive liver assay to:
- Exclude presence of hepatic fibrosis
- Assess likelihood of liver fibrosis in newly diagnosed chronic HCV infection
- Estimate fibrosis severity in alcoholic liver disease
- Substantiate mildly fibrotic liver biopsy results that lack sensitivity for cirrhosis due to sampling error
- Is a marker of liver damage from toxic agents, including acetaminophen, ethanol and bacterial lipopolysaccharide |
| Limitations: Results obtained with different assay methods or kits cannot be used interchangeablyFasting specimens best, as eating slightly increases hyaluronic acid (HA) |
| Follow-up:
If elevated may need to perform liver biopsy
|
References
General References
Adams LA, Angulo P. Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty liver disease. Clin Liver Dis.
2007;
11(
1):
25-35, viii.
Adams LA, Bulsara M, Rossi E, DeBoer B, Speers D, George J, Kench J, Farrell G, McCaughan GW, Jeffrey GP. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem.
2005;
51(
10):
1867-1873.
Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise review. Am J Gastroenterol.
2004;
99(
6):
1160-1174.
de Franchis R, Dell'Era A. Non-invasive diagnosis of cirrhosis and the natural history of its complications. Best Pract Res Clin Gastroenterol.
2007;
21(
1):
3-18.
Dufour DR. Assessment of liver fibrosis: Can serum become the sample of choice?. Clin Chem.
2005;
51(
10):
1763-1764.
Gressner OA, Weiskirchen R, Gressner AM. Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and reality. J Cell Mol Med.
2007;
11(
5):
1031-1051.
McHutchison JG, Blatt LM, de Medina M, Craig JR, Conrad A, Schiff ER, Tong MJ. Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Consensus Interferon Study Group. J Gastroenterol Hepatol.
2000;
15(
8):
945-951.
Stauber RE, Lackner C. Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C. World J Gastroenterol.
2007;
13(
32):
4287-4294.
Stickel F, Poeschl G, Schuppan D, Conradt C, Strenge-Hesse A, Fuchs FS, Hofmann WJ, Seitz HK. Serum hyaluronate correlates with histological progression in alcoholic liver disease. Eur J Gastroenterol Hepatol.
2003;
15(
9):
945-950.
Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology.
2007;
46(
2):
582-589.
Medical Reviewers
Grenache, David G., Ph.D. Medical Director, Special Chemistry at ARUP Laboratories; Assistant Professor, Clinical Pathology, University of Utah
Comprehensive Review: May 2008
Last Update: May 2008
