J Korean Med Sci.  2010 Jan;25(1):67-74. 10.3346/jkms.2010.25.1.67.

Usefulness of Non-invasive Markers for Predicting Significant Fibrosis in Patients with Chronic Liver Disease

Affiliations
  • 1Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea. umsh@korea.ac.kr
  • 2Department of Pathology, College of Medicine, Korea University, Seoul, Korea.
  • 3Department of Statistics, Korea University, Seoul, Korea.

Abstract

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Keyword

Liver Cirrhosis; Biological Markers; Chronic Liver Disease

MeSH Terms

Adult
Biological Markers/blood
Chronic Disease
Fatty Liver/complications
Female
Fibrosis
Haptoglobins/analysis
Hepatitis B/complications
Hepatitis C/complications
Humans
Hyaluronic Acid/blood
Liver Cirrhosis/complications/*diagnosis
Liver Diseases/complications/*diagnosis
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
ROC Curve
alpha-Macroglobulins/analysis
Biological Markers
Haptoglobins
alpha-Macroglobulins
Hyaluronic Acid

Figure

  • Fig. 1 Box plots of each marker of fibrosis according to the stage of liver fibrosis. The top and bottom of each box are the 25th and 75th percentiles, giving the interquartile range. The line through the middle of each box represents the median. The error bars are the 5th and 95th percentiles. PIIINP, procollagen III N-terminal peptide; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase.

  • Fig. 2 AHH index according to significant liver fibrosis.

  • Fig. 3 ROC curve of the AHH index for the prediction of significant liver fibrosis: F0-1 vs. F2-4.


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