Basement membrane peptides as markers of liver disease in chronic hepatitis C.
OBJECTIVE
Chronic hepatitis C is characterised by slow progression to liver fibrosis. In liver fibrosis, basement membrane components are increasingly deposited around the vessels and in the portal tracts. Serum assays can measure the two major components of the basement membrane, type IV collagen and laminin. The aim of this study was to determine whether serum levels of type IV collagen and laminin are related to severity of liver injury in chronic hepatitis C.


METHODS
Thirty-seven patients with chronic hepatitis C (CHC) and five healthy controls were studied. Serum type IV collagen was measured by a one-step sandwich EIA kit (Fuji, Japan) and serum laminin was measured by RIA (CIS, UK). Liver biopsies in patients with CHC were scored using a previously described grading and staging system. Liver biopsy scores were compared to serum levels of laminin, type IV collagen and alanine aminotransferase (ALT). Receiver operating characteristic (ROC) analysis was used to compare the ability of the assays to detect advanced liver injury.


RESULTS
The median serum concentration of type IV collagen was 127.1 ng/ml (range 17.7 to 317.4) in CHC patients compared to a median of 61.3 ng/ml (range 11.5 to 102.3) in controls, p=0.006. The median serum concentration of laminin was 1.12 U/ml (range 0.74 to 2.46) in CHC compared to a median of 0.87 U/ml (range 0.83 to 1.06) in controls, p=0.07. Both serum type IV collagen and laminin were significantly correlated with the fibrotic stage and also with the necroinflammatory injury scores- histological activity index, portal inflammation and periportal hepatitis. Serum ALT was significantly correlated with portal inflammation. Using ROC analysis, the area under the curve for type IV collagen and laminin was 0.83 (p=0.001) and 0.82 (p=0.0017), respectively, while the area under the curve for ALT was 0.54 (p=0.1).


CONCLUSIONS
Serum assays of basement membrane peptides are accurate non-invasive markers of liver fibrosis and liver inflammation in chronic hepatitis C. These markers are superior to serum ALT in reflecting liver injury and they have high specificity and sensitivity in detecting advanced liver disease in chronic hepatitis C.
Walsh
K M
KM
Department of Human Nutrition, Royal Infirmary, Glasgow, UK. Kevin.Walsh@btinternet.com
Fletcher
A
A
MacSween
R N
RN
Morris
A J
AJ
D001485:Basement Membrane / Q000378:metabolism*; D015415:Biomarkers; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008297:Male; D012372:ROC Curve; D012044:Regression Analysis; D012680:Sensitivity and Specificity
D015415:Biomarkers; D007797:Laminin; D003094:Collagen