Effects of Alcohol Consumption on Eight Circulating Markers of Liver Fibrosis

Abstract

A number of circulating breakdown products of collagen or other components of extracellular matrix, matrix degrading metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been proposed as markers of hepatic fibrosis. However, the published results lack consistency. Since many of the patients with fibrosis studied were alcoholics, the question was raised whether recent alcohol consumption may affect the results obtained. Using sandwich-type assays of radioimmunoassay technology with corresponding antibodies, we studied eight markers of liver fibrosis: laminin, tenascin, undulin, TIMP-1, collagen VI, procollagen type III (PIIINP), hyaluronic acid (HA) and MMP-2. A group of 10 alcoholics was studied after significant alcohol consumption and following 2 weeks of abstinence, verified with repeated breath alcohol measurement. Laminin was significantly reduced at 1 week (22%) and at 2 weeks (30%). Similarly, tenascin and undulin were also significantly decreased. By contrast, TIMP-1, collagen VI, PIIINP, HA and MMP-2 did not significantly change. The mode of action of alcohol on these tests is unknown. These differences must be considered when using those measurements to assess liver fibrosis.

Value of Fibrosis Markers for Staging Liver Fibrosis in Patients With Precirrhotic Alcoholic Liver Disease

“…We have shown that chronic alcohol consumption may affect the levels of some of these fibrosis markers (Nouchi et al, 1987;Ponomarenko et al, 2002). Moreover alcohol metabolism itself can contribute to the posttranslational modification of these proteins, altering their representation in the blood stream and therefore their significance.…”

“…In an early study (Nouchi et al, 1987) we have shown that PIIINP and laminin as well as some other markers (Ponomarenko et al, 2002) may be affected by acute alcohol intoxication and its withdrawal; this factor was usually not taken into account and might have affected some of the results published before. Moreover, laminin, a major noncollagenous glycoprotein of basement membrane was found to be elevated in alcoholic hepatitis and cirrhosis (Nouchi et al, 1987) and increased hepatic levels were later demonstrated in alcoholic liver disease (Niemela¨et al, 1990).…”

TIMP-1 in patients with cirrhosis: relation to liver dysfunction, portal hypertension, and hemodynamic changes

“…Moreover, active alcohol consumption does not seem to affect the concentration of TIMP-1. This is important in populations including patients with alcoholic liver disease, but new prospective studies are needed to totally rule out an acute effect of alcohol on TIMP-1 levels in cirrhosis [20].…”

Plasma phosphatidylcholine hydroperoxide as a new marker of oxidative stress in alcoholic patients

“…Although various serum markers, such as ␥-GTP (17), carbohydrate-deficient transferrin (17,18), metalloproteinase-9 (19,20), tissue polypeptide-specific antigen (21), type 4 collagen (22), laminin (20), hyaluronic acid (23), and CYP2E1 activity (24), have been introduced for the evaluation of alcohol consumption and ALD, it has remained unclear which is the best marker.…”