Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis

Abstract

The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.

Bone Turnover Markers and Probable Advanced Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Men and Postmenopausal Women With Type 2 Diabetes

“…In extremely obese patients with an average body mass index of 44 kg/m 2 , liver biopsy confirmed that the increased stages of fibrosis were independently associated with higher levels of P1NP (29). The P1NP has also been reported to be related to liver fibrosis in other chronic hepatic diseases (10,30,31). In primary biliary cirrhosis patients, P1NP levels were higher than in controls (30).…”

“…In alcoholic cirrhosis patients, the mean serum P1NP concentration was significantly higher than in the control group and appeared to vary depending on the severity of the liver damage (i.e., the concentration of P1NP was significantly higher in Child-Pugh class C than in class A) (10). The concentration of P1NP in the femoral artery blood was also significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function (31).…”

“…P1NP is commonly used as a marker of bone formation because it can be synthesized and secreted by osteoblasts (32). Furthermore, P1NP can also be secreted by hepatic stellate cells and detected in the arterial and hepatic or venous blood (31). In the healthy human liver, the most abundant collagens are the fibril-forming types I and III.…”

Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats

“…As PINP propeptides in part are cleared by liver endothelial cells, and these cells may be injured secondary to inflammation due to the BDL, a part of the observed increase could be due to failure of damaged endothelial cells to clear PINP [35]. As an example, patients presenting with alcoholic liver fibrosis with acute inflammation, N-terminal propeptide of type III collagen (PIIINP), a marker of type III collagen formation, is significantly increased, whereas in cirrhosis, PIIINP is only moderately increased [8].…”

Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies

“…Procollagen by-products such as N-terminal propeptide from types I and III collagen (PIMP and PIIINP) have been largely studied as markers of both inflammation and fibrosis and appear to correlate well with advanced fibrosis/cirrhosis (with 0.72 and 0.76 AUROCs, respectively). 60 – 62 YKL-40, a glycoprotein associated with extracellular matrix remodeling expressed in hepatic stellate cells, has been found to correlate well with liver fibrosis with promising diagnostic performance in cirrhosis (AUROC 0.80). 63 , 64 Finally, serum concentrations of metalloproteinases and their inhibitors (matrix metalloproteinases and tissue inhibitor of metalloproteinases [TIMPs]), involved in extracellular matrix degradation, have also been correlated with advanced fibrosis and cirrhosis, but with less reliable prediction capabilities in significant fibrosis.…”