Propeptide Of Type III Procollagen Research Articles

Supplemental Fuzhenghuayu capsule therapy for improving liver fibrosis markers in patients with chronic hepatitis B following unsatisfactory outcome of nucleos(t)ide analogue monotherapy

To investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy. One-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis. The baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects. For CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment.

Hepatocyte destruction with enhanced collagen synthesis: characteristic feature of chronic hepatitis C patients on haemodialysis

Hepatitis C virus (HCV) infection is frequent among patients with end-stage renal disease on haemodialysis and is considered to be an independent risk factor for mortality in this setting. However, only a few of these patients are treated with anti-hepatitis virus treatment before the development of end-stage renal disease. Recent guidelines recommend identification of patients with good prognoses who are in need of interferon treatment, but we know little of patients who must be treated urgently. Ninety-eight patients on haemodialysis (48 anti-HCV-positive and 50 anti-HCV-negative patients) were enrolled in this study; HCV RNA was detected in 43 anti-HCV-positive patients. Univariate analysis and multivariate regression analysis were applied to identify variables independently associated with persistent HCV infection. Seven variables were proven to be associated with persistent HCV infection. Among them, type IV collagen 7S and N-terminal propeptide of type III procollagen (P-III-P) were defined as independent variables useful in distinguishing HCV RNA-positive patients from HCV RNA-negative patients with 0.91 sensitivity, 0.91 specificity, 0.89 positive predictive value and 0.93 negative predictive value. Our observations suggest that hepatocyte destruction with enhanced liver fibrosis is a characteristic clinical feature of persistent HCV infection. Type IV collagen 7S of ≥ 5 ng/mL and/or P-III-P of ≥ 5 U/mL would be useful markers to identify patients in need of interferon treatment, which supports the idea of the Kidney Disease: Improving Global Outcomes guidelines that a good prognosis in patients with HCV infection on haemodialysis should prompt consideration for IFN treatment when applicable.

Perinatal collagen turnover markers in intrauterine growth restriction

Objective: To investigate bone and connective tissue collagen turnover in intrauterine growth restricted (IUGR) pregnancies, by determining circulating markers of type I collagen synthesis (carboxy-terminal propeptide of type I procollagen [PICP], representing bone formation) and degradation (cross-linked telopeptide of type I collagen [ICTP], representing bone resorption) as well as type III collagen synthesis (N-terminal propeptide of type-III procollagen [PIIINP], reflecting growth and tissue maturity).Methods: Plasma PICP, ICTP and PIIINP concentrations were measured in 40 mothers and their 20 asymmetric IUGR and 20 appropriate for gestational age (AGA) full-term fetuses and neonates on postnatal day 1-(N1) and 4-(N4).Results: Fetal PICP, fetal and N4 ICTP, as well as fetal, N1 and N4 PIIINP concentrations were higher in the IUGR group (p ≤ 0.038, in all cases). In both groups, maternal PICP, ICTP and PIIINP concentrations were lower than fetal, N1 and N4 ones (p < 0.001, in each case).Conclusions: Type I collagen turnover is enhanced in IUGR than AGA fetuses/neonates. Similarly, fetal/neonatal PIIINP concentrations are elevated in IUGR, probably due to stress, responsible for induction of tissue maturation, and/or to impaired excretory renal function, leading to reduced protein clearance. Fetal/neonatal PICP, ICTP and PIIINP concentrations are higher than maternal concentrations, possibly reflecting increased skeletal growth and collagen turnover in the former.

Increased type III procollagen in serum and skin of patients with amyotrophic lateral sclerosis.

Collagen abnormalities of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning the aminoterminal propeptide of type III procollagen (PIIIP) and type III collagen in ALS. The aim of this study is to measure PIIIP, a precursor form of type III collagen, in skin and serum of ALS. We studied PIIIP immunoreactivity of skin and measured serum levels of PIIIP in ALS patients, and the results were compared with those of control subjects. Collagen bundles in the dermis of ALS were immunohistochemically strongly positive for PIIIP as compared with those of controls. The optical density of PIIIP immunostaining reactivity in ALS patients was significantly higher than in controls, and was significantly increased with duration of illness. Serum PIIIP levels in patients with ALS were significantly increased as compared with those in diseased control subjects and those in healthy control ones, and were positively and significantly associated with duration of illness. There was an appreciable positive correlation between concentrations of serum PIIIP and the density of PIIIP immunoreactivity of skin in ALS patients. These data suggest that a metabolic alteration of PIIIP may take place in the skin of ALS and the increased levels of serum PIIIP may reflect the increased PIIIP immunoreactivity of skin in ALS.

Relationship between Hemostatic Markers and Circulating Biochemical Markers of Collagen Metabolism in Patients with Aortic Aneurysm

Our objective was to determine the relationship between plasma levels of hemostatic molecular markers – D-dimer and thrombin-antithrombin III complex (TAT) – and circulating biochemical markers of collagen metabolism – aminoterminal propeptide of type III procollagen (PIIIP) and carboxyterminal propeptide of type I procollagen (PICP) – in patients with aortic aneurysm. The subjects were 43 patients with aortic aneurysm (AA; mean age 71 years) and 26 age-matched controls (mean age 75 years). The mean D-dimer, TAT and PIIIP levels were higher in the patients than in the controls (p < 0.0001, 0.0001 and 0.012, respectively), while the mean PICP level was similar to that in the controls. Increased D-dimer had a significant correlation with PIIIP (r = 0.412, p = 0.006) and PICP (r = 0.342, p = 0.0246), while TAT correlated with PIIIP (r = 0.3194, p = 0.0374), but not with PICP. There was also a significant correlation (r = 0.306, p = 0.0463) between PIIIP and PICP. As shown by the significant positive correlations among D-dimer, TAT and PIIIP, accelerated fibrinolysis and thrombogenesis induce an increase of collagen degradation and procollagen synthesis in atherosclerotic lesions. These findings show that D-dimer and TAT, especially the former, may be useful markers to monitor the progression and predict the prognosis of AA.

Invasive and non-invasive monitoring of hepatitis C virus-induced liver fibrosis: alternatives or complements?

Chronic hepatitis C virus (HCV) infection results in the development of liver fibrosis and cirrhosis in 20 to 25% of patients. The main task of the physician when examining a patient with a verified HCV infection is to identify the activity of inflammatory and necrotic processes in the liver, as well as the stage of fibrosis, and the reversibility of detected changes. Along with other clinical and laboratory parameters, this plays a major role in forecasting the course of hepatitis, as well as determines the therapeutic approach in each specific case. Liver biopsy remains the best way to assess the severity of chronic hepatitis C. The risk of developing cirrhosis depends on the stage (degree of fibrosis) and the grade (degree of inflammation and necrosis) observed in the initial liver biopsy. Non-invasive diagnostic approaches attempt to evaluate the serum markers of fibrogenesis. Biochemical markers of fibrosis scoring include thrombocyte counts, the prothrombin time, ratio of alaninaminotransferase (ALT) and aspartataminotransferase (AST) levels, the level of g-glutamyl transferase and the quantity of blood serum albumin. Another set of markers is based on the detection of molecular junctions that activate fibrosis, or participate in the generation of the liver extracellular matrix. The most applicable include hyaluronic acid (HA), type IV collagen (IV-C), N-terminal propeptide of type III procollagen (PIIIP), metalloproteinases (MMP), inhibitors of metalloproteinases (TIMP), and growth-transforming factor betta (GTFbeta). The review discusses the clinical significance of each of the criteria and possibility of their combination in the non-invasive monitoring of liver fibrosis.

Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following alpha-interferon therapy.

It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with alpha-interferon (IFN-alpha) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. These findings suggest that IFN-alpha treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C.

Coagulation-fibrinolysis system and markers of collagen metabolism in lung cancer.

Evidence suggests that the fibrinolysis system and peritumoral connective tissue play important roles in tumor spread. In this study, the authors evaluated the following parameters in 30 consecutive patients with lung cancer: thrombin-antithrombin complex (TAT), cross-linked fibrin split products D-dimer (DD), plasmin-alpha 2-antiplasmin inhibitor complex (PAP), and two antigens related to connective tissue, the aminoterminal propeptide of type III procollagen (PIIIP) and the 7S domain of type IV collagen (7S-collagen). Each parameter was increased significantly in the patients with cancer compared with the control subjects. Except for PIIIP, their concentration in blood was elevated to a significantly greater extent in the patients with distant metastases. The PAP concentration correlated well with the plasma concentration of TAT (r = 0.5; P < 0.01) and DD (r = 0.9; P < 0.0001). There was also a strong correlation between the serum concentrations of PIIIP and 7S-collagen (r = 0.7; P < 0.001). In patients with localized disease, DD levels were correlated significantly with those of PIIIP (Spearman rank-order correlation [rs] = 0.6; P < 0.025) and 7S-collagen (rs = 0.6; P < 0.01). In the group with disseminated metastases, there was a significant inverse relationship between serum PAP concentrations and serum concentrations of 7S-collagen (rs = -0.6; P < 0.025). These results confirm the presence of a subclinical chronic activation of the parameters of intravascular clotting-fibrinolysis and alterations in the extracellular matrix of patients with lung cancer. These parameters may be useful as indicators of the clinical progression of malignant disease, particularly of lung cancer.

Biochemical markers of hepatic fibrosis in primary biliary cirrhosis

We studied the behavior of some biochemical markers of fibrosis, the aminoterminal propeptide of type III procollagen (P-III-P), laminin, hyaluronate and fibronectin, in the sera of patients with primary biliary cirrhosis (PBC). Significant increases were found in serum laminin, hyaluronate and P-III-P and, more important, a significant correlation was found between the histological stage of the disease and serum hyaluronate. This parameter seems to distinguish between early PBC (I and II stages) and advanced disease with fibrosis. Moreover, a correlation between the histological stage and serum levels of both laminin and P-III-P was observed. Serum laminin, however, increases particularly in advanced disease, whereas high levels of sP-III-P are already present in the early stage. Finally, no significant differences were found between the plasma fibronectin levels of patients with primary biliary cirrhosis and those of controls.

Basement membrane-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease

To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting the degree of liver fibrosis, we measured radioimmunologically the concentrations of 7S collagen, laminin fragment P1, and the aminoterminal propeptide of type III procollagen (P-III-P) in serum from 48 patients with chronic viral liver disease: chronic persistent hepatitis (9), chronic active hepatitis (13), chronic active hepatitis with lobular disorganization (17), and liver cirrhosis (9). Concentrations of 7S collagen, laminin P1, and P-III-P in serum were increased in respectively 92%, 69%, and 77% of the patients with both chronic active hepatitis with lobular disorganization and liver cirrhosis. Concentrations of 7S collagen and laminin P1 in serum correlated well (r = 0.65, P less than 0.001, and r = 0.55, P less than 0.001, respectively) with the histological grade of liver fibrosis, whereas P-III-P correlated only weakly (r = 0.33, P less than 0.05). Evidently, measurement of serum 7S collagen is a reliable noninvasive test for detection of fibrosis in chronic viral liver disease.

N-Terminal Propeptide of Type-III Procollagen Concentrations in the Cord Blood: An Index of Newborn Maturity

Cord serum concentrations of the N-terminal propeptide of type-III procollagen(PIIIP), insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH) and free thyroxine were measured in 149 neonates, consisting of 22 small for gestational age, 95 appropriate for gestational age, 21 large for gestational age and 11 neonates of less than 24 weeks of gestation. Their gestational ages (GAs) ranged from 20 to 41 weeks. A significant negative correlation was found between PIIIP levels and GA (r = -0.83, p less than 0.001). No significant difference was found in PIIIP levels between SGA and LGA neonates, when there were no difference in their GAs, in spite of a significant difference in their birth body weights (p less than 0.01). The high concentrations of the cord serum PIIIP did not appear to be influenced by either IGF-I or thyroid hormones, nor was there any relationship between PIIIP and the birth body weight, but only with GA, suggesting that determining cord levels of PIIIP seems to provide a useful parameter for the assessment of newborn maturity.

Evaluation of serum aminoterminal procollagen type III propeptide as an index of portal hypertension and esophageal varices in chronic liver diseases

The concentration of the aminoterminal propeptide of type III procollagen (P-III-P) was determined in serum of cubital vein and hepatic vein of patients with various types of chronic liver diseases ( n = 111) and correlated with the portal venous pressure and with the degree of esophageal varices. The P-III-P level in all chronic liver diseases was correlated ( r s 0.542, p < 0.001 ) with the portal venous pressure, but in liver fibrotic subjects ( n = 29) this correlation ( r s 0.310) was not significant, in liver cirrhosis ( n = 30) the respective correlation was found to be weak ( r s 0.333, p < 0.05 ) and similar to that in patients with unspecified chronic liver diseases ( n = 52) ( r s 0.425, p < 0.01). Sensitivity and specificity of P-III-P at a cut-off concentration of 12 ng/ml for portal hypertension (portal vein pressure 5 mm Hg) are 0.93 and 0.42, respectively, the diagnostic efficiency is 0.67. Predictive values at the same cut-off level of P-III-P and an assumed prevalence of portal hypertension of 50% are 0.62 and 0.85 for the positive and negative test result, respectively. The level of P-III-P is not related to the degree of esophageal varices. The mean P-III-P concentration in the hepatic vein was found to be significantly ( p < 0.001) higher (about 35%) than that in the cubital vein. It is concluded that P-III-P is not an useful parameter for diagnosis of portal hypertension and monitoring of portal vein pressure and of the degree of esophageal varices.

Serum procollagen III peptide in chronic myeloproliferative disorders.

Using a radioimmunoassay the serum concentration of the N-terminal propeptide of type III procollagen (P-III-P) was measured in 35 patients with chronic myeloproliferative disorders, including idiopathic myelofibrosis (n = 10), osteomyelosclerosis (n = 4), transitional myeloproliferative disorder (n = 5), polycythaemia vera (n = 10) and chronic myelogenous leukaemia (n = 6). The normal range in 35 healthy controls was 4.9-11.7 ng/ml. The serum concentration of P-III-P increased with increasing degrees of bone marrow reticulin fibrosis. By contrast, almost normal levels were detected in osteomyelosclerosis with an indolent clinical course, in which an excessive deposition of mature collagen fibres was found, representing mainly type I collagen. These observations indicate that the serum P-III-P level is positively correlated to the degree of bone marrow reticulin fibrosis, whereas levels are near normal in patients with osteomyelosclerosis and stable disease. Measurement of serum P-III-P may be a useful indicator of disease activity in myelofibrosing conditions.