Measurement of carboxy terminal peptide of type I procollagen in sera of patients with viral hepatitis and liver cirrhosis

In the present investigation, a radioimmunoassay for carboxy terminal peptide of human type I procollagen (type 1 C-peptide) was developed. Its clinical implication for serodiagnosis of hepatic fibrosis in 85 patients with viral hepatitis, 45 patients with post-hepatitic liver cirrhosis and 37 patients with alcoholic liver diseases was evaluated in comparison with that of the previously established amino terminal peptide (type III N-peptide) assay. Anti-sera against type I procollagen was obtained by immunization of rabbit with purified type I procollagen from culture medium of IMR-90. The serum level of type I C-peptide in normal subjects was found to be 42 ng/ml (s.d. = 19). Type I C-peptide levels in patients with acute hepatitis were within normal range, while in chronic hepatitis, the mean type I C-peptide level increased as the grade of fibrosis advanced from grade I to III. However, there was no statistically significant difference between the mean type I C-peptide level of grade III and that of liver cirrhosis. Increments of type I C-peptide levels were also observed in alcoholic liver fibrosis (fatty liver with fibrosis and liver cirrhosis). On the other hand, type III N-peptide assay appeared to reflect not only the degree of hepatic fibrosis, but also the degree of hepatic inflammation, giving the high levels in acute viral hepatitis. Collectively, the results indicate the usefulness of type I C-peptide assay for monitoring hepatic fibrosis in viral hepatitis as well as in alcoholic liver disease.     

Serum Type I Collagen and N-terminal Peptide of Type III Procollagen in Patients with Alcoholic Liver Disease: Relationship to Liver Histology

This study compared, in patients with alcoholic liver disease, the serum concentration of N-terminal peptide of type III procollagen and of a novel serum marker, type I collagen, with liver histological data and assessed the role of these markers in the diagnosis and follow-up of liver changes. Ninety-six patients (mean age 51 years, 61 men and 35 women) were included. All had alcoholic liver disease diagnosed on usual clinical, biochemical, and histological criteria. Two histological scores, one for alcoholic hepatitis and one for fibrosis, were established. Serum N-terminal peptide of type III procollagen and type I collagen were assayed by liquid phase radioimmunoassay. Significant correlations between serum type I collagen and score of fibrosis (r = 0.34, p less than 0.001) and between serum N-terminal peptide of type III procollagen and score of alcoholic hepatitis (r = 0.60, p less than 0.0001) were noted. There was no significant correlation between serum aminotransferases and the score of alcoholic hepatitis. In 25 patients with alcoholic hepatitis reassessed between 3 and 6 months, serum N-terminal peptide of type III procollagen significantly decreased (p less than 0.05) as did the score of alcoholic hepatitis, but serum type I collagen and the score of fibrosis were not modified. These serum markers of collagen metabolism could be useful for the assessment and follow-up in patients with alcoholic liver disease.     

Evaluation of hepatic fibrosis by serum proline and amino-terminal type III procollagen peptide levels in alcoholic patients

In patients with alcoholic liver disease, serum proline and amino-terminal type III procollagen peptide levels were evaluated as a marker of hepatic fibrosis. Thirty-one patients with alcoholic liver disease (2 with nonspecific change, 3 with alcoholic hepatitis, 17 with hepatic fibrosis without cirrhosis, and 9 with cirrhosis) and 15 controls were investigated. Hepatic fibrosis was estimated in each liver biopsy specimen by morphometric analysis, and the ratio of fibrotic change to total area (AREA-F) was calculated by morphometric analysis. In patients with hepatic fibrosis, serum proline levels and routine liver function tests were not significantly correlated to AREA-F value, while serum peptide levels showed a significant positive correlation to AREA-F value (r=0.733,P<0.001). These results suggest that the determination of serum amino-terminal type III procollagen peptide level may serve as a good marker for the diagnosis of liver fibrosis in the alcoholic.This study was supported in part by grants 57570273 and 59480207 from the Japanese Ministry of Education, Science and Culture.     

Serum procollagen III peptide in alcoholic and other chronic liver diseases

Increased levels of serum procollagen III peptide (P-III-P) have been found in patients with alcoholic hepatitis and cirrhosis. Serum P-III-P was increased (greater than 15 micrograms/l) in 38 of 44 (86%) patients with alcoholic liver cirrhosis, in 6 of 20 (30%) with fatty liver, in 1 of 13 (8%) with non-alcoholic fatty liver, and in 3 of 14 (21%) with other chronic liver diseases. Median serum P-III-P was almost three times higher in alcoholic liver cirrhosis than in alcoholic fatty liver (p less than 0.001). Serum P-III-P was increased in three of six patients with alcoholic fatty liver and periportal fibrosis. In the total material (n = 91), a statistically significant negative correlation between serum P-III-P and albumin (r = -0.71, p less than 0.001) and Normotest (r = -0.63, p less than 0.001), respectively, and a positive correlation between serum P-III-P and bilirubin (r = 0.65, p less than 0.001) were found. The serum level of P-III-P had no prognostic value concerning the mortality in patients with alcoholic cirrhosis.     

Serum type III procollagen peptide and laminin (Lam-P1) detect alcoholic hepatitis in chronic alcohol abusers

The diagnosis of alcoholic hepatitis is difficult to establish by conventional clinical and laboratory methods, and a firm diagnosis relies on liver histology. Since there are severe limitations in following patients with repeated liver biopsies, noninvasive procedures are needed to assess the presence of alcoholic hepatitis in chronic alcohol abusers. It has been suggested that serum Type III procollagen peptide levels correlates with the degree of inflammation in chronic liver disease. Since inflammation is a major histological finding in alcoholic hepatitis, we therefore studied the usefulness of measuring serum Type III procollagen peptide and laminin values in 45 consecutive chronic alcohol abusers, with or without cirrhosis, in detecting those with alcoholic hepatitis. The results showed that both Type III procollagen peptide and laminin values were elevated in all of the patients with established liver damage. However, the values were highest in those with liver cirrhosis plus alcoholic hepatitis (Type III procollagen peptide 50.4 +/- 36.4 ng per ml vs. 8.1 +/- 2.6 in controls, p less than 0.01; laminin 4.50 +/- 1.49 units per liter vs. 1.24 +/- 0.26 units per liter in controls, p less than 0.01), followed by subjects with alcoholic hepatitis alone (Type III procollagen peptide 23.5 +/- 17.6 ng per ml, p less than 0.01; laminin 2.60 +/- 1.09 units per liter, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum Procollagen Type III N-Terminal Peptides and Laminin P1 Peptide in Alcoholic Liver Disease

The appearance of perivenular fibrosis on liver biopsy reflects the beginning of the fibrotic process that ultimately results in liver cirrhosis. To examine whether the fibrogenic activity can be detected by blood tests, we evaluated whole antibody radioimmunoassay (RIA) of procollagen type III N-terminal peptides (P-III-P), RIA of these peptides using Fab fragments (Fab-P-III-P), and RIA of the laminin P1 peptide in alcoholics within 1 week of alcohol abstinence. The Fab-P-III-P levels in subjects with perivenular fibrosis were significantly higher than those in patients with simple fatty liver. Values in 63% of subjects with perivenular fibrosis exceeded the upper limit of the fatty liver group. Patients with simple fatty liver had significantly lower values than nonalcoholic controls. Serum levels of P-III-P and laminin were elevated in patients with alcoholic hepatitis and correlated well with the degree of inflammation. With abstinence, Fab-P-III-P levels increased in all alcoholics. P-III-P values increased in patients with normal P-III-P values on admission. By contrast, the values of laminin decreased during abstinence. Therefore, to interpret serum levels of Fab-P-III-P, P-III-P, and laminin, the duration of abstinence must be taken into consideration. P-III-P, Fab-P-III-P and laminin measurements in the serum within 1 week of abstinence can contribute to the detection of alcoholic liver disease and the determination of its stage.     

Aminoterminal propeptide of type III procollagen in serum in alcoholic liver disease

An assay of serum antigens related to the aminoterminal propeptide of type III procollagen has been suggested for monitoring fibrotic processes in the liver. These antigens were measured here in 61 alcoholics who were divided into four groups on the basis of liver histology: normal light microscopy, fatty liver, alcoholic cirrhosis with hepatitis, and inactive cirrhosis. All the subjects having alcoholic hepatitis with cirrhosis had elevated values in the assay, whereas some of those with either fatty liver or inactive cirrhosis still had normal values. It was, therefore, not possible on the basis of this method alone to distinguish fatty liver from cirrhosis or alcoholic hepatitis, although very high values were suggestive of alcoholic hepatitis. In a follow-up study, the aminopropeptide value decreased slowly during recovery from alcoholic hepatitis and increased rapidly after a new drinking bout. The antigens detected by the assay are heterogeneous in human serum. The proportions of the three main peptide forms varied during recovery from alcoholic hepatitis, the authentic propeptide being the main one at the acute stage, but almost disappearing later. The usefulness of the assay could probably be improved if distinct assays were available for the different antigen forms.     

Serum laminin and portal pressure in alcoholic cirrhosis. A study of 39 patients

A correlation between serum laminin, a glycoprotein found in basement membranes, and hepatic wedge pressure has previously been reported in a small number of patients with various liver diseases. To study this relationship in patients with alcoholic cirrhosis, we measured the wedge hepatic pressure and venous gradient, in comparison with serum concentrations of laminin and collagen metabolism products: N-terminal peptide of type III procollagen, collagen type I, and collagen type III in 39 patients. A statistically significant correlation was observed between serum laminin and wedged hepatic pressure (r = 0.529; p less than 10(-3] or hepatic venous gradient (r = 0.482; p = 0.002). By contrast, no statistically significant correlation was found between hemodynamic parameters and serum concentrations of N-terminal peptide of type III procollagen, collagen type I or collagen type III. These results suggest that, in patients with alcoholic cirrhosis, portal pressure may be estimated by serum concentration of laminin, and that perisinusoidal fibrosis, especially basement membrane thickening, may play an important role in the pathogenesis of portal hypertension in these patients.     

Serum procollagen peptides and collagen type VI for the assessment of activity and degree of hepatic fibrosis in schistosomiasis and alcoholic liver disease.

Schistosomiasis, in contrast to alcoholic liver disease, leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Because conventional liver function tests and liver biopsy specimens provide little information about the dynamics of the fibrotic process, we measured the serum concentrations of procollagen type III N-propeptide and procollagen type I C-propeptide, believed to mainly reflect collagen synthesis, and procollagen type IV C-propeptide and collagen type VI, two presumptive markers of collagen degradation. Determinations were performed in 15 healthy control subjects, 69 patients with various stages of infection with Schistosoma mansoni/Schistosoma haematobium (28 with an early active infection and no organ involvement, 27 with hepatosplenic involvement and 14 with complications of portal hypertension) and 16 patients with alcoholic cirrhosis. In addition, liver biopsy specimens were obtained from 30 schistosomal patients (18 with hepatosplenic involvement and 12 with complications of portal hypertension for histopathological grading and collagen histochemistry. Procollagen type III N-propeptide was significantly elevated in the three patient groups with schistosomiasis when compared with controls (p less than 0.01). Also, patients with higher histological grading showed significantly higher procollagen type III N-propeptide values (p less than 0.05). In alcoholic patients, procollagen type III N-propeptide was even higher and increased parallel to the severity of the disease, determined by using a combined clinical and laboratory index. Procollagen type I C-propeptide was only elevated in early infection (p less than 0.05) and steadily decreased with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum type III procollagen peptide concentrations in severe chronic active hepatitis: relationship to cirrhosis and disease activity

To analyze the correlations between the presence of cirrhosis and hepatocellular inflammation and the serum concentrations of the amino-terminal peptide of procollagen type III in chronic liver disease, we measured procollagen type III concentrations in paired serum samples from 46 patients (17 had cirrhosis) with severe chronic active hepatitis during a therapeutic treatment trial. Coded sera were analyzed for procollagen type III concentrations using both a standard and a recently described Fab radioimmunoassay to compare their relative diagnostic accuracy. Mean procollagen type III levels were elevated to the same extent in the cirrhotic and noncirrhotic groups at entry into the study. In response to immunosuppressive therapy, the initially elevated procollagen type III levels improved to normal values at remission in both groups. Qualitatively, the results were similar using either assay, but the standard assay was more sensitive for identifying the clinical stage of disease (i.e., active disease vs. disease in remission) than the Fab assay. Since both procollagen type III levels and standard liver function tests correlated well individually with the presence or absence of active disease, they also correlated with each other when both entry and remission values were considered. However, procollagen type III levels correlated poorly with indicators of inflammation (histologic grade and serum transaminase levels) during active disease. It is concluded that procollagen type III levels change in concert with standard liver function tests but do not quantitatively reflect inflammation or static measurements of hepatic fibrosis in severe chronic active hepatitis. However, these preliminary results suggest that procollagen type III can distinguish active disease from chronic active hepatitis in remission.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性乙型肝炎肝纤维化分期与血清肝纤维化标志物的相关性分析

目的 探讨血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原等血清肝纤维化标志物与慢性肝炎肝组织炎症活动度及纤维化程度的相关性。方法 278例慢性肝炎患者经肝脏活栓后常规病理检查,肝活检前同时采血检测血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原,结果应用x^2检验及t检验进行统计学处理。结果 肝组织纤维化程度与炎症活动度呈正相关关系,透明质酸可反映中度以上慢性肝炎炎症活动度及纤维化程度,且呈正相关;肝脏存在纤维化时层粘蛋白水平升高,与纤维化程度正相关;Ⅲ型前胶原、Ⅳ型胶原水平升高与炎症活动度有关。结论 血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原可不同程度反映肝纤维纤维化程度,可作为血清肝纤维化检测指标,透明质酸更可反映肝硬化发展趋势。     

Serum type I collagen and N-terminal peptide of type III procollagen in chronic hepatitis. Relationship to liver histology and conventional liver tests.

The aim of this study was to compare serum N-terminal peptide of type III procollagen to aminotransferases and gamma-globulins as a marker for histological activity in patients with chronic hepatitis and to assess the role of type I collagen, a new serum marker, as a marker of fibrosis in these patients. Sixty patients with biopsy-proven chronic hepatitis were included in this study. Liver disease was virus B-related in 29, autoimmune in five, drug-induced in five, and of unknown etiology in 21. Each biopsy was independently assessed by two liver pathologists. Two histological scores, a score of activity and a score of fibrosis, were established. Serum N-terminal peptide of type III procollagen and type I collagen were assayed by liquid phase RIA. Significant correlations were noted between serum N-terminal peptide of type III procollagen and scores of activity (r = 0.70, p less than 10(-4)) and fibrosis (r = 0.45, p = 0.0005), and between serum type I collagen and scores of activity (r = 0.46, p = 0.0004) and fibrosis (r = 0.67, p less than 10(-4)). When the correlation between scores of activity and fibrosis (r = 0.52, p = 10(-4)) was considered by partial correlation, serum N-terminal peptide of type III procollagen was correlated with the score of activity (r = 0.63, p less than 10(-3)) but not with the score of fibrosis, and serum type I collagen was correlated with the score of fibrosis (r = 0.58, p less than 10(-3)), but not with the score of activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biliary excretion of procollagen type III peptide in healthy humans and in patients with alcoholic cirrhosis of the liver

Serum concentrations of procollagen type III peptide are found to be elevated in liver disease and to correlate with fibrosis activity in liver tissue. These elevated serum levels may be due to enhanced synthesis, decreased excretion, or release from deposits of the propeptide in connective tissue. To quantitatively investigate the excretion of procollagen type III peptide, we studied its presence in the bile and urine of 10 healthy controls and 11 patients with alcoholic cirrhosis of the liver. Biliary excretion rates of procollagen propeptide were determined by the duodenal perfusion method. The serum concentrations of procollagen type III peptide were 2.5 +/- 0.5 ng/ml in the healthy controls and 33.6 +/- 6.8 ng/ml in the patients with cirrhosis. Procollagen type III peptide was found in the bile; the healthy controls excreted 0.4 +/- 0.07 nmol/h and the cirrhotics excreted 0.98 +/- 0.27 nmol/h. A fragment of the procollagen propeptide, Col 1, was excreted in urine; the healthy controls excreted 0.25 +/- 0.04 nmol/h, and the cirrhotics excreted 0.11 +/- 0.03 nmol/h. These data demonstrate that the biliary excretion of procollagen type III peptide represents a quantitatively important pathway.     

Clinicopathological Study of Alcoholic Fibrosis

Among 112 patients with alcoholic liver injury, 45 had alcoholic fibrosis. The incidence of alcoholic fibrosis was 40.2% which was the highest among various types of alcoholic liver injury (fatty liver: 3.6%, alcoholic hepatitis; 2.7% and liver cirrhosis: 31.3%). Clinical features of alcoholic fibrosis were milder than those of liver cirrhosis and more severe than those of fatty liver. The mean laboratory values in alcoholic fibrosis were significantly different from those in fatty liver and liver cirrhosis. The laboratory data were well correlated with the presence of pericellular fibrosis and thickening of the terminal hepatic venule, but only partially with hepatic cell necrosis and not with fatty metamorphosis. Two patients with alcoholic fibrosis who developed cirrhosis without any clinical and histological features of hepatitis were observed during 5-yr follow-up. These results indicate that alcoholic fibrosis is the most common type of alcoholic liver injury in Japan and is an independent clinicopathological entity distinct from the classical types of alcoholic liver injury. Pericellular fibrosis and thickening of the terminal hepatic venule which are the main histological features of alcoholic fibrosis may play an important role in its transition to liver cirrhosis.     

Clinical detection of the hepatic lesion of pericentral sclerosis in chronic alcoholics.

It has been shown that a specific liver lesion--that is, pericentral sclerosis associated with pericellular fibrosis--is the precursor of alcoholic liver sclerosis. It is, however, difficult to diagnose this hepatic lesion in chronic alcoholics, using only clinical data without liver biopsy. To investigate the possibility of a clinical test reflecting the presence of this hepatic lesion, ethanol (0.75 g/kg body weight) was given orally to chronic alcoholics, and serum glycoprotein levels (prealbumin, alpha HS glycoprotein, haptoglobin, alpha 2-macroglobulin) were measured before and six hours after. Chronic alcoholics were divided into three groups according to the histological findings in the liver at the time of study. Group I (alcoholic fatty liver or non-specific change) consisted of seven cases without pericentral sclerosis. Group II (alcoholic hepatic fibrosis or alcoholic hepatitis) consisted of five cases with pericentral sclerosis and pericellular fibrosis. Group III consisted of five cases with alcoholic liver cirrhosis. After the ethanol administration, serum glycoprotein levels decreased significantly in group I (P less than 0.05), whereas they increased in group II and group III. Their alternative ratios (see text) apparently differed (P less than 0.005) between group I and group II, and between group I and group III. These results indicate that the determination of serum glycoprotein levels before and after oral ethanol administration is useful way of discriminating alcoholic patients with hepatic pericentral sclerosis and pericellular fibrosis from alcoholics without such lesions.     

Serum type III procollagen and basement membrane proteins as noninvasive markers of hepatic pathology in Indian childhood cirrhosis

While serum concentrations of antigens of the aminopropeptide of type III procollagen have been considered as indicators of hepatic pathology in adults, the high concentrations normally found in children during growth may preclude their use in pediatric liver disease. To clarify this and to determine the role of other circulating connective tissue-related substances in children, we have measured serum concentrations of antigens related to aminopropeptide of type III procollagen, the 7S domain of type IV collagen and the P1 fragment of laminin in healthy subjects aged 1 month to 4 years and in children with Indian childhood cirrhosis, a particularly aggressive form of liver disease. In healthy subjects, there was a considerable age variation in serum aminopropeptide of type III procollagen but not in 7S collagen or laminin P1. In Indian childhood cirrhosis, all three serum antigens were increased (p less than 0.001) above the upper limit of normal for age. Both the serum 7S collagen and laminin P1 concentrations showed a significant correlation with the degree of intralobular fibrosis and also with the severity of necrosis and cellular infiltration, suggesting that these serum antigens may be a noninvasive means of assessing and monitoring events associated with hepatic fibrosis in Indian childhood cirrhosis. The raised serum aminopropeptide of type III procollagen in Indian childhood cirrhosis did not correlate with any histological parameter assessed. Gel filtration of serum showed that, in healthy subjects, the predominant antigenic form of aminopropeptide of type III procollagen was a degradation peptide smaller than authentic aminopropeptide of type III procollagen; while in Indian childhood cirrhosis the authentic peptide and a larger degradation peptide predominated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is determination of serum N-terminal procollagen type III peptide (sPIIIP) a marker of hepatic fibrosis?

Serum N-terminal procollagen type III peptide (sPIIIP) levels were evaluated in 58 patients affected by chronic liver disease, in order to assess the usefulness of sPIIIP as a marker of hepatic fibrosis. In 45 patients sPIIIP was also correlated to liver histology; biopsies were scored by two of the authors, without knowledge of diagnosis. Compared to normal controls, sPIIIP concentration was found to be significantly elevated in chronic active hepatitis (CAH) and in cirrhosis, but not in fatty liver. Patients affected by chronic persistent hepatitis (CPH) had values of sPIIIP higher than normal in four of 11 cases considered. A close correlation was found between sPIIIP values and histological parameters of inflammation, necrosis, and degeneration, while the relationship between sPIIIP levels and fibrosis was weaker. These data suggest that sPIIIP determination may reflect the extent of inflammatory changes in the liver; but it cannot be considered a reliable index of hepatic fibrosis.     

Serum laminin and type IV collagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis

BACKGROUND/AIMS: Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver biopsy. Extracellular matrix serum markers have been proposed as non-invasive diagnostic tools in alcoholic liver disease. The aim of this study was to determine the accuracy of 5 extracellular matrix serum markers, i.e. laminin (Lam), N-terminal peptide of type III procollagen (PIIINP), type I (CI), type III (CIII) and type IV (CIV) collagens in identifying patients with severe histologic alcoholic hepatitis from among those with cirrhosis and suspected alcoholic hepatitis. METHODS: We studied 80 consecutive patients with alcoholic cirrhosis and clinical suspicion of alcoholic hepatitis referred for transvenous liver biopsy. Clinical severity of alcoholic hepatitis was assessed according to Maddrey's score. Histological severity was scored using the sum of the 3 following items: polynuclear infiltration (0-3); hepatocytes alterations (0-3); Mallory bodies (0-2). According to this score, patients were divided into 3 groups: mild (1-3), moderate (4-6), and severe (7-8) alcoholic hepatitis. Serum levels of the 5 extracellular matrix serum markers were measured at the time of biopsy using radioimmunoassays. Diagnostic value for histologically severe alcoholic hepatitis of the 5 extracellular matrix serum markers was assessed using receiver operating characteristic curves. RESULTS: Histological alcoholic hepatitis was present in 67 patients (mean alcoholic hepatitis score: 3.4+/-2.3). Maddrey's score was 66% sensitive and 69% specific for the diagnosis of severe histologic alcoholic hepatitis. The serum Lam and CIV concentrations were the most accurate in identifying correctly patients with severe histologic alcoholic hepatitis. At a cut-off of 4.1 UI/ml, Lam was 90% sensitive and 77% specific, whereas at a cut-off of 150 ng/ml, CIV was 89% sensitive and 77% specific. Combination of markers did not result in improved diagnostic value. CONCLUSION: In patients with cirrhosis, determination of serum Lam or CIV could represent a simple and accurate non-invasive method for identification of patients with histologically severe alcoholic hepatitis eligible for corticosteroid treatment.     

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse. Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan

Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.     

Latent myocardiopathy in chronic alcoholic patients with or without hepatic involvement

Infraclinical myocardial lesions were searched for in patients with various types of liver disease due to chronic alcoholic intoxication. During a single procedure, a transjugular liver and right endoventricular biopsy and hemodynamic evaluation were performed in 26 patients without clinical evidence of cardiac involvement. Patients were classified into 5 groups: I, no liver disease (n = 4); II, fatty liver (n = 7); III, acute alcoholic hepatitis (n = 3); IV, cirrhosis (n = 7); V, cirrhosis with alcoholic hepatitis (n = 5). The study also included the determination of the serum thiamine level, a 24 h non-stop EKG recording and a M mode echocardiography. The cardiac-thoracic ratio, the EKG and Holter monitoring were normal. The serum thiamine levels decreased regularly from group I to group V, but there was no significant difference between patients with cirrhosis (group IV and V) and the others (group I to III). The same findings applied to the echocardiographic data. At rest, hemodynamic data were normal in all patients. Various degrees of myocardial lesions were present in 86 p. 100 of the cases. They included: cellular hypertrophy, contraction bands, interstitial fibrosis, fibroblastic infiltrate, perinuclear, cellular and or interstitial edema. Although frequent, these lesions were moderate and not specific. No correlation was found between the myocardial lesions and the type of liver disease. Myocardial lesions without cardiac manifestations have therefore been observed in vivo in nearly all patients with chronic alcoholic intoxication. These lesions were not correlated with the stage of alcoholic liver disease.