Serum hyaluronate correlates with histological progression in alcoholic liver disease

OBJECTIVES: Chronic alcohol consumption may lead to the development of liver cirrhosis. Serum concentrations of hyaluronate were suggested as a predictor in chronic liver disease, but its power to distinguish between severity of fibrosis and inflammation had not been assessed. In order to evaluate hyaluronate as a marker to detect early stages of alcoholic liver disease and to establish a possible correlation with hepatic histology, serum concentrations were measured by radioimmunoassay in 87 patients with biopsy-proven fatty liver, fatty liver and mild fibrosis, fatty liver and inflammation, severe fibrosis and inflammation, and cirrhosis, and in 12 non-alcoholic control subjects. In addition, serum hyaluronate was determined in 40 non-cirrhotic alcoholic patients with either a normal serum aspartate aminotransferase (AST) or an AST elevated at least two-fold. RESULTS: Serum hyaluronate increased significantly with advanced stages of alcoholic liver disease, while levels in patients with fatty liver were elevated only slightly without reaching significance. Hyaluronate correlated well with histological stage and was highly sensitive for detecting fibrosis in general and perivenular fibrosis as an indicator of progression to cirrhosis. Hyaluronate levels were not influenced by AST levels. CONCLUSION: Serum hyaluronate is a good predictor of the presence of even moderate hepatic fibrosis in alcoholic liver disease, justifying its clinical use to assess morphological alterations of the liver in alcoholics.     

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.     

Type III procollagen N-terminal peptide (P-III-P, prolyl hydroxylase (PH), and laminin P1 levels in serum and BALF of radiotherapy patients]

The etiology of pulmonary fibrosis remains unclear, and at present there are no definite biochemical markers of its activity. We measured serum and BALF levels of type III procollagen N-terminal peptide (P-III-P), prolyl hydroxylase (PH), and laminin P1 in patients who had undergone radiotherapy for malignant neoplasms, and investigated their value as biochemical markers in a model of pulmonary fibrosis. The following results were obtained: 1) Patients with abnormal liver function had significantly higher serum P-III-P levels and showed a tendency to have higher serum PH levels. If P-III-P or PH are to be used as markers of pulmonary fibrosis, the effect of liver function must be taken into consideration; however, no significant difference was detected with respect to laminin P1 levels. 2) Serum P-III-P levels were significantly elevated by radiotherapy. 3) Laminin P1 levels rose in a similar manner to P-III-P levels after radiotherapy, but no significant change was detected. 4) In most cases, the levels of all markers in BALF were below the threshold of detection, nevertheless all three markers were elevated in a patient who developed diffuse radiation pneumonitis during radiotherapy. Increases in the lymphocyte count were found in BALF of this patient. 5) BALF hyaluronic acid levels were negative in the 3 cases assayed. 6) A significant correlation between P-III-P and laminin P1 in serum was shown, but no significant correlations could be found between the other combinations of markers in serum. Thus it appears that serum P-III-P and laminin P1 are valid biochemical markers of pulmonary fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum proline and blood lactate levels in alcoholic patients without hepatic failure: relationship with alcohol ingestion and histological activity

It has not yet been established whether serum proline and blood lactate levels are increased in alcoholic liver disease. We measured serum proline and blood lactate in controls and in patients with different stages of alcoholic liver disease in the absence of hepatic failure. Samplings were done in both abstinent and drinking alcoholics. Compared to controls, there was a striking increase in serum proline levels in 52 abstinent alcoholics with little or no hepatic fibrosis by histological assessment (0.10 +/- 0.01 vs. 0.155 +/- 0.008; p less than 0.005). Blood lactate levels were within the normal range and did not correlate with serum proline levels. On the other hand, serum proline and blood lactate levels were independent of hepatic necrosis and inflammation scores. In addition, in 10 patients with blood alcohol concentrations between 0.3 mg/ml and 7.8 mg/ml, serum lactate and proline were significantly elevated (2.42 +/- 0.29 mg/ml and 0.275 +/- 0.0026 mg/ml, respectively; p less than 0.005). These results show that there is an association between serum proline levels and the abstinence period in alcoholic patients. They further suggest that in alcoholic patients neither serum proline nor blood lactate concentrations are reliable markers for liver histological activity (necrosis and inflammation) or fibrosis.     

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 mitochondrial aspartate aminotransferase as a marker of chronic alcoholism: diagnostic value and interpretation in a liver unit

Serum mitochondrial aspartate aminotransferase activity was measured using an immunochemical method in 251 subjects, of whom 140 were chronic alcoholics. The alcoholic patients included 37 with normal liver routine tests (Group I), 61 with noncirrhotic alcoholic liver disease (Group II) and 42 with cirrhosis (Group III), of whom 21 had been abstainers for at least 2 months. All of the remaining 111 subjects were nonalcoholic: 61 had various types of liver disease (Group IV) and 50 were healthy controls. A second assay of serum mitochondrial aspartate aminotransferase activity was performed in 76 alcoholics after a period of abstinence of about 7 days. In addition, serial mitochondrial aspartate aminotransferase determinations were performed in four nonalcoholic volunteers prior to, during and following an alcohol bout. Mean mitochondrial aspartate aminotransferase and mitochondrial aspartate aminotransferase/total aspartate aminotransferase ratio were significantly increased in the alcoholics whatever their liver status, with a sensitivity of the ratio of 81, 85 and 66% for Group I, Group II and the 21 drinkers of Group III, respectively. Only 1 of the 21 cirrhotic abstainers had an increased ratio. Among the 61 nonalcoholic patients with liver disease, 11 had an increased mitochondrial aspartate aminotransferase/total aspartate aminotransferase ratio, specificity of which was 82%. After drinking had been stopped for about 1 week, mitochondrial aspartate aminotransferase decreased by more than 50% and therefore appears as a reliable tool to assess abstinence. In the four cases of alcohol bouts, no significant modifications in mitochondrial aspartate aminotransferase serum values were observed, thus suggesting that mitochondrial aspartate aminotransferase is indeed a marker of chronic, but not of acute, alcohol intake.     

Diagnostic Value of Serum γ-Glutamyl-Transferase Activity and Mean Corpuscular Volume in Alcoholic Patients with or without Cirrhosis

In an attempt to assess the diagnostic values of serum gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) variations as markers of liver disease and of abstinence in alcoholic patients, we compared 174 patients with alcoholic cirrhosis, 175 with noncirrhotic alcoholic liver disease and 67 patients with nonalcoholic cirrhosis. GGT and MCV values were checked three times, the day of admission, 7 days later, and on the last sample available during follow-up (1 to 12 months), and were compared according to the liver disease and abstinence. A decrease of GGT activity during the 1st week of hospitalization was noted in alcoholics with (-9 IU/liter) or without (-13 IU/liter) cirrhosis and not in nonalcoholic cirrhosis (+8 IU/liter), without MCV variations. During follow-up, median GGT activity was strikingly different in abstinent patients with (27 IU/liter) or without (21 IU/liter) cirrhosis and in nonabstinent patients (99 IU/liter and 123 IU/liter, respectively) (p less than 0.001). MCV decrease was noted in alcoholics whatever their abstinence or not, contrasting with the absence of decrease in nonalcoholic patients. For the diagnosis of alcoholism in cirrhotic patients, the positive predictive value (PPV) of a GGT or a MCV decrease during the 1st week of hospitalization was 0.82 and 0.78, respectively, and the negative predictive value (NPV) was 0.33 and 0.70, respectively. For abstinence during follow-up, the PPV of a GGT activity less than 50 IU/liter was 0.92 and the NPV was 0.65.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic Value of Serum Procollagen Peptide Measurements in Alcoholic Liver Disease

Procollagen type I carboxyterminal and type III aminoterminal peptide concentrations were measured in sera of 60 patients with alcoholic and 14 with nonalcoholic liver disease to study whether these assays are useful as clinical tests to differentiate various stages of alcoholic liver injury. Both propeptides were markedly elevated in alcoholic hepatitis and cirrhosis: procollagen type III peptide in 90% and type I peptide in 60-80% of these patients. Moderately increased values were found less frequently in patients with fatty liver. These tests did not differentiate patients with simple fatty liver from those with fatty liver and early fibrosis. There was a significant difference in serum procollagen type III peptide between fatty liver and both alcoholic hepatitis and cirrhosis (p less than 0.001), and in type I peptide between fatty liver and alcoholic hepatitis (p less than 0.005). Although serum peptide values correlated with the degree of liver fibrosis, appreciable overlap of values was found between the various groups. The peptide concentrations also seemed to be related to the degree of hepatic inflammation, and the highest values were observed in a subgroup of patients with alcoholic hepatitis in whom numerous Mallory bodies were found. The data suggest that in alcoholic liver diseases, serum collagen propeptide determination may be useful in diagnosing severe alcoholic hepatitis.     

Changes in laminin content in livers of patients with alcoholic liver disease

Abstract: An increase in serum laminin levels has been reported in patients with liver disease; however, the mechanisms for this increase have not yet been clarified. In the present study, the laminin content of liver biopsy specimens obtained from patients with alcoholic liver disease and nonalcoholic liver disease was determined with a one-step sandwich enzymeimmunoassay system, using monoclonal antibodies for human placental laminin. Hepatic laminin content was significantly higher in patients with liver disease than in normal controls. In alcoholic liver disease, the content in patients with mild fibrosis was lower than in patients with advanced types of alcoholic liver disease. In non-alcoholic liver disease, the hepatic laminin content tended to increase in parallel with the progression of fibrosis. The laminin content in alcoholic liver disease was significantly higher than in the corresponding type of non-alcoholic liver disease. Hepatic total collagen content increased in parallel with the progression of fibrosis in both alcoholic liver disease and non-alcoholic liver disease. The ratio of laminin to total collagen content was highest in alcoholic liver disease showing mild fibrosis and decreased in parallel with the progression of fibrosis. In contrast, the ratio was low in all types of nonalcoholic liver disease. The ratio in patients with alcoholic liver disease was significantly higher than in those with the corresponding non-alcoholic liver disease. Hepatic laminin content increased in parallel with the increase in hepatic type IV collagen in alcoholic liver disease, and the correlation was statistically significant. However, a similar correlation was not found in non-alcoholic liver disease. These results indicate that the response of laminin synthesis to alcoholic liver disease is strong in mild fibrosis and reached a plateau at a relatively early stage of fibrosis. The stimulation for laminin synthesis in non-alcoholic liver disease is different from that in alcoholic liver disease.     

Parameters of connective tissue metabolism as markers in acute and chronic pancreatitis. A retrospective study with a cohort of normal subjects

It is suggested that during active phases of acute and chronic pancreatitis (aP and cP) a major breakdown of extracellular matrix occurs. Since our group previously established that serum levels of the precollagen-III-peptide (P-III-P) are good markers for changes in the extracellular matrix in liver disease (e.g. fibrosis and cirrhosis), we investigated whether this would also serve as a possible marker for pancreatitis. A total of 52 patients with pancreatitis were studied (aP = 17; cP = 35) and compared to 194 controls. Diagnosis of pancreatitis was done on the basis of established classifications. Concomitant diseases, e.g. of the liver, were excluded. Serum levels of P-III-P (three assays with polyclonal and monoclonal antibodies and Fab-Fragments), hyaluronic acid (HA) and laminin (LAM) were measured by RIA or IRMA. Patients with pancreatitis displayed elevated levels in all groups, when compared with the controls. Since the P-III-P-Fab RIA measures the Col1-fragment by 50%, which is considered to be a degradation product of P-III-P, this could mean that neogenesis of collagen is paralleled by degradation during the initial course of an acute episode of pancreatitis. The ratio (quotient) of P-III-P-Fab and P-III-PMoAb (nl = 127.3 +/- 27) is changed in patients with pancreatitis towards P-III-P-Fab (aP: 115.4 +/- 84.7*, cP: 94.9 +/- 21.8*, cP-I: 89.3 +/- 9.2*; * = p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical Significance of Hepatitis GB Virus C Infection in Alcoholic Liver Disease

Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and γ-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.     

Increased serum tissue polypeptide specific antigen (TPS) in alcoholics: a possible marker of alcoholic hepatitis

BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is widely used as a tumor proliferation marker. There is some evidence of an increase in serum TPS in benign liver diseases. The aim of the study was to evaluate serum TPS levels in alcoholics. METHODS: Seventy-seven alcoholics (64 men and 13 women) admitted to the hospital with ethanol withdrawal syndrome entered the study. Twenty-three patients were biopsied (12 of them had alcoholic hepatitis and 11 steatosis or fibrosteatosis). Serum TPS was determined by enzyme immunoassay in all cases. Results were compared with those of 24 healthy controls. RESULTS: Serum TPS levels were significantly increased in alcoholic patients compared with controls (median 365 units/liter and range 41-6400 units/liter versus median 79 units/liter and range 19-235 units/ liter, respectively, p < 0.0001). Seventeen alcoholics (22%) had a TPS value 10 times higher than the upper normal threshold level (> or = 1000 units/liter). Among alcoholics, serum TPS levels were higher in patients with alcoholic hepatitis than in those with steatosis or fibrosteatosis (median 1486 units/liter and range 176-5023 units/liter versus median 106 units/liter and range 41-221 units/liter, respectively, p = 0.0001), offering a better discriminant value for the diagnosis of alcoholic hepatitis than usual liver function parameters. Serum TPS values showed significant correlation with liver cell necrosis and Mallory's hyaline degeneration. TPS values decreased after alcohol abstinence during hospital admission. CONCLUSIONS: Serum TPS is frequently increased in alcoholics and may be a marker of alcoholic hepatitis. Specificity of this molecule as a tumor marker is limited in alcoholics.     

Characteristics of Serum Hyaluronate Concentrations in Patients with Alcoholic Liver Disease

It has been reported that serum hyaluronate [hyaluronic acid (HA)] concentrations are increased in liver diseases, especially in alcoholic liver disease (ALD). However, the characteristics of serum HA concentration in patients with ALD have not been studied. In this study, first, we measured serum HA concentrations in patients with different stages of both ALD and non-ALD to clarify the characteristics of serum HA concentration in patients with ALD. Second, we measured serum HA concentrations in patients with ALD sequentially after abstinence. We also measured serum HA concentrations in patients with chronic type C hepatitis before and after treatment with interferon. Finally, we analyzed the relationship between serum HA concentrations and the contents of type IV collagen and laminin in the livers of both ALD and non-ALD patients. Serum HA concentrations in liver disease were higher than the cut-off value, and increased significantly ( p < 0.001) in parallel with the progression of hepatic fibrosis in both ALD and non-ALD patients. Serum HA concentrations in patients actively drinking with ALD were significantly higher ( p < 0.001) than those in non-ALD. After 4 weeks of abstinence, these concentrations fell to the levels of non-ALD. Although serum ALT levels were decreased in 80% of patients treated with interferon, serum HA concentrations were not changed or increased. A significant correlation between serum HA concentrations and hepatic type IV collagen and laminin content was present in ALD, but not in non-ALD. These results clearly suggest that the increase of serum HA concentrations in ALD may be associated with not only hepatic fibrosis, but also alcohol drinking.     

Serum gamma-glutamyl transpeptidase and chronic alcoholism

Serum gamma-glutamyl transpeptidase was determined in 123 alcoholic patients and found elevated in all patients with liver disease but in only 52% of patients without significant liver disease. In patients without clinically obvious liver disease, the elevations were two to three times the upper limit of normal and decreased to normal in 80% of patients, eight weeks after abstinence. By contrast, in patients with liver disease, the elevations of serum gamma-glutamyl transpeptidase were of the order of eight to 10 times above normal and persisted at these high levels following eight weeks of abstinence. The degree of abnormality of the serum enzyme did not correlate with the daily amount of alcohol ingested or with the total length of time of alcohol consumption in these alcoholic patients. This study shows that serum gamma-glutamyl transpeptidase is persistently elevated in patients with clinically obvious liver injury, but only in 22% of chronic alcoholics without significant liver disease.     

Lipocytes and transitional cells in alcoholic liver disease: a morphometric study

Lipocytes and transitional cells in alcoholic liver disease were analyzed by quantitative morphometry in liver biopsy specimens of 17 alcoholic patients. In fatty livers, 93% of the perisinusoidal cells were lipocytes with a volume of lipid droplets occupying more than 20% of the individual cell volume. In fatty livers with perivenular fibrosis, 83% of the cells were lipocytes and 17% were transitional cells with lipid droplets of less than 20% of the cell volume. In cirrhosis, 45% of the cells were lipocytes and 55% of the cells were transitional cells. Thus, the process of hepatic fibrosis was associated with a shift from lipocytes to transitional cells. The percentage of transitional cells (expressed as total perisinusoidal cells) was 5.1% in fatty livers, 16.5% in fatty livers with perivenular fibrosis (not significantly different when compared to fatty livers) and 59.7% in cirrhotic livers (p less than 0.025) when compared to fatty livers or fatty livers with perivenular fibrosis). The number of transitional cells per 100 hepatocytes was estimated to be 0.5 in fatty livers, 1.3 in fatty livers with perivenular fibrosis and 2.1 in cirrhotic livers. The appearance of transitional cells was associated with a corresponding decrease in the number of lipocytes, supporting the hypothesis that transitional cells were derived from lipocytes. In comparison to lipocytes, the surface area of transitional cells (as measured by digitized morphometry) was 30 to 46% smaller (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinicopathologic study of alcohol-like liver disease in non-alcoholics; non-alcoholic steatohepatitis and fibrosis.

Alcohol-like liver injury (ALLI) in non-alcoholics has not been elucidated in Japan. The present study attempted to characterize the clinicopathologic features of ALLI in routine liver biopsies. ALLI was found in 1% of 561 biopsy cases obtained from 1988 to May, 1991 at Kanazawa University Hospital. Laboratory data characteristically showed only a mild to moderate degree of dysfunction, and none of the cases exhibited jaundice. Hepatic histology showed a mild to moderate degree of perivenular, pericellular and/or portal stellate fibrosis with a varying degree of fatty change and inflammatory cell infiltration. Portal stellate fibrosis with a varying degree of cell infiltration was more severe than the centrilobular or pericellular fibrosis in all cases. Intralobular inflammatory cell infiltration was associated with spotty or single hepatocyte necrosis, but extensive hepatocyte necrosis was not observed. Neutrophil infiltration was absent or minimal, and lymphocytes predominated in all cases. Mallory bodies were rare and were found in a few hepatocytes of only one of the 7 cases. The above histologic findings in ALLI were very similar to those seen in liver disease in Japanese alcoholics, and were somewhat different from ALLI reported in Western countries. In cases in which hepatic fibrosis, characterized by pericellular, perivenular or portal stellate fibrosis dominated without apparent hepatic necrosis and inflammation, the term "non-alcoholic steatofibrosis" is more suitable to depict its liver histology, being very similar to the alcoholic fibrosis frequently seen in Japanese alcoholics.     

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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.     

Clinicopathologic study of alcohol-like liver disease in non-alcoholics; non-alcoholic steatohepatitis and fibrosis

Alcohol-like liver injury (ALLI) in non-alcoholics has not been elucidated in Japan. The present study attempted to characterize the clinicopathologic features of ALLI in routine liver biopsies. ALLI was found in 1% of 561 biopsy cases obtained from 1988 to May, 1991 at Kanazawa University Hospital. Laboratory data characteristically showed only a mild to moderate degree of dysfunction, and none of the cases exhibited jaundice. Hepatic histology showed a mild to moderate degree of perivenular, pericellular and/or portal stellate fibrosis with a varying degree of fatty change and inflammatory cell infiltration. Portal stellate fibrosis with a varying degree of cell infiltration was more severe than the centrilobular or pericellular fibrosis in all cases. Intralobular inflammatory cell infiltration was associated with spotty or single hepatocyte necrosis, but extensive hepatocyte necrosis was not observed. Neutrophil infiltration was absent or minimal, and lymphocytes predominated in all cases. Mallory bodies were rare and were found in a few hepatocytes of only one of the 7 cases. The above histologic findings in ALLI were very similar to those seen in liver disease in Japanese alcoholics, and were somewhat different from ALLI reported in Western countries. In cases in which hepatic fibrosis, characterized by pericellular, perivenular or portal stellate fibrosis dominated without apparent hepatic necrosis and inflammation, the term “non-alcoholic steatofibrosis” is more suitable to depict its liver histology, being very similar to the alcoholic fibrosis frequently seen in Japanese alcoholics.     

Assays of serum laminin and type III procollagen peptide for monitoring the clinical course of diabetic microangiopathy

Thickening of the capillary basement membrane is a characteristic feature of diabetes and is considered to cause diabetic microangiopathy. Serum levels of both laminin, a glycoprotein in the basement membrane, and type III procollagen peptide (P-III-P) were measured by specific radioimmunoassays according to the methods of Brocks et al. and Rohde et al. respectively and analyzed with regard to diabetic microangiopathy, glycemic control, diabetic duration and treatment. As a result, serum levels of both laminin and P-III-P showed higher values with development of diabetic microangiopathy, suggesting that progressive changes in diabetic microangiopathy occur with synthesis of laminin and P-III-P. Serum laminin and P-III-P appear to be good non-invasive markers for measuring basement membrane metabolism and type III collagen accumulation. High values of serum laminin and P-III-P levels were suspected to be due to improper treatment, using hypoglycemic agents without adherence to the diet regimen.     

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS: Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.