Plasma prolidase and prolinase activity in alcoholic liver disease

Prolidase (EC 3.4.13.9) and prolinase (EC 3.4.13.8) activity was measured in the plasma of 53 patients with alcoholic liver disease. Plasma prolinase activity was not correlated with histological characteristics in liver biopsies. In contrast, prolidase activity rose significantly (p less than 0.02) in cirrhotic patients with alcoholic hepatitis in comparison with those without alcoholic hepatitis. It also showed a significant positive correlation with ASAT activity (r = 0.505, p less than 0.001) and with the ASAT/ALAT ratio (r = 0.452, p less than 0.001). Plasma prolidase activity did not allow the differentiation of patients with reversible fibrosis from those with cirrhosis. The interest of this new marker is discussed.     

Survival of and hepatoma development in patients with liver cirrhosis

A follow-up study was made on 75 patients with liver cirrhosis. The patients were divided into 5 groups (discontinued alcoholic group, continued alcoholic group, hepatitis B group, male non-alcoholic non-hepatitis B group, and female non-alcoholic non-hepatitis B group). Hepatoma developed in 50% of the hepatitis B group, but in 1-9% of the other 4 groups. Abstinence did not accelerate the development of hepatoma. As for survival after onset of liver cirrhosis, the 1-4-year survival of the female non-alcoholic non-hepatitis B group and the final (8-year) survival of the hepatitis B group appeared to be lower than that of the other groups. Though the survival of the discontinued alcoholic group was seemingly higher that that of the continued alcoholic group, the difference was small and not significant.     

Hepatitis B antigens and antibodies in asymptomatic carriers and in chronic liver diseases.

88% of asymptomatic hepatitis B surface antigen (HBsAg) carriers and 97% of HBsAg positive patients with chronic hepatitis or non-alcoholic liver cirrhosis showed high titers of antibody to hepatitis B core antigen (anti-HBc). A high titer of anti-HBc, thus suggested to be an indicator of persistent hepatitis B virus infection, was found rarely in seronegative patients with chronic hepatitis, non-alcoholic cirrhosis, or alcoholic liver diseases. It was not revealed in idiopathic portal hypertension or Budd-Chiari syndrome. In asymptomatic HBsAg carriers of 20--29 years of age, hepatitis B e-antigen (HBeAg) was significantly more frequently found in males than in females. There were differences in sex ratio, age, and history of blood transfusion between B type and non-B type of chronic hepatitis and non-alcoholic liver cirrhosis.     

1-14C]Ethanol breath test in alcoholic liver disease

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.     

Natural History of Alcoholic Hepatitis. IV. GLYCOSAMINOGLYCURONANS AND COLLAGEN IN THE HEPATIC CONNECTIVE TISSUE

The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI) 相似文献   

Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis.

Delayed cutaneous hypersensitivity was studied in 10 patients with severe alcoholic hepatitis, 9 patients with either inactive alcoholic cirrhosis or alcoholic fatty liver, and 10 agematched controls. The mean response of the alcoholic hepatitis group was significantly less compared to controls for SK-SD (P less than 0.001), mumps (P less than 0.001), trichophyton (P less than 0.025), and Candida albicans (P less than 0.025). Upon clinical recovery, the response of the 6 surviving patients with alcoholic hepatitis was similar to controls for 4 of the 5 antigens tested, and the improvements in response to SK-SD and Candida albicans were significant (P less than 0.02 and P less than 0.05). The mean percentage and absolute numbers of thymus-derived lymphocytes were significantly less in the alcoholic hepatitis group compared with controls. Both the alcoholic hepatitis patients and patients with less advanced alcoholic liver disease had a diminished response to concanavalin A and phytohemagglutinin. This study demonstrates a reversible depression of delayed cutaneous hypersensitivity in alcoholic hepatitis. Several mechanisms may help account for this finding. We recommend that skin tests in patients with alcoholic hepatitis be interpreted with this phenomenon in mind.     

Erythrocyte aldehyde dehydrogenase activity in alcoholic subjects and its value as a marker for hepatic aldehyde dehydrogenase in subjects with and without liver disease

Erythrocyte aldehyde dehydrogenase activity was assayed in actively drinking alcoholics, patients with alcoholic liver disease who claimed to be abstaining, patients with non-alcoholic liver disorders and normal controls. Hepatic cytosolic aldehyde dehydrogenase was also assayed in the majority of the subjects. Actively drinking alcoholics had significantly lower erythrocyte aldehyde dehydrogenase activity than controls (P less than 0.01) but abstaining alcoholic liver disease and non-alcoholic liver disorder subjects did not. There was a significant correlation between erythrocyte and hepatic cytosolic aldehyde dehydrogenase activity in the control group (r = 0.94, P less than 0.05) but not in the other study groups.     

Pharmacokinetic disposition of isoxicam in hepatic cirrhosis

To determine the effect of liver dysfunction on the absorption and disposition of isoxicam, we administered a single oral dose of 200 mg to 8 patients with alcoholic cirrhosis, and followed the plasma concentration-time curve for 96 h. The calculated isoxicam disappearance t 1/2 of 30 +/- 19.1 h in these patients was not different from the mean value of 31 +/- 5.7 h obtained in 10 normal subjects studied earlier by our group; however, interindividual variation was larger. No differences in lag time (0.42 +/- 0.3 vs 0.49 +/- .2 h) or time to peak concentration (9.0 +/- 2.5 vs 10.0 +/- 2.9 h) were observed. However, the peak plasma isoxicam concentrations and the areas under the plasma concentration-time curves (AUC) were reduced 32% (p less than 0.01) and 41% (p less than 0.01), respectively. Plasma protein binding of isoxicam studied by equilibrium dialysis was 80 +/- 16% in the cirrhotic patients compared with 96 +/- 1.4% in the normal volunteers (p less than 0.02), again with larger interindividual variation noted in patients with cirrhosis. The binding did not correlate significantly with any laboratory tests of liver function or with the AUC for plasma isoxicam. As compared to the normal subjects, these cirrhotic patients had decreased plasma isoxicam binding, peak plasma isoxicam concentrations and AUC, without a significant change in the apparent disappearance half-life of total plasma isoxicam after a single oral dose.     

Serum beta 2-microglobulin in chronic liver diseases

Serum beta 2-microglobulin was determined in 53 patients with chronic liver diseases. No elevation was shown in fatty liver due to obesity or alcoholism. Serum beta 2-microglobulin was abnormal only in 4% of the patients with chronic hepatitis. Determination of serum beta 2-microglobulin seems not useful for the differential diagnosis between chronic hepatitis and fatty liver due to obesity or alcoholism. Serum beta 2-microglobulin was elevated in 29% of the patients with alcoholic liver cirrhosis, in 41% of those with non-alcoholic liver cirrhosis, and in 75% of those with primary liver carcinoma. The average serum beta 2-microglobulin concentration was significantly higher in non-alcoholic liver cirrhosis than in alcoholic liver cirrhosis. There was a significant correlation between serum beta 2-microglobulin and gamma-globulin concentrations in liver cirrhosis.     

Red blood cell status in alcoholic and non-alcoholic liver disease.

Macrocytosis is most commonly associated with vitamin B(12) and folic acid deficiency, followed by alcoholism, liver disease, and other pathologic conditions. We studied the red cell and vitamin status in 423 consecutive patients with various liver diseases, including 31 with acute viral hepatitis (AVH), 105 with chronic hepatitis (CH), and 134 with alcoholic liver disease (ALD), who consisted of 84 with non-cirrhotic alcoholic liver disease (NCALD) and 50 with alcoholic liver cirrhosis (ALC), 60 with non-alcoholic liver cirrhosis (NALC), and 93 with hepatocellular carcinoma (HCC). The mean corpuscular volume (MCV) and red cell distribution width (RDW) were significantly higher in patients with ALD and NALC, and among them macrocytosis occurred more frequently in patients with ALC. Macrocytic anemia was mostly found in cirrhotic patients, in which the Child-Pugh score was closely related to the development of macrocytic anemia. In ALD, the MCV was significantly correlated with the estimated alcohol consumption and inversely correlated with the serum folic acid level, which, however, was often maintained within the normal range in patients with macrocytic ALC. After abstinence from alcohol, the MCV and RDW were reduced significantly and were associated with an increasing serum folic acid level. This suggests that macrocytic anemia was a common feature of alcoholic and non-alcoholic liver cirrhosis and that alcohol abuse and folic acid deficiency play a secondary role in macrocytosis.     

Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)     

酒精性肝病患者血清TGF-β、IL-6和IL-8水平及临床意义

目的探讨酒精性肝病患者血清转化生长因子（transforming growth factor-β,TGF-β）白细胞介素-6（inter-leukin-6,IL-6）和白细胞介素-8（interleukin-8,IL-8）在酒精性肝病中的作用。方法 60例酒精性肝病患者按酒精性脂肪肝（n=20）、酒精性肝炎（n=20）和酒精性肝硬化（n=20）分为3组。采用ELISA法检测20例健康对照组和60例各类酒精性肝病患者血清中TGF-β、IL-6和IL-8水平。结果血清TGF-β、IL-6和IL-8水平随着肝脏病变程度加重而递增,酒精性脂肪肝组、酒精性肝炎组和酒精性肝硬化组3项指标水平均高于正常对照组,差异显著（P〈0.01）,其中以酒精性肝硬化组3项指标水平为最高。结论 TGF-β、IL-6和IL-8在酒精性肝病中具有重要作用,酒精性肝病患者血清TGF-β、IL-6和IL-8水平的检测可作为酒精性肝病病情监测和预后判断的有效指标。     

Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients

In liver biopsy material of eighty-nine patients with suspected liver disease the drug-metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P-450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7-ethoxycoumarin, p-nitroanisol and cytochrome c). From the eight-nine patients sixty-one had various liver diseases not related to ethanol and twenty-eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7-ethoxycoumarin O-deethylase (EOD: 76.9 +/- 31.1 pmol min-1 mg-1 protein, mean +/- SD) than the non-alcoholic liver disease group (42.7 +/- 14.1). The inducing effect of ethanol was most striking on the EOD activity, less for the O-demethylation of p-nitroanisol (PNA) and not present for the NADPH-cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n = 7) had the highest EOD activities (108.9 +/- 25.0), patients with alcoholic hepatitis (n = 10) had significantly less activity (66.0 +/- 1.9) than the former group. However, alcoholics without liver damage (n = 6) had activities not significantly different (46.0 +/- 15.8) from controls (39.4 +/- 9.1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous ambulatory peritoneal dialysis in patients with hepatitis B liver disease.

OBJECTIVE: We hypothesized that patients with hepatitis B virus infection and cirrhosis are more susceptible to peritonitis as a complication of peritoneal dialysis (PD). METHODS: A retrospective study was carried out to compare peritonitis rates between cirrhotic and non-cirrhotic patients with hepatitis B virus infection. RESULTS: Between 1994 and 2004, 25 PD patients with hepatitis B cirrhosis and 36 patients with hepatitis B without cirrhosis were included for analysis. Mean follow-up duration was 52 months. Subjects with hepatitis B cirrhosis consisted of more males and had higher total body weight. No cirrhotic patients (20 of them being Child-Pugh class A, 2 class B, and 3 class C) had undergone portosystemic shunting or liver transplantation. Cirrhotic patients had slightly higher bilirubin concentration than the non-cirrhotic group (22 +/- 50 vs 9 +/- 4 micromol/L, p = 0.16). There was no difference in median peritonitis-free survival between cirrhotic and non-cirrhotic patients (40 vs 37 months, p = 0.64 by log-rank test). The average peritonitis rate was 1 episode every 19.2 patient-months in the cirrhotic group and 1 episode every 20.5 patient-months in the non-cirrhotic group. Time to first peritonitis did not differ between the two groups with respect to gram-negative organisms (p = 0.88) or gram-positive organisms (p = 0.52). Cirrhotic patients had more frequent Streptococcus species peritonitis, which accounted for 13% of all peritonitis episodes, as opposed to 2% among the non-cirrhotic patients (p = 0.01). Overall treatment response rate and outcome did not differ between patients with and patients without cirrhosis. CONCLUSIONS: Peritonitis-free survival of cirrhosis patients infected by hepatitis B virus compares favorably with thatin patients without cirrhosis. The presence of liver cirrhosis does not appear to compromise PD outcome.     

Cell-mediated immunity to acetaldehyde in alcoholic liver disease demonstrated by leukocyte migration test.

To determine whether a sensitization to ethanol metabolites occurs in alcoholic liver disease, reactivity of lymphocytes to nontoxic amounts of acetaldehyde was studied by direct elaboration of migration inhibitory factor (MIF) production. Eighteen alcoholics with various degrees of biopsy-proven liver damage showed increased MIF production in response to acetaldehyde; the mean value of the group differed significantly from 15 healthy controls, 15 subjects with nonalcoholic liver disease, and 15 alcoholics without liver involvement (P less than 0.001, P less than 0.001, P less than 0.02, respectively). Among the alcoholics with liver disease, none individuals (50%) with histological signs of advanced alcoholic hepatitis showed the highest percentage of inhibition of migration; the value differed significantly from the remaining patients with lesser degrees of hyaline necrosis in liver biopsies (P less than 0.005). These results indicate that acetaldehyde is involved in the pathogenesis of alcoholic hepatitis. Clinically, this test might facilitate the selection of patients with alcoholic hyaline necrosis.     

酒精性肝病的实验室诊断的临床研究

目的研究实验室诊断在酒精性肝病的诊断中临床应用价值。方法通过测定健康者、酒精性肝病患者、非酒精性肝病（甲肝、乙肝、肝硬化、肝癌）患者发病期（ALT≥65U／L）及治疗后（ALT≤65U／L）血液中天冬氨酸转氨酶同工酶（m-AST）、纤维结合蛋白（Fn）、γ-谷氨酰转移酶（r-GT）的变化进行分析。结果m-AST在ALD组和NALD组中的阳性检出率分别为75％与46％（P〈0．05）,Fn在ALD组和NALD组中的阳性检出率57％与60％（P〉0．05）,γ-GT在ALD组及NALD组中阳性检出率90％与88％（P〉0．05）;in-Asr在ALD组19．3±10．3U／L与对照组t检验P〈0．05与NALD组t检验P〈0．05;Fn在ALD组335。6±59．5mg／L与对照组t检验P〈0．05与NALD组t检验P〉0。05;r-GT在ALD组67．5±54．4U／L与对照组t检验P〈0．05与NALD组t检验P〉0．05;AID组治疗前后m-AST、Fn下降较为明显,经t检验P〈0．05说明治疗前后m-AST、Fn的结果有显著性差异。结论血清m-AST活性测定对有无活动性酒精性肝病有诊断和鉴别、及疗效有诊断价值;Fn的测定对早期判断酒精性肝病以及治疗疗效有一定价值,是判断病情严重程度、预后的良好指标;r-GT酶诊断酒精性损伤的敏感性甚高但γ-GT增高的特异性不高。     

Diagnostic significance of estimation of serum apolipoprotein A along with alpha-fetoprotein in alcoholic cirrhosis and hepatocellular carcinoma patients

The serum apolipoprotein A (Apo A) and alpha-fetoprotein (AFP) were evaluated in histologically verified 30 cases of alcoholic cirrhosis and 18 cases of hepatocellular carcinoma (HCC). The latter were also divided into subgroups depending on the presence or absence of associated cirrhosis. Serum Apo A levels were found to be significantly decreased in cirrhotics (p less than 0.001) compared to controls and non-cirrhotic HCC patients. In 22 cases of alcoholic cirrhosis (AFP less than 10 ng/ml) and 12 cases of HCC (AFP greater than 600 ng/ml), the AFP levels itself were diagnostic, but in the remaining cases, AFP levels (100-600 ng/ml) were not able to differentiate between cirrhosis and malignancy. In this later group of patients with low pathological range of AFP, serum Apo A levels found to be significantly decreased in alcoholic cirrhotic patients (p less than 0.001) compared to HCC patients. Thus, estimation of Apo A levels may be helpful to interpret the AFP values at lower pathological range due to suspected liver pathology.     

Autonomic neuropathy and chronic liver disease

Autonomic neuropathy has been reported in association with alcoholic cirrhosis but there is no information on its occurrence in non-alcoholic liver disease. We have examined autonomic function in 64 patients with biopsy-proven liver disease (22 with alcoholic liver disease and 42 with non-alcoholic liver disease) together with 29 age-matched controls. Forty-five per cent of patients with alcoholic liver disease and 43 per cent with non-alcoholic liver disease showed evidence of parasympathetic damage; 11 per cent of patients with alcoholic liver disease and 12 per cent with non-alcoholic liver disease had sympathetic damage. Forty-five per cent of patients with alcoholic liver disease and 22 per cent with non-alcoholic liver disease had peripheral neuropathy on clinical examination. Sixty-eight per cent of those with peripheral neuropathy also had autonomic neuropathy. This study confirms that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggests that the neurological defect may be secondary to the disturbed liver function. The implications of these observations with regard to prognosis of chronic liver disease are discussed.     

Fasting plasma somatostatin in alcoholic liver disease

Fasting level of somatostatin-like immunoreactivity (SLI) in plasma was measured by a highly sensitive radioimmunoassay in 36 patients with alcoholic liver disease verified by histopathology (10 patients with steatosis and 26 with cirrhosis of the liver). The median value of SLI was markedly elevated in patients with steatosis of the liver as compared to normal subjects, P less than 0.01, while the median value of SLI in the cirrhotic group was even higher, P less than 0.05, as compared to the steatotic group. Correlations of SLI to se-bilirubin and p-coagulation factors 2, 7 and 10 were significant, P less than 0.001 and P less than 0.01, respectively, whereas no correlation to plasma insulin could be elicited. These results suggest that in alcoholic liver disease fasting plasma somatostatin is correlated to the degree of hepatic failure and indicate that the liver is an important site for clearance of portal vein somatostatin.     

Survival rates of early-stage HCV-related liver cirrhosis patients without hepatocellular carcinoma are decreased by alcohol

Although alcohol abuse is the most common cause of liver cirrhosis in the United States, the enhancing effects of alcohol on the long-term prognosis of hepatitis C virus (HCV) related liver cirrhosis has not been clarified. To investigate how alcohol abuse influences the prognosis of hepatitis virus related liver cirrhosis, we studied 716 Japanese patients. Cumulative survival and hepatocellular carcinoma (HCC) development rates were analyzed in alcohol abusive, cirrhotic patients with or without hepatitis virus infection. Patients who abused alcohol were younger (p<0.0001) than HCV infected, non-abusive patients. The overall survival rate among patients with alcoholic cirrhosis (Al group), HCV related cirrhosis (HCV group), and HCV infected + alcoholic cirrhosis (HCV + Al group), showed no significant differences, although the 10-year cumulative survival rate of Al group was the highest of the three groups. The HCC development rate of Al group was the lowest. In addition, alcohol abuse decreased the survival rates of HCV group in the early stage with no HCC (p = 0.0028). In conclusion, alcohol abuse might affect the progression of liver damage in HCV infected patients with liver cirrhosis in the early stage, although the influence of alcohol abuse on the long term prognosis seems to be rather small.