Difference of hepatic circulation between alcoholic and non-alcoholic hepatic cirrhosis

Comparisons were made of hepatic circulation between alcoholic and non-alcoholic cirrhosis. The wedged hepatic venous pressure and per cent intrahepatic shunt measured by the method of continuous infusion of D-galactose-1-14C were similarly markedly increased. On the other hand, the wedged hepatic venography showed the main portal trunk and extrahepatic collaterals, namely, the tendency of reverse or stagnant portal flow, more frequently in alcoholic cirrhosis than in non-alcoholic cirrhosis. The nodules shown by slow low-pressure hepatic sinusoidography were larger in non-alcoholic cirrhosis than in alcoholic cirrhosis.     

gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.     

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.     

Hepatic collagen proline hydroxylase activity in alcoholic liver disease.

The activity of hepatic collagen proline hydroxylase was examined in biopsy samples as a factor in collagen synthesis in 77 patients with alcoholic liver disease. The urinary excretion of peptide bound hydroxyproline was also measured in most of the patients, as an index of collagen degradation. The highest activities of collagen proline hydroxylase were found in the patients with alcoholic hepatitis. Enzyme activity was markedly increased in patients with non-specific changes on liver biopsy, whereas, patients with fatty infiltration had only mild elevations, and those with inactive cirrhosis had normal enzyme activity. Urinary hydroxyproline was elevated only in patients with alcoholic hepatitis and inactive cirrhosis. Follow-up determinations in 16 patients with alcoholic hepatitis, after 4 to 5 weeks, revealed a decrease in enzyme activity, but no change in urinary hydroxyproline. We conclude that among the types of alcohol-related liver diseases, alcoholic hepatitis is associated with the greatest turnover of hepatic collagen.     

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.     

Serum immunoreactive prolyl hydroxylase in liver disease

The concentration of serum immunoreactive prolyl hydroxylase (SIRPH) was measured in thirty patients with chronic active hepatitis, thirteen with primary biliary cirrhosis, four with alcoholic or idiopathic cirrhosis, and four with acute hepatitis; the values were compared with those in twenty-three control subjects. Increases in SIRPH were found in all the groups with liver diseases, individual values being highest in primary biliary cirrhosis in which about two-thirds of patients had values more than two standard deviations above the mean value in the control subjects. No correlation was found between SIRPH and other tests of liver function or some routine laboratory tests. SIRPH may reflect some hitherto unknown of unmeasured process in the diseased hepatic cells.     

Liver disease of the alcoholic.

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.     

Value of Doppler sonography in assessing the progression of chronic viral hepatitis and in the diagnosis and grading of cirrhosis.

OBJECTIVE: The purpose of this study was to evaluate the value of Doppler sonography in assessing the progression of chronic viral hepatitis and in the diagnosis and grading of cirrhosis. METHODS: Abdominal sonographic and liver Doppler studies were performed in 3 groups: 36 patients with chronic viral hepatitis, 63 patients with cirrhosis, and 30 control subjects with no evidence of liver disease. A series of Doppler indices of hepatic vascularity, including portal vein velocity, portal vein pulsatility score, flow volume of the portal vein, resistive and pulsatility indices of the hepatic artery, modified hepatic index, hepatic vascular index, waveform of the hepatic vein, and focal acceleration of flow, were measured and correlated with liver and spleen size, portal and splenic vein diameter, and presence of ascites and collateral vessels. These indices were compared across the 3 study groups and within the patient groups with respect to presence of inflammation, fibrosis, and steatosis, as determined by histologic evaluation. RESULTS: The most useful indices were portal vein velocity, the modified hepatic index, and nontriphasic flow in the hepatic vein, which were helpful in distinguishing patients from control subjects. Hepatic vascular and modified hepatic indices were useful for differential diagnosis of cirrhosis and chronic viral hepatitis. However, all measurements were limited in their ability to determine the severity of chronic hepatitis. CONCLUSIONS: Doppler sonography is sensitive to hemodynamic alterations resulting from inflammation and fibrosis, and if sonography is the study of choice to follow the progression of hepatitis, it will not be adequate without Doppler imaging. Doppler sonography has high diagnostic accuracy in cirrhosis despite some false-positive conditions. However, it has a limited role in clinical grading.     

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)     

肝硬化患者768例病因及临床特点分析

目的 探讨云南省昆明地区肝硬化患者病因及临床特点.方法 选择云南省第三人民医院消化内科2006年10月至2010年8月期间住院确诊的肝硬化患者768例,回顾性分析患者的临床资料和各项实验室检查结果.结果 768例肝硬化患者中单纯乙型肝炎病毒感染所致肝硬化354例(46.1%),单纯饮酒所致肝硬化162例(21.1%),单纯丙型肝炎病毒感染所致肝硬化39例(5.1%),酒精合并肝炎病毒共同损伤所致肝硬化86例(11.2%),原发性胆汁性肝硬化45例(5.9%),血吸虫性肝硬化32例(4.2%),血色病等遗传及代谢性疾病所致肝硬化21例(2.7%),不明原因肝硬化29例(3.8%).肝硬化并发症依次为上消化道出血(53.4%),肝性脑病(37.1%),继发感染(21.2%),原发性肝癌(16.4%)和肝肾综合征(5.9%).结论 云南省昆明地区的肝硬化病因以乙型肝炎病毒感染为主,其次为长期饮酒,单纯肝炎病毒感染所致肝硬化的临床表现以门脉系统高压为主,酒精中毒则以肝功能损伤为主,肝炎病毒感染与嗜酒重叠容易导致原发性肝癌的发生.     

超声下肝总动脉旁淋巴结肿大的探讨

在超声下对２３０例观察者的肝动脉及门静脉周围的淋巴结进行了检查，结果表明：肝动脉旁淋巴结的总发生率为３４％，病毒性肝炎、肝硬化、肝癌淋巴结肿大的发生率明显高于正常人及其它肝病的患者（Ｐ值＜０．００５），但肝癌与病毒性肝炎、肝硬化比较，无明显差异（Ｐ值＞０．０５）。我们认为肝动脉旁淋巴结的肿大，同肝脏的良性病变关系较为密切，对于肝癌不能做为一项诊断的指标     

Localization of T and B cells and alpha fetoprotein in hepatic biopsies from patients with liver disease.

Peripheral blood and hepatic tissue T- and B-lymphocyte distributions, serum alpha fetoprotein (AFP) concentrations, and hepatic AFP were studied in 46 patients undergoing diagnostic percutaneous liver biopsy. The patients included 26 with alcoholic liver disease, 13 with nonalcoholic hepatitis or cirrhosis, and 7 with either normal histology or minor nonspecific changes. Serum AFP was determined by radioimmunoassay and hepatic tissue AFP by indirect immunofluorescence. Peripheral blood T lymphocytes were identified by the sheep red-cell rosette technique; and B lymphocytes by fluoresceinated anti-immunoglobulin antisera and IgG aggregates. Tissue identification of T lymphocytes was accomplished using an extensively absorbed rabbit antihuman thymocyte antiserum and indirect immunofluorescence; tissue B lymphocytes were identified using pepsin F (ab')2 fragments of rabbit IgG antibodies to human immunoglobulins. T lymphocytes predominanted in hepatic lymphoid infiltrates from patients with alcoholic liver disease (91+/-4%), whereas in patients with chronic active or chronic persistant hepatitis, viral hepatitis, or cryoptogenic cirrhosis proportions of T and B lymphocytic infiltrates were similar (50+/-15%). Hepatic tissue AFP was detected in 9 of 18 patients with alcoholic hepatitis; serum AFP concentration was increased in only 1 of these 9 patients. Tissue AFP was not observed in the remaining biopsy material nor were serum AFP concentrations increased. Peripheral blood T-cell numbers were significantly decreased in patients with alcoholic liver disease (P less than 0.01) and in nonalcoholic hepatitis or cirrhosis (P less than 0.025). A close relationship between peripheral blood T-lymphocytopenia and hepatic T-cell infiltrates was observed in patients with alcoholic liver disease; this relationship was less apparent in patients with nonalcoholic hepatitis or cirrhosis.     

Risk lesions in cirrhosis and development of hepatocellular carcinoma: an autopsy study

Non-neoplastic morphologic changes in various types of cirrhosis were evaluated in relationship to the presence or absence of hepatocellular carcinoma (HCC), using autopsy livers from Hokuriku (Japan) and Los Angeles (USA). Macronodular cirrhosis was closely related to HCC in B-viral cirrhosis, alcoholic cirrhosis and cirrhosis of uncertain type. Liver cell dysplasia was most frequently seen in cases with and without HCC in B-viral cirrhosis but was significantly more frequent with HCC in cases of alcoholic cirrhosis and cirrhosis of uncertain type. Nodular bulging activity within regenerative nodules was closely related to HCC in alcoholic cirrhosis. A positive relationship between HCC and Mallory bodies was found in non-alcoholic cirrhosis. These data suggest that patients with macronodular cirrhosis, liver cell dysplasia, nodular bulging activity and Mallory bodies may have an increased risk of developing, or having HCC dependent on the etiology of cirrhosis. The geography and race differences had some relationship to the incidence of HCC.     

Accessory ultrasonographic findings in chronic liver disease: diameter of splenic and hepatic arteries, fasting gallbladder volume, and course of left portal vein

We have assessed the incidence and significance of changes in the caliber of the splenic and hepatic arteries, in fasting gallbladder volume, and in the intrahepatic course of the left portal vein in a group of 46 patients affected by chronic liver disease (24 with chronic active hepatitis and 22 with liver cirrhosis). Thirty normal subjects were examined as a control group. Mean diameters of the splenic and hepatic arteries were significantly greater in cases of liver cirrhosis than in the control group. In the case of chronic active hepatitis, only the splenic artery proved significantly enlarged in comparison with the control group. These results demonstrate that caliber modification occurs in the splenic and hepatic arteries during chronic liver disease. In particular, changes in the splenic artery precede the onset of clinically evident portal hypertension. Gallbladder volume was significantly increased in patients affected by liver cirrhosis. Finally, statistical analysis did not reveal any significant difference in the angles formed by the transverse and longitudinal tracts of the left portal vein in controls and in subjects with liver disease.     

Current problems of viral and alcohol diseases of the liver

517 cases of acute viral hepatitis (AVH) and 1203 cases of hepatic cirrhosis (HC) have been analysed. In recent 20-28 year the trend to a decline in the role of HBV infection in the origin of both AVH and HC. The least lethality was reported for viral C-cirrhoses. When the sale of heavy drinks was limited by the law, lethality of alcoholic hepatic cirrhosis came down 2.5-fold. Among hepatic cirrhoses, the percentage of alcoholic forms has increased from 35.6% in 1972-1984 to 41.5% in 1996-2000. The worst prognosis is now stated for alcoholic-viral and polyviral hepatic cirrhoses. The data for 4.5 years evidence for at least 50% lethality in this group.     

Experimental liver cirrhosis induced by alcohol and iron.

To determine if alcoholic liver fibrogenesis is exacerbated by dietary iron supplementation, carbonyl iron (0.25% wt/vol) was intragastrically infused with or without ethanol to rats for 16 wk. Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals. In both ethanol-fed and control rats, the supplementation produced a two- to threefold increase in the mean hepatic non-heme iron concentration but it remained within or near the range found in normal human subjects. As previously shown, the concentrations of liver malondialdehyde (MDA), liver 4-hydroxynonenal (4HNE), and serum aminotransferases (ALT, AST) were significantly elevated by ethanol infusion alone. The addition of iron supplementation to ethanol resulted in a further twofold increment in mean MDA, 4HNE, ALT, and AST. On histological examination, focal fibrosis was found < 30% of the rats fed ethanol alone. In animals given both ethanol and iron, fibrosis was present in all, with a diffuse central-central bridging pattern in 60%, and two animals (17%) developed micronodular cirrhosis. The iron-potentiated alcoholic liver fibrogenesis was closely associated with intense and diffuse immunostaining for MDA and 4HNE adduct epitopes in the livers. Furthermore, in these animals, accentuated increases in procollagen alpha 1(I) and TGF beta 1 mRNA levels were found in both liver tissues and freshly isolated hepatic stellate cells, perisinusoidal cells believed to be a major source of extracellular matrices in liver fibrosis. The dietary iron supplementation to intragastric ethanol infusion exacerbates hepatocyte damage, promotes liver fibrogenesis, and produces evident cirrhosis in some animals. These results provide evidence for a critical role of iron and iron-catalyzed oxidant stress in progression of alcoholic liver disease.     

Pathogenesis, diagnosis, and treatment of alcoholic liver disease

Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.     

Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage

Apoptosis occurs in the normal liver and in various forms of liver disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, and liver cells in animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system to investigate CD95-mediated apoptotic liver damage. Treatment of fresh human hepatocytes with low concentrations of agonistic antibodies against CD95 resulted in apoptosis of > 95% of the cultured liver cells within 4 and 7.5 h. Immunohistology of a panel of explanted liver tissues revealed that hepatocytes in normal livers (n = 5) and in alcoholic cirrhosis (n = 13) expressed low constitutive levels of CD95. CD95 receptor expression was highly elevated in hepatocytes in hepatitis B virus-related cirrhosis (n = 9) and in acute liver failure (n = 8). By in situ hybridization CD95 ligand messenger RNA expression was absent in normal liver but detected at high levels in livers with ongoing liver damage. In cases of hepatitis B virus- related cirrhosis and acute hepatic failure, ligand expression was found primarily in areas with lymphocytic infiltration. In contrast, in patients with alcoholic liver damage, high CD95 ligand messenger RNA expression was found in hepatocytes. These findings suggest that liver destruction in hepatitis B may primarily involve killing of hepatocytes by T lymphocytes using the CD95 receptor-ligand system. In alcoholic liver damage, death of hepatocytes might occur by fratricide and paracrine or autocrine mechanisms mediated by the hepatocytes themselves.     

酒精性肝病患者健康相关生存质量研究

目的研究酒精性肝病患者健康相关生存质量及其与疾病严重程度的关系以及对比酒精性肝病与慢性乙型肝炎患者健康相关生存质量的差别。方法 2010年12月至2011年10月收治的70例男性酒精性肝病患者(非肝硬化组45例,肝硬化组25例),56例男性慢性乙型肝炎患者(非肝硬化组24例,肝硬化组32例)以及42例男性健康对照组受试者参与试验。所有受试者回答SF-36V2(中文版)量表,通过SF-36V2软件计算出:生理功能、生理职能、躯体疼痛、总体健康、活力、社会功能、情感职能、精神健康共8个维度,以及躯体健康总评和精神健康总评。使用协方差分析对比健康对照组,酒精性肝病非肝硬化组,以及酒精性肝病肝硬化组健康相关生存质量;对比酒精性肝病与慢性乙型肝炎患者健康相关生存质量。结果和健康对照组相比,酒精性肝病患者随着疾病的加重,SF-36V2各维度评分明显降低(P<0.05)。酒精性肝病非肝硬化组患者较慢性乙型肝炎非肝硬化组患者仅生理功能、生理职能、活力、躯体健康总评四项评分轻度受损(P<0.05)。酒精性肝病肝硬化组与慢性乙型肝炎肝硬化组患者SF-36V2各维度评分相似(P>0.05)。结论酒精性肝病患者健康相关生存质量降低,且病情越重,健康相关生存质量越差。酒精性肝病患者健康相关生存质量与慢性乙型肝炎患者相似。     

117例慢性肝炎超声诊断与病理对照分析

目的对慢性肝炎患者进行超声检查，并在超声引导下肝穿活检作组织病理学诊断，以明确肝脏的炎症活动分级与肝纤维化程度分期。方法对117例慢性肝炎患者，进行超声检查后，采用超声引导自动活检方法取得标本，送病理检查。结果117例病例中组织病理学诊断：轻度慢性肝炎75例；中度慢性肝炎4例；早期肝硬化13例；肝硬化25例。超声诊断轻度50例；中度39例；肝硬化可能18例；肝硬化10例。结论慢性肝炎的超声声像图与病理分级分期有部分相关性。