Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C

In the past decade it became accepted that free radicals, lipid peroxidation and antioxidant defense play a role in various tissues damages, thus in certain liver diseases as well. Since only limited data have been reported concerning the oxidative stress in viral hepatitis, a comparative study was performed in patients (pts) with chronic hepatitis C and alcoholic liver disease. In addition, the effects of a flavonolignan drug silymarin were assessed. 10 pts with chronic hepatitis C, 5 pts with alcoholic hepatitis and 13 pts with alcoholic cirrhosis have been investigated. Biochemical liver tests (serum bilirubin, aminotransferases, ALT, AST, lactate dehydrogenase (LDH), pseudocholinesterase, prothrombin), malandialdehyde (MDA) levels in plasma and red blood cell (RBC) hemolysate, superoxide radical generating capacity of stimulated polymorphonuclear granulocytes (PMN), plasma concentrations of reduced (GSH) and oxidized (GSSG) glutathione, vitamin A, luteine and beta carotene, furthermore RBC superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were determined. The level of plasma MDA--as the marker of lipid peroxidation--was highest in alcoholic cirrhosis (five times of normal) (p < 0.05), the RBC hemolysate MDA was most elevated in chronic hepatitis C (p < 0.05). The mean PMNs' superoxide radical generating capacity was 116.6% of normal control in alcoholic hepatitis, where the mean GSH level was the lowest (89.8% of normal). Plasma vitamin A content was lowest in alcoholic cirrhosis (68% of control) (p < 0.05). SOD activity was elevated in both chronic hepatitis C and alcoholic cirrhosis, where GPx activity was decreased (p < 0.05). There was a correlation between LDH and SOD activities (r = 0.77, p = 0.015). Silymarin treatment of one month duration resulted in normalization of serum bilirubin in 55% of treated pts, AST became normal in 45%, and RBC hemolyzate MDA level normalized in similar rate. A significant increase in both GSH and retinoids was found. Alterations in oxidative stress and antioxidant defense system were shown in chronic hepatitis C, not only in alcoholic liver disease. The parameters of lipid peroxidation and antioxidant defense may be useful surrogate markers for monitoring pts with liver disease during hepatoprotective treatment.     

Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: a nationwide cohort study in Denmark

Mortality from cirrhosis of the liver has been examined in few long-term follow-up studies. In the Danish National Registry of Patients, 1982-1989, we identified a cohort of 10,154 patients with liver cirrhosis and divided them according to the etiology of their liver disease. Causes of death were identified in the Danish Death Registry, 1982-1993. We estimated relative survival and standardized mortality ratios by comparing with the mortality in the general population. The 10-year relative survival was worse in patients with alcoholic cirrhosis (34%) or nonspecified cirrhosis (32%) than in patients with primary biliary cirrhosis (58%) or chronic hepatitis (66%). The standardized mortality ratio for all causes of death combined was 12-fold increased, 5-fold excluding cirrhosis-related causes. Mortality in all disease categories was increased, even in those not traditionally related to cirrhosis. In conclusion, patients with cirrhosis of the liver face reduced life expectancy due to several causes of death.     

Diagnostic value of the determination of serum alpha2-HS-glycoprotein]

Opsonic glycoprotein, alpha 2-HS-glycoprotein concentration was studied in the serum of 753 patients with various hematological, malignant, immunological, metabolic, endocrine and liver diseases and 68 healthy controls. Decreased serum alpha 2-HS-glycoprotein levels were detected in patients with acute leukemias, chronic granulocyte and myelomonocyte leukemias, lymphomas, myelofibrosis, multiple myeloma, metastatizing solid tumors, systemic lupus erythematosus, rheumatoid arthritis, acute alcoholic hepatitis, fatty liver, chronic active hepatitis, liver cirrhosis, acute and chronic pancreatitis, and Crohn's disease. Elevated levels were measured in patients with B and NANB/C hepatitis. Further decreased levels were observed in some groups with secondary infections. Serum alpha 2-HS-glycoprotein levels are affected by many factors, influencing the synthesis and elimination of the protein. The detection of serum alpha 2-HS-glycoprotein concentration has no specific diagnostic value as a marker for tumors or other diseases, however, its determination can be useful for the assessment of a non-specific regulator of the host defence.     

Blood-lead levels in patients with chronic liver diseases

Blood-lead concentrations (Pb-B) were measured in 318 adult inpatients with chronic liver diseases. The Pb-B was highest (387 +/- 96 micrograms/l) in 102 patients with alcoholic liver disease without cirrhosis. The Pb-B was still high, but significantly lower in 60 patients with compensated alcoholic cirrhosis (342 +/- 100 micrograms/l) and in 72 patients with decompensated alcoholic cirrhosis (312 +/- 97 micrograms/l). This difference was in part due to a significant decrease of the hematocrit which fell from 44.4 +/- 4.9% to 42.4 +/- 27.2% and to 39.2 +/- 7.4% respectively. In patients with viral or cryptogenic liver diseases the Pb-B was 211 +/- 69 micrograms/l in 11 patients with chronic persistent hepatitis, 219 +/- 72 micrograms/l in 19 with chronic active hepatitis, 206 +/- 94 micrograms/l in 28 with compensated cirrhosis, and 226 +/- 98 micrograms/l in 26 with decompensated cirrhosis, without any significant difference. The Pb-B of the male patients showed no correlation to age, with the exception of 25 male patients with chronic persistent and active hepatitis (r = 0.626, P less than 0.001).     

Alcohol and dietary intake in the development of chronic pancreatitis and liver disease in alcoholism

Alcohol and dietary intake were determined in alcoholic patients with chronic pancreatitis and alcoholic liver disease. Patients with chronic pancreatitis, alcoholic hepatitis, and cirrhosis ingested approximately 50% of their calories as alcohol, and all had low mean intakes of protein, carbohydrate, and fat as compared with control subjects. Patients with severe alcoholic hepatitis had the lowest intake of nonalcohol calories and protein. Women with chronic pancreatitis had ingested alcohol for a shorter period of time than men whereas women with alcoholic hepatitis and cirrhosis had ingested less alcohol per kilogram body weight per day as compared with men. This study does not support the hypothesis that consumption of a high-protein and high-fat diet is a factor in the development of chronic pancreatitis in the alcoholic patient. The increased susceptibility of women as compared with men to alcoholic liver disease is established.     

Binge drinking and nitric oxide metabolites in chronic liver disease

AIMS: The effect of binge drinking in the production of nitric oxide metabolites has not been studied in patients with chronic viral liver disease. METHODS: We therefore studied serum levels of nitrites and nitrates (NOx) in 13 patients with chronic viral hepatitis and nine patients with compensated viral cirrhosis, after administration of 80 g alcohol. 15 patients with compensated alcoholic cirrhosis and seven healthy individuals were used as controls. Serum NOx levels were measured by a modification of the Griess reaction before and at 2, 12 and 24 h after alcohol consumption. RESULTS: An increase of serum NOx levels, that was statistically significant at 12 h, was found in healthy controls (P < 0.05). A similar pattern of NOx levels was observed in patients with chronic hepatitis. By contrast, in patients with cirrhosis, either viral or alcoholic, no significant increase was found after alcohol administration. However, basal levels in cirrhotics were significantly elevated (82.2 +/- 13.8 vs. 43.1 +/- 7.2 micro mol/l, P < 0.01) compared to healthy controls. CONCLUSIONS: Binge drinking causes a significant increase of serum NOx evident after 12 h with a return after 24 h at pre-drinking levels in healthy controls and patients with chronic viral hepatitis. In cirrhosis, such an increase is not observed serum levels being constantly elevated throughout the study period.     

Fulminant hepatitis A in patients with chronic liver disease

Fulminant hepatitis is a rare complication of acute hepatitis A virus (HAV) infection. We report three cases of fulminant hepatic failure with death due to HAV infection in patients with pre-existing chronic liver disease. Data from the literature also indicate a high case fatality rate during HAV superinfection in patients with chronic hepatitis B, particularly those with cirrhosis, and in patients with alcoholic cirrhosis. In patients with chronic hepatitis C, results are conflicting with some reports indicating a high fatality rate of HAV superinfection and others not, irrespective of the presence or absence of cirrhosis. Based on our observations and this review of the literature, we suggest that patients with chronic liver disease should be vaccinated against hepatitis A.     

High incidence of antibodies to hepatitis C virus in alcoholic cirrhosis: fact or fiction?

An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus was used to test serum samples from 39 patients with alcoholic cirrhosis and 34 patients with alcoholic hepatitis or fatty liver. The frequency of a positive result in the cirrhotics was significantly higher than in the alcoholics without cirrhosis (38.5% vs 8.8%, P less than 0.01). However, the positive results in the cirrhotics were associated with high gammaglobulin concentrations, and optical density values in the assay correlated closely with serum globulin (r = 0.73, P less than 0.01). The findings suggest that serum from patients with alcoholic cirrhosis may contain a component that give false-positive results in the assay.     

酒精性肝病患者血浆内毒素水平检测及临床意义

目的　检测不同阶段酒精性肝病患者的外周血内毒素水平 ,探讨此类肝病患者内毒素血症的发病情况 ,以指导治疗。方法　选择酒精性脂肪肝、酒精性肝炎、酒精性肝硬化患者与正常对照组 ,4组共 98例。测外周血浆内毒素定量。结果　酒精性脂肪肝、酒精性肝炎、酒精性肝硬化内毒素血症的发病率分别为 1 2 1 2 %、55 55 %及68 0 1 % ,高于正常对照组 (9 0 0 % ) ,酒精性肝炎、酒精性肝硬化与正常对照组比较差异显著 (P <0 .0 1 )。酒精性脂肪肝、酒精性肝炎、酒精性肝硬化血浆内毒素含量较正常对照组相比升高 ,后二者同正常对照组比较差异显著 (P <0 .0 1 )。结论　酒精性肝病患者内毒素血症发病率增高 ,纠正内毒素血症治疗 ,对酒精性肝病恢复有重要作用     

酒精性肝病患者血清m-AST的变化及临床意义

目的 探讨酒精性肝病（ALD）患者血清天门冬氨酸氨基转移酶线粒体同工酶（m-AST）活性的变化及临床意义。方法 采用m—AST免疫比浊法测定63例ALD患者，30例健康人血清中m—AST活性水平，并计算出与天门冬氨酸氨基转移酶（L-AST）活性的比值及m—AST升高百分比。结果 ALD患者血清m—AST活性水平显著高于正常人（P〈0．01），人院2周酒精性脂肪肝（AFL）患者病情好转者，血清m—AST水平下降（P〈0．01），酒精性肝炎（AH））及酒精性肝硬化（AC）患者下降不显著（P〉0．05）。结论 血清m—AST活性的测定及m—AsT／L—AST比值可作为ALD的早期诊断及判断病情和预后的良好指标。     

病患者血清免疫球蛋白及T淋巴细胞亚群检测及其意义

目的　通过对不同肝病患者与正常对照组外周血清免疫球蛋白及T淋巴细胞亚群的检测 ,探讨肝病患者的机体免疫状态及临床意义。方法　选取正常对照组 2 0例 ,慢性乙型肝炎 1 8例 ,肝硬化 2 2例 ,肝癌 1 6例 ,取外周血测定血清免疫球蛋白水平及T淋巴细胞亚群。血清免疫球蛋白应用散射比浊法 ,T淋巴细胞亚群应用流式细胞仪检测。结果　与正常对照组相比 ,慢性肝炎、肝硬化组免疫球蛋白明显增高 (P <0 .0 5) ,肝癌组免疫球蛋白下降 (P<0 .0 5)。与正常对照组比较 ,慢性肝炎、肝硬化、肝癌的CD4 下降 (P <0 .0 5) ,CD8升高 (P <0 .0 5) ,CD4 /CD8比值明显降低 ,CD3略有下降。结论　肝病患者存在免疫功能紊乱 ,监测其免疫功能对追踪此类肝病演变及通过纠正免疫紊乱指导肝病治疗有重要意义     

Nutrition and alcoholic liver disease

While the rate of malnutrition is relatively modest in alcoholic patients without alcoholic liver disease, the rate of malnutrition is virtually 100% in patients with alcoholic hepatitis and/or alcoholic cirrhosis. The reasons for malnutrition in the alcoholic hepatitis patient include various factors such as anorexia, poor diet, malabsorption, and altered metabolic state. When the patient is hospitalized, the malnutrition frequently worsens because of fasting for tests, continued anorexia, and complications such as gastrointestinal bleeding. Patients with severe acute hepatitis appear to be both hypermetabolic and hypercatabolic, whereas data are much more conflicting concerning patients with more stable liver disease. Most studies suggest that patients with alcoholic liver disease require at least 60 g of protein per day to maintain positive nitrogen balance. Consistent alterations in plasma amino acid profiles occur in alcoholic liver disease, and specialized nutritional formulations have been devised to correct this amino acid profile with the intent of improving overall nutritional status, hepatic encephalopathy, and mortality. The effects of nutritional support (including use of specialized products) on outcome, on acute hepatic encephalopathy, and on chronic or latent portal systemic encephalopathy are reviewed.     

慢性肝炎肝硬化及原发性肝癌患者血清肿瘤坏死因子-α及白细胞介素-10水平变化

目的观察慢性肝炎、肝硬化以及原发性肝癌血清肿瘤坏死因子受体、白细胞介素-10水平的变化。方法回顾性分析2010年1月-2011年12月某院收治的63例肝炎肝硬化患者和57例原发性肝癌患者的血清检验资料,分析肿瘤坏死因子-α(TNF-α)及白细胞介素-10(IL-10)水平变化。结果①慢性肝炎肝硬化Child C级患者TNF-α水平(1.32±0.12)高于ChildB级(1.86±0.19)、A级(2.35±0.32),比较差异有统计学意义(P﹤0.05);慢性肝炎肝硬化Child A级患者IL-10水平(0.037±0.010)高于Child B级(0.024±0.009)、C级(0.013±0.004),比较差异有统计学意义(P﹤0.05)。②原发性肝癌组患者血清TNF-α水平(3.56±0.15)高于慢性肝炎肝硬化组患者(2.32±0.22)、对照组患者(0.63±0.10),比较差异有统计学意义(P﹤0.05);原发性肝癌患者组血清IL-10水平(0.014±0.009)低于慢性肝炎肝硬化组患者(0.027±0.012)、对照组患者(0.046±0.004),比较差异有统计学意义(P﹤0.05)。结论TNF-α和IL-10均参与慢性肝炎肝硬化和原发性肝癌的病理过程,TNF-α水平变化趋势与疾病严重程度一致,IL-10水平变化趋势与疾病严重程度相反。     

Delta virus and hepatitis B surface antigen in chronic liver diseases.

This work was carried out on 45 patients with chronic liver diseases, including 24 cases of liver cirrhosis and 21 cases of chronic hepatitis. Their ages ranged from 2 to 15 years (median 5). All cases were examined clinically and assessed biochemically for liver function tests. Serological studies were performed to detect hepatitis B surface antigen (HBsAg) and delta IgG antibody (IgG anti-HD) using Enzyme Immunoassay (EIA) technique. The study showed that IgG anti-HD was detected in 8.9% of cases with chronic liver diseases (all positive cases were with liver cirrhosis). On the other hand, HBsAg was detected in 53.3% of cases (54.2% of them with cirrhosis and 45.8% with chronic hepatitis) with no significant association between HBsAg positivity and type of hepatic illness. Moreover, IgG anti-HD was positive in only 4.2% of HBsAg positive cases, while 14.3% of HBsAg negative cases were positive for IgG anti-HD. A significant association was also found between delta positivity and serum glutamic oxaloacetic transferase level (SGOT). We concluded that chronic delta hepatitis appeared to be more severe than other types of chronic viral hepatitis, as all delta positive cases were with liver cirrhosis and had elevated SGOT levels. Screening of delta markers in addition to hepatitis B viral markers could improve the understanding of a number of obscure cases of chronic hepatic illnesses and would help in the control of HBV and consequently HDV infection in the general population.     

High prevalence of anti-hepatitis delta virus antibody in chronic liver disease in Somalia.

We have assessed the prevalence of hepatitis delta virus (HDV) infection in people with histologically proven chronic liver disease living in Somalia. Among 104 patients studied (14 with chronic persistent hepatitis, 74 with chronic active hepatitis, and 16 with active cirrhosis), 52 were positive for hepatitis B surface antigen; of these, 26 (50%) carried anti-delta antibodies. HDV infection was detected more frequently in sera from hepatitis B e antigen (HBeAg) negative patients (60.9%) than in HBeAg positive patients (9.1%). Using the dot-blot hybridization technique, serum hepatitis B virus deoxyribonucleic acid was revealed in 73.1% of patients without HDV infection, while it was detected in only 7.7% of anti-delta positive patients. It is concluded that HDV is strongly associated with chronic liver disease in Somalia.     

血清肝细胞生长因子水平变化与肝病的相关性探讨

目的：评价血清中肝细胞生长因子（HGF）水平与肝硬化、肝癌和慢性肝炎的关系,探讨血清HGF水平作为肝脏疾病临床指标的价值。方法：采用固相酶联免疫吸附法（ELISA）检测血清中HGF的水平。结果：肝硬化患者的HGF水平显著高于正常对照组（P〈0.01）,肝癌（HCC）和慢性肝炎（CH）患者的HGF水平明显高于正常对照组（P〈0.05）。结论：HGF水平检测可作为肝脏疾病临床诊断和治疗的有价值指标。     

Cytotoxic T-lymphocyte antigen-4 A49G polymorphism is associated with susceptibility to and severity of alcoholic liver disease in Italian patients

AIMS: To determine whether the functional A49G polymorphism of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a T-cell surface molecule that modulates T-lymphocyte activation and influences the risk of developing alcohol-induced autoantibodies, plays a role in susceptibility to alcoholic liver disease (ALD) and influences disease severity in Italian alcohol abusers. METHODS: One hundred and eighty-three patients with chronic ALD (61 cirrhosis), 115 end-stage HCV cirrhosis, 102 non-alcoholic fatty liver disease (NAFLD), 93 healthy subjects and 43 heavy drinkers without liver disease were studied. CTLA-4 gene polymorphism was analysed by restriction analysis. RESULTS: The frequency of the CTLA-4 polymorphism was higher in patients with ALD than in patients with HCV chronic hepatitis and NAFLD, healthy subjects (P < 0.0001), and heavy drinkers without liver disease (P = 0.02). In patients with ALD, homozygosity for the CTLA-4 polymorphic allele (G/G genotype) was more represented in subjects with cirrhosis (P = 0.047), and independently associated with the risk of cirrhosis (OR 3.5; P = 0.03). CONCLUSIONS: The CTLA-4 polymorphic G allele, probably by interfering with the immune response, may confer susceptibility to ALD and, in homozygous state, to alcoholic cirrhosis.     

125例慢性乙肝病毒感染住院患者临床特征分析

目的通过调查分析某院慢性HBV感染住院患者的临床特征,为制定传染病防制对策提供参考依据。方法采用回顾性描述研究的方法,调查患者的一般情况、临床表现、病程、外周血血小板检测结果等。结果慢性乙肝的发病年龄以20~35岁居多,肝硬化和肝癌均在35岁以上;临床表现:慢性乙肝以乏力、纳差为主,肝硬化除乏力纳差外,腹胀明显,肝癌除乏力外,肝区痛较为突出;三者均有不同程度的外周血血小板减少,特别是肝硬化患者血小板减少最为明显。结论慢性HBV感染危害大,应积极推广成年人乙肝疫苗的预防接种;定期作好健康体检,及早诊断,及时治疗,以阻断HBV的持续感染。     

Decreased serum selenium in alcoholics as related to liver structure and function

Serum selenium was evaluated in relation to hepatic structure and function in 46 alcoholics with diagnostic liver biopsy classified into 4 groups by hepatic histology. Their serum selenium concentration varied from 12 to 88 micrograms/l and was lower (p less than 0.001) in all groups of alcoholics, ie patients with normal liver (53.0 +/- 20.7 micrograms/l, mean +/- SD), fatty liver (55.8 +/- 21.2 micrograms/l), alcoholic hepatitis (46.0 +/- 14.1 micrograms/l), and cirrhosis (41.1 +/- 12.8 micrograms/l), than in 25 healthy controls (88.7 +/- 11.0 micrograms/l). Serum selenium level was related to the severity of liver disease, and most reduced in subjects with decompensated alcoholic cirrhosis. Their serum selenium level (29.2 +/- 13.7 micrograms/l) was below (p less than 0.05) that obtained in alcoholics with normal liver and fatty liver respectively. Both inadequate dietary selenium intake and alcohol-induced changes in hepatic structure and function may have contributed to the decrease of serum selenium in the subjects studied.     

Vitamin E deficiency in adults with chronic liver disease

In order to determine the frequency of vitamin E deficiency in adults with chronic liver disease, we measured serum vitamin E concentrations and calculated the ratio of serum vitamin E to total serum lipids (E/lipids) in forty-two patients with primary biliary cirrhosis (PBC) (Group A), fifteen patients with other forms of chronic liver disease (Group B), and twenty-five healthy adult control subjects (Group C). Although the mean serum vitamin E concentration did not differ significantly among the three groups, the ratio of serum vitamin E/lipids was significantly lower in Group A than Groups B and C. Vitamin E deficiency, as defined by the ratio of serum vitamin E/lipids below 0.8 mg/gm, was present in seven (17%) Group A and one (7%) Group B patients. Serum cholylglycine, sulfated lithocholate conjugates, and bilirubin were significantly higher and the mean duration of symptomatic primary biliary cirrhosis was significantly longer (6.6 vs 2.3 years) in the vitamin E-deficient compared to the vitamin E-sufficient Group A patients. Our study demonstrates that vitamin E deficiency may occur in adults with severe, prolonged cholestatic liver disease.