-238 G>A polymorphism of tumor necrosis factor alpha gene (TNFA) is associated with alcoholic liver cirrhosis in alcoholic Spanish men

BACKGROUND: The tumor necrosis factor alpha gene (TNFA) has been recently associated to alcoholic steatohepatitis. We have analyzed the distribution of genotypes and alleles of two polymorphisms at positions -238 and -308 in the promoter region of the TNFA gene in a Spanish male population of alcoholics with and without alcoholic liver cirrhosis. METHODS: 149 male alcoholics (84 without alcoholic liver disease, and 65 with alcoholic liver cirrhosis) and 90 control subjects were included. Genotyping was done by polymerase chain reaction and digestion with restriction enzymes. RESULTS: No significant differences in the distribution of genotypes and alleles of the -308 TNFA gene polymorphism were observed between alcoholics and non-alcoholics, or between alcoholics with liver cirrhosis and those without liver disease. However, we found an association between the -238 TNFA polymorphism and alcoholic liver cirrhosis; the frequency of the heterozygous genotype being significantly higher in alcoholics with cirrhosis than in those without liver damage. CONCLUSION: The -238 TNFA-A allele is associated with a higher risk to develop alcoholic liver cirrhosis. This polymorphism could be considered as a genetic factors that confer predisposition to suffer liver cirrhosis in the alcoholic population of Castile and León.     

Hemodynamics in the immediate post-transplantation period in alcoholic and viral cirrhosis

AIM:To study the hemodynamics in the immediate post transplant period and compare patients with alcoholic vs viral cirrhosis. METHODS:Between 2000-2003,38 patients were transplanted for alcoholic cirrhosis and 28 for postviral cirrhosis.Heart rate(HR),central venous pressure(CVP), mean arterial pressure(MAP),pulmonary capillary wedge pressure(PCWP),cardiac index(CI),systemic vascular resistance index(SVRI),pulmonary artery pressure(PAP),and pulmonary vascular resistance index(PVRI)were measured immediately ...     

Muscle hematoma： A critically important complication of alcoholic liver cirrhosis

An iliopsoas hematoma can occur either spontaneously or secondary to trauma or bleeding tendency due to hemophilia and anticoagulant therapy. Although liver cirrhosis is commonly associated with coagulopathy, iliopsoas hematoma is very rare. We herein, present a case of bilateral iliopsoas hematoma in a patient with alcoholic cirrhosis, and review the literature on muscle hematoma associated with cirrhosis. A 56-year-old man with alcoholic cirrhosis was admitted in a state of shock with anemia. The cause of anemia could not be detected, and the patient was treated conservatively. The site of bleeding was not detected with either gastroduodenal endoscopy or upper abdominal computed tomography, the latter of which did not include the iliopsoas muscle. He died on the 10th day of admission and bilateral iliopsoas hematomas were found on autopsy. An iron stain was positive in the iliopsoas muscle. Eight cases of muscle hematoma associated with cirrhosis, including the present case, were found in a review of the literature. Four of these cases involved the rectus abdominis muscle, 3 involved the iliopsoas muscle and 1 involved combined muscles. Alcoholic cirrhosis accounted for 75% of the cases. One case （12.5%） was associated with virus- related cirrhosis, and another with combined virus- and alcohol-related cirrhosis. The mortality rate was 75% despite early diagnosis and low risk scores for cirrhosis. Muscle hematoma in patients with cirrhosis is closely related to alcoholism, and the mortality rate of the condition is extremely high. In conclusion, muscle hematoma should be recognized as an important complication of cirrhosis.     

S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial

BACKGROUND/AIM: The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis. METHODS: A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg/day, orally) or placebo for 2 years. All patients had alcoholic cirrhosis, and histologic confirmation of the diagnosis was available in 84% of the cases. Seventy-five patients were in Child class A, 40 in class B, and 8 in class C. Sixty-two patients received AdoMet and 61 received placebo. RESULTS: At inclusion into the trial no significant differences were observed between the two groups with respect to sex, age, previous episodes of major complications of cirrhosis, Child classification and liver function tests. The overall mortality/liver transplantation at the end of the trial decreased from 30% in the placebo group to 16% in the AdoMet group, although the difference was not statistically significant (p = 0.077). When patients in Child C class were excluded from the analysis, the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group (29% vs. 12%, p = 0.025), and differences between the two groups in the 2-year survival curves (defined as the time to death or liver transplantation) were also statistically significant (p = 0.046). CONCLUSIONS: The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis, especially in those with less advanced liver disease.     

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data

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Association of the epsilon 2 allele of APOE gene to hypertriglyceridemia and to early-onset alcoholic cirrhosis

Background: The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease. The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis. Methods: In a case and control study, 86 patients with AC divided into hyperlipidemic (H) and non‐hyperlipidemic (non‐H) groups, and 133 healthy individuals (C) matched by age and sex were studied. Lipid profile and liver function tests were measured by enzymatic methods. The APOE genotypes were identified by PCR‐RFLP′s. Results: A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein‐cholesterol (HDL‐c) was detected in young‐aged patients (31.2 ± 6.2 years old vs. 46.3 ± 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non‐H group. Conclusions: This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process.     

Polymorphism of N-acetyltransferase 2 gene and the susceptibility to alcoholic liver cirrhosis: interaction with smoking

Background: Polymorphism of N‐acetyltransferase 2 gene was reported to be associated with the susceptibility of various cancers and liver diseases. However, its relationship to alcoholic liver disease is controversial and open to debate. The aim of this study was to evaluate the relationship of NAT2 genetic polymorphisms and the susceptibility to alcoholic liver cirrhosis (ALC) in Chinese, with special emphasis on the interaction of smoking. Methods: Peripheral white blood cell DNA from 148 patients with ALC, 104 patients with long‐term alcoholic drinking but without cirrhosis (ANC) and 209 healthy controls were genotyped for NAT2 using a polymerase chain reaction–restriction fragment length polymorphism method. The possible confounding factors were included for analysis. Results: There was no statistical difference in the frequency of NAT2 genotype or NAT2 acetylator status among the 3 groups. However, among the chronic alcoholic drinkers, the rapid acetylators with smoking habits had higher percentage of ALC than those without smoking habit (18.9% vs. 9.5%, p = 0.002). The adjusted odds ratio for rapid acetylator smoker to have ALC was 3.45 (95% CI = 1.53 to 7.76, p = 0.003). Conclusions: The genetic factor, NAT2 polymorphism, may interact with environmental factor, smoking, to confer different susceptibilities to ALC. NAT2 rapid acetylators with smoking habit may increase the risk of ALC in Chinese.     

A prospective study of alcoholic liver disease and mortality

We report the 10-year survival of 510 patients with a histological diagnosis of alcoholic liver disease. Eight centres in Scotland and North England contributed to this study. Information was available on 92% of the initial cohort. Age was important, with each decade increasing mortality by 55%. A highly significant interaction between sex and histology was observed with a marked survival benefit for males with non-cirrhotic alcoholic liver disease, while in cirrhotic subjects the pattern was reversed. Patients with decompensated liver disease had a relative increase in mortality in excess of 86% while the increase in mortality for alcoholic hepatitis, 'active' cirrhosis and 'inactive' cirrhosis were 52%, 57% and 91% relative to fatty liver. Alcohol intake at the time of diagnosis did not influence outcome. This study emphasises yet again the increased mortality rate of individuals abusing alcohol compared with the general population.     

Post-transplantation outcome in non-alcoholic steatohepatitis cirrhosis: Comparison with alcoholic cirrhosis

Introduction and objectivesNon-alcoholic steatohepatitis (NASH) indication of liver transplant (LT) has increased recently, whereas alcoholic cirrhosis remains a major indication for LT. To characterize NASH-related cases and to compare the post-transplant outcome of these two conditions represents our major objective.Material and methodsPatients undergoing LT for NASH between 1997 and 2016 were retrieved. Those transplanted between 1997 and 2006 were compared to an “age and LT date” matched group of patients transplanted for alcoholic cirrhosis (ratio 1:2). Baseline features and medium-term outcome measures were compared.ResultsOf 1986 LT performed between 1997 and 2016, 40 (2%) were labeled as NASH-related indications. NASH-related cases increased initially (from 0.8% in 1997–2001 to 2.7% in 2002–2006) but remained stable in subsequent years (2.3%). Hepatocellular carcinoma (HCC) prevalence was greater in NASH-vs alcohol-related cirrhosis (40% vs 3%, p = 0.001). The incidence of overweight, obesity, arterial hypertension, dyslipidemia, diabetes, hyperuricemia, renal insufficiency and cardiovascular (CV) disease was similar in both groups at 5 years post-LT. Five-year survival was higher in NASH but without reaching statistical significance (83% vs 72%, p = 0.21). The main cause of mortality in NASH-LT patients was HCC recurrence.ConclusionMost previously considered cryptogenic cases are actually NASH-cirrhosis. While the incidence of this indication is increasing in many countries, it has remained relatively stable in our Unit, the largest LT center in Spain. HCC is common in these patients and represents a main cause of post-transplant mortality. Metabolic complications, CV-related disease and 5-yr survival do not differ in patients transplanted for NASH vs alcohol.     

MELD-Na评分对肝硬化患者血脂和预后的影响

目的 探讨肝硬化患者血脂水平与终末期肝病模型（MELD-Na）评分的相关性。方法 回顾性分析2011年1月至2012年12月我院收治的肝硬化患者120例,根据患者入院时MELD-Na评分将患者分为MELD-Na高分组(≥18分)和MELD-Na低分组（<18分）,比较两组患者血脂水平和临床预后。结果 35例高分组和85例低分组患者血清总胆固醇分别为[（3.90±1.13） mmol/L 和（5.49±1.47） mmol/L,P<0.001];甘油三脂分别为[（0.9±0.3） mmol/L 和（1.3±0.4） mmol/L,P<0.001];高密度脂蛋白分别为[（1.0±0.2） mmol/L 和（1.3±0.3） mmol/L,P<0.001];低密度脂蛋白分别为[（1.8±0.5） mmol/L 和（2.6±0.5） mmol/L,P<0.001];载脂蛋白A1分别为[（120.5±17.4） mmol/L 和（135.8±16.5） mg/dl,P<0.001];载脂蛋白B分别为[（69.1±14.7） mmol/L 和（94.7±14.7） mg/dl,P<0.001];高分组患者3年内肝性脑病、肝肾综合征、消化道出血和死亡发生率分别为37.1%、25.7%、48.6%和34.3%,显著高于低分组的1.2%、2.4%、4.7%和1.2%。结论 MELD-Na评分明显与肝硬化患者血脂水平相关。     

肝硬化患者营养状态的主观全面营养评估

目的将主观全面营养评估(subjective global assessment,SGA)用于评估肝硬化患者的营养状况,分析患者的营养状况与肝脏功能状态之间的关系。方法选取2010年1月-2013年1月入住遂宁市中心医院消化内科的177例肝硬化患者,入院后48~72 h内完成对患者入院时营养状况进行评价,并随访半年。将患者Child-Pugh评分情况与SGA营养状况相比较。统计分析不同营养状态患者的体质量、体质量指数(BMI)、中臂围、三头肌皮褶厚度以及饮食情况。结果严重营养不良的患者体质量、BMI、中臂围、三头肌皮褶厚度与营养状况良好的患者相比差异有统计学意义(P0.05)。132例患者饮食合理,且营养状况均良好,但45例不合理饮食的患者仅有2例营养状况良好,17例轻-中度营养不良,26例严重营养不良。经SGA评估患者营养状况良好的患者109例,其中Child A 65例,Child B 44例。重度营养不良患者26例,其中Child B 15例,Child C 11例。结论 SGA可用于评估肝硬化患者的营养状态。患者营养状态与肝脏储备功能Child分级相关。     

The role of TAP1 and TAP2 gene polymorphism in idiopathic bronchiectasis in children

Bronchiectasis is characterized by permanent changes in the structure and function of the airways. Its cause cannot be identified in some cases. A genetic disease can predispose to bronchiectasis in our country, where consanguinity of parents is common. Transporter associated with antigen presentation (TAP) deficiency syndrome is characterized by recurrent bacterial lower respiratory tract infections, which cause bronchiectasis. Our aim was to document the relationship between idiopathic bronchiectasis and TAP gene polymorphisms. Forty-four patients with idiopathic bronchiectasis and 100 healthy individuals as the control group were included. DNA was extracted and gene polymorphisms for TAP1 and TAP2 were studied. When compared to healthy controls, in the patient group, Ile/Ile genotype was decreased and Ile/Val genotype was increased in TAP1-333 polymorphism analysis; Asp/Asp and Gly/Gly genotypes were decreased and Asp/Gly frequency was increased in TAP1-637 polymorphism analysis; Ile/Val genotype was increased and Ile/Ile genotype was decreased in TAP2-379 polymorphism analysis; and Thr/Thr genotype frequency was decreased and Thr/Ala and Ala/Ala genotypes were increased in TAP2-665 polymorphism analysis. No statistically significant difference between patient and control groups was noted only in TAP2-565 polymorphism analysis. These results indicate that TAP gene polymorphisms may have had a role in the development of bronchiectasis in our patient group. Therefore, TAP deficiency syndrome should be considered in children with idiopathic diagnosis, since early diagnosis of the disease will improve life quality and survival.     

腺苷蛋氨酸与多烯磷脂酰胆碱治疗酒精性肝硬化的疗效比较

目的探讨腺苷蛋氨酸与多烯磷脂酰胆碱治疗酒精性肝硬化的疗效。方法选取酒精性肝硬化患者92例,随机分为腺苷蛋氨酸组30例,多烯磷脂酰胆碱组30例,联合组32例,分别采用腺苷蛋氨酸、多烯磷脂酰胆碱和二者联合进行治疗,对三组患者疗效进行比较。结果与治疗前比较,治疗后三组患者各项指标均有显著变化(P0.05);且联合组各项指标变化幅度显著优于腺苷蛋氨酸组和多烯磷脂酰胆碱组,两两相比,差异有统计学意义(P0.05);联合组总有效率(96.88%)明显优于腺苷蛋氨酸组(83.33%)和多烯磷脂酰胆碱组(73.33%);三组比较,差异有统计学意义(P0.05)。结论采用多烯磷脂酰胆碱与S-腺苷蛋氨酸治疗酒精性肝硬化,两药均能显著改善肝功能,但二者联合应用后,改善程度及治疗效果均明显提高,值得临床借鉴和应用。     

Serum leptin in patients with alcoholic liver disease

BACKGROUND: The mechanisms by which overweight makes the liver more susceptible to alcoholic liver injury remain to be determined. Therefore, we conducted the following studies to further elucidate the role of leptin in the pathogenesis of steatosis and cirrhosis caused by chronic alcohol consumption in human beings. METHODS: Two-hundred nine consecutive patients with alcoholic liver disease were studied. Serum leptin concentrations were measured by using radioimmunoassay, and the relationships between serum leptin level and liver lesions were studied. Statistical analysis used logistic regressions. RESULTS: When serum leptin, serum cholesterol, and body mass index (BMI) were considered together in the multiple logistic regression analysis, compared with patients with severe steatosis, serum leptin remains significantly lower in patients without steatosis (p<0.05) and in patients with mild or moderate steatosis (p<0.05). When age, serum leptin, serum cholesterol, and steatosis grade were considered together in the logistic regression analysis, serum leptin (p<0.01) and age (p<0.02) were positively and independently correlated with the presence of cirrhosis. After BMI introduction in the statistical model, serum leptin was no more correlated with the presence of cirrhosis. CONCLUSION: In patients with alcoholic liver disease, serum leptin is independently correlated with steatosis grade and might play an important role in severity of fibrosis as fatty liver is more vulnerable than normal liver to factors that lead to fibrosis.     

Alcohol metabolism and cardiovascular response in an alcoholic patient homozygous for the ALDH2*2 variant gene allele

BACKGROUND: Alcohol metabolism is one of the biological determinants that can influence drinking behavior. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes involved in ethanol metabolism. Allelic variation of the ADH and ALDH genes can significantly affect vulnerability for the development of alcoholism. Homozygosity of the variant ALDH2*2 allele previously was believed to fully protect East Asian populations against the development of alcoholism. METHODS: Eighty Han Chinese alcoholics who met DSM-III-R criteria for alcohol dependence and 144 nonalcohol-dependent subjects were recruited and their data combined with data from 340 alcohol-dependent and 545 nonalcohol-dependent subjects described in an earlier report (Chen et al., 1999) to assess risk for alcoholism by logistic regression analysis. Genotypes of ADH2, ADH3, and ALDH2 were determined by polymerase chain reaction and restriction fragment length polymorphism. The ALDH2 genotype was confirmed by direct nucleotide sequencing. Blood ethanol concentration was determined by headspace gas chromatography and acetaldehyde concentration by high-performance liquid chromatography with fluorescence detection of the derivatized product. Cardiovascular hemodynamic parameters were measured by two-dimensional Doppler echocardiography and sphygmomanometry. Extracranial arterial blood flow was measured by Doppler ultrasonography. RESULTS: An alcohol-dependent patient was identified to be ALDH2*2/*2, ADH2*2/*2, and ADH3*1/*2. Following challenge with a moderate oral dose of ethanol (0.5 g/kg of body weight), the patient exhibited peak concentrations for ethanol (55.7 mg/dl) and acetaldehyde (125 microM). During 130 min postingestion, the patient generally displayed similar or even less intense cardiovascular hemodynamic alterations when compared to a previously published study of nonalcoholic individuals with ALDH2*2/*2 who had received a lower dose of ethanol (0.2 g/kg). Logistic regression analysis of the combinatorial genotypes of ADH2 and ALDH2 in 420 alcohol-dependent and 689 nonalcohol-dependent subjects indicated that risk for alcoholism was 100-fold lower for the ADH2*2/*2-ALDH2*2/*2 individuals than the ADH2*1/*1-ALDH2*1/*1 individuals. CONCLUSIONS: The gene status of ALDH2*2/*2 alone can tremendously but not completely (as thought previously) protect against development of alcohol dependence. Individuals carrying the combinatorial genotype of ADH2*2/*2-ALDH2*2/*2 are at the least risk for the disease in East Asians. Physiological tolerance or innate insensitivity to the accumulation of blood acetaldehyde following alcohol ingestion may be crucial for the development of alcoholism in individuals homozygous for ALDH2*2.     

Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis

AIM:To investigate the adipokine levels of leptin,adiponectin,resistin,visfatin,retinol-binding protein 4(RBP4),apelin in alcoholic liver cirrhosis(ALC).METHODS:Forty non-diabetic ALC patients[median age:59 years,males:35(87.5%),Child-Pugh(CP)score:median 7(5-12),CP A/B/C:18/10/12,Model for End-stage Liver Disease(MELD):median 10(6-25),follow-up:median 32.5 mo(10-43)]were prospectively included.The serum adipokine levels were estimated in duplicate by ELISA.Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis.Pearson’s rank correlation coefficient was used to assess possible associations with adipokine levels.Univariate and multivariate Cox regression analysis was used to determine independent predictors for overallsurvival.RESULTS:Body mass index:median 25.9(range:20.1-39.3),fat:23.4%(7.6-42.1),fat mass:17.8(5.49-45.4),free fat mass:56.1(39.6-74.4),total body water(TBW):40.6(29.8-58.8).Leptin and visfatin levels were positively associated with fat mass(P0.001/P=0.027,respectively)and RBP4 with TBW(P=0.025).Median adiponectin levels were significantly higher in CPC compared to CPA(CPA:7.99±14.07,CPB:7.66±3.48,CPC:25.73±26.8,P=0.04),whereas median RBP4 and apelin levels decreased across the spectrum of disease severity(P=0.006/P=0.034,respectively).Following adjustment for fat mass,visfatin and adiponectin levels were significantly increased from CPA to CPC(both P0.001),whereas an inverse correlation was observed for both RBP4 and apelin(both P0.001).In the multivariate Cox regression analysis,only MELD had an independent association with overall survival(HR=1.53,95%CI:1.05-2.32;P=0.029).CONCLUSION:Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis.