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Cirrhosis
Kinds of Cirrhosis Terms modified by Cirrhosis Selected AbstractsALPHA-1-ANTITRYPSIN DEFICIENCY IN A 78-YEAR-OLD WOMAN WITH ISOLATED LIVER CIRRHOSISJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2010Nathalie Voide MD No abstract is available for this article. [source] OPEN HEART SURGERY IN A PATIENT WITH LIVER CIRRHOSIS AND THROMBOCYTOPENIAANZ JOURNAL OF SURGERY, Issue 1 2000Hitoshi Yaku No abstract is available for this article. [source] Peroxisome proliferator-activated receptor-, as emerging target in liver diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2010Bernd Schnabl Abstract Liver fibrosis is characterized by an excessive deposition of extracellular matrix (ECM) proteins that occurs in chronic liver disease of any origin, including nonalcoholic steatohepatitis (NASH), alcohol abuse, and viral hepatitis. Cirrhosis occurs with the development of regenerating nodules of hepatocytes and is a major health burden worldwide. Patients with decompensated liver cirrhosis have a poor prognosis, with liver transplantation often being necessary. The current treatment paradigm for patients with hepatic fibrosis is to treat the underlying liver disease. However, if this cannot be achieved, there are currently no effective antifibrotic treatments for patients with chronic liver diseases. With the advent of basic molecular technology providing insight into the mechanisms of the development of hepatic fibrosis, there is now an opportunity to develop therapeutic interventions for human clinical use. In this review, the function of peroxisome proliferator-activated receptor-, (PPAR ,) will be summarized with a special emphasis on ligand activation as potential use in liver disease. Drug Dev Res 2009. © 2009 Wiley-Liss, Inc. [source] Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C,HEPATOLOGY, Issue 4 2010Robert Roomer Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C virus (HCV) infection is a common cause of dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and can be attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to identify potential risk factors for infections during HCV treatment. In this single-center cohort study, 2,876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions, and potential risk factors for infection during HCV treatment. The baseline mean absolute neutrophil count (ANC) was 3,420 cells/,L, and 16 patients had a baseline ANC of <1,500 cells/,L. During treatment, neutropenia, which was defined as ANC <750 cells/,L, was observed in 95 patients (29.7%) and ANC <375/,L was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. Multivariate logistic regression analysis revealed that age >55 years (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.19-3.56, P = 0.01) and baseline hyperglycemia (OR 2.17, 95% CI 1.15-4.10, P = 0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease were not risk factors for infection. Conclusion: Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus have a greater risk of developing infections during HCV treatment. (HEPATOLOGY 2010) [source] Adenosine reverses a preestablished CCl4 -induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in ratsHEPATOLOGY, Issue 4 2001Rolando Hernández-Muñoz Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl4 -induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl4 (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of ,-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl4 discontinuation (5 weeks), increased persitance of ,-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl4 withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl4 -induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery. [source] New insights into the pathobiology of portal hypertensionHEPATOLOGY RESEARCH, Issue 10 2009Praveen Guturu Portal Hypertension is a frequent complication of cirrhosis and causes significant morbidity and mortality. Increased intrahepatic resistance is the primary factor but portal hypertension is also associated with changes in systemic and porto-sytemic collateral circulation. Cirrhosis is a state of vasoregulatory imbalance with excess vasoconstrictors and less vasodilators in hepatic circulation and the reverse is true for systemic circulation. Multiple pathophysiologic mechanisms including endothelial dysfunction, sinusoidal remodeling and angiogenesis are involved in increasing resistance in hepatic vascular bed. Current evidence suggests that these changes in vasoreactivity contribute to a significant proportion of intrahepatic vascular resistance and that they are reversible, providing an attractive target for therapeutic intervention. [source] Liver Cirrhosis and InfectionHPB, Issue S1 2005Article first published online: 17 FEB 200 First page of article [source] Hepatocellular carcinoma in Sydney South West: late symptomatic presentation and poor outcome for mostINTERNAL MEDICINE JOURNAL, Issue 8 2007L. Gellert Abstract Background: Hepatocellular cancer (HCC) is a serious complication of cirrhosis and chronic hepatitis B infection. The aim of the study was to determine the characteristics of patients with HCC presenting within the South West Sydney area, including an analysis of the rates and benefits of hepatocellular surveillance. Methods: Data from patients with HCC presenting to Liverpool and Bankstown Hospitals from July 1993 to June 2003 were analysed retrospectively, predominantly from hospital records. Results: Of the 151 HCC patients, 41% were Asian born. Most of the patients required an interpreter. Chronic viral hepatitis infection was present in 91 patients, of whom only 7% had previously received antiviral therapy. Alcohol alone was considered responsible in 31 patients. Cirrhosis could be documented in 58% of patients. Most of the patients (75%) presented symptomatically. The median survival was 5.1 months. When HCC was detected by surveillance, the tumours were slightly but not significantly more likely to be operable and the patients tended to be offered some form of active treatment more frequently. Multivariate analysis identified detection by surveillance, lower Child,Pugh score, smaller tumour size and eligibility for some form of treatment to be associated with a more favourable outcome. Conclusion: We observed low rates of surveillance for HCC, low recognition of cirrhosis before development of HCC and low rates of prior treatment of viral hepatitis. The poor outcome of HCC in the small group who had some sort of community surveillance is also a concern requiring further investigation. [source] Dysphagia and Unexpected Myasthenia Gravis Associated with Primary Biliary Cirrhosis, Ulcerative Colitis and VitiligoJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2004Peter McCann MRCP No abstract is available for this article. [source] QT Interval Correction in Patients with CirrhosisJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2007ANDREA ZAMBRUNI M.D. Introduction: QT interval prolongation is a common electrophysiological abnormality in patients with cirrhosis. As QT interval varies with the heart rate, many QT correction formulas have been proposed, the Bazett's one being the most criticized because it overcorrects the QT interval and may be misleading. This study focused on the QT-RR relationship in patients with cirrhosis to derive a population-specific QT correction formula. Methods: One hundred cirrhotic patients of different etiology and severity and 53 healthy controls comparable for age and sex were enrolled. The QT-RR relationship was analyzed in patients by five regression analysis models to derive the population-specific QT-RR equation. The QTc was calculated and compared with those calculated by four common QT correction formulas (Bazett, Fridericia, Framingham, and Hodges). The correlation coefficient QTc-RR was calculated as a measure of the independence of QTc from the original RR interval. Results: In patients the QT-RR relationship was best described by the power equation "QT = 453.65 × RR1/3.02" (R2= 0.41), similar to the Fridericia's formula. Bazett's formula led to the longest QTc (P < 0.0001), which was still significantly influenced by the RR interval (R =,0.39; P < 0.0001), while the estimated equation led to a QTc value not influenced by RR (R =,0.014). Conclusion: Bazett's correction should be avoided in patients with cirrhosis because it still provides a rate-dependent QTc value and might be misleading, particularly when assessing the overall preoperative cardiac risk and the effect of drugs affecting the QT interval. In its place, our formula or that of Fridericia can be confidently employed. [source] Evaluation of Quantitative Portal Venous, Hepatic Arterial, and Total Hepatic Tissue Blood Flow Using Xenon CT in Alcoholic Liver Cirrhosis,Comparison With Liver Cirrhosis Related to Hepatitis C Virus and Nonalcoholic SteatohepatitisALCOHOLISM, Issue 2010Hideaki Takahashi Background/Aims:, Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis related to nonalcoholic steatohepatitis (NASH), (NASH-LC), and hepatitis C virus (HCV), (C-LC). Methods:, Xe-CT was performed on 22 patients with AL-LC, 7 patients with NASH-LC, and 24 patients with C-LC. Severity of LC was classified according to Child-Pugh classification. Correlations between hepatic TBF, Child-Pugh classification, and indocyanin green retention (ICG) rate after 15 minutes (ICG15R) were examined. Correlations of hepatic TBF in Child-Pugh class A to AL-LC, NASH-LC, and C-LC were also examined. Results:, Portal venous TBF (PVTBF) displayed a significant negative correlation with Child-Pugh score and ICG15R (r = ,0.432, p < 0.01, r = ,0.442, p < 0.01, respectively). Moreover, ICG15R displayed a significant positive correlation with Child-Pugh score (r = 0.661, p < 0.001). Meanwhile, mean PVTBF and total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC (p < 0.05). Mean PVTBF was significantly lower in Child-Pugh class A to AL-LC and NASH-LC than in that to C-LC (p < 0.05). Similarly, mean THTBF was significantly lower in Child-Pugh class A to NASH-LC than in that to C-LC (p < 0.05). Conclusions:, Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease. [source] A Functional Polymorphism of the NFKB1 Gene Increases the Risk for Alcoholic Liver Cirrhosis in Patients With Alcohol DependenceALCOHOLISM, Issue 11 2009Miguel Marcos Background:, The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-,B, the NF-,B inhibitor , (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-, in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC. Methods:, A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the ,94ins/delATTG NFKB1, 3,-UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance. Results:, We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC. Conclusions:, The deletion allele of the ,94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data. [source] Understanding and Treating Patients With Alcoholic Cirrhosis: An UpdateALCOHOLISM, Issue 7 2009Giovanni Addolorato Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease (ALD) and one of the main causes of death among alcohol abusers. The aim of this review was to provide an update on alcoholic cirrhosis, with an emphasis on recent findings. Increased alcohol consumption in developing countries is expected to increase cirrhosis mortality. There is a need, therefore, to develop new approaches to the prevention of ALD, including more attention to co-factors that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection, and smoking). Furthermore, a better understanding of the pathological mechanisms on the basis of alcohol cirrhosis represents a cornerstone in order to develop new pharmacological treatments. Inflammatory and immune responses along with oxidative stress and alterations in adipokine secretion might contribute in different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may be considered in a motivated patient with nutritional support. Current studies do not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally, achieving total alcohol abstinence should represent the main aim in the management of patients affected by any stage of cirrhosis. In the last decades, several drugs able to increase abstinence and prevent alcohol relapse have been evaluated and some of them have obtained approval for alcohol dependence. Patients with alcoholic cirrhosis; however, are usually excluded from such treatments. A recent study demonstrated the efficacy and safety of baclofen in inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent patients with cirrhosis. All together the information available suggests the need of a multimodal approach in the clinical management of these patients. [source] Low Bone Mineral Density and Impaired Bone Metabolism in Young Alcoholic Patients Without Liver Cirrhosis: A Cross-Sectional StudyALCOHOLISM, Issue 2 2009Peter Malik Background:, Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol,s direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. Methods:, In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1,L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. Results:, In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z -score , ,2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D < 30 ng/ml). Conclusions:, Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism. [source] MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol ConsumptionALCOHOLISM, Issue 1 2009Carlo Fabris Background:, A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies. Methods:, Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification. Results:, Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002). Conclusions:, The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC. [source] Association of the ,2 Allele of Apoe Gene to Hypertriglyceridemia and to Early-Onset Alcoholic CirrhosisALCOHOLISM, Issue 4 2008Zamira H. Hernández-Nazará 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. [source] Echocardiographic features, mortality, and adrenal function in patients with cirrhosis and septic shockACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2008S. THIERRY Objectives: Cirrhosis of the liver is associated with an increased susceptibility to bacterial infections capable of causing septic shock and with a basal hyperdynamic circulatory state. The primary objective of this study was to delineate the echocardiographic characteristics and outcomes of septic shock in patients with liver cirrhosis. The secondary objective was to determine whether adrenal insufficiency, which may contribute to hyperdynamic syndrome, was more marked in patients with cirrhosis than in other patients with septic shock. Design: Prospective single-center cohort study. Patients and methods: Thirty-four patients admitted to the intensive care unit (ICU) for septic shocks were included, 14 with and 20 without liver cirrhosis. Echocardiography was performed within the first 24 h to measure the cardiac index (CI), systolic index (SI), and left ventricular ejection fraction (LVEF). A Synacthen test was performed. Results: Patients with cirrhosis had higher values for the CI (3.69±1.0 vs. 2.86±0.8 l/min/m2; P=0.02), SI (37.5±8 vs. 32.4±7 ml/m2; P=0.04), and LVEF (67±7 vs. 55.9±12%; P=0.005). ICU mortality was 53% overall, 64% in patients with cirrhosis, and 45% in patients without cirrhosis (P=0.27). Serum cortisol levels under basal conditions (H0) and after stimulation (H1) showed no significant differences between patients with and without cirrhosis. The proportion of patients with no response to Synacthen was 77% among patients with cirrhosis and 50% among patients without cirrhosis (P=0.18). Conclusion: In a population with septic shock, left ventricular function was more hyperdynamic in the subset with cirrhosis. Relative adrenal insufficiency occurred in similar proportions of patients with and without cirrhosis. [source] Clinical Characteristics of Portal Hemodynamics in Alcoholic Liver CirrhosisALCOHOLISM, Issue 2004Mami Hirata Background: Low incidence of reversal blood flow at the portal vein has been reported by measurement in larger and extrahepatic blood vessels but not in intrahepatic blood vessels in patients with liver cirrhosis. Moreover, there is little information regarding the incidence of reversal blood on the basis of the cause of liver cirrhosis. The aim of this study was to measure the reversal blood flow in the portal vein including intrahepatic branches in patients with alcoholic and viral cirrhosis. Methods: The blood flow in the portal vein and existence of portosystemic shunt were studied in 52 and 27 patients with alcoholic and viral cirrhosis, respectively, by Doppler ultrasonography. The parameters of liver function test and the prevalence of ascites and esophageal varices were compared between patients with and without reversal blood flow. Results: Reversal blood flow at the portal vein was found only in patients with only alcoholic cirrhosis (17 of 52 patients) but not in any patients with viral cirrhosis (0 of 27 patients; p < 0.05). The incidence of portosystemic ascites and red color of esophageal varices was also higher in patients with alcoholic cirrhosis with reversal blood flow in the portal vein compared with patients without reversal blood flow (p < 0.05). Conclusions: Reversal blood flow in the portal vein is a characteristic feature of alcoholic cirrhosis. The presence of reversal blood flow indicates severe liver diseases, and this feature may have prognostic importance for patients with alcoholic cirrhosis. [source] Predictive factors of bleeding related to post-banding ulcer following endoscopic variceal ligation in cirrhotic patients: a case-control studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010G. Vanbiervliet Aliment Pharmacol Ther 2010; 32: 225,232 Summary Background, Life-threatening bleeding caused by early spontaneous slippage of rubber bands has been described after variceal ligation in cirrhotic patients. Aim, To determine the predictive factors of this complication in cirrhotic patients. Methods, Among 605 patients, 21 patients (mean age 56.6 ± 13.5 years) developed 23 spontaneous band slippages with bleeding on post banding ulcer, as confirmed by endoscopy. Cirrhosis was alcoholic in 13 patients (62%), post viral hepatitis in three (14%) and from other causes in five (24%). A case-control study was performed comparing 17 from these patients who presented the complication after a first ligation with 84 of the 584 controls who underwent first endoscopic variceal ligation without bleeding complication. Results, Bleeding occurred 13.5 days ± 7.3 (2,29) following ligation. Eleven patients died following the bleeding complication (52%). Using a multivariate analysis, previous upper variceal digestive bleeding [OR 12.07, 95%CI (2.3,63.43)], peptic oesophagitis [OR 8.9, 95%CI (1.65,47.8)], high platelet ratio index (APRI) score [OR 1.54, 95%CI (1.11,2.16)] and low prothrombin index [OR 0.54, 95% CI (0.31,0.94)] were independent predictive factors of bleeding. Conclusions, Bleeding related to post-banding ulcer is a rare, but severe complication. The proposed predictive factors should be looked for and minimized before variceal ligation. [source] Outcomes of critically ill patients with cirrhosis admitted to intensive care: an important perspective from the non-transplant settingALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010S. J. Thomson Aliment Pharmacol Ther 2010; 32: 233,243 Summary Background, Hospital admissions for cirrhosis have been increasing in the United Kingdom, leading to increased pressure on intensive care (ICU) services. Outcome data for patients admitted to ICU are currently limited to transplant centre reports, with mortality rates exceeding 70%. These tertiary reports could fuel a negative bias when patients with cirrhosis are reviewed for ICU admission in secondary care. Aims, To determine whether disease severity and mortality rates in non-transplant general ICU are less severe than those reported by tertiary datasets. Methods, A prospective dual-centre non-transplant ICU study. Admissions were screened for cirrhosis and physiological and biochemical data were collected. Disease-specific and critical illness scoring systems were evaluated. Results, Cirrhosis was present in 137/4198 (3.3%) of ICU admissions. ICU and hospital mortality were 38% and 47%, respectively; median age 50 [43,59] years, 68% men, 72% alcoholic cirrhosis, median Child Pugh Score (CPS) 10 [8,11], Model for End-Stage Liver Disease (MELD) 18 [12,24], Acute Physiology and Chronic Health Evaluation II score (APACHE II) 16 [13,22]. Conclusions, Mortality rates and disease staging were notably lower than in the published literature, suggesting that patients have a more favourable outlook than previously considered. Transplant centre data should therefore be interpreted with caution when evaluating the merits of intensive care admission for patients in general secondary care ICUs. [source] The haemodynamic response to propranolol in cirrhosis with arterial hypertension: a comparative analysis with normotensive cirrhotic patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010P. Sharma Aliment Pharmacol Ther 2010; 32: 105,112 Summary Background, Cirrhosis with arterial hypertension is not uncommon. Haemodynamic alterations in these patients and the effects of beta-blocker on hepatic venous pressure gradient (HVPG) and systemic haemodynamics have not been evaluated. Aims, To compare the systemic haemodynamic alterations in hypertensive and normotensive cirrhotics, and to investigate the effects of propranolol on these parameters. Methods, A retrospective analysis of consecutive hypertensive cirrhotic patients (n = 33) who underwent haemodynamic assessment and paired HVPG measurement was done. Normotensive cirrhotics (n = 50) served as controls. Results, Hypertensive patients had a significantly higher heart rate, systemic (SVRI), and pulmonary vascular resistance. There was a significant reduction in mean arterial pressure (MAP) in the hypertensive cirrhotic group from 112 (107,130) mmHg to 95 (77,114) mmHg (P < 0.01), but no change in the normotensives. SVRI remained the same in the hypertensive cirrhotic group, but it increased in the normotensives. There was no correlation between MAP reduction and HVPG reduction. Conclusions, The frequency of HVPG response with propranolol treatment in hypertensive cirrhotics is similar to normotensive cirrhotics. Propranolol treatment reduces MAP significantly in hypertensive patients with cirrhosis. Treatment with a nonselective beta-blocker is a good strategy for hypertensive cirrhotic patients. [source] Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010K. K. SNOW Aliment Pharmacol Ther,31, 719,734 Summary Background, Primary analysis of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial showed long-term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. Aim, To assess the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms and sexual health in HALT-C patients. Methods, A total of 517 HALT-C patients received peginterferon alfa-2a (90 ,g/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores and symptoms were serially assessed by repeated-measures analyses of covariance. Results, Patients with cirrhosis (n = 427) reported lower general well-being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusion, Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164). [source] Review article: the management of hepatocellular carcinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010R. CABRERA Aliment Pharmacol Ther,31, 461,476 Summary Background, Hepatocellular carcinoma is the leading cause of death in cirrhosis. A majority of patients present at an advanced stage with poor prognosis. Aim, To review the current screening, diagnosis and management strategies involved in hepatocellular carcinoma. Methods, A literature search was performed using PubMed for publications with a predetermined search string to identify relevant studies. Results, Hepatocellular carcinoma is dramatically increasing in incidence that is mostly attributed to chronic hepatitis C and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and its clinical phenotype diabetes and obesity. Cirrhosis is the major predisposing risk factor and its presence necessitates close surveillance for hepatocellular carcinoma with serial imaging studies. Hepatocellular carcinoma can be diagnosed by its unique radiological behaviour of arterial enhancement and washout on delayed images. The Barcelona Clinic Liver Cancer staging classification system is a clinically useful algorithm for the management of patients with hepatocellular carcinoma. The simultaneous presence of cirrhosis in the patients complicates their management and monitoring for cirrhosis-related complications is important. Conclusions, Early diagnosis and definitive treatment remains the key to long-term outcome. A multidisciplinary approach is critical to the successful management of hepatocellular carcinoma. Studies combining sorafenib with locoregional or other targeted molecular therapies are likely to improve responses and outcome. [source] Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009G. T. EVERSON Summary Backgroud, The impact of virologic response on hepatic function has not been previously defined. Aim, To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) ± ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR). Methods, Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24- 13C]cholate, galactose and 99mTc-sulfur colloid were administered intravenously; [2,2,4,2- 2H]cholate, [1- 13C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath 13CO2, monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. Results, Rates of SVR were 18,26% in patients with good function by QLFTs, but ,6% in patients with poor function. Hepatic metabolism, measured by caffeine kelim (P = 0.02), antipyrine kelim (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cloral (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. Conclusion, Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM. [source] Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shuntALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007G. T. EVERSON Summary Background, Measurement of portal inflow and portal-systemic shunt using cholate clearances could be useful in monitoring patients with liver disease. Aim, To examine relationships of cholate clearances and shunt to cirrhosis and varices and to define minimal sampling requirements. Methods, Five hundred forty-eight studies were performed in 282 patients enrolled in the Hepatitis C Antiviral Long-term Treatment to prevent Cirrhosis (HALT-C) trial. Stable, non-radioactive isotopes of cholate were administered intravenously and orally, clearances (Cliv and Cloral) were calculated from [dose/area under curve (AUC)] and cholate shunt from [(AUCoral:AUCiv) x (Doseiv:Doseoral) x 100%]. Results, Cholate Cloral and cholate shunt correlated with prevalences of both cirrhosis and varices (P < 0.0001 for all). Peripheral venous sampling at 5, 20, 45, 60 and 90 min defined the minimal model. Linear regression of cholate shunt determined from five points within 90 min vs. the standard method of 14 points over 3 h yielded slope of 1.0 and intercept 0.5% (r2 = 0.98, P < 0.0001). Results were identical in the 189 validation studies (slope 1.0, intercept 0.5%, r2 = 0.99, P < 0.0001). Conclusions, Cholate Cloral and cholate shunt may be useful in monitoring patients with liver disease. The 5-point model enhances application of cholate Cloral and cholate shunt in the non-invasive assessment of the portal circulation. [source] A distinct nitric oxide and adenosine A1 receptor dependent hepatic artery vasodilatatory response in the CCl4 -cirrhotic liverLIVER INTERNATIONAL, Issue 7 2010Alexander Zipprich Abstract Increase of portal venous vascular resistance is counteracted by decrease of hepatic arterial vascular resistance (hepatic arterial buffer response). This process is mediated by adenosine in normal livers. In cirrhosis, hepatic arterial vascular resistance is decreased but the involvement of adenosine in this process is unknown. The aim of our study was to identify the signalling pathway responsible for the decreased hepatic arterial resistance in cirrhotic livers. Methods: Cirrhosis was induced by CCl4. Using a bivascular liver perfusion dose,response curves to adenosine of the HA were performed in the presence and the absence of pan-adenosine blocker (8-SPT), A1 blocker (caffeine) or nitric oxide synthase-blocker (l -NMMA) after preconstriction with an ,1-agonist (methoxamine). Western blot of the HA were used to measure the density of the A1 and A2a receptors. Results: Adenosine caused a dose dependent relaxation of the hepatic artery of both cirrhotic and control animals that were blocked in both groups by 8-SPT (P<0.02). The response to adenosine was greater in cirrhotic rats (P=0.016). Both l -NMMA (P=0.003) and caffeine reduced the response to adenosine in cirrhotic but not in control animals. Western blot analysis showed a higher density of A1 and a lower density of A2a receptor in cirrhotic animals (P<0.05). Conclusion: The adenosine-induced vasodilatation of the HA is increased in cirrhotic rats suggesting a role for adenosine-NO in the decreased hepatic arterial vascular resistance found in cirrhosis. This significantly greater response in cirrhosis by the A1 receptor follows the same pathway that is seen in hypoxic conditions in extra-hepatic tissues. [source] Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosisLIVER INTERNATIONAL, Issue 7 2007Xiao X. Huang Abstract Background/Aims: Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Method: Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Results: Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. Conclusion: PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis. [source] Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patientsLIVER INTERNATIONAL, Issue 1 2004Isabelle Colle Abstract: Objectives: Sildenafil is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). As sildenafil potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects of sildenafil on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis. Methods: Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01,10 mg/kg) and after intravenous (i.v.) (0.01,10 mg/kg) administration of sildenafil. Results: Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection of sildenafil significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL. Conclusion: Sildenafil increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribing sildenafil to patients with cirrhosis. [source] Nitrogen isotopic composition in hair protein is different in liver cirrhotic patientsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2006Klaus J. Petzke The stable-isotopic composition of nitrogen (,15N) or carbon (,13C) of body tissues depends on the isotopic composition of food sources and on shifts due to isotopic fractionation during metabolism. As little is known about the effects of pathophysiological conditions we measured ,15N and ,13C values in hair and hair amino acids of patients with cirrhosis (n,=,21) and compared the results with those of healthy subjects (n,=,100) randomly selected from the 1987,1988 VERA German nutrition survey population. Cirrhosis was reflected in lower hair 15N abundances (6.7 vs. 9.9, ,15N; P <0.001) whereas hair 13C abundances did not differ from healthy subjects (,19.4 vs. ,19.6, ,13C). Distinct patterns of ,15N and ,13C values were measured in hair amino acids. The ,15N values of phenylalanine were significantly higher in cirrhotics (P,<,0.001). With the exception of isoleucine, threonine, and proline all other measured amino acids showed lower ,15N values than healthy subjects (P,<,0.001). Lower hair ,15N values were associated with cirrhotic liver disease which suggests that under this condition the altered liver amino acid metabolism affects the nitrogen isotopic composition of the amino acids used for hair protein synthesis. It remains to be determined in controlled studies whether the altered nitrogen isotopic composition directly reflects the pathophysiological condition or is related to differences in dietary protein intake from plant or animal food sources. Copyright © 2006 John Wiley & Sons, Ltd. [source] Promising Diagnostic Biomarkers for Primary Biliary Cirrhosis Identified With Magnetic Beads and MALDI-TOF-MSTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2009Yong-Zhe Li Abstract (PBC) is not a rare disease worldwide. Most patients are diagnosed at the advanced stage, primarily because there are not yet any valid biomarkers available for early diagnosis. Useful biomarkers are absolutely necessary for early detection of PBC. Fortunately, the use of MALDI-TOF-MS and pattern recognition software has been successful in finding specific markers for the early detection of the disease. To screen for potential protein biomarkers in the serum for diagnosing PBC, MALDI-TOF-MS combined with magnetic beads and pattern recognition software was used to investigate 119 serum samples from 44 patients with PBC, 32 controls with other hepatic disease, and 43 healthy controls. A total of 69 discriminant m/z peaks were identified as being associated with PBC. Of them, the m/z peaks at 3445, 4260, 8133, and 16,290 were used to construct a model for the diagnosis of PBC. This diagnostic model can distinguish PBC from non-PBC controls with a sensitivity of 93.3% and a specificity of 95.1%. In our blind test, it demonstrated good sensitivity and specificity: 92.9% and 82.4%, respectively. These results indicate that useful serum biomarkers for PBC can be discovered by MALDI-TOF-MS combined with the use of magnetic beads and pattern recognition software. The pattern of multiple markers provides a powerful and reliable diagnostic method for PBC with high sensitivity and specificity. Anat Rec, 292:455,460, 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||