Different Stages Of Cirrhosis Research Articles

Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver.

There are no reliable methods in clinical practice to diagnose adrenal insufficiency (AI) in patients with cirrhosis owing to variable cortisol-binding protein levels. This leads to unreliable results in ACTH stimulated serum cortisol test. We aimed to estimate the long-acting porcine (LA)ACTH-stimulated serum and salivary cortisol levels of patients at different stages of cirrhosis using second generation electrochemiluminescence and to determine the prevalence of true adrenal insufficiency in these patients. We included 135 noncritical patients with cirrhosis (45 each from CHILD A, Band C) and 45 healthy controls. Serum and salivary samples were collected at baseline in the morning and at 1and 2 h after LA-ACTH injection. In healthy subjects, the 2.5th centile of 2 h ACTH stimulated serum and salivary cortisol were 19.8and 0.97 μg/dL, which were used as cut-offs for defining AI based on serum and saliva respectively. The median (interquartile-range) 2-h stimulated salivary cortisol in Child A, B, C categories and controls were 1.36(1.23-2.38), 1.46(1.18-2.22), 1.72(1.2-2.2) and 2.12(1.42-2.72) μg/dLrespectively. Six subjects (4.4%) were diagnosed to have AI based on stimulated salivary cortisol cut-off, whereas 39 (28.9%) cirrhosis subjects had inadequately stimulated serum cortisol. Three patients (symptomatic) required steroid replacement therapy. Hypoalbuminemia was identified as a major risk factor for the misdiagnosis of adrenal insufficiency by serum cortisol-based testing. Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver. Stimulated salivary cortisol is a promising investigation for evaluation of adrenal function in cirrhosis and more studies are required for its further validation before clinical use.

Albumin, an interesting and functionally diverse protein, varies from ‘native’ to ‘effective’ (Review)

Albumin, an interesting and functionally diverse protein, varies from ‘native’ to ‘effective’ (Review)

Baveno VII criteria for recompensation predict transplant-free survival in patients with hepatitis B-related decompensated cirrhosis

The latest Baveno VII consensus has provided guidance for identifying patients who have truly recompensated from those with hepatic decompensation. This study aimed to evaluate patients' transplant-free survival in three different stages of cirrhosis. All patients with chronic HBV infection and liver cirrhosis treated with oral nucleos(t)ide analogues from March 2006 to December 2022 were identified from a territory-wide database in Hong Kong. Patients with follow-up duration of <1 year were excluded. Participants were classified into three mutually exclusive groups: (1) no decompensated events (i.e. compensated group); (2) decompensated events occurred (i.e. decompensated group); or (3) decompensated events occurred followed by recompensation according to Baveno VII criteria (i.e. recompensated group). A time-dependent Cox proportional hazard model was adopted for evaluation. The follow-up period was 5 years. A total of 4,701 patients with cirrhosis and HBV who were treated with entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) were identified. During a median follow-up of 5 years (interquartile range 3.7, 5 years), 3,327 (70.8%), 1,347 (29.2%), and 265 (5.6%) patients had compensated, decompensated, and recompensated cirrhosis, respectively, at least once before the end of the study. In the time-dependent multivariable model, the recompensated grouphad similar transplant-free survival compared with the compensated group (adjusted hazard ratio 1.16; 95% CI 0.72-1.86; p= 0.536). The 5-year transplant-free survival rate was 89.3% for the compensated group, whereas it was 76.0% for the recompensated group, reflecting a minimal difference between the two groups. The clinical significance of recompensation of cirrhosis in improving patient outcomes for individuals with CHB infection was highlighted in this study. Early identification and treatment with nucleos(t)ide analogues might promote hepatic recompensation and thus reduce mortality in patients with CHB. The latest Baveno VII consensus introduces the new concept of hepatic recompensation, which refers to the reversal of the structural and functional changes of cirrhosis after removal, cure, or suppression of the aetiologyof cirrhosis. It is essential to investigate the transplant-free survival rates of patients who are able to achieve hepatic recompensation, as this has significant implications for the medical resources required to manage liver failure and transplantation. This study features the clinical significance of hepatic recompensation by comparing patient outcomes of those who achieve it to those who do not. The early identification and use of antiviral treatment with nucleos(t)ide analogues is a pivotal strategy to promote hepatic recompensation, which has the potential to significantly reduce mortality rates in patients with chronic HBV infection and ultimately aid in the elimination of hepatitis.

Abstract 91: ACTH stimulated salivary cortisol is a better indicator of adrenal insufficiency compared to stimulated serum cortisol in subjects with cirrhosis liver

Background: There are no reliable methods in clinical practice to diagnose adrenal insufficiency (AI) in patients with cirrhosis due to variably decreased cortisol binding protein levels. This leads to unreliable results on ACTH stimulated serum cortisol test.Aims and Objectives: To estimate the Long Acting (LA)-ACTH stimulated salivary cortisol levels of patients in different stages of cirrhosis using 2nd generation electrochemiluminescence and to find the prevalence of adrenal insufficiency in them.Results: LA-ACTH stimulated serum and saliva samples of 135 non-critically ill patients with cirrhosis (45 each from CHILD A, B and C) and 40 normal subjects were collected at baseline, 60 and 120-minutes. In healthy subjects, the 2.5th centile of 2 hr ACTH stimulated serum and salivary cortisol were 19.8 μg/dl and 0.97 μg/dl, which were used as cut-offs for defining AI based on serum and saliva respectively. The median (interquartile-range) 2-hour stimulated salivary cortisol in Child A,B,C categories and controls were 1.36 (1.23-2.38), 1.46 (1.18-2.22), 1.72 (1.2-2.2) and 2.12 (1.42-2.72) μg/dl respectively. 7 subjects (5.1%) were diagnosed to have AI based on stimulated salivary cortisol cut-off, whereas 39 (28.9%) cirrhosis subjects had inadequately stimulated serum cortisol. Three (symptomatic) subjects required steroid replacement.Conclusions: ACTH stimulated serum cortisol is a poor test to diagnose AI in patients with cirrhosis. ACTH stimulated salivary cortisol has a high reliability for the same.

Correlation of CT portography vascularture to child: Pugh classification of cirrhotic patients

Aim: To study CT Portography vascularture in different stages of cirrhosis. Materials and Methods: Using 16 slice TOSHIBHA acquillon CT scanner machine liver triple phase study was performed in 80 cirrhotic patients. Based on the clinical and lab parameters like serum albumin and prothrombin time the patients were categorized into child “A” (40 patients),”B” (20 patients) and “C” (20 patients) “A” is compensated “B” and “C” are decompensated cirrhosis. Results: Esophageal and paraesophageal varices are the most common portosystemic collaterals. Ectopic varices, transhepatic shunts and extrahepatic shunts were seen mainly in the decompensated cirrhosis. All patients with child pugh “C” score had hepatic encephalopathy. Conclusion: Portosystemic collaterals can be correlated with child pugh classification in assessing the progression of liver cirrhosis to decompensated stage. So, from gastroesophageal varices to transhepatic and extrahepatic shunts the child pugh classification tends to increase representing a linear correlation.

Faecal cytokine profiling as a marker of intestinal inflammation in acutely decompensated cirrhosis.

Background & AimsGut dysbiosis and inflammation perpetuate loss of gut barrier integrity (GBI) and pathological bacterial translocation (BT) in cirrhosis, contributing to infection risk. Little is known about gut inflammation in cirrhosis and how this differs in acute decompensation (AD). We developed a novel approach to characterise intestinal immunopathology by quantifying faecal cytokines (FCs) and GBI markers.MethodsFaeces and plasma were obtained from patients with stable cirrhosis (SC; n = 16), AD (n = 47), and healthy controls (HCs; n = 31). A panel of 15 cytokines and GBI markers, including intestinal fatty-acid-binding protein-2 (FABP2), d-lactate, and faecal calprotectin (FCAL), were quantified by electrochemiluminescence/ELISA. Correlations between analytes and clinical metadata with univariate and multivariate analyses were performed.ResultsFaecal (F) IL-1β, interferon gamma, tumour necrosis factor alpha, IL-21, IL-17A/F, and IL-22 were significantly elevated in AD vs. SC (q <0.01). F-IL-23 was significantly elevated in AD vs. HC (p = 0.0007). FABP2/d-lactate were significantly increased in faeces in AD vs. SC and AD vs. HC (p <0.0001) and in plasma (p = 0.0004; p = 0.011). F-FABP2 correlated most strongly with disease severity (Spearman's rho: Child-Pugh 0.466; p <0.0001; model for end-stage liver disease 0.488; p <0.0001). FCAL correlated with plasma IL-21, IL-1β, and IL-17F only and none of the faecal analytes. F-cytokines and F-GBI markers were more accurate than plasma in discriminating AD from SC.ConclusionsFC profiling represents an innovative approach to investigating the localised intestinal cytokine micro-environment in cirrhosis. These data reveal that AD is associated with a highly inflamed and permeable gut barrier. FC profiles are very different from the classical innate-like features of systemic inflammation. There is non-specific upregulation of TH1/TH17 effector cytokines and those known to mediate intestinal barrier damage. This prevents mucosal healing in AD and further propagates BT and systemic inflammation.Lay summaryThe gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients.

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis. A cross-sectional study was carried out in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score). The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV- and HCV-infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7). Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients.

To salt or not to salt?-That is the question in cirrhosis.

Ascites is the most common complication of patients with cirrhosis, resulting from portal hypertension and vasodilatation. It is associated with an increased risk for the development of hyponatraemia and renal failure and has a high mortality rate of 20% per year. The development of ascites represents a baleful sign in the course of disease in cirrhosis. To prevent complications of cirrhosis and improve quality of life, an effective management of ascites is pivotal. Combined salt restriction and diuretic therapy is recommended as first-line therapy in numerous clinical practice guidelines. In contrast, there has been a debate on whether a strict salt-restricted diet for cirrhosis patients should be used at all since salt restriction may increase the risk for malnutrition which in turn may negatively impact on quality of life and survival. This review aims to summarize the current pros and cons regarding salt restriction in patients with cirrhosis and proposes the importance of achieving a sodium balance throughout different stages of cirrhosis.

High prevalence of antibodies to core+1/ARF protein in HCV-infected patients with advanced cirrhosis.

Hepatitis C virus (HCV) possesses a second open reading frame (ORF) within the core gene encoding an additional protein, known as the alternative reading frame protein (ARFP), F or core+1. The biological significance of the core+1/ARF protein remains elusive. However, several independent studies have shown the presence of core+1/ARFP antibodies in chronically HCV-infected patients. Furthermore, a higher prevalence of core+1/ARFP antibodies was detected in patients with HCV-associated hepatocellular carcinoma (HCC). Here, we investigated the incidence of core+1/ARFPantibodies in chronically HCV-infected patients at different stages of cirrhosis in comparison to chronically HCV-infected patients at earlier stages of disease. Using ELISA, we assessed the prevalence of anti-core+1 antibodies in 30 patients with advanced cirrhosis [model for end-stage liver disease (MELD) ≥15] in comparison with 50 patients with mild cirrhosis (MELD <15) and 164 chronic HCV patients without cirrhosis. 28.7 % of HCV patients with cirrhosis were positive for anti-core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV patients. Moreover, there was significantly higher positivity for anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %) compared to those with early cirrhosis (24 %) (P<0.05). These findings, together with the high prevalence of anti-core+1 antibodies in HCV patients with HCC, suggest that core+1 protein may have a role in virus-associated pathogenesis, and provide evidence to suggest that the levels of anti-core+1 antibodies may serve as a marker for disease progression.

From stable disease to acute-on-chronic liver failure: Circulating cytokines are related to prognosis in different stages of cirrhosis

IntroductionAlthough both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis. MethodsThis prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n=118), and (2) subjects hospitalized for acute decompensation (AD) (n=130). Thirty healthy subjects served as control group. ResultsPatients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF. ConclusionsThe pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.

Progressive alterations of cardiopulmonary hemodynamics accompanied by increasing levels of C reactive protein (CRP) occur in patients in different stages of cirrhosis and predict death in decompensated cirrhosis

Progressive alterations of cardiopulmonary hemodynamics accompanied by increasing levels of C reactive protein (CRP) occur in patients in different stages of cirrhosis and predict death in decompensated cirrhosis

Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients

Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension

Portal hypertension is the haemodynamic abnormality associated with the most severe complications of cirrhosis, including ascites, hepatic encephalopathy and bleeding from gastroesophageal varices. Variceal bleeding is a medical emergency associated with a mortality that, in spite of recent progress, is still in the order of 10–20% at 6 weeks. The evaluation of diagnostic tools and the design and conduct of good clinical trials for the treatment of portal hypertension have always been difficult. Awareness of these difficulties has led to the organisation of a series of consensus meetings. The first one was organised by Andrew Burroughs in Groningen, the Netherlands in 1986 [1]. After Groningen, other meetings followed, in Baveno, Italy in 1990 (Baveno I) [2], and in 1995 (Baveno II) [3,4], in Milan, Italy in 1992 [5], in Reston, U.S.A. [6] in 1996, in Stresa, Italy, in 2000 (Baveno III) [7,8], again in Baveno in 2005 (Baveno IV) [9,10], in Atlanta in 2007 [11], and again in Stresa in 2010 (Baveno V) [12,13]. The aims of these meetings were to develop definitions of key events in portal hypertension and variceal bleeding, to review the existing evidence on the natural history, the diagnosis and the therapeutic modalities of portal hypertension, and to issue evidence-based recommendations for the conduct of clinical trials and the management of patients. All these meetings were successful and produced consensus statements on some important points, although several issues remained unsettled. To continue the work of the previous meetings, a Baveno VI workshop was held on April 10–11, 2015. The workshop was attended by many of the experts responsible for most of the major achievements of the last years in this field. Many of them had attended the previous meetings as well. A concept that has gained wide acceptance over the past few years is the fact that patients in different stages of cirrhosis have different risks of developing complications and of dying. Accordingly, the Baveno VI workshop was entitled ‘‘Stratifying

Predicting risk factors for rebleeding, infections, mortality following peptic ulcer bleeding in patients with cirrhosis and the impact of antibiotics prophylaxis at different clinical stages of the disease.

BackgroundInfections in cirrhotic patients with upper gastrointestinal bleeding are a common event causing severe complication and mortality. This study aimed to identify risk factors that may predict rebleeding, bacterial infections, and the impact of antibiotic prophylaxis on mortality at different stages of cirrhosis following acute peptic ulcer bleeding (PUB).MethodsA hospital-based retrospective cohort study was conducted on 235 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures between January 2008 and January 2014 (n = 235); of these, 88 patients received prophylactic intravenous ceftriaxone (antibiotic group) and 147 patients did not (nil-antibiotic group). The recorded outcomes were length of hospital stay, bacterial infection, rebleeding, and in-hospital mortality.ResultsForty-eight (20.4 %) patients experienced ulcer rebleeding and 46 (19.6 %) developed bacterial infections. More patients suffered from infection and recurrent bleeding in the nil-antibiotic group than the antibiotic group (25.2 % vs. 10.2 %, p = 0.005 and 30.6 % vs. 3.4 %; p < 0.001, respectively). The predictive risk factors for rebleeding were the Rockall score (p = 0.004), units of blood transfusion (p = 0.031), and no antibiotic prophylaxis (p <0.001); for bacterial infections, they were the Child-Pugh score (p = 0.003), active alcoholism (p = 0.035), and no antibiotic prophylaxis (p = 0.009). Overall, 40 (17 %) patients died during hospitalization. The Rockall score and rebleeding were predictive factors for in-hospital mortality. In subgroup analysis, survival was significantly reduced in decompensated patients (p = 0.034).ConclusionsThis study suggests that antibiotic prophylaxis after endoscopic hemostasis for acute PUB prevented infections and reduced rebleeding events in cirrhotic patients. Antibiotic prophylaxis improved survival among decompensated cohort following PUB. The Rockall score and rebleeding were predictive risk factors for in-hospital mortality.

B-type natriuretic peptide and cirrhosis progression.

Brain natriuretic peptide (BNP) is used as a marker of cardiac dysfunction to predict heart failure mortality. The significance of the prognostic ability of BNP for liver cirrhosis remains unknown, although the levels of BNP seen in cirrhosis are high. We aimed to determine whether the BNP level is related to the stage of cirrhosis and could serve as a prognostic marker of cirrhosis (predict the 1-year all-cause mortality). We recruited 92 patients at different stages of cirrhosis and 81 controls matched by age and gender for this study. At admission, cardiac physical examination and BNP measurements were performed. Upon discharge, the 89 patients were followed up for 12 months. The median BNP levels of patients with cirrhosis were 167.0 pg/mL, which were significantly higher than those of the control group (167.0 vs 34.8 pg/mL, P = 0.001). Serum BNP levels were positively correlated with the Child score, the grade of esophageal varices, a history of spontaneous bacterial peritonitis, and the presence of ascites and collateral circulation. BNP levels above the median were associated with an increased occurrence of death within 12 months of discharge (log rank P = 0.025), as determined by univariate and multivariate Cox regression analyses. Esophageal varices, large/medium volume ascites, and BNP levels were related to the clinical outcome (P = 0.034, 0.030, and 0.025, respectively). Together, these results suggested that serum BNP levels are significantly correlated with the stage of cirrhosis, suggesting that BNP levels might serve as a significant predictor for 1-year all-cause mortality.

Evaluation of regional myocardial mechanics of right ventricle in patients with liver cirrhosis using velocity vector imaging combined with isometric stress test

Objective To study regional myocardial function of right ventricle at different stages of cirrhosis,using velocity vector imaging combined with standard isometric grip strength test to reveal the mechanical function in patients with liver cirrhosis at early stage further,and to benefit reliable quantitative evaluation and efficacy indicators for the establishment of the early diagnostic criteria of cirrhotic cardiomyopathy by echocardiography,and found myocardial mechanics basis for explicit pathogenesis of cirrhotic cardiomyopathy.Methods Accorded to Child-Pugh score,the cirrhosis experimental groups were divided into three groups:group A (42 patients),group B (28 patients) and group C (12 patients).There were 31 patients in group A to be conducted standard isometric grip strength test.While 34 healthy people were selected as the control group.The dynamic gray scale long-axis view images of the right ventricle were collected in 3 complete cardiac cycles in apical four-chamber view.Peak systolic longitudinal strain (Smax) and global ejection fraction of the right ventricle were derived from 6 myocardial segments with the Syngo VVI workstation off-line.Results 1)Compared with the control group,in group A,global ejection fraction of the right ventricle was normal,there were not significant change of Smax of each segment (P ＞0.05).In group B,there was not significant change of global ejection fraction of the right ventricle,the Smax of each segment were increased mainly (P ＜0.05-0.01).In group C,global ejection fraction of the right ventricle was significantly lower (P ＜ 0.01),the Smax of each segment reduced mainly (P ＜ 0.05-0.01).2)Compared with group A,in group B,there was no significant difference of blood pressure and global ejection fraction of the right ventricle,while including the Smax of each segment in systole and diastole.Compared with group A and group B,in group C,systolic and diastolic blood pressure and global ejection fraction of the right ventricle decreased significantly; the Smax of each segment were reduced mainly (P ＜ 0.05-0.01).3)Compared with the resting state,after the standard isometric grip strength test,the global ejection fraction of the right ventricle decreased significantly,there was a significant reduction mainly in Smax of each segment (P ＜ 0.01).Conclusions The regional myocardial function of right ventricle in patients with liver cirrhosis is abnormality even at early stage and could be revealed by standard isometric stress test.The right ventricular systolic dyfunction is related to the stages of liver cirrhosis disease. Key words: Echocardiography ; Liver cirrhosis ; Ventricular function, right ; Velocity vector imaging

Regression effect of hepatocyte nuclear factor 4α on liver cirrhosis in rats

The aim of this study was to determine whether cirrhosis could be reversed after treated with hepatocyte nuclear factor 4α (HNF4α), a key transcriptional regulator of hepatocyte differentiation and function. Early and advanced stages of liver cirrhosis were induced by thioacetamide (TAA) administration. The adenovirus carrying HNF4α gene was injected into cirrhotic rats via the tail vein. The effect of HNF4α on cirrhosis was evaluated by histological and immunohistochemical examination. Early stage of cirrhosis was remarkably resolved by HNF4α to a nearly-normal extent and advanced cirrhosis was partially ameliorated in vivo. The enforced expression of HNF4α downregulated profibrogenic factors remarkably including α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, fibroblast-specific protein (FSP)-1, collagen I and III. In vivo and in vitro studies revealed that HNF4α administration inhibited extracellular signal-regulated kinase (ERK) signaling pathway through the downregulation of phosphorated ERK and phosphorated JunD. In addition, HNF4α readjusted the balance between extracellular matrix deposition and degradation through the upregulation of matrix metalloproteinase and downregulation of its inhibitors. Moreover, HNF4α treatment inhibited angiogenesis as determined by CD31 and CD34 immunostaining. Our findings broaden the knowledge on the reversibility of different stages of cirrhosis as HNF4α could present a promising alternative for the treatment of liver cirrhosis.

The Expression Patterns and Clinical Significance of microRNAs in Liver Diseases and Hepatocellular Carcinoma

MicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs that constitute silencers of target gene expression and have emerged as key regulatory molecules of mammalian cell functions. Aberrant miRNA expression promotes pathologic conditions including hepatocellular carcinoma (HCC) and a variety of precancerous liver diseases, especially chronic hepatitis B and C, and liver cirrhosis. miRNAs may contribute to HCC development by acting as oncogenes or tumor suppressors. Specific alterations of miRNA expression have also been related to clinical features of HCC, such as stage, differentiation, prognosis, and response to adjuvant therapy. miRNA signatures may help define molecular profiles of liver diseases as biomarkers, and allow classification of different stages of cirrhosis and HCC progression. Either miRNAs, or anti-miRNA oligonucleotides (antagomirs) could be used for in vivo modulation of miRNA actions, and thus have significant potential in molecularly targeted therapy.

Prediction of Six and Twelve Month Mortality by Patients with Liver Cirrhosis Using a New LiMAx Test

Background: Recently, much effort was put into improvement of the liver waiting list allocation system. Still obviously, none of the newly developed scores is significantly beneficent in compare to MELD score. The new LiMAx test might have a potential to improve the prediction of mortality by patients with liver cirrhosis. Methods: A prospective observational single center study has been conducted in our department. In the on-going study 400 patients with different stages of cirrhosis are to be included and followed at 6, 12 and 24 months. Standard clinical parameters, biochemical blood tests as well as the LiMAx test were performed by inclusion. The end points are: death or liver transplantation. T-test comparison between the groups, as well as a multivariate logistic Regression was performed. Results: Up to now 240 patients are included in the study. After excluding patients who became liver transplantation 148 and 96 patients reached 6 and 12 months follow up respectively. 54% of the patients suffer of alcohol cirrhosis, 20% was HCV positive. The Child-B stadium was observed in 41%, Child-C in 27% of cases. The 6 and 12 month mortality was 13.5 and 31.3% respectively. The patients who died at 6 and 12 month had significantly lower LiMAx value (91 and 99 μg/kg/h) than those who survived (132 and 147μg/kg/h, p=.008). LiMAx value, creatinine- and sodium serum level were the only significant parameters in the multivariate regression analysis including also other laboratory parameters like total bilirubin or coagulation factors. Conclusions: The LiMAx test might predict a liver dependent death by patients with liver cirrhosis. Final results of the study are needed to estimate the exact value of LiMAx test in evaluation of patient with liver cirrhosis.

Antibiotic prophylaxis during bleeding for portal hypertension: authors’ reply

Sirs, We are grateful for the correction regarding the number of patients with bacterial infection in the norfloxacin group from the Fernandez et al. trial.1, 2 The corrected relative risk is 0.42 (95% CI 0.13, 1.15; P-value 0.069), which is not a major change from the one reported in our article.3 We concur with Garcia-Pagan that evidence must be sought, to understand if patients with advanced cirrhosis or poorer liver function benefit as much from antibiotic prophylaxis. Unfortunately, the trials included in our meta-analysis did not provide precise information on efficacy by disease stage or liver function. We attempted to contact authors to gather information from the individual trials, but few replied and we were forced to restrict our study to the available aggregated information. Relevant information regarding comparisons between antibiotics is available in the complete version of this meta-analysis on The Cochrane Library.4 Summarising, we conducted a test for interaction and failed to observe a differential effect by antibiotic group on overall mortality (cephalosporins vs. quinolones, P = 0.39; quinolones vs. quinolones plus beta-lactams, P = 0.17). Therefore, until new evidence points towards a specific antibiotic group offering more benefit, antibiotics must be selected considering specific setting conditions (i.e. availability, resistance, cost) and patient characteristics. Although the association of antibiotic prophylaxis and reduced rebleeding rate has been known to be biologically plausible,5 previous clinical evidence was conflicting.6, 7 Our meta-analysis presents consistent findings, showing the potential benefit of prophylaxis to reduce the number of rebleeding episodes, as well as early rebleeding (within 7 days). However, we recognise that given the limited number of trials (three) more research on this outcome is still needed. Despite extensive antibiotic use and abuse, current evidence provides increasing support of their efficacy for prophylaxis in old and new outcomes. Doubtless, further trials evaluating diverse antibiotic schemas in patients at different stages of cirrhosis must be conducted to assess the robustness of the benefits of antibiotic prophylaxis. Declaration of personal and funding interests: None.