Showing papers on "Ascites published in 2015"

Non-selective β-blockers are associated with improved survival in patients with ascites listed for liver transplantation

Abstract: Objective Recent data have suggested that non-selective β-blockers (NSBB) are associated with increased mortality in patients with cirrhosis and refractory ascites. However, other evidence implies that NSBB may be beneficial in this setting by reducing bacterial translocation. Our aim was to determine whether NSBB use was a risk factor for mortality in patients with end-stage chronic liver disease and ascites awaiting liver transplantation. Design This was a single-centre retrospective study of 322 patients with ascites listed January 2007 to July 2011. Results NSBB patients (n=159) and non-NSBB patients (n=163) were comparable with regards to listing model for end-stage liver disease score (p=0.168), frequency of hepatocellular carcinoma (p=0.193) and refractory ascites (35.2% vs. 37.4%, p=0.681). 82 patients died, 221 patients were transplanted and 19 patients were removed from the list during a median follow-up duration of 72 days; the median time to death was 150 and 54 days in the NSBB and non-NSBB groups, respectively. In a multivariate competing risk Cox model, patients on NSBB had reduced mortality compared with propensity risk score-matched non-NSBB patients (HR 0.55; 95% CI 0.32 to 0.95, p=0.032). Similarly, in the subgroup of patients with refractory ascites (n=117), NSBB remained independently associated with less waitlist death (adjusted HR 0.35; 95% CI 0.14 to 0.86, p=0.022). Conclusions NSBB in patients with ascites and refractory ascites listed for liver transplantation are not detrimental, and instead are associated with reduced waitlist death. Our findings argue that NSBB are safe and may confer benefit in patients with ascites complicating end-stage liver disease.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): Impact of the inter-stages course on morbi-mortality and implications for management

Abstract: Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was recently developed to induce rapid hypertrophy and reduce post-hepatectomy liver failure in patients with insufficient remnant liver volume (RLV). However, mortality rates >12% have been reported. This study aimed to analyze the perioperative course of ALPPS and to identify factors associated with morbi-mortality. Methods Between April 2011 and September 2013, 62 patients operated in 9 Franco-Belgian hepatobiliary centres underwent ALPPS for colorectal metastases (N = 50) or primary tumors, following chemotherapy (N = 50) and/or portal vein embolization (PVE; N = 9). Results Most patients had right (N = 31) or right extended hepatectomy (N = 25) (median RLV/body weight ratio of 0.54% [0.21–0.77%]). RLV increased by 48.6% [−15.3 to 192%] 7.8 ± 4.5 days after stage1, but the hypertrophy decelerated beyond 7 days. Stage2 was cancelled in 3 patients (4.8%) for insufficient hypertrophy, portal vein thrombosis or death and delayed to ≥9 days in 32 (54.2%). Overall, 25 patients (40.3%) had major complication(s) and 8 (12.9%) died. Fourteen patients (22.6%) had post-stage1 complication of whom 5 (35.7%) died after stage2. Factors associated with major morbi-mortality were obesity, post-stage1 biliary fistula or ascites, and infected and/or bilious peritoneal fluid at stage2. The latter was the only predictor of Clavien ≥3 by multivariate analysis (OR: 4.9; 95% CI: 1.227–19.97; p = 0.025). PVE did not impact the morbi-mortality rates but prevented major cytolysis that was associated with poor outcome. Conclusions The inter-stages course was crucial in determining ALPPS outcome. The factors of high morbi-mortality rates associated with ALPPS are linked to the technique complexity.

Hyponatremia in cirrhosis: Pathophysiology and management

Abstract: Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension The development of ascites in patients with cirrhosis is multi-factorial Portal hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system, sympathetic nervous system and antidiuretic hormone (ADH) The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of ascites Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solute- free water This leads to additional compensatory mechanisms including non-osmotic secretion of ADH, also known as arginine vasopressin, further worsening excess water retention and thereby hyponatremia Hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic marker both before and after liver transplant The management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious In this review, we discuss the pathophysiology and various treatment modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with cirrhosis

Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer

Abstract: Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, we investigated an alternative strategy of targeting macrophage functions to reverse the vascular pathology of malignant ascites using fluid from human patients and an immunocompetent murine model (ID8) of EOC that mirrors human disease by developing progressive vascular disorganization and leakiness culminating in massive ascites. We demonstrate that the macrophage content in ascites fluid from human patients and the ID8 model directly correlates with vascular permeability. To further substantiate macrophages' role in the pathogenesis of malignant ascites, we blocked macrophage function in ID8 mice using a colony-stimulating factor 1 receptor kinase inhibitor (GW2580). Administration of GW2580 in the late stages of disease resulted in reduced infiltration of protumorigenic (M2) macrophages and dramatically decreased ascites volume. Moreover, the disorganized peritoneal vasculature became normalized and sera from GW2580-treated ascites protected against endothelial permeability. Therefore, our findings suggest that macrophage-targeted treatment may be a promising strategy toward a safe and effective means to control malignant ascites of EOC.

Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis

Abstract: Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis

Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?

Abstract: The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ65Cu was observed within the cirrhosis population and δ65Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ65Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ65Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.

Idiopathic non-cirrhotic portal hypertension: a review

Abstract: Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare disease characterized of intrahepatic portal hypertension in the absence of cirrhosis or other causes of liver disease and splanchnic venous thrombosis. The etiology of INCPH can be classified in five categories: 1) immunological disorders (i.e. association with common variable immunodeficiency syndrome, connective tissue diseases, Crohn’s disease, etc.), 2) chronic infections, 3) exposure to medications or toxins (e.g. azathioprine, 6- thioguanine, arsenic), 4) genetic predisposition (i.e. familial aggregation and association with Adams-Oliver syndrome and Turner disease) and 5) prothrombotic conditions (e.g. inherited thrombophilias myeloproliferative neoplasm antiphospholipid syndrome). Roughly, INCPH diagnosis is based on clinical criteria and the formal exclusion of any other causes of portal hypertension. A formal diagnosis is based on the following criteria: 1) presence of unequivocal signs of portal hypertension, 2) absence of cirrhosis, advanced fibrosis or other causes of chronic liver diseases, and 3) absence of thrombosis of the hepatic veins or of the portal vein at imaging. Patients with INCPH usually present with signs or symptoms of portal hypertension such as gastro-esophageal varices, variceal bleeding or splenomegaly. Ascites and/or liver failure can occur in the context of precipitating factors. The development of portal vein thrombosis is common. Survival is manly limited by concomitant disorders. Currently, treatment of INCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied aimed to modify the natural history of the disease. Anticoagulation therapy can be considered in patients who develop portal vein thrombosis.

Risk factors for development of spontaneous bacterial peritonitis and subsequent mortality in cirrhotic patients with ascites.

Abstract: Background Patients with ascites are at risk for developing spontaneous bacterial peritonitis (SBP) – a severe complication associated with high mortality. We aimed to identify risk factors for SBP development and mortality to optimize stratification for primary prophylaxis and therapeutic strategies to improve survival. Methods 575 patients with cirrhosis and ascites undergoing paracentesis at a tertiary care hospital were included in this retrospective cohort study. Demographical, clinical and laboratory parameters were recorded at first paracentesis and during follow-up. Multivariate logistic regression analysis was used to identify independent predictors of SBP development and mortality. Results Child–Pugh stage C (OR: 3.323; P = 0.009), ascitic fluid polymorph-nuclear cell (PMN) count (OR: 1.544; P = 0.028) and low serum sodium (OR: 0.917; P = 0.029) emerged as independent risk factors for SBP development. SBP-naive patients undergoing paracentesis and presenting with PMN-counts ≥100 cells/μl, or hyponatraemia <125 mM were at highest risk for developing SBP. Increases in MELD and CRP levels indicated SBP development, while no changes where observed in a matched control group with sterile ascites at multiple paracenteses. MELD score (OR: 1.565; P = 0.001) and CRP (OR: 1.067; P = 0.037) were identified as independent risk factors for 30-day mortality after SBP diagnosis. In particular SBP patients with MELD≥22, CRP ≥3.5 mg/dl and development of grade III/IV hepatic encephalopathy showed highest mortality. Conclusions Low serum sodium levels, Child-Pugh stage C and elevated ascites PMN counts (≥100 cells/μl) indicate a significant risk for SBP development. SBP-related mortality is highest in patients with MELD≥22 and elevated CRP levels.

Portal hypertension: pathophysiology, diagnosis and management.

Abstract: Portal hypertension is an important complication of liver disease. As a result of elevated pressures within the portal vein several complications can arise, including the development of oesophageal and gastric varices, ascites, hepatic encephalopathy as well as complications secondary to circulatory dysfunction, such as hepatorenal syndrome, portopulmonary syndrome and hepatopulmonary syndrome. This review outlines the pathogenesis and diagnosis of portal hypertension and outlines the management of these various important clinical sequelae. The management of oesophageal and gastric varices is particularly important, and both the emergency management together with prophylactic management of this condition are described.

Neutrophil‐to‐lymphocyte ratio predicts mortality in patients listed for liver transplantation

Abstract: Background & Aims In the absence of overt infection, the systemic inflammatory response is increasingly recognised as a pathogenetic factor in the circulatory dysfunction of advanced cirrhosis Our aim was to determine whether the neutrophil-to-lymphocyte ratio, a marker of systemic inflammation, is predictive of mortality in patients with end-stage cirrhosis listed for liver transplantation Methods A single centre study of 570 patients listed for first elective single-organ liver transplantation January 2007–June 2011 Results The median listing neutrophil-to-lymphocyte ratio was 29 (IQR 19–47) Neutrophil-to-lymphocyte ratio demonstrated a positive correlation with listing serum bilirubin (P < 0001), negative correlation with serum sodium (P < 0001), and positive correlation with the MELD score (P < 0001) Neutrophil-to-lymphocyte ratio increased with increasing severity of ascites (P < 0001) A higher neutrophil count (P < 0001) and lower lymphocyte count (P = 0001) were predictors of wait-list death In a multivariate competing risk Cox model, neutrophil-to-lymphocyte ratio remained independently associated with mortality (HR 110; 95% CI 105–115, P < 0001) The proportion of patients with a neutrophil-to-lymphocyte ratio <2, 2–49, and ≥5 who had died by 3 months of listing was 3%, 138% and 373% respectively (P < 0001) After adjusting for MELD, increasing increments of neutrophil-to-lymphocyte ratio were predictive of death by 3 months (P = 0043) Conclusions The blood neutrophil-to-lymphocyte ratio, a simple and readily available marker of systemic inflammation, is an independent predictor of mortality in patients with liver failure listed for liver transplantation

Activated regulatory and memory T-cells accumulate in malignant ascites from ovarian carcinoma patients

Abstract: Invasive ovarian cancer is associated with poor outcome. The presence of infiltrating regulatory T-cells (Tregs) suppresses protective anti-tumor immune responses, and their accumulation into the tumor microenvironment correlates with reduced survival in ovarian cancer patients. Here, we conducted a detailed characterization of CD4+ T-cells, CD8+ T-cells and Treg subsets in the peripheral blood and malignant ascites fluid from seventeen patients with ovarian carcinoma of epithelial origin. Cell distribution, activation status and proliferation status were assessed by multi-color flow cytometry. In ascites fluid, a significant accumulation of CD8+ cytotoxic T-cells and Tregs was observed compared to peripheral blood. Furthermore, a skewing toward the CD45RA− effector/memory compartment was observed in all T-cell subsets in the ascites fluid, but was most pronounced in the Treg population. Regulatory T-cells in the malignant ascites were more activated and had a higher proliferation rate compared to blood-derived cells from the same patient, and their number in ascites was positively correlated with the number of epithelial cells in effusion. In summary, we demonstrate an accumulation of activated CD4+, CD8+ and regulatory T-cells in the cancer microenvironment of ovarian carcinoma.

Long-term clinical outcome of patients with cirrhosis and refractory ascites treated with transjugular intrahepatic portosystemic shunt insertion.

Abstract: Background and Aim Transjugular intrahepatic portosystemic shunt (TIPS) is indicated for the treatment of refractory ascites in cirrhosis. The long-term outcome of TIPS for refractory ascites is unknown. The aim of this study is to describe the natural history of patients with refractory ascites post-TIPS, and compare between polytetrafluoroethylene (PTFE)-covered versus bare stents. Methods A retrospective chart review of patients who had TIPS for refractory ascites was conducted. Prospectively collected data include demographics, angiographic data, blood work, and urinary sodium excretion. Results There were 136 patients who received TIPS (bare = 104, covered = 32) for over 22 years. Patients with PTFE stents had lower international normalized ratio and model for end-stage liver disease score. More patients with bare stents developed shunt dysfunction (74.0% vs 24.1%, P < 0.0001) and required more TIPS revisions (1.6 ± 0.2/patient vs 0.2 ± 0.1, P < 0.0001). Urinary sodium excretion increased significantly from first month and progressed to 98 ± 9 mmol/day at 12th month post-TIPS (P < 0.001 vs baseline), concurrent with improved renal function. Most patients (77.6%) completely cleared the ascites without diuretics, but many achieved this beyond 2 years. Number of TIPS revision was predictive of complete response at 12 months (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5–0.9, P < 0.05). Age (hazard ratio [HR] = 1.05 [95% CI 1.02–1.08], P < 0.01), complete response (HR = 0.22 [95% CI 0.12–0.40], P < 0.0001) and polytetrafluoroethylene stents (HR = 0.23 [95% CI 0.05–0.97], P < 0.05) were predictive of survival. Conclusion TIPS is an effective treatment for cirrhotic refractory ascites. Ascites clearance is dependent on number of TIPS revision, whereas survival is predicted by younger age, complete response, and covered stent use, although era effect likely contributed to improved survival with covered stent use.

Prognosis of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis: A Prospective Cohort Study.

Abstract: Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality. Methods. Prospective cohort study at a major US liver transplant center. A nephrologist's review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other. Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other (p = 0.04 overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p = 0.99). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p = 0.05) and acute tubular necrosis (p = 0.04). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment. Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management.

Evaluation and treatment of malignant ascites secondary to gastric cancer.

Abstract: Malignant ascites affects approximately 10% of patients with gastric cancer (GC), and poses significant difficulties for both patients and clinicians. In addition to the dismal general condition of affected patients and the diversity of associated complications such as jaundice and ileus, problems in assessing scattered tumors have hampered the expansion of clinical trials for this condition. However, the accumulation of reported studies is starting to indicate that the weak response to treatment in GC patients with malignant ascites is more relevant to their poor prognosis rather than to the ascites volume at diagnosis. Therefore, precise assessment of initial state of ascites, repetitive evaluation of treatment efficacy, selection of suitable treatment, and swift transition to other treatment options as needed are paramount to maximizing patient benefit. Accurately determining ascites volume is the crucial first step in clinically treating a patient with malignant ascites. Ultrasonography is commonly used to identify the existence of ascites, and several methods have been proposed to estimate ascites volume. Reportedly, the sum of the depth of ascites at five points (named "five-point method") on three panels of computed tomography images is well correlated to the actual ascites volume and/or abdominal girth. This method is already suited to repetitive assessment due to its convenience compared to the conventional volume rendering method. Meanwhile, a new concept, "Clinical Benefit Response in GC (CBR-GC)", was recently introduced to measure the efficacy of chemotherapy for malignant ascites of GC. CBR-GC is a simple and reliable patient-oriented evaluation system based on changes in performance status and ascites, and is expected to become an important clinical endpoint in future clinical trials. The principal of treatment for GC patients with ascites is palliation and prevention of ascites-related symptoms. The treatment options are various, including a standard treatment based on the available guidelines, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), laparoscopic HIPEC alone, intravenous chemotherapy, intraperitoneal chemotherapy, and molecular targeting therapy. Although each treatment option is valid, further research is imperative to establish the optimal choice for each patient.

Presentation and complications associated with cirrhosis of the liver

Abstract: Objective:To provide an understanding of the detrimental impact of cirrhosis and its complications, strengths and weaknesses of current treatment options for the management of these complications, and new developments in this rapidly changing field.Research design and methods:Relevant publications were identified via PubMed and Cochrane databases, with additional references obtained by reviewing bibliographies from selected articles.Results:Cirrhosis, a progressive liver disease, is characterized by fibrosis caused by chronic liver injury. Liver fibrosis impairs hepatic function and causes structural changes that result in portal hypertension. Most patients with cirrhosis remain asymptomatic until they develop decompensated cirrhosis. At this stage, patients experience complications associated with portal hypertension (i.e., the abnormal increase in portal vein pressure), including ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), hepatorenal syndrome, portopulmonary h...

Low 25-Hydroxyvitamin D Levels Are Associated with Infections and Mortality in Patients with Cirrhosis.

Abstract: Background & Aims Vitamin D, best known to regulate bone mineralization, has numerous additional roles including regulation inflammatory pathways. Recently, an increased incidence of 25-hydroxyvitamin D3 (25(OH)D3) deficiency has been found in subjects suffering from liver diseases. We here investigated if low vitamin D levels might be associated with prognosis, inflammation and infectious complications in patients with cirrhosis. Methods We performed a prospective cohort study investigating the relation between 25(OH)D3 levels and stages of cirrhosis, mortality and complications of cirrhosis, including infections. Results 251 patients with cirrhosis were enrolled into the present prospective cohort study. 25(OH)D3 levels were quantified by radioimmunoassay from serum samples obtained at study inclusion. The mean follow-up time was 411 ± 397 days with a range of 1-1382 days. 30 (12.0%) patients underwent liver transplantation and 85 (33.8%) individuals died within the study. The mean serum 25(OH)D3 concentration was 8.93 ± 7.1 ng/ml with a range of 1.0 to 46.0 ng/ml. 25(OH)D3 levels differed significantly between Child Pugh scores and showed a negative correlation with the model of end stage liver disease (MELD) score. Patients with decompensated cirrhosis and infectious complications, had significantly lower 25(OH)D3 levels compared to subjects without complications. Low 25(OH)D3 was associated with mortality in uni- as well as multivariate Cox regression models. Conclusions 25(OH)D3 deficiency is associated with advanced liver disease and low 25(OH)D3 levels are an indicator for a poor outcome and are associated with infectious complications.

Management of cirrhotic ascites

Abstract: The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic ascites and its complications betters quality of life and increases survival. This paper summarizes the pathophysiology behind cirrhotic ascites and the diagnostic approaches, as well as outlining the current treatment options. Despite improved medical treatment of ascites, liver transplantation remains the ultimate treatment and early referral of the patient to a highly specialized hepatology unit should always be considered.

Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis

Abstract: Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

The impact of repeated autologous infusion of haematopoietic stem cells in patients with liver insufficiency

Abstract: The worldwide shortage of donor livers has prompted the search for alternative cell therapies Previous data from our laboratory proved a supportive role for stem cell therapy in the treatment of end-stage liver disease patients Therefore; this study was conducted to assess the clinical and biochemical effects of repeated stem cell infusion Ninety patients with liver cirrhosis were randomized to receive either one session treatment (G-I) or two sessions 4 months apart (G-II) of autologous haematopoietic stem cells (HSCs) transplantation and a control group (G-III) who received regular liver treatment G-CSF was administered to transplanted patients before infusion; HSCs were isolated from 400 cc bone marrow (BM) aspirate CD34+/CD133+ cells were purified: 50 % of the cells were infused locally in the portal vein on the same day and the other 50 % were differentiated to MSC and infused systemically in a peripheral vein (one session treatment G-I) In G-II, the same process was repeated after 4 months from the first treatment (two session’s treatment G-II) Liver function was monitored for 12 months after stem cell therapy (SCT) Statistically significant improvement was reported in the transplanted patients (G-1) as regards the mean serum albumin, bilirubin and INR levels which started to improve after 2 weeks of treatment and continued to improve till the 6th month in the single infusion group The two sessions infused group (G-II) showed sustained response which continued throughout the all follow-up period (12 month) By the end of the study, 367 % of the patients in G-I and 667 % in G-II showed improvement in the degree of ascites compared to the control group (G-III) We also reported an improvement in the hepatic functional reserve as assessed by the Child-Pugh and MELD score Safety of the procedure was evidenced by the low incidence of complications encountered In patients with end-stage liver disease, the repeated infusion with combined routes portal and peripheral veins has a beneficial effect on liver functions with minimal adverse events and more lasting clinical efficacy after repeated HSCs infusion

The treatment of vasopressin V2-receptor antagonists in cirrhosis patients with ascites: a meta-analysis of randomized controlled trials

Abstract: Ascites is the most common complication of cirrhosis. It may lead to the consequence of poor prognosis and the deterioration of quality of life. Asopressin V2 receptor antagonists is a kind of vaptans, and it has been proved to be effective in hyponatremia patients. We conducted a meta-analysis about treatment of vaptans in cirrhosis patients with ascites. Following our selection criteria, we collected a total of 14 studies containing 16 randomized controlled trials (2620 patients) from a series of database about the treatment with vaptans for cirrhosis with ascites patients. The included studies compared the treatment effect of lixivaptan (VPA 985), or RMJ-351647, or satavaptan, or tolvaptan with placebo. The included vaptans (asopressin V2 receptor antagonists) showed significant effect of increasing the serum sodium concentration for cirrhosis patients (WMD = 2.11 mmol/L, p 145 mmol/L) was more frequently noted in patients under the employment of vaptans (RR = 2.14, 95 % CI [1.45, 3.16], p = 0.0001). Whether with the administration of vaptans for short-term or long-term, no survival benefit was detected from the selected studies. Asopressin V2 receptor antagonists could play an effective and safe role in symptomatic treatment for cirrhosis patients with ascites, especially for refractory ascites patients who presented insufficient response to conventional diuretics.

Natural History of Cirrhosis

Abstract: Cirrhosis is a dynamic and potentially reversible disease. The natural history of cirrhosis is not the continuum of a single entity but is a progression across different prognostic stages, with the compensated and decompensated stages being the most important. Within the compensated stage, the presence or absence of varices is a key determinant in prognosis. In patients without varices, the main stratifying marker is a hepatic venous pressure gradient of 10 mmHg. Within decompensated cirrhosis, the occurrence of specific complications (ascites, variceal hemorrhage, and encephalopathy) adds to the prognostic granularity of the stage. A stage of “further” decompensation, as defined by the development of refractory ascites, hepatorenal syndrome, recurrent variceal hemorrhage, and recurrent/persistent hepatic encephalopathy, is likely to provide a larger prognostic differential among patients with decompensated cirrhosis. A final stage characterized by multi-organ failure, termed “acute-on-chronic” liver failure, is associated with the worst prognosis. This chapter provides an overview of the various prognostic stages and their significance for patients with cirrhosis.

The ratio of calprotectin to total protein as a diagnostic and prognostic marker for spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites.

Abstract: BACKGROUND Diagnosis of spontaneous bacterial peritonitis (SBP) is based on a differential ascites leukocyte count which does not provide prognostic information. We performed a pilot study to assess calprotectin in ascites as an alternative diagnostic and prognostic marker. METHODS We collected ascites from patients with liver cirrhosis from March 2012 to July 2013. Routine clinical and laboratory data of the patients were recorded. Ascites calprotectin levels were determined by ELISA. RESULTS Overall, we collected 120 ascites samples from 100 patients with liver cirrhosis and from eight patients with malignant peritoneal effusion as disease control. Samples without infection had significantly lower calprotectin levels (median 34 ng/mL, range 5-795) than SBP samples (median 928 ng/mL, range 21-110,480; p<0.001) and malignant effusions (median 401, range 47-2596 ng/mL; p<0.001). In non-infected ascites, calprotectin levels were higher in Child-Pugh stage B versus C (median 57 ng/mL vs. 17 ng/mL; p<0.001) and in alcoholic versus viral cirrhosis (median 37 ng/mL vs. 10 ng/mL; p=0.015). The ratio of ascites calprotectin to total protein was a better marker for SBP than calprotectin alone (AUROC=0.93; p<0.001; sensitivity 93%, specificity 79%; positive predictive value 60%; negative predictive value 97%). In addition, high levels of the ratio to total protein were associated with poor 30-day survival (p=0.042). CONCLUSIONS The ratio of ascites calprotectin to total protein may be a promising new diagnostic and prognostic marker in patients with liver cirrhosis and SBP and should be evaluated further.

Successful surgical management of ruptured umbilical hernias in cirrhotic patients

Abstract: Acute umbilical hernia rupture in patients with hepatic cirrhosis and ascites is an unusual, but potentially life-threatening complication, with postoperative morbidity about 70% and mortality between 60%-80% after supportive care and 6%-20% after urgent surgical repair. Management options include primary surgical repair with or without concomitant portal venous system decompression for the control of the ascites. We present a retrospective analysis of our centre’s experience over the last 6 years. Our cohort consisted of 11 consecutive patients (median age: 53 years, range: 36-63 years) with advanced hepatic cirrhosis and refractory ascites. Appropriate patient resuscitation and optimisation with intravenous fluids, prophylactic antibiotics and local measures was instituted. One failed attempt for conservative management was followed by a successful primary repair. In all cases, with one exception, a primary repair with non-absorbable Nylon, interrupted sutures, without mesh, was performed. The perioperative complication rate was 25% and the recurrence rate 8.3%. No mortality was recorded. Median length of hospital stay was 14 d (range: 4-31 d). Based on our experience, the management of ruptured umbilical hernias in patients with advanced hepatic cirrhosis and refractory ascites is feasible without the use of transjugular intrahepatic portosystemic shunt routinely in the preoperative period, provided that meticulous patient optimisation is performed.

Impact of acute kidney injury on prognosis of patients with liver cirrhosis and ascites: A retrospective cohort study.

Abstract: Background and Aim Acute kidney injury (AKI) is a common complication in patients with liver cirrhosis, and its impact on the clinical course is increasingly recognized. Diagnostic classification systems for AKI in cirrhosis have been suggested. The prognostic significance of the respective AKI stages remains to be evaluated in decompensated cirrhosis with ascites. Methods Data of consecutive patients with cirrhosis and ascites undergoing paracentesis at a tertiary care center were analyzed. AKI was defined as an increase in serum creatinine of ≥ 0.3 mg/dL or by ≥ 50% within 7 days after paracentesis, and classified according to (i) revised Acute Kidney Injury Network (AKIN) criteria and (ii) modified AKI criteria for cirrhosis (C-AKI). In contrast to AKIN, C-AKI stage A discriminates prognosis based on an absolute creatinine cut-off at < 1.5 mg/dL versus C-AKI stage B at ≥ 1.5 mg/dL. Results The final study cohort included 239 patients. Median transplant-free survival was 768 days (95% confidence interval [CI]: 331–1205 days) without AKI, 198 (0–446) in AKI-1, 91 (0–225) in AKI-2, 19 (0–40) and in AKI-3, whereas it was 89 (20–158) days in C-AKI-A, 384 (0–1063) in C-AKI-B, and 22 (7–776) in C-AKI-C. Mild AKI was already associated with significantly increased 30-day mortality (AKI-1:26.4%, C-AKI-A:33.3%) as compared with patients without AKI (14.3%), even when serum creatinine remained within normal range (< 1.2 mg/dL) we observed a significant 30-day mortality. Conclusion AKIN criteria—considering small increases in serum creatinine rather than absolute thresholds—seem to be more accurate for estimating prognosis of AKI after paracentesis than C-AKI criteria. Even patients developing AKI-1 with “normal” serum creatinine are at increased risk for mortality.

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPSS) in 40 patients with hepatocellular carcinoma

Abstract: Summary Background Portal hypertension and hepatocellular carcinoma (HCC) are major complications of advanced liver cirrhosis. Thus, patients are often affected by both complications. Transjugular intrahepatic portosystemic shunt (TIPSS) is an effective treatment for portal hypertension and its complications. However, no established guidelines for the treatment of symptomatic portal hypertension in HCC patients are currently available. In addition, only limited information exists about the consequence of TIPSS implantation in patients with HCC. Aim To evaluate the efficacy, safety and overall survival in HCC patients who underwent TIPSS implantation. Methods Forty HCC patients with portal hypertension who were treated with TIPSS between 1995 and 2012 were included in the analysis. Medical records and imaging studies were analysed. The indication for TIPSS implantation, procedure-related complications, treatment success and overall survival were assessed. Results TIPSS implantation was performed in 23 patients (57.5%) due to treatment refractory ascites, in 14 patients (35.0%) due to recurrent variceal bleeding and in three patients (7.5%) due to ascites and variceal bleeding. Primary technical success was assessed in all patients. After TIPSS implantation, no variceal bleeding reoccurred and ascites was controlled in 74.1%. No severe procedure-related complications and no deterioration of liver function were observed. Post-TIPSS hepatic encephalopathy occurred in 40.0% of all patients. 30-day, 90-day-, 1-year- and 5-year survival rates were 97.5%, 75.0%, 42.5% and 7.5%, respectively. Median overall survival after TIPSS implantation was 180 days. Conclusion Transjugular intrahepatic portosystemic shunt implantation is an effective and safe treatment for portal hypertension in patients with HCC.