Effects of ascites resolution after successful TIPS on nutrition in cirrhotic patients with refractory ascites

OBJECTIVE: Malnutrition is common in patients with decompensated cirrhosis and refractory ascites. The use of transjugular intrahepatic portosystemic stent shunt (TIPS) is effective in eliminating ascites. The purpose of this study was to investigate the effect of TIPS and resolution of refractory ascites on the nutritional status of patients with decompensated cirrhosis. METHODS: Fourteen consecutive patients with refractory ascites and a Pugh score of 9.0+/-0.5 had a TIPS insertion. Biochemical data, resting energy expenditure (REE), total body nitrogen (TBN), body potassium (TBK), body fat (TBF), muscle force (MF), and food intake were recorded before TIPS, and at 3 and 12 months after the procedure. RESULTS: Ten patients completed the study. Baseline values for REE, TBN, TBF, MF, and energy intake were below normal at baseline. There was a significant increase in dry weight, TBN, and REE at 3 and 12 months compared with baseline. TBF improved significantly at 12 months. There was a trend toward an increase in energy intake (p = 0.072). There was no change in protein intake, TBK, MF, and Pugh score. CONCLUSION: In cirrhotic patients with refractory ascites, resolution of the ascites after TIPS placement resulted in improvement of several nutritional parameters, especially for body composition.     

Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites

Aim

Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra‐abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites.

Methods

Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non‐contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins.

Results

The inter‐observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One‐year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67–5.20) and a high Model for End‐stage Liver Disease score combined with serum sodium level (MELD‐Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00–5.74) were significant independent predictors of mortality.

Conclusions

Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD‐Na score.     

Six-minute walk test before and after large-volume paracentesis in cirrhotic patients with refractory ascites: A pilot study

Background/AimsFunctional impairment is common among cirrhotic patients with refractory ascites, and improvement in functional impairment is an expected issue after paracentesis. The six-minute walk test (6MWT) is considered an objective test for functional activity. No published data have evaluated the 6MWT among cirrhotic patients with refractory ascites before and after large-volume paracentesis. The research aim was to assess the feasibility of performing the 6MWT among cirrhotic patients who had refractory ascites before and after large-volume paracentesis.Materials and MethodsThirty-one cirrhotic inpatients with refractory ascites were subjected to pulmonary function tests (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], FEV1/FVC) and diffusion lung capacity for carbon monoxide (DLCO) before and 48 h after therapeutic large-volume paracentesis. Dyspnoea as assessed by the Borg scale and functional capacity as assessed by the 6MWT were also evaluated.ResultsPrior to paracentesis, the mean values of FVC and FEV1 were lower than the predicted values, and a significant increase was observed after paracentesis. There was improvement in the mean DLCO values after paracentesis (P < 0.05). Regarding the 6MWT, significant increases in the walked distance (6MWD) (310.7 ± 73 vs. 348.7 ± 72.3 m) and oxygen saturation after paracentesis (P = 0.001) were observed. Significant improvement in the dyspnoea scale also occurred after paracentesis (P = 0.001). A significant positive correlation between the 6MWD before paracentesis and serum albumin levels was demonstrated (r = 0.373, P = 0.039).ConclusionWe found a decrease in pulmonary function and the 6MWD in patients who had refractory ascites, which improved significantly following large-volume paracentesis. The 6MWT is useful in detecting impaired functional capacity among cirrhotic patients.     

External validation of a prognostic model for predicting survival of cirrhotic patients with refractory ascites

OBJECTIVE: Cirrhotic patients with refractory ascites (RA) have a poor prognosis, although individual survival varies greatly. A model that could predict survival for patients with RA would be helpful in planning treatment. Moreover, in cases of potential liver transplantation, a model of these characteristics would provide the bases for establishing priorities of organ allocation and the selection of patients for a living donor graft. Recently, we developed a model to predict survival of patients with RA. The aim of this study was to establish its generalizability for predicting the survival of patients with RA. METHODS: The model was validated by assessing its performance in an external cohort of patients with RA included in a multicenter, randomized, controlled trial that compared large-volume paracentesis and peritoneovenous shunt. The values for actual and model-predicted survival of three risk groups of patients, established according to the model, were compared graphically and by means of the one-sample log-rank test. RESULTS: The model provided a very good fit to the survival data of the three risk groups in the validation cohort. We also found good agreement between the survival predicted from the model and the observed survival when patients treated with peritoneovenous shunt and with paracentesis were considered separately. CONCLUSION: Our survival model can be used to predict the survival of patients with RA and may be a useful tool in clinical decision making, especially in deciding priority for liver transplantation.     

Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study

BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics.The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics.CONCLUSION Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites.A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria,thus improving the systemic inflammatory state.     

术前穿刺置管持续腹水引流对肝硬化伴顽固性腹水患者肝移植效果的影响

目的 评价术前穿刺置管持续腹水引流对拟行肝移植的肝硬化伴顽固性腹水患者肝移植效果的影响.方法 将2003年2月-2005年12月在我院行肝移植术的肝硬化伴顽固性腹水患者随机分为对照组(单纯药物治疗)和实验组(术前加穿刺置管腹水引流),分析治疗效果,并对肝移植疗效(包括随访)进行比较.结果 实验组穿刺置管腹水引流操作中无并发症发生,治疗后症状缓解率明显高于对照组,体重降低,尿量增加,尿蛋白降低,移植后半年血肌酐明显低于治疗前.对照组治疗后较治疗前MELD评分分值显著性升高.结论 术前穿刺置管持续腹水引流技术安全稳定,相比单纯药物治疗,综合治疗能够提高肝硬化伴顽固性腹水患者的术前状况.     

Effects of repeated atrial natriuretic peptide bolus injections in cirrhotic patients with refractory ascites

The renal and hormonal effects of repeated atrial natriuretic peptide (ANP) boli (1 microgram/kg of body weight) were studied in eight cirrhotic patients with refractory ascites. Under basal conditions the patients showed a striking activation of the renin-angiotensin-aldosterone system (plasma renin activity 19.3 +/- 3.0 ng/ml.h, plasma aldosterone concentration 3.87 +/- 0.58 ng/ml) and a tenfold elevation in plasma ANP levels compared to healthy subjects (131.7, range 47.0-288.6, vs. 9.8, range 5.0-15.0, fmol/ml, p less than 0.001). The first ANP injection was followed by a remarkable increase in plasma ANP levels and by a slight increase in urinary cyclic guanosine-monophosphate excretion (from 1050.8 +/- 454.8 to 1446.6 +/- 822.2 pmol/min). A significant reduction of mean blood pressure (MBP) occurred 5 min after the first injection (from 86.7 +/- 7.2 to 79.9 +/- 5.8 mmHg, p less than 0.05), but values gradually returned to the baseline after 30 min. Heart rate (HR) increased 10 min after the first bolus injection (from 83.75 +/- 4.7 to 88.1 +/- 4.6 beats/min) and reached baseline values after 30 min. Similar behaviour of MBP and HR was observed after the second, third and fourth bolus injections. Urinary sodium excretion, urinary flow, glomerular filtration rate, plasma renin activity, and plasma aldosterone concentration did not show any significant modification during ANP administration, nor did these parameters change in the following 12-h recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of peritoneovenous shunt in refractory cirrhotic ascites in Indian patients.

Ten patients with tense and refractory cirrhotic ascites underwent a modified peritoneovenous shunt procedure. Nine patients responded with complete resolution of ascites, mean weight gain of 5 (range 0-8) Kg, and rise in serum albumin level of 0.6 g/dL. Six patients improved from Child's class B to A. The longest survival period was 2.3 years. The main constraint in a developing country is the high cost of the shunt.     

TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites:An updated meta-analysis

AIM:To compare the liver transplantation-free(LTF)survival rates between patients who underwent transjugular intrahepatic portosystemic shunts(TIPS)and those who underwent paracentesis by an updated meta-analysis that pools the effects of both number of deaths and time to death.METHODS:MEDLINE,EMBASE,and the Cochrane Library were searched from the inception to October2012.LTF survival,liver transplantation,liver diseaserelated death,non-liver disease-related death,recurrent ascites,hepatic encephalopathy(HE)and severe HE,and hepatorenal syndrome were assessed as outcomes.LTF survival was estimated using a HR with a95%CI.Other outcomes were estimated using OR with95%CIs.Sensitivity analyses were performed to assess the effects of potential outliers in the studies according to the risk of bias and the study characteristics.RESULTS:Six randomized controlled trials with 390patients were included.In comparison to paracentesis,TIPS significantly improved LTF survival(HR=0.61,95%CI:0.46-0.82,P<0.001).TIPS also significantly decreased liver disease-related death(OR=0.62,95%CI:0.39-0.98,P=0.04),recurrent ascites(OR=0.15,95%CI:0.09-0.24,P<0.001)and hepatorenal syndrome(OR=0.32,95%CI:0.12-0.86,P=0.02).However,TIPS increased the risk of HE(OR=2.95,95%CI:1.87-4.66,P=0.02)and severe HE(OR=2.18,95%CI:1.27-3.76,P=0.005).CONCLUSION:TIPS significantly improved the LTF survival of cirrhotic patients with refractory ascites and decreased the risk of recurrent ascites and hepatorenal syndrome with the cost of increased risk of HE compared with paracentesis.Further studies are warranted to validate the survival benefit of TIPS in clinical practice settings.     

Current approaches to the management of patients with cirrhotic ascites

This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords:“liver cirrhosis,”“portal hypertension,”“ascites,”“pathogenesis,”“diagnostics,” and “treatment.” Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.     

Predictors of clinical response to transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with refractory ascites

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) is used increasingly as a treatment for refractory ascites. The aim of the present study was to determine the prognostic value of different parameters in predicting a favorable evolution following TIPS in a cohort of 53 cirrhotic patients without organic renal disease and with refractory ascites. METHODS: Patients were classified as good responders if they survived more than 6 months, without severe chronic hepatic encephalopathy and with good control of ascites. The prognostic value for a good outcome was evaluated using age, creatinine clearance, plasma renin activity, plasma aldosterone, and Pugh score. RESULTS: Good control of ascites was obtained in 90%. The cumulative survival rate was 54% at 6 months, 48% at 1 yr, and 39% at 2 yr. The vast majority of patients died of complications of hepatic insufficiency. Severe chronic hepatic encephalopathy developed in 26%. Overall, a good clinical response was observed in 47%. Creatinine clearance was identified as the only pre-TIPS factor to be significantly and independently associated with a good clinical response to TIPS for refractory ascites. A good clinical response was observed in 57% of patients with a creatinine clearance >36 ml/min compared to 9% of those with a clearance <36 ml/min (p < 0.01). This cutoff point in creatinine clearance had a sensitivity of 96% and a specificity of 36%; positive predictive and negative predictive values were 57% and 90%, respectively. CONCLUSIONS: TIPS might be useful for the treatment of refractory ascites in cirrhotic patients without severe renal function impairment. However, the TIPS usefulness still has to be demonstrated compared to large volume paracentesis or Leveen shunt. In patients with poor renal function or with liver failure after TIPS, liver transplantation should be considered.     

The use of terlipressin in cirrhotic patients with refractory ascites and normal renal function: a multicentric study

Ascites is a common complication of liver cirrhosis, occurring in more than 50-60% of the patients within 10 years of the diagnosis. In 5-10% of patients, ascites cannot be mobilized, or its early recurrence cannot be prevented by medical treatment. This condition is known as “refractory ascites”. The use of terlipressin in cirrhotic patients with refractory ascites and normal renal function has not been evaluated. This prospective study was aimed at evaluating whether terlipressin in addition to standard therapy (diuretics plus albumin) might improve the outcome of refractory ascites in cirrhotic patients without HRS.

Patients

26 cirrhotic patients with refractory ascites were prospectively enrolled in this study. All the patients had tense (grade 3) ascites, and 10/26 showed also massive peripheral edema. Patients received maximum diuretic treatment plus albumin and terlipressin.

Results

Complete response was seen in 16/26 patients. The higher response to therapy was seen during the 2nd week of treatment. 6 patients showed a decrease of at least two points in the ascites score. No differences in clinical response to treatment were seen according to the etiology of the disease.

Conclusions

In conclusion, our study shows a synergistic effect of terlipressin vs treatment with albumin plus diuretics in patients with refractory ascites. One could speculate that albumin might enhance the vasoconstrictive response to terlipressin, thus contributing to counterbalance the negative effects of systemic vasodilation, which characterizes the hyperdynamic circulation of cirrhotic patients.     

Acute effects of peritoneovenous shunting on plasma atrial natriuretic peptide in cirrhotic patients with massive refractory ascites

Plasma immunoreactive alpha-human atrial natriuretic peptide (ANP) was measured in six cirrhotic patients with massive refractory ascites, under strict metabolic conditions, while they were receiving a 20-meq sodium diet, both before and at two-hour intervals for eight hours following peritoneovenous shunting (PVS). The mean preoperative level of ANP was 75 +/- 18 pg/ml, which was found to be significantly higher than the normal range for this laboratory (8 to 24 pg/ml) (p less than 0.05). This value was also significantly higher than the value of 21 +/- 5 pg/ml (p less than 0.05) obtained in six patients with cirrhosis but without ascites. Following shunt insertion, an immediate natriuresis and diuresis were observed in five of the six cirrhotic patients with refractory ascites. In these five, right atrial pressure and ANP rose immediately, followed by a rise in the level of urinary cyclic guanosine monophosphate. The sixth subject had a delayed rise in right atrial pressure, and correspondingly the rise in ANP, the diuresis, and natriuresis were delayed. The changes in ANP following PVS were positively correlated with changes in right atrial pressure (p less than 0.05), urinary cyclic guanosine monophosphate (p less than 0.05), urinary sodium excretion (p less than 0.05), and urine volume (p less than 0.01). These results suggest that ANP may be important in mediating the acute response to PVS.     

如何理解肝硬化腹水患者限钠与补钠问题

近年肝硬化腹水、肝肾综合征(HRS)文章较多,对其发病机制是否有指导意义提出了异议,出现了限钠与不限钠(或补钠)两种截然不同的观点,对以下问题应予以关注.     

肝硬化腹水合并低钠血症补充钠盐治疗的临床意义

目的:探讨对肝硬化腹水合并低钠血症患者积极补充钠盐治疗的临床意义。方法:测定120例肝硬化腹水低钠血症患者的血钠水平,并依结果将患者分为轻、中、重度低钠血症组,分析其并发症的发生率。根据患者血钠水平,在综合治疗和利尿的基础上补充氯化钠,观察治疗后病情的转归情况。结果:轻、中、重度低钠血症组合并低渗性脑病的发生率分别为0%、10.4%和37.5%,肝肾综合征的发生率分别为0%、8.2%和25.0%,合并顽固性腹水的发生率分别为7.5%、20.8%和43.8%。积极补充钠盐后,随血钠浓度的提高,患者24h尿量显著增加,腹水明显消退,低渗性脑病症状明显减轻或消失,肾功能明显好转。结论:肝硬化腹水合并低钠血症患者并发症的发生率与血钠水平呈负相关,适当及时补充钠盐是重要的辅助治疗措施,有利于腹水的消退及临床症状的改善。     

Intestinal permeability in cirrhotic patients with and without ascites

OBJECTIVE: It has been suggested that increased intestinal permeability plays a pathogenic role in bacterial infections, such as spontaneous bacterial peritonitis, in patients with liver cirrhosis. The aim of this study was to assess whether intestinal permeability is altered in cirrhotic patients with and without ascites. MATERIAL AND METHODS: Intestinal permeability was assessed by a (51)Cr-EDTA permeability test in 20 cirrhotic patients (10 with and 10 without ascites) along with 20 age- and gender-matched healthy controls. In six patients with ascites, the test was performed before and after therapeutic paracentesis. RESULTS: The median (IQR) 24-h urinary excretion of (51)Cr-EDTA was higher in patients with cirrhosis (1.94% (1.21-2.70%)) compared with that in controls (1.40% (1.09-1.99%); p<0.05). Patients with (2.05% (1.50-3.46%); p<0.05) but not those without ascites (1.94% (1.13-2.53%); p>0.1) had significantly higher excretion values compared with those of controls. Only one patient without ascites and a total of four patients with ascites had increased intestinal permeability ((51)Cr-EDTA excretion > 95% confidence than that of controls; p>0.1). Paracentesis did not affect urinary (51)Cr-EDTA excretion significantly (1.69% (1.16-2.86%) versus 1.30% (1.08-1.79%) before and after, respectively; p>0.1). No significant correlation was found between clinical severity scores for liver disease and intestinal permeability. CONCLUSIONS: Only a small proportion of patients with liver cirrhosis have increased intestinal permeability and it is unlikely that this plays any major role in predisposing these patients to infections.