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Article

Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis

by
Zhaohui Bai
1,2,
Le Wang
2,
Hanyang Lin
2,
Frank Tacke
3,
Gang Cheng
1,* and
Xingshun Qi
1,2,*
1
NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang 110016, China
2
Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
3
Department of Hepatology & Gastroenterology, Charité University Medical Center, 10117 Berlin, Germany
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2022, 11(19), 5928; https://doi.org/10.3390/jcm11195928
Submission received: 6 August 2022 / Revised: 15 September 2022 / Accepted: 28 September 2022 / Published: 8 October 2022
(This article belongs to the Special Issue Liver Cirrhosis: Advances in Clinical Management)
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Abstract

:
Background. Hyponatremia is a common complication of liver cirrhosis and aggravates patients’ outcomes. It may be corrected by human albumin (HA) infusion. Herein, we have conducted a systematic review and meta-analysis to evaluate the efficacy of intravenous HA administration for the prevention and treatment of hyponatremia in liver cirrhosis. Methods. Literature was searched in the PubMed, EMBASE, and Cochrane Library databases. If possible, a meta-analysis would be conducted. Incidence of hyponatremia, rate of resolution of hyponatremia, and serum sodium level were compared between cirrhotic patients who received and did not receive HA infusion. Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results. Initially, 3231 papers were identified. Among them, 30 studies, including 25 randomized controlled trials (RCTs) and 5 cohort studies, were eligible. Among cirrhotic patients without hyponatremia, the HA infusion group had significantly lower incidence of hyponatremia (OR = 0.55, 95%CI = 0.38–0.80, p = 0.001) and higher serum sodium level (MD = 0.95, 95%CI = 0.47–1.43, p = 0.0001) as compared to the control group. Among cirrhotic patients with hyponatremia, the HA infusion group had a significantly higher rate of resolution of hyponatremia (OR = 1.50, 95%CI = 1.17–1.92, p = 0.001) as compared to the control group. Generally, the quality of available evidence is low. Conclusions. Based on the current evidence, HA may be considered for preventing the development of hyponatremia in liver cirrhosis, especially in those undergoing LVP, and treating hyponatremia. Well-designed studies are required to clarify the effects of HA infusion on hyponatremia in liver cirrhosis.

1. Introduction

Hyponatremia, a common complication of liver cirrhosis [1], is divided into mild (serum sodium level 135–130 mmol/L), moderate (130–125 mmol/L), and severe (<125 mmol/L) [2]. The prevalence of serum sodium levels of <135 mmol/L, <130 mmol/L, <125 mmol/L, and <120 mmol/L is 49.4%, 21.6%, 5.7%, and 1.2% in total cirrhotic patients, respectively [3]. Mild hyponatremia is often asymptomatic; by comparison, moderate and severe hyponatremia can cause nausea, cognitive impairment, headache, and even coma [4]. Hyponatremia is classified as hypovolemic, euvolemic, and hypervolemic according to the volume status on the clinical examinations [1]. In patients with liver cirrhosis, about 90% of hyponatremia is hypervolemic, which is primarily due to increased extracellular fluid volume (Figure 1), and the remaining 10% is hypovolemic or euvolemic, which is frequently caused by over-diuresis [5]. Hyponatremia is significantly associated with worse outcomes in liver cirrhosis [6,7,8]. More importantly, serum sodium level has been incorporated into the model for end-stage liver disease (MELD) score, which is defined as the MELD-Na score, to determine the priority of liver transplantation [9].
Currently, water restriction and isotonic saline are the mainstay treatment options for hyponatremia, but their efficacy is limited [10]. Additionally, discontinuation of diuretics [11], correction of hypokalemia [12,13], and use of vasopressin receptor antagonists [14,15] have been attempted to manage mild and moderate hyponatremia, but their efficacy and safety remain to be further validated. Hypertonic saline is only reserved for severe symptomatic hyponatremia, such as seizure, cardiopulmonary distress, and coma [16].
The use of human albumin (HA) in the management of liver cirrhosis with hyponatremia remains controversial among the current practice guidelines. Japanese and Italian practice guidelines suggest that HA should be used to prevent and/or treat hyponatremia in liver cirrhosis [17,18], but the American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Chinese guidelines have not recommended the use of HA in such cases yet [19,20,21]. The heterogeneity in the guideline recommendations may be attributed to the scarcity of high-quality evidence.
To the best of our knowledge, only several previous meta-analyses partly evaluated the role of HA infusion in the prevention of hyponatremia in liver cirrhosis after large volume paracentesis (LVP) [22,23,24,25,26,27], but the conclusions were heterogeneous among them. Additionally, the preventive and therapeutic effects of HA infusion on hyponatremia in general liver cirrhosis have not been systematically evaluated. Herein, we attempted to collect all existing evidence regarding this topic and combine the relevant data to further address this issue.

2. Methods

2.1. Registration

The current study was registered in the PROSPERO. The registration number is CRD42021233576.

2.2. Literature Search

We searched 3 major electronic databases (i.e., PubMed, EMBASE, and Cochrane Library). The last search date was 13 September 2022. Search items were as follows: ((colloid [All Fields]) OR (albumin [All Fields]) OR (HSA [All Fields])) AND ((cirrhosis [All Fields]) OR (cirrhotic [All Fields])) AND ((hyponatremia [All Fields]) OR (hyponatraemia [All Fields]) OR (sodium [All Fields]) OR (Na [All Fields])).

2.3. Study Selection Criteria

Two researchers (Dr. Bai and Dr. Wang) individually selected eligible studies by screening the title, abstract, and full text. Studies would be eligible for inclusion if they explored the effect of HA on the prevention or treatment of hyponatremia in cirrhotic patients. Exclusion criteria were as follows: (1) duplicates; (2) guidelines, reviews, or meta-analyses; (3) case reports, comments, or letters; (4) experimental or animal studies; (5) studies unrelated to liver cirrhosis; (6) studies unrelated to HA; (7) studies unrelated to hyponatremia; (8) the sample size was less than 10.

2.4. Definitions and Outcomes

Definitions of hyponatremia in liver cirrhosis are in accordance with those of each included study. The primary outcome is the incidence of hyponatremia after treatment. The secondary outcome is serum sodium level after treatment.

2.5. Data Extraction

Data were extracted by 2 researchers (Dr. Bai and Dr. Wang) from each study, mainly including first author, publication year, country, characteristics of patients, sample size, etiology of liver cirrhosis, the definition of hyponatremia, dosage of HA infused, the total number of patients, number of patients with hyponatremia, and serum sodium level after treatment. Disagreement was resolved by discussion among researchers.

2.6. Study Quality Assessment

For randomized controlled trials (RCTs), the Cochrane Risk of Bias tool was used to assess the risk of bias, which includes random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. For cohort studies, the Newcastle-Ottawa Scale (NOS) was used to assess the study quality, which includes 3 parts (i.e., selection, comparability, and outcomes) and 8 indicators. High-quality cohort studies are defined if 5 or more points are given.

2.7. Statistical Analysis

Meta-analysis was performed by the Review Manager software (Version 5.3, The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata SE (Version 12.0, Stata Corp, College Station, TX, USA). Dichotomous outcomes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs), and continuous outcomes were expressed as mean differences (MDs) with 95% CIs. A random-effects model was employed. A p-value < 0.05 was considered statistically significant. Cochrane Q test and I² statistics were employed to assess the heterogeneity, and a p-value < 0.1 or I² > 50% was considered a statistically significant heterogeneity. Sensitivity analyses, meta-regression analyses, and subgroup analyses were used to explore the source of heterogeneity. Meta-regression analyses were performed by 5 covariates, which included publication year (before and after 2000), region (Asia, Europe, America, and Africa), sample size (> and <100), type of control group, and LVP or not. Subgroup analyses were also conducted in terms of the above-mentioned variables. When there were ≥10 studies included in a meta-analysis, the publication bias was assessed by a visual assessment of funnel plot asymmetry [28,29,30]. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system [31] was employed to assess the quality of evidence for the meta-analysis.

3. Results

3.1. Study Selection

Overall, we identified 3231 papers from the PubMed, Embase, and Cochrane Library databases and manual retrieval. Thirty-four studies were potentially eligible. Notably, four studies were further excluded, because they explored malignant ascites, acute-on-chronic liver failure with ascites, and unclassified ascites [32,33,34], or the sample size was less than 10 [35]. Finally, 30 studies were included [36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65] (Figure 2).

3.2. Study Characteristics

The characteristics of included studies are listed in Table 1 and Table S1. Twenty-nine studies were published as full texts and one as abstract. According to the countries where studies were conducted, five studies were conducted in Spain [36,37,42,48,61], three in the USA [55,59,60], three in Mexico [40,41,46], three in France [43,47,49], three in Egypt [54,56,62], three in Italy [38,44,65], three in the UK [51,63,64], two in India [50,53], two in Germany [45,52], one in Argentina [39], one in Pakistan [57], and one in Iran [58]. The sample size ranged from 16 to 1126. The publication year ranged from 1988 to 2022.

3.3. Study Quality

Seventeen studies had low risk in random sequence generation [36,37,40,42,43,44,46,48,49,52,53,54,55,56,58,61,62], nineteen had low risk in allocation concealment [36,37,38,39,40,42,43,44,46,47,48,49,52,53,54,55,56,58,61], three had low risk in blinding of participants and personnel [53,55,61], three had low risk in blinding of outcome assessment [53,55,61], twenty-two had low risk in incomplete outcome data [36,37,38,39,40,42,43,44,46,47,48,49,50,53,54,55,56,57,58,61,62,64], twenty-three had low risk in selective reporting [36,37,38,39,40,42,43,44,46,47,48,49,50,52,53,54,55,56,57,58,61,62,64], and nine had low risk in other bias [40,42,44,46,47,49,50,61,62] (Figure S1). Among the five cohort studies, all were of high quality [45,59,60,63,65] (Table S2).

3.4. HA for the Prevention of Hyponatremia

3.4.1. Incidence of Hyponatremia

Eighteen studies, including 1318 cirrhotic patients, provided data regarding the effect of HA on the development of hyponatremia [36,37,38,39,40,41,42,43,45,46,47,48,49,50,54,61,62,64]. Meta-analysis showed that the incidence of hyponatremia was significantly lower in HA infusion groups than in control groups (OR = 0.55, 95%CI = 0.38–0.80, p = 0.001) (Figure 3). Publication bias was not statistically significant (Figure S2A). The heterogeneity was not statistically significant (I2 = 0%, p = 0.95) (Figure 3). Thus, sensitivity, meta-regression, and subgroup analyses were not performed.

3.4.2. Serum Sodium Level

Nineteen RCTs, including 1295 cirrhotic patients, provided data regarding the effect of HA infusion on serum sodium levels [36,37,38,39,40,42,43,44,46,48,50,52,53,54,55,56,57,58,62]. Meta-analysis showed that serum sodium level was significantly higher in HA infusion groups than control groups (MD = 0.95, 95%CI = 0.47–1.43, p = 0.0001) (Figure 4). Publication bias was statistically significant (Figure S2B). The heterogeneity was statistically significant (I2 = 79%, p < 0.00001) (Figure 4). Sensitivity analysis did not find the source of heterogeneity (Figure S3). Meta-regression analysis found that the source of heterogeneity might be the target population (Table S3). Subgroup analyses demonstrated that the heterogeneity might be related to the type of control group because the heterogeneity was not statistically significant in the studies where dextran (I2 = 0%, p = 0.97) and midodrine (I2 = 33%, p = 0.21) were used in the control group (Table S4).

3.5. HA for the Treatment of Hyponatremia

3.5.1. Resolution of Hyponatremia

Two studies, including 1270 cirrhotic patients, provided data regarding the effect of HA on the resolution of hyponatremia [60,65]. Meta-analysis showed that the resolution of hyponatremia was significantly more common in the HA infusion group than in the control group (OR = 1.50, 95%CI = 1.17–1.92, p = 0.001). Publication bias could not be evaluated, because the number of included studies was <10 in this meta-analysis. Among them, the heterogeneity was not statistically significant (I2 = 0%, p = 0.32) (Figure 5). Thus, sensitivity, meta-regression, and subgroup analyses were not performed.

3.5.2. Serum Sodium Level

Three studies reported a change in serum sodium level after HA infusion in patients with hyponatremia, and all of them demonstrated significantly increased serum sodium levels after HA infusion in patients with hyponatremia. However, their data expression was so heterogeneous that a meta-analysis could not be performed. In detail, an RCT by Jalan et al. [51] reported that the mean serum sodium level after HA infusion was increased from 124 ± 2 mmol/L to 133 ± 6 mmol/L in 12 patients with serum sodium levels < 130 mmol/L; a retrospective cohort study by Shen et al. [59] reported that the mean increase in serum sodium level in HA infusion group was 5.043 ± 19.0 mmol/L in 55 patients with serum sodium level < 130 mmol/L; and secondary analysis of data from an RCT by China et al. [63] reported that the mean increase in serum sodium level when HA infusion group was compared with control group was 1.77 mmol/L (95%CI = 1.04–2.51) in 103 patients with serum sodium level < 130 mmol/L.

3.6. Quality of Evidence

Based on the GRADE summaries, the quality of evidence is low or very low (Table S5).

4. Discussion

The current systematic review and meta-analysis of 30 studies involving 3298 cirrhotic patients comprehensively explored the effect of HA on the prevention and treatment of hyponatremia. We found that HA might be considered for preventing the development of hyponatremia in liver cirrhosis, especially in those undergoing LVP, and treating hyponatremia. However, the evidence is of low quality and insufficient.
To our knowledge, six previous meta-analyses by Bernardi [22], Kwok [23], Kütting [24], Simonetti [25], Zheng [26], and Shrestha [27], primarily evaluated the efficacy of HA infusion for the prevention of post-paracentesis circulatory dysfunction in cirrhotic patients undergoing LVP, also reported the relevant data regarding its impact on the prevention of hyponatremia after LVP. By comparison, the current meta-analysis has several strengths. First, six previous meta-analyses just included cirrhotic patients undergoing LVP [22,23,24,25,26,27], but the current meta-analysis included general cirrhotic patients. Second, six previous meta-analyses just explored the prevention of hyponatremia after LVP [22,23,24,25,26,27]; by comparison, the current meta-analysis not only explored the prevention of hyponatremia, but also the treatment of hyponatremia. Third, six previous meta-analyses just pooled the incidence of hyponatremia after LVP [22,23,24,25,26,27]; by comparison, the current meta-analysis not only pooled the incidence and improvement rate of hyponatremia but also pooled the serum sodium level after treatment. Fourth, Bernardi’s [22], Kwok’s [23], Kütting’s [24], Zheng’s [26], Simonetti’s [25] and Shrestha’s [27] meta-analyses included 13, 7, 14, 17, 11, and 13 studies, respectively; by comparison, the current meta-analysis included 25 studies regarding the prevention of hyponatremia. Finally, Bernardi’s [22], Kwok’s [23], Kütting’s [24], Zheng’s [26], and Shrestha’s [27] meta-analyses did not assess the quality of evidence, but the current meta-analysis and Simonetti’s [25] meta-analysis assessed it based on the GRADE system.
HA has been widely used for various complications of decompensated cirrhosis [66], including spontaneous bacterial peritonitis [67,68], hepatorenal syndrome [69], ascites [70], and hepatic encephalopathy [71]. However, the evidence supporting its use for hyponatremia is very limited. The current meta-analysis showed that HA might be advantageous for hyponatremia in liver cirrhosis. The benefits of HA can be explained by the pathological mechanism of hyponatremia in liver cirrhosis and the physiological function of HA (Figure 1).
The pathogenesis of hyponatremia in liver cirrhosis is multifactorial. Increased intrahepatic vascular resistance leads to the development of portal hypertension in advanced liver cirrhosis, which can induce hyperdynamic circulatory status [72,73]. Additionally, inflammatory factors are significantly increased in decompensated cirrhotic patients [74]. Both of them can lead to the overproduction of vasodilators, which mainly include nitric oxide, substance P, platelet-activating factor, and prostacyclin [75]. Splanchnic vasodilation will cause hypovolemia in the peripheral circulatory system, and then activate the renin-angiotensin-aldosterone-system and the secretion of antidiuretic hormone [4,16]. Aldosterone can activate the mineralocorticoid receptor on the distal convoluted tubule and collecting duct, and then reserve water and sodium [76]. Antidiuretic hormone can activate the V2 receptor on the renal collecting duct, and then reserve a large volume of water and increase urinary sodium excretion [77,78], subsequently developing hypervolemic hyponatremia.
HA is responsible for maintaining colloid osmotic pressure and influencing inflammatory pathways [79,80,81,82]. Therefore, it may act on the upstream pathogenesis of hyponatremia by improving the hyperdynamic circulatory status and clearing inflammatory factors [83]. By comparison, dextran, hydroxyethyl starch, hemaccel, midodrine, and terlipressin could improve hypovolemia and/or hyperdynamic circulatory status, but not clear inflammatory factors.
It should be acknowledged that the therapeutic value of HA for hyponatremia in liver cirrhosis is evaluated based on only one small RCT published as an abstract [51] and four cohort studies [59,60,63,65]. Additionally, the heterogeneity in study design is obvious among them. First, in Shen’s [59], China’s [63], and Zaccherini’s [65] studies, HA was selectively infused in the control group; by comparison, in Bajaj’s [60] study, no HA infusion was given in the control group. Second, HA was infused at a total dosage of 225 g in Bajaj’s [60] study, a total dosage of 239.4 g in China’s [63] study, and a dosage of 40 g twice weekly for 2 weeks, and then 40 g weekly in Zaccherini’s [65] study, but the dosage of HA infused was unclear in Shen’s [59] study. Third, baseline serum sodium level was 126.1 ± 4 mmol/L and 128.66 ± 4.69 mmol/L in Shen’s [59] and Bajaj’s [60] studies, respectively. By comparison, 78% of patients had mild hyponatremia with a serum sodium level of 130–135 mmol/L in Zaccherini’s [65] study, and the severity of hyponatremia was unclear in China’s [63] study. Fourth, the resolution of hyponatremia was evaluated in Bajaj’s [60] and Zaccherini’s [65] studies; by comparison, the change in serum sodium level was evaluated in Shen’s [59] and China’s [63] studies.
A major limitation of the current systematic review and meta-analysis is that most included studies focused on the prevention of hyponatremia in liver cirrhosis with ascites undergoing LVP. Notably, hyponatremia is also an important risk factor for ascites without LVP [84,85,86], hepatic encephalopathy [87,88], hepatorenal syndrome [89,90,91], and spontaneous bacterial peritonitis [92,93]. However, the role of HA for hyponatremia has not been separately explored in such complications. Another limitation is that the drugs/interventions employed in control groups are heterogeneous among included studies. Furthermore, cardiac disease, hepatorenal syndrome, and infection could also influence the development of hyponatremia in cirrhotic patients [94], but such relevant variables could not be extracted, thereby compromising further subgroup analyses. Finally, the impact of the prevention and correction of hyponatremia by HA on the survival of patients with liver cirrhosis could not be explored in the current meta-analysis due to the absence of relevant data.
In conclusion, HA may be beneficial for the prevention and treatment of hyponatremia in liver cirrhosis. However, its optimal dosage and duration remain unclear and may depend on the patient’s characteristics and response to treatment (e.g., guided by a change of serum albumin and/or sodium level). In the future, the role of HA in the prevention and treatment of hyponatremia in liver cirrhosis with ascites and other complications should be further explored by large-scale well-designed studies, preferably RCTs.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm11195928/s1, Table S1: Characteristics of included studies regarding the treatment of hyponatremia, Table S2: Quality of included cohort studies, Table S3: Meta-regression analysis regarding the human albumin infusion for the prevention of the decreasing of serum sodium level, Table S4: Subgroup analysis of human albumin infusion to prevent the decreasing of serum sodium level in liver cirrhosis, Table S5: Quality of evidence, Figure S1: Risk of bias of RCTs, Figure S2: Publication bias among studies regarding the effect of human albumin infusion on the development of hyponatremia (A) and serum sodium level (B) in liver cirrhosis without hyponatremia, Figure S3: Sensitivity analysis regarding effect of human albumin infusion on serum sodium level in liver cirrhosis without hyponatremia [95].

Author Contributions

Z.B.: reviewed and searched the literature, wrote the protocol, collected the data, performed the statistical analysis and quality assessment, interpreted the data, and drafted the manuscript. L.W., H.L., F.T. and G.C.: checked the data, discussed the findings, and gave critical comments. X.Q.: conceived the work, reviewed and searched the literature, wrote the protocol, performed the statistical analysis, interpreted the data, and revised the manuscript. All authors have made an intellectual contribution to the manuscript and approved the submission. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist. The ethical approval is not applicable for this study.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created in this study.

Acknowledgments

We are indebted to the responses by Rajiv Jalan about the data from his original study (Journal of Hepatology, 2007; 46: S95) and Alastair O’Brien about the data from his original study (Am J Gastroenterol 2021; 116(11): 2292–5). The abstract was partly published at the Asian-Pacific Association for the Study of the Liver (APASL) 2022 Conference as a poster presentation (https://doi.org/10.1007/s12072-022-10337-4, accessed on 5 August 2022).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Alukal, J.J.; John, S.; Thuluvath, P.J. Hyponatremia in Cirrhosis: An Update. Am. J. Gastroenterol. 2020, 115, 1775–1785. [Google Scholar] [CrossRef]
  2. Aithal, G.P.; Palaniyappan, N.; China, L.; Härmälä, S.; Macken, L.; Ryan, J.M.; Wilkes, E.A.; Moore, K.; Leithead, J.A.; Hayes, P.C.; et al. Guidelines on the management of ascites in cirrhosis. Gut 2021, 70, 9–29. [Google Scholar] [CrossRef]
  3. Angeli, P.; Wong, F.; Watson, H.; Ginès, P. CAPPS-Investigators. Hyponatremia in cirrhosis: Results of a patient population survey. Hepatology 2006, 44, 1535–1542. [Google Scholar] [CrossRef] [PubMed]
  4. Ginès, P.; Guevara, M. Hyponatremia in cirrhosis: Pathogenesis, clinical significance, and management. Hepatology 2008, 48, 1002–1010. [Google Scholar] [CrossRef]
  5. Attar, B. Approach to Hyponatremia in Cirrhosis. Clin. Liver Dis. 2019, 13, 98–101. [Google Scholar] [CrossRef] [Green Version]
  6. Kim, W.R.; Biggins, S.W.; Kremers, W.K.; Wiesner, R.H.; Kamath, P.S.; Benson, J.T.; Edwards, E.; Therneau, T.M. Hyponatremia and mortality among patients on the liver-transplant waiting list. N. Engl. J. Med. 2008, 359, 1018–1026. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Yang, S.-M.; Choi, S.-N.; Yu, J.H.; Yoon, H.-K.; Kim, W.H.; Jung, C.-W.; Suh, K.-S.; Lee, K.H. Intraoperative hyponatremia is an independent predictor of one-year mortality after liver transplantation. Sci. Rep. 2018, 8, 18023. [Google Scholar] [CrossRef] [Green Version]
  8. Borroni, G.; Maggi, A.; Sangiovanni, A.; Cazzaniga, M.; Salerno, F. Clinical relevance of hyponatraemia for the hospital outcome of cirrhotic patients. Dig. Liver Dis. 2000, 32, 605–610. [Google Scholar] [CrossRef]
  9. Available online: https://optn.transplant.hrsa.gov/governance/policy-initiatives/liver/ (accessed on 1 July 2022).
  10. Sigal, S.H.; Amin, A.; Chiodo, J.A., 3rd; Sanyal, A. Management Strategies and Outcomes for Hyponatremia in Cirrhosis in the Hyponatremia Registry. Can. J. Gastroenterol. Hepatol. 2018, 2018, 1579508. [Google Scholar] [CrossRef] [Green Version]
  11. Hix, J.K.; Silver, S.; Sterns, R.H. Diuretic-associated hyponatremia. Semin. Nephrol. 2011, 31, 553–566. [Google Scholar] [CrossRef]
  12. Verbalis, J.G.; Goldsmith, S.R.; Greenberg, A.; Korzelius, C.; Schrier, R.W.; Sterns, R.H.; Thompson, C.J. Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. Am. J. Med. 2013, 126, S1–S42. [Google Scholar] [CrossRef] [PubMed]
  13. Berl, T.; Rastegar, A. A patient with severe hyponatremia and hypokalemia: Osmotic demyelination following potassium repletion. Am. J. Kidney Dis. 2010, 55, 742–748. [Google Scholar] [CrossRef] [PubMed]
  14. Pose, E.; Solà, E.; Piano, S.; Gola, E.; Graupera, I.; Guevara, M.; Cárdenas, A.; Angeli, P.; Ginès, P. Limited Efficacy of Tolvaptan in Patients with Cirrhosis and Severe Hyponatremia: Real-Life Experience. Am. J. Med. 2017, 130, 372–375. [Google Scholar] [CrossRef]
  15. Cárdenas, A.; Ginès, P.; Marotta, P.; Czerwiec, F.; Oyuang, J.; Guevara, M.; Afdhal, N.H. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J. Hepatol. 2012, 56, 571–578. [Google Scholar] [CrossRef] [PubMed]
  16. John, S.; Thuluvath, P.J. Hyponatremia in cirrhosis: Pathophysiology and management. World J. Gastroenterol. 2015, 21, 3197–3205. [Google Scholar] [CrossRef] [PubMed]
  17. Caraceni, P.; Angeli, P.; Prati, D.; Bernardi, M.; Liumbruno, G.M.; Bennardello, F.; Piccoli, P.; Velati, C. AISF-SIMTI position paper: The appropriate use of albumin in patients with liver cirrhosis. Blood Transfus. 2016, 14, 8–22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Fukui, H.; Saito, H.; Ueno, Y.; Uto, H.; Obara, K.; Sakaida, I.; Shibuya, A.; Seike, M.; Nagoshi, S.; Segawa, M.; et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J. Gastroenterol. 2016, 51, 629–650. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  19. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J. Hepatol. 2018, 69, 406–460. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  20. Runyon, B.A.; Committee, A.P.G. Management of adult patients with ascites due to cirrhosis: An update. Hepatology 2009, 49, 2087–2107. [Google Scholar] [CrossRef] [PubMed]
  21. Chinese Society of Hepatology, Chinese Medical Association; Xu, X.; Duan, Z.; Ding, H.; Li, W.; Jia, J.; Wei, L.; Linghu, E. Chinese guidelines on the management of ascites and its related complications in cirrhosis. Hepatol. Int. 2019, 13, 1–21. [Google Scholar] [CrossRef]
  22. Bernardi, M.; Caraceni, P.; Navickis, R.J.; Wilkes, M.M. Albumin infusion in patients undergoing large-volume paracentesis: A meta-analysis of randomized trials. Hepatology 2012, 55, 1172–1181. [Google Scholar] [CrossRef] [PubMed]
  23. Kwok, C.S.; Krupa, L.; Mahtani, A.; Kaye, D.; Rushbrook, S.M.; Phillips, M.G.; Gelson, W. Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: A systematic review and meta-analysis. Biomed. Res. Int. 2013, 2013, 295153. [Google Scholar] [CrossRef] [PubMed]
  24. Kütting, F.; Schubert, J.; Franklin, J.; Bowe, A.; Hoffmann, V.; Demir, M.; Pelc, A.; Nierhoff, D.; Töx, U.; Steffen, H. Insufficient evidence of benefit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis. J. Gastroenterol. Hepatol. 2017, 32, 327–338. [Google Scholar] [CrossRef] [PubMed]
  25. Simonetti, R.G.; Perricone, G.; Nikolova, D.; Bjelakovic, G.; Gluud, C. Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis. Cochrane Database Syst. Rev. 2019, 6, CD004039. [Google Scholar] [CrossRef] [PubMed]
  26. Zheng, Y.J.; Zhuo, S.J.; Huang, B.; Su, S. A meta-analysis of the efficacy and safety of human serum albumin treatment in patients with ascites due to cirrhosis undergoing drainage. Asian J. Surg. 2021, 44, 1116–1117. [Google Scholar] [CrossRef]
  27. Shrestha, D.B.; Budhathoki, P.; Sedhai, Y.R.; Baniya, R.; Awal, S.; Yadav, J.; Awal, L.; Davis, B.; Kashiouris, M.G.; Cable, C.A. Safety and efficacy of human serum albumin treatment in patients with cirrhotic ascites undergoing paracentesis: A systematic review and meta-analysis. Ann. Hepatol. 2021, 26, 100547. [Google Scholar] [CrossRef]
  28. Sterne, J.A.C.; Sutton, A.J.; Ioannidis, J.P.A.; Terrin, N.; Jones, D.R.; Lau, J.; Carpenter, J.; Rücker, G.; Harbord, R.M.; Schmid, C.H.; et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011, 343, d4002. [Google Scholar] [CrossRef] [Green Version]
  29. Lau, J.; Ioannidis, J.P.; Terrin, N.; Schmid, C.H.; Olkin, I. The case of the misleading funnel plot. BMJ 2006, 333, 597–600. [Google Scholar] [CrossRef] [Green Version]
  30. Begg, C.B.; Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994, 50, 1088–1101. [Google Scholar] [CrossRef]
  31. Guyatt, G.H.; Oxman, A.D.; Vist, G.E.; Kunz, R.; Falck-Ytter, Y.; Alonso-Coello, P.; Schünemann, H.J. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008, 336, 924–926. [Google Scholar] [CrossRef]
  32. Jhaveri, K.D.; Chawla, A.; Xu, C.; Hazzan, A. Intravenous albumin infusion is an effective therapy for hyponatremia in patient with malignant ascites. Indian J. Nephrol. 2014, 24, 51–53. [Google Scholar] [CrossRef] [PubMed]
  33. Arora, V.; Vijayaraghavan, R.; Maiwall, R.; Sahney, A.; Thomas, S.S.; Ali, R.; Jain, P.; Kumar, G.; Sarin, S.K. Paracentesis-Induced Circulatory Dysfunction with Modest-Volume Paracentesis Is Partly Ameliorated by Albumin Infusion in Acute-on-Chronic Liver Failure. Hepatology 2020, 72, 1043–1055. [Google Scholar] [CrossRef] [PubMed]
  34. Sen Sarma, M.; Yachha, S.K.; Bhatia, V.; Srivastava, A.; Poddar, U. Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease. J. Hepatol. 2015, 63, 1126–1132. [Google Scholar] [CrossRef] [PubMed]
  35. McCormick, P.A.; Mistry, P.; Kaye, G.; Burroughs, A.K.; McIntyre, N. Intravenous albumin infusion is an effective therapy for hyponatraemia in cirrhotic patients with ascites. Gut 1990, 31, 204–207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Ginès, P.; Titó, L.; Arroyo, V.; Planas, R.; Panes, J.; Viver, J.; Torres, M.; Humbert, P.; Rimola, A.; Llach, J.; et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988, 94, 1493–1502. [Google Scholar] [CrossRef]
  37. Planas, R.; Ginès, P.; Arroyo, V.; Llach, J.; Panés, J.; Vargas, V.; Salmerón, J.M.; Ginès, A.; Toledo, C.; Rimola, A.; et al. Dextran-70 versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis. Results of a randomized study. Gastroenterology 1990, 99, 1736–1744. [Google Scholar] [CrossRef]
  38. Salerno, F.; Badalamenti, S.; Lorenzano, E.; Moser, P.; Incerti, P. Randomized comparative study of hemaccel vs. albumin infusion after total paracentesis in cirrhotic patients with refractory ascites. Hepatology 1991, 13, 707–713. [Google Scholar] [CrossRef]
  39. Fassio, E.; Terg, R.; Landeira, G.; Abecasis, R.; Salemne, M.; Podesta, A.; Rodriguez, P.; Levi, D.; Kravetz, D. Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites. Results of a randomized study. J. Hepatol. 1992, 14, 310–316. [Google Scholar] [CrossRef]
  40. Garcia-Compeán, D.; Villarreal, J.Z.; Cuevas, H.B.; Cantü, D.A.G.; Estrella, M.; Tamez, E.G.; Castillo, R.V.; Barragán, R.F. Total therapeutic paracentesis (TTP) with and without intravenous albumin in the treatment of cirrhotic tense ascites: A randomized controlled trial. Liver 1993, 13, 233–238. [Google Scholar] [CrossRef]
  41. Hernández Pérez, R.E.; Aguilar Ramírez, J.R.; Hernández López, J.M.; Gómez Maganda y Silva, T.G. Massive paracentesis and administration of dextran 70 vs. albumin in cirrhotic patients with tense ascites. Rev. Gastroenterol. Mex 1995, 60, 22–26. [Google Scholar]
  42. Gines, A.; Fernandez-Esparrach, G.; Monescillo, A.; Vila, C.; Domenech, E.; Abecasis, R.; Angeli, P.; Ruiz-Del-Arbol, L.; Planas, R.; Sola, R.; et al. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology 1996, 111, 1002–1010. [Google Scholar] [CrossRef]
  43. Altman, C.; Bernard, B.; Roulot, D.; Vitte, R.L.; Ink, O. Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis. Eur. J. Gastroenterol. Hepatol. 1998, 10, 5–10. [Google Scholar] [CrossRef]
  44. Gentilini, P.; Casini-Raggi, V.; Di Fiore, G.; Romanelli, R.G.; Buzzelli, G.; Pinzani, M.; La Villa, G.; Laffi, G. Albumin improves the response to diuretics in patients with cirrhosis and ascites: Results of a randomized, controlled trial. J. Hepatol. 1999, 30, 639–645. [Google Scholar] [CrossRef]
  45. Zaak, D.; Paquet, K.J.; Kuhn, R. Prospective study comparing human albumin vs. reinfusion of ultrafiltrate-ascitic fluid after total paracentesis in cirrhotic patients with tense ascites. Z. Gastroenterol. 2001, 39, 5–10. [Google Scholar] [CrossRef]
  46. García-Compean, D.; Blanc, P.; Larrey, D.; Daures, J.-P.; Hirtz, J.; Mendoza, E.; Maldonado, H.; Michel, H. Treatment of cirrhotic tense ascites with Dextran-40 versus albumin associated with large volume paracentesis: A randomized controlled trial. Ann. Hepatol. 2002, 1, 29–35. [Google Scholar] [CrossRef]
  47. Moreau, R.; Asselah, T.; Condat, B.; De Kerguenec, C.; Pessione, F.; Bernard, B.; Poynard, T.; Binn, M.; Grangé, J.D.; Valla, D.; et al. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: A randomised pilot study. Gut 2002, 50, 90–94. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Sola-Vera, J.; Miñana, J.; Ricart, E.; Planella, M.; González, B.; Torras, X.; Rodríguez, J.; Such, J.; Pascual, S.; Soriano, G.; et al. Randomized trial comparing albumin and saline in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients with ascites. Hepatology 2003, 37, 1147–1153. [Google Scholar] [CrossRef]
  49. Moreau, R.; Valla, D.-C.; Durand-Zaleski, I.; Bronowicki, J.-P.; Durand, F.; Chaput, J.-C.; Dadamessi, I.; Silvain, C.; Bonny, C.; Oberti, F.; et al. Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid: A randomised controlled pilot trail. Liver Int. 2006, 26, 46–54. [Google Scholar] [CrossRef] [PubMed]
  50. Singh, V.; Kumar, R.; Nain, C.K.; Singh, B.; Sharma, A.K. Terlipressin versus albumin in paracentesis-induced circulatory dysfunction in cirrhosis: A randomized study. J. Gastroenterol. Hepatol. 2006, 21, 303–307. [Google Scholar] [CrossRef] [PubMed]
  51. Jalan, R.; Mookerjee, R.; Cheshire, L.; Williams, R.; Davies, N. Albumin infusion for severe hyponatremia in patients with refractory ascites: A randomized clinical trial. J. Hepatol. 2007, 46, S95. [Google Scholar] [CrossRef]
  52. Appenrodt, B.; Wolf, A.; Grünhage, F.; Trebicka, J.; Schepke, M.; Rabe, C.; Lammert, F.; Sauerbruch, T.; Heller, J. Prevention of paracentesis-induced circulatory dysfunction: Midodrine vs albumin. A randomized pilot study. Liver Int. 2008, 28, 1019–1025. [Google Scholar] [CrossRef] [PubMed]
  53. Singh, V.; Dheerendra, P.C.; Singh, B.; Nain, C.K.; Chawla, D.; Sharma, N.; Bhalla, A.; Mahi, S.K. Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: A randomized pilot study. Am. J. Gastroenterol. 2008, 103, 1399–1405. [Google Scholar] [CrossRef] [PubMed]
  54. Abdel-Khalek, E.E.; Arif, S.E. Randomized trial comparing human albumin and hydroxyethyl starch 6% as plasma expanders for treatment of patients with liver cirrhosis and tense ascites following large volume paracentesis. Arab. J. Gastroenterol. 2010, 11, 24–29. [Google Scholar] [CrossRef]
  55. Bari, K.; Miñano, C.; Shea, M.; Inayat, I.B.; Hashem, H.J.; Gilles, H.; Heuman, D.; Garcia-Tsao, G. The Combination of Octreotide and Midodrine Is Not Superior to Albumin in Preventing Recurrence of Ascites After Large-Volume Paracentesis. Clin. Gastroenterol. Hepatol. 2012, 10, 1169–1175. [Google Scholar] [CrossRef] [Green Version]
  56. Hamdy, H.; ElBaz, A.A.; Hassan, A.; Hassanin, O. Comparison of midodrine and albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients: A randomized pilot study. J. Clin. Gastroenterol. 2014, 48, 184–188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Khan, M.U.; Ur Rahim, I.; Latif, M. Hemaccel as a cheaper alternative to human albumin for plasma expansion during paracentesis in cirrhotic patients. Pak. J. Med. Health Sci. 2015, 9, 948–950. [Google Scholar]
  58. Abootalebi, A.; Khazaei, S.; Minakari, M.; Nasr-Isfahani, M.; Esmailian, M.; Heydari, F. Comparing the Effects of Hydroxyethyl Starch and Albumin in Cirrhotic Patients with Tense Ascites; a Randomized Clinical Trial. Adv. J. Emerg. Med. 2017, 1, e7. [Google Scholar] [CrossRef] [PubMed]
  59. Shen, N.T.; Barraza, L.H.; Anam, A.K.; Patel, P.; Schneider, Y.; Jesudian, A. Benefit of albumin infusion in hospitalized patients with cirrhosis and hyponatremia: A retrospective cohort study. J. Gastroenterol. Hepatol. Res. 2017, 6, 2441–2445. [Google Scholar] [CrossRef] [Green Version]
  60. Bajaj, J.S.; Tandon, P.; O’leary, J.G.; Biggins, S.W.; Wong, F.; Kamath, P.S.; Garcia-Tsao, G.; Maliakkal, B.; Lai, J.C.; Fallon, M.; et al. The Impact of Albumin Use on Resolution of Hyponatremia in Hospitalized Patients with Cirrhosis. Am. J. Gastroenterol. 2018, 113, 1339. [Google Scholar] [CrossRef]
  61. Solà, E.; Solé, C.; Simón-Talero, M.; Martín-Llahí, M.; Castellote, J.; Martinez, R.G.; Moreira, R.; Torrens, M.; Márquez, F.; Fabrellas, N.; et al. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial. J. Hepatol. 2018, 69, 1250–1259. [Google Scholar] [CrossRef]
  62. Yosry, A.; Soliman, Z.A.; Eletreby, R.; Hamza, I.; Ismail, A.; Elkady, M.A. Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: Results of a pilot study. Eur. J. Gastroenterol. Hepatol. 2019, 31, 345–351. [Google Scholar] [CrossRef] [PubMed]
  63. China, L.; Freemantle, N.; Forrest, E.; Kallis, Y.; Ryder, S.D.; Wright, G.; O’Brien, A. Targeted Albumin Therapy Does Not Improve Short-Term Outcome in Hyponatremic Patients Hospitalized with Complications of Cirrhosis: Data from the ATTIRE Trial. Am. J. Gastroenterol. 2021, 116, 2292–2295. [Google Scholar] [CrossRef] [PubMed]
  64. Smart, H.L.; Triger, D.R. A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites. J. Hepatol. 1990, 10, 191–197. [Google Scholar] [CrossRef]
  65. Zaccherini, G.; Baldassarre, M.; Tufoni, M.; Nardelli, S.; Piano, S.; Alessandria, C.; Neri, S.; Foschi, F.G.; Levantesi, F.; Bedogni, G.; et al. Correction and prevention of hyponatremia in patients with cirrhosis and ascites—Post hoc analysis of the ANSWER study database. Am. J. Gastroenterol. 2022. [Google Scholar] [CrossRef]
  66. Arroyo, V.; García-Martinez, R.; Salvatella, X. Human serum albumin, systemic inflammation, and cirrhosis. J. Hepatol. 2014, 61, 396–407. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Salerno, F.; Navickis, R.J.; Wilkes, M.M. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: A meta-analysis of randomized trials. Clin. Gastroenterol. Hepatol. 2013, 11, 123–130.e1. [Google Scholar] [CrossRef]
  68. Sort, P.; Navasa, M.; Arroyo, V.; Aldeguer, X.; Planas, R.; Ruiz-Del-Arbol, L.; Castells, L.; Vargas, V.; Soriano, G.; Guevara, M.; et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N. Engl. J. Med. 1999, 341, 403–409. [Google Scholar] [CrossRef] [Green Version]
  69. Wong, F.; Pappas, S.C.; Curry, M.P.; Reddy, K.R.; Rubin, R.A.; Porayko, M.K.; Gonzalez, S.A.; Mumtaz, K.; Lim, N.; Simonetto, D.A.; et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N. Engl. J. Med. 2021, 384, 818–828. [Google Scholar] [CrossRef]
  70. Caraceni, P.; Riggio, O.; Angeli, P.; Alessandria, C.; Neri, S.; Foschi, F.G.; Levantesi, F.; Airoldi, A.; Boccia, S.; Svegliati-Baroni, G.; et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): An open-label randomised trial. Lancet 2018, 391, 2417–2429. [Google Scholar] [CrossRef]
  71. Bai, Z.; Bernardi, M.; Yoshida, E.M.; Li, H.; Guo, X.; Méndez-Sánchez, N.; Li, Y.; Wang, R.; Deng, J.; Qi, X. Albumin infusion may decrease the incidence and severity of overt hepatic encephalopathy in liver cirrhosis. Aging 2019, 11, 8502–8525. [Google Scholar] [CrossRef] [PubMed]
  72. Iwakiri, Y.; Groszmann, R.J. The hyperdynamic circulation of chronic liver diseases: From the patient to the molecule. Hepatology 2006, 43, S121–S131. [Google Scholar] [CrossRef] [PubMed]
  73. Bosch, J. Vascular deterioration in cirrhosis: The big picture. J. Clin. Gastroenterol. 2007, 41 (Suppl. S3), S247–S253. [Google Scholar] [CrossRef] [PubMed]
  74. Clària, J.; Stauber, R.E.; Coenraad, M.J.; Moreau, R.; Jalan, R.; Pavesi, M.; Amorós, A.; Titos, E.; Alcaraz-Quiles, J.; Oettl, K.; et al. Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure. Hepatology 2016, 64, 1249–1264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Martell, M.; Coll, M.; Ezkurdia, N.; Raurell, I.; Genescà, J. Physiopathology of splanchnic vasodilation in portal hypertension. World J. Hepatol. 2010, 2, 208–220. [Google Scholar] [CrossRef]
  76. Funder, J.W. Aldosterone and Mineralocorticoid Receptors-Physiology and Pathophysiology. Int. J. Mol. Sci. 2017, 18, 1032. [Google Scholar] [CrossRef] [Green Version]
  77. Nielsen, S.; Marples, D.; Frøkiaer, J.; Knepper, M.; Agre, P. The aquaporin family of water channels in kidney: An update on physiology and pathophysiology of aquaporin-2. Kidney Int. 1996, 49, 1718–1723. [Google Scholar] [CrossRef] [Green Version]
  78. Knepper, M.A. Molecular physiology of urinary concentrating mechanism: Regulation of aquaporin water channels by vasopressin. Am. J. Physiol. 1997, 272, F3–F12. [Google Scholar] [CrossRef]
  79. He, X.M.; Carter, D.C. Atomic structure and chemistry of human serum albumin. Nature 1992, 358, 209–215. [Google Scholar] [CrossRef] [Green Version]
  80. Wilkinson, P.; Sherlock, S. The effect of repeated albumin infusions in patients with cirrhosis. Lancet 1962, 2, 1125–1129. [Google Scholar] [CrossRef]
  81. Arroyo, V. Review article: Albumin in the treatment of liver diseases—New features of a classical treatment. Aliment. Pharm. Ther. 2002, 16 (Suppl. S5), 1–5. [Google Scholar] [CrossRef]
  82. Quinlan, G.J.; Martin, G.S.; Evans, T.W. Albumin: Biochemical properties and therapeutic potential. Hepatology 2005, 41, 1211–1219. [Google Scholar] [CrossRef] [PubMed]
  83. Caraceni, P.; Angeli, P.; Prati, D.; Bernardi, M.; Berti, P.; Bennardello, F.; Fiorin, F.; Piccoli, P. AISF-SIMTI position paper on the appropriate use of albumin in patients with liver cirrhosis: A 2020 update. Blood Transfus. 2021, 19, 9–13. [Google Scholar] [CrossRef] [PubMed]
  84. Leiva, J.G.; Salgado, J.M.; Estradas, J.; Torre, A.; Uribe, M. Pathophysiology of ascites and dilutional hyponatremia: Contemporary use of aquaretic agents. Ann. Hepatol. 2007, 6, 214–221. [Google Scholar] [CrossRef]
  85. Arroyo, V.; Rodés, J.; Gutiérrez-Lizárraga, M.A.; Revert, L. Prognostic value of spontaneous hyponatremia in cirrhosis with ascites. Am. J. Dig. Dis. 1976, 21, 249–256. [Google Scholar] [CrossRef]
  86. Sersté, T.; Gustot, T.; Rautou, P.-E.; Francoz, C.; Njimi, H.; Durand, F.; Valla, D.; Lebrec, D.; Moreau, R. Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites. J. Hepatol. 2012, 57, 274–280. [Google Scholar] [CrossRef]
  87. Guevara, M.; E Baccaro, M.; Torre, A.; Gómez-Ansón, B.; Ríos, J.; Torres, F.; Rami, L.; Monté-Rubio, G.C.; Martín-Llahí, M.; Arroyo, V.; et al. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: A prospective study with time-dependent analysis. Am. J. Gastroenterol. 2009, 104, 1382–1389. [Google Scholar] [CrossRef]
  88. Bossen, L.; Ginès, P.; Vilstrup, H.; Watson, H.; Jepsen, P. Serum sodium as a risk factor for hepatic encephalopathy in patients with cirrhosis and ascites. J. Gastroenterol. Hepatol. 2019, 34, 914–920. [Google Scholar] [CrossRef]
  89. Ginès, A.; Escorsell, A.; Ginès, P.; Saló, J.; Jiménez, W.; Inglada, L.; Navasa, M.; Clària, J.; Rimola, A.; Arroyo, V.; et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology 1993, 105, 229–236. [Google Scholar] [CrossRef]
  90. Janičko, M.; Veselíny, E.; Abraldes, J.G.; Jarčuška, P. Serum sodium identifies patients with cirrhosis at high risk of hepatorenal syndrome. Z. Gastroenterol. 2013, 51, 628–634. [Google Scholar] [CrossRef]
  91. Licata, A.; Maida, M.; Bonaccorso, A.; Macaluso, F.S.; Cappello, M.; Craxì, A.; Almasio, P.L. Clinical course and prognostic factors of hepatorenal syndrome: A retrospective single-center cohort study. World J. Hepatol. 2013, 5, 685–691. [Google Scholar] [CrossRef] [Green Version]
  92. Schwabl, P.; Bucsics, T.; Soucek, K.; Mandorfer, M.; Bota, S.; Blacky, A.; Hirschl, A.M.; Ferlitsch, A.; Trauner, M.; Peck-Radosavljevic, M.; et al. Risk factors for development of spontaneous bacterial peritonitis and subsequent mortality in cirrhotic patients with ascites. Liver Int. 2015, 35, 2121–2128. [Google Scholar] [CrossRef] [PubMed]
  93. Dănulescu, R.M.; Stanciu, C.; Trifan, A. Evaluation of Prognostic Factors in Decompensated Liver Cirrhosis with Ascites and Spontaneous Bacterial Peritonitis. Rev. Med. Chir. Soc. Med. Nat. Iasi 2015, 119, 1018–1024. [Google Scholar] [PubMed]
  94. Sigal, S.H. Hyponatremia in cirrhosis. J. Hosp. Med. 2012, 7 (Suppl. S4), S14–S17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Potential mechanisms of human albumin infusion on hyponatremia.
Figure 1. Potential mechanisms of human albumin infusion on hyponatremia.
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Figure 2. Flow chart of study selection.
Figure 2. Flow chart of study selection.
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Figure 3. Forrest plots showing the effect of human albumin infusion on the development of hyponatremia in liver cirrhosis without hyponatremia.
Figure 3. Forrest plots showing the effect of human albumin infusion on the development of hyponatremia in liver cirrhosis without hyponatremia.
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Figure 4. Forrest plots showing the effect of human albumin infusion on serum sodium level in liver cirrhosis without hyponatremia.
Figure 4. Forrest plots showing the effect of human albumin infusion on serum sodium level in liver cirrhosis without hyponatremia.
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Figure 5. Forrest plots showing the effect of human albumin infusion on the resolution of hyponatremia in liver cirrhosis with hyponatremia.
Figure 5. Forrest plots showing the effect of human albumin infusion on the resolution of hyponatremia in liver cirrhosis with hyponatremia.
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Table
Table 1. Characteristics of included studies regarding the prevention of hyponatremia.
Table 1. Characteristics of included studies regarding the prevention of hyponatremia.
First Author
(Year)		CountryStudy DesignSample Size
(n)		Alcoholic Cirrhosis
(%)		Definition of HyponatremiaControl GroupHA Dose
Ginès
(1988) [36]		SpainRCT10565.71% (69/105)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.No intervention40 g per time of LVP.
Smart
(1990) [64]		UKRCT4045.00% (18/40)Serum Na < 130 mmol/L.Filtration40 g per time of LVP.
Planas
(1990) [37]		SpainRCT8867.05% (59/88)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.Dextran8 g/L of ascites removed.
Salerno
(1991) [38]		ItalyRCT5446.30% (25/54)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.Hemaccel6 g/L of ascites removed.
Fassio
(1992) [39]		ArgentinaRCT4182.93% (34/41)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.Dextran6 g/L of ascites removed.
Garcia-Compean
(1993) [40]		MexicoRCT3571.43% (25/35)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.No intervention5 g/L of ascites removed.
Hernández Pérez
(1995) [41]		MexicoRCT16NANADextran6 g/L of ascites removed.
Ginès
(1996) [42]		SpainRCT19070.00% (133/190)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.Dextran8 g/L of ascites removed.
Altman
(1998) [43]		FranceRCT6083.33% (50/60)Decrease in serum Na > 10 mmol/L to serum Na < 120 mmol/L after treatment.Hydroxyethyl starch8 g/L of ascites removed.
Gentilini
(1999) [44]		ItalyRCT6823.53% (16/68)NANo intervention12.5 g/day.
Zaak
(2001) [45]		GermanyCohort3588.57% (31/35)NAFiltration5 g/L of ascites removed.
García-Compean
(2002) [46]		MexicoRCT9680.21% (77/96)Decrease in serum Na > 5 mmol/L after treatment.DextranNA
Moreau
(2002) [47]		FranceRCT2085.00% (17/20)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.Terlipressin8 g/L of ascites removed.
Sola-Vera
(2003) [48]		SpainRCT7255.56% (40/72)Decrease in serum Na > 10 mmol/L to serum Na < 125 mmol/L after treatment.Saline8 g/L of ascites removed.
Moreau
(2006) [49]		FranceRCT68100.00% (68/68)Decrease in serum Na > 5 mmol/L to serum Na < 130 mmol/L after treatment.PolygelineNA
Singh
(2006) [50]		IndiaRCT4070.00% (28/40)Decrease in serum Na > 5 mmol/L to serum Na < 130 mmol/L after treatment.Terlipressin8 g/L of ascites removed.
Appenrodt
(2008) [52]		GermanyRCT2479.20% (19/24)NAMidodrine8 g/L of ascites removed.
Singh
(2008) [53]		IndiaRCT4065.00% (26/40)Decrease in serum Na > 5 mmol/L to serum Na < 130 mmol/L after treatment.Midodrine8 g/L of ascites removed.
Abdel-Khalek
(2010) [54]		EgyptRCT135NADecrease in serum Na > 5 mmol/L to serum Na < 130 mmol/L after treatment.Hydroxyethyl starch8 g/L of ascites removed.
Bari
(2012) [55]		USARCT2552.00% (13/25)NAOctreotide8 g/L of ascites removed.
Hamdy
(2014) [56]		EgyptRCT50NANAMidodrine8 g/L of ascites removed.
Khan
(2015) [57]		PakistanRCT50NANAHemaccel6 g/L of ascites removed.
Abootalebi
(2017) [58]		IranRCT72NANAHydroxyethyl starch5 g/L of ascites removed.
Solà
(2018) [61]		SpainRCT17356.07% (97/173)NAPlacebo40 g/15 days.
Yosry
(2019) [62]		EgyptRCT500 (0/50)Decrease in serum Na > 5 mmol/L or serum Na < 130 mmol/L after treatment.Midodrine8 g/L of ascites removed.
Abbreviations: HA, human albumin; Na, sodium; LVP, large volume paracentesis; RCT, randomized control trial; NA, not available.
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Bai, Z.; Wang, L.; Lin, H.; Tacke, F.; Cheng, G.; Qi, X. Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis. J. Clin. Med. 2022, 11, 5928. https://doi.org/10.3390/jcm11195928

AMA Style

Bai Z, Wang L, Lin H, Tacke F, Cheng G, Qi X. Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2022; 11(19):5928. https://doi.org/10.3390/jcm11195928

Chicago/Turabian Style

Bai, Zhaohui, Le Wang, Hanyang Lin, Frank Tacke, Gang Cheng, and Xingshun Qi. 2022. "Use of Human Albumin Administration for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis" Journal of Clinical Medicine 11, no. 19: 5928. https://doi.org/10.3390/jcm11195928

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