Opinion Review Open Access
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2023; 15(10): 1084-1090
Published online Oct 27, 2023. doi: 10.4254/wjh.v15.i10.1084
Dietary salt in liver cirrhosis: With a pinch of salt!
Ramesh Kumar, Sudheer Marrapu, Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
ORCID number: Ramesh Kumar (0000-0001-5136-4865); Sudheer Marrapu (0009-0002-8209-8648).
Author contributions: Kumar R designed the manuscript, collected data, and wrote the manuscript; Marrapu S collected data, and wrote the manuscript.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ramesh Kumar, MD, Additional Professor, Department of Gastroenterology, All India Institute of Medical Sciences, 4th Floor, IPD Block-C, Patna 801507, India. docrameshkr@gmail.com
Received: July 12, 2023
Peer-review started: July 12, 2023
First decision: September 11, 2023
Revised: September 21, 2023
Accepted: October 8, 2023
Article in press: October 8, 2023
Published online: October 27, 2023
Processing time: 103 Days and 17.5 Hours

Abstract

Patients with liver cirrhosis are advised to limit their sodium consumption to control excessive fluid accumulation. Salt is the most common form in which sodium is consumed daily. Consequently, various recommendations urge patients to limit salt intake. However, there is a lack of consistency regarding salt restriction across the guidelines. Moreover, there is conflicting evidence regarding the efficacy of salt restriction in the treatment of ascites. Numerous studies have shown that there is no difference in ascites control between patients with restriction of salt intake and those without restriction. Moreover, patients with cirrhosis may have several negative effects from consuming too little salt, although there are no recommendations on the lower limit of salt intake. Sodium is necessary to maintain the extracellular fluid volume; hence, excessive salt restriction can result in volume contraction, which could negatively impact kidney function in a cirrhotic patient. Salt restriction in cirrhotic patients can also compromise nutrient intake, which can have a negative impact on the overall outcome. There is insufficient evidence to recommend restricted salt intake for all patients with cirrhosis, including those with severe hyponatremia. The existing guidelines on salt restriction do not consider the salt sensitivity of patients; their nutritional state, volume status and sodium storage sites; and the risk of hypochloremia. This opinion article aims to critically analyze the existing literature with regard to salt recommendations for patients with liver cirrhosis and identify potential knowledge gaps that call for further research.

Key Words: Salt; Cirrhosis; Sodium; Hyponatremia; Ascites; Malnutrition

Core Tip: There are still many inconsistencies in the guidelines regarding salt recommendations for patients with liver cirrhosis. Although controlling ascites is the core tenet of salt restriction, there is insufficient data to back up this assertion. Moreover, the guidelines have no recommendations for minimum salt intake, even though too little salt consumption may have a variety of negative effects on patients with liver cirrhosis. To achieve optimal salt consumption in these patients, several factors need to be considered. This article discusses several important aspects of salt consumption in patients with cirrhosis.



INTRODUCTION

Sodium is essential for fluid balance and cellular homeostasis[1]. Under normal conditions, effective sodium balance, and hence extracellular fluid volume, is maintained by a complex interplay between various systems that regulate renal sodium excretion[2]. For example, a progressive increase in sodium intake activates natriuretic systems while suppressing the sodium retaining systems to maintain an effective sodium balance. However, in patients with liver cirrhosis, portal hypertension-related splanchnic vasodilatation reduces effective arterial blood volume, which in turn activates the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and, in later stages, arginine vasopressin, all of which result in renal sodium and fluid retention and, eventually, ascites[3]. Therefore, limiting sodium intake is suggested for the treatment of ascites in such patients[4]. Salt is the most common source of sodium consumed by humans; hence, the guidelines have focused on dietary salt restriction to achieve sodium limitation.

Data on the effectiveness of salt restriction for the management of ascites are not conclusive[5-7], and there are still many inconsistencies in the guidelines for salt recommendations in patients with liver cirrhosis[8-11]. Although the guidelines have suggested the upper limit, a lower limit for salt consumption was not included. Severe salt restriction could potentially result in hyponatremia and cause volume contraction, which might adversely affect kidney function in a cirrhotic patient. Salt restriction in cirrhosis compromises nutrient intake and has a negative impact on the overall outcomes[12,13]. There is a paucity of evidence regarding the dietary salt recommendation for patients with compensated cirrhosis and decompensated cirrhosis with severe hyponatremia[14,15]. The ability of salt to expand extracellular volume, known as salt sensitivity, varies among individuals; thus, a ‘one size fits all’ approach to dietary salt recommendations may not be appropriate[16]. Furthermore, a new finding indicating that sodium is also stored in a third compartment (interstitium and endothelial surface layer) in a non-osmotic equilibrium can have significant impact on our understanding of sodium intake and homeostasis in cirrhotic patients[17]. This opinion article covers all the aforementioned issues and emphasizes the knowledge gaps and the need for additional research in the area.

SALT AND CIRRHOSIS: IMPORTANT ISSUES
How much salt should cirrhotic patients consume, and are the current recommendations supported by data?

The recommended limits of salt consumption for cirrhotic patients with ascites varies from 4.6 g to 6.9 g/d, although most guidelines recommend around 5 g of salt, which corresponds to a teaspoon of cooking salt (Table 1). As per current recommendations, salt restriction should be considered for all cirrhotic patients with ascites, including those with refractory ascites. When it comes to the grade of ascites at which salt restriction should start, the International Ascites Club suggests grade 1, and the European Association for the Study of the Liver (EASL) suggests grade 2; however, the American Association for the Study of Liver Diseases does not provide any specific grade of ascites to this purpose[8,9,11]. The goal of salt restriction is to avoid sodium overload. Hence, the net sodium intake must be equal or lower than the sodium excretion; this can be achieved either by lowering the dietary salt intake or by increasing natriuresis using diuretics. For patients with grade 2 or higher ascites, salt restriction alone would be insufficient and diuretic therapy would need to be implemented. The first-line diuretics are often aldosterone antagonists, such as spironolactone, which can be administered alone or in conjunction with a loop diuretic such as furosemide. Restriction of fluid intake is required only in patients with dilutional hyponatremia.

Table 1 Recommendations for salt consumption in patients with liver cirrhosis.
Scientific society/GuidelinesRecommended salt intakePatient group
EASL practice guidelines (2010)[8]4.6-6.9 g/dCirrhosis with grade II or more ascites
AASLD practice guidelines (2021)[9]5.1 g/dCirrhosis with ascites
British Society of Gastroenterology (2021)[10]5–6.5 g/dCirrhosis with ascites
International Ascites Club (2003)[11]5.2 g/dCirrhosis with ascites

Several studies, including randomized controlled trials (RCTs), have examined the role of salt restriction in patients with cirrhosis and ascites[5,6,7,12,13,18]. The amount of salt restriction ranged from a salt-free diet to 7 g of salt per day. The majority of these studies are old with varying methodology and sub-optimal quality, making it challenging to draw clear conclusions. Some of these studies found a faster elimination and better control of ascites with strict salt restriction[5,6]. Some studies found no difference in ascites control between patients with and without salt restriction[12,18]. Furthermore, two recent RCTs found that a salt-unrestricted diet (5-6.5 g/d) was superior to a salt-restricted diet (5 g/d) in resolving ascites in a larger proportion of patients (45% vs 16%) and in reducing the need for large volume paracentesis[7,13]. Authors proposed that worsening hyponatremia caused by salt restriction can weaken the effects of diuretics and reduces renal blood flow, both of which worsen ascites[7]. This idea is further supported by research showing that the use of hypertonic saline solutions in conjunction with diuretics enhance fluid mobilization in patients with cirrhosis and refractory ascites[19]. The proposed mechanisms for these advantageous effects of salt loading include an increase in intravascular volume, an osmotic shift of fluid from the tissues, an increase in renal blood flow and a decrease in sympathetic tone. For the management of ascites in cirrhosis, each of these pathways is important. Therefore, although managing ascites is the fundamental premise of salt restriction in cirrhosis patients, there is conflicting evidence regarding this claim.

What adverse effects might cirrhosis patients experience with a salt-restricted diet?

The significant adverse events with salt restriction reported by various studies include hyponatremia, reduced caloric intake, higher risk of renal impairment, hepatic encephalopathy and mortality[5,6,7,12,13]. In a randomized trial, Reynolds et al[5] concluded that unrestricted salt intake decreased the likelihood of hyponatremia and azotemia. The risk of hyponatremia is significantly increased by concurrent use of diuretic medication. Severe salt restriction makes the food unpalatable and alters dietary patterns, which might promote protein-calorie malnutrition and increase mortality risk[4,20,21]. Notably, malnutrition and sarcopenia are already prevalent in patients with advanced cirrhosis[22,23]. In a study of cirrhotic patients with ascites requiring repeated paracentesis, salt restriction without nutritional support resulted in a 3.9-fold higher risk of mortality within one year, compared to that of unrestricted sodium intake with nutritional support[13]. In the small intestine, sodium absorption facilitates the absorption of chloride, amino acids, glucose and water[24]. Thus, severe salt restriction may affect the absorption of these substances, contributing to malnutrition.

Another issue concerns compliance with a salt-restricted diet. The average salt consumption by the general population is significantly above the levels recommended by the World Health Organization. A recent systemic review reported that most European countries consume between 4.2 g and 18.5 g of salt per day per capita[25]. Salt intake in India and China is about 10 g/d[26,27]. A cross-sectional survey indicated that only about a third of cirrhotic patients were compliant with salt restriction, with an additional 45% incorrectly stating that they were compliant[28]. Another potentially significant but unappreciated issue with low salt consumption, particularly with concurrent diuretic medication, is the development of hypochloremia, i.e., a low level of serum chloride. Serum chloride, the most important anion in the blood, has received less attention in cirrhosis patients, even though hypochloremia has been recognized as an important prognostic marker in patients with advanced cirrhosis. According to the findings of two recent studies, hypochloremia may be an even better predictor of mortality in patients with decompensated cirrhosis than serum sodium[29,30]. Chloride reabsorption in the renal tubule constitutes a crucial process for the auto-regulation of the acid-base balance as well as the electrochemical equilibrium. Moreover, hypochloremia causes activation of the RAAS and the upregulation of NaCl channels in the distal convoluted tubules, which can aggravate sodium retention and contribute to diuretic resistance[31].

Thus, existing evidence tends to suggest that severe salt-restricted diets (< 5 g/d) may not significantly improve ascites control and could even lead to complications. Considering the excessive salt consumption by the general population, a moderate salt restriction, with daily salt intake of no more than 5–6.5 g may be advisable for such patients. This translates to a ‘no added salt diet’ with avoidance of high sodium containing meals. Table 2 provides a list of foods with high sodium content so that doctors can counsel patients on their consumption. Also, one must be mindful while recommending salt restriction in advanced cirrhosis patients with hyponatremia as such patients generally have relative hypovolemia where salt restriction could cause volume contraction and renal dysfunction.

Table 2 Food items with a high content of sodium.
Food categoryHigh sodium-content fooda
Cereals, breads, and, grains Biscuits, pancakes, pizza, sandwiches, burgers, bread with salted tops, potato crisps, and salty snack foods
Vegetables, fruits, and soupsCanned vegetables and vegetable juices, pickles, commercially prepared pasta and tomato sauces, canned soup, and cup-noodles
Dairy productsButter milk, processed and cottage cheese
Meat products and eggsSmoked, salted or canned meat, fish or poultry, omelettes
Fats, desserts and sweetsSalted butter or margarine, soy sauce, bottled salad dressings, instant pudding and cake, ketchup
Legumes and nutsSalted nuts and beans
Is unrestricted salt intake justified for patients with compensated cirrhosis?

For patients with preascitic compensated cirrhosis, guidelines do not recommend dietary salt restriction. Nonetheless, a study has found that even compensated cirrhosis patients retain sodium when faced with high salt intake[14]. However, compensatory activation of atrial natriuretic peptide and inhibition of the RAAS result in a new steady state of sodium balance in such patients, which tends to prevent ascites. Nevertheless, Jalan et al[15] found that the degree of portal hypertension had a significant impact on the sodium handling capacity in patients with compensated cirrhosis. In fact, it is now believed that clinically significant portal hypertension (CSPH) is the main driver of decompensation in cirrhotic patients[32]. Compensated cirrhotic patients with baseline hepatic venous portal gradient > 20 mmHg had a 47% risk of decompensation in a mean duration of just 1.6 years, compared to < 10% over 4 years when it is < 10 mmHg[33,34]. Therefore, it is reasonable to assume that the compensatory natriuretic mechanism might be overwhelmed with the rising portal pressure, and as a result, sodium retention with high dietary salt intake may result in decompensation in the form of ascites in compensated cirrhosis patients. Hence, until further data emerge, salt restriction may be considered in compensated cirrhotic patients with CSPH. This extrapolation, however, needs to be tested in a controlled trial.

What are the implications of high salt intake for cirrhotic patients and the general population?

Studies from different countries found that dietary salt intake in the general population was approximately 10 g/d[25-27]. Directly or indirectly, high salt consumption adversely affects multiple organs in the body and may have some serious implications in patients with liver cirrhosis. Consuming excessive amounts of salt has been associated with oxidative stress, insulin resistance, vascular endothelial damage, sympathetic nerve sensitization, alteration of gut-microbiome and an increased risk of cancer (Figure 1). There is a strong positive association between dietary salt intake and cardiovascular diseases[35]. Therefore, the World Health Organization has recommended a daily salt intake of less than 5 g/d, which is approximately 2 g of sodium, for the general population[36]. According to this viewpoint, the dietary salt recommendation for advanced cirrhosis patients is similar to that of the normal healthy population. In a population-based study, subjects with intermediate salt intake (6–10 g/d) and high salt intake (> 10 g/d) were found to have a higher risk of hepatocellular carcinoma with a multivariable hazard ratio (HR) of 1.49 and 1.9, respectively, compared to those with low salt intake (< 6 g/d)[37]. A recent cohort study from Iran reported that high dietary intake of salt (9.5–15 g/d) increases the rate of mortality in patients with cirrhosis (HR 2.26). Moreover, moderate salt restriction (3–5 g/d), as compared to salt elimination, decreases the risk of death (HR 0.72)[38].

Figure 1
Figure 1 Adverse consequences of too little and too high salt consumption. Salt consumption < 5 g/d appears to have no advantage on the control of ascites. Severe salt restriction (< 3 g/d) as well as very high salt consumption (> 10 g/d) can produce many deleterious consequences in cirrhosis patients. The World Health Organization has recommended a daily salt intake of approximately 5 g/d in the general population which is similar to the recommendation for cirrhosis patients with ascites.
What could be the implications of salt sensitivity and third space sodium storage in patients with liver cirrhosis?

The ability of salt to expand extracellular volume, known as salt sensitivity, varies among individuals. It is estimated that around 26% of normotensive and 51% of hypertensive persons are salt sensitive[39,40]. The remaining individuals are salt resistant – their hemodynamic parameters are likely to be unaffected due to change in dietary salt consumption. Although the relevance of salt sensitivity in cirrhotic patients has never been assessed in the context of dietary salt intake, extrapolation of data from the general population suggests that between half and three-quarters of patients would be salt resistant. It would be safe to assume that a major restriction in dietary salt consumption at the cost of nutritional compromise would be undesirable in a large number of patients. Therefore, instead of having a ‘one size fits all’ salt recommendation for cirrhotic patients, the salt sensitivity of individual patients should also be considered.

Recently, a third compartment (skin interstitium and endothelial surface layer) of sodium storage sites, in which sodium can accumulate in a non-osmotic equilibrium and hence without concurrent water retention, have been identified[41,42]. This can have implications for sodium homeostasis, osmoregulation and the hemodynamic response to salt intake, all of which are relevant to patients with cirrhosis. In the third space, sodium can be osmotically inactivated following binding to negatively charged glycosaminoglycans[42]. Due to the changes in the dynamics of the interstitium, alterations in glycosaminoglycans and endothelial damage in cirrhotic patients, the amount of dietary salt intake can affect sodium homeostasis. Moreover, high interstitial sodium concentrations stimulate lymph angiogenesis via vascular endothelial growth factor-C, which helps in the mobilization of excess fluid from the skin via lymphatics[43]. Therefore, it would be interesting to see whether a salt-restricted diet worsens pre-existing lymphatic dysfunction in patients with advanced cirrhosis[44].

What are the practical issues with ensuring a pre-defined sodium consumption?

Measuring sodium intake in individuals is challenging as sodium is so widespread in food items. Even with extensive food labelling, it is often difficult to quantify the sodium content of food. Commonly used approaches include 24-h urine sodium measurement, 24-h dietary recall and food questionnaires[45]. Dietary sodium intake can be calculated by dividing the urine sodium excretion by 0.9, based on the assumption that 10% of sodium intake is lost through sweat and feces, and thus urinary excretion accounts for 90% of intake. Therefore, 24-h urine collection is considered the most reliable method. However, a systematic review found that measured urinary sodium varied as widely as 76%–122% of ingested sodium amount, making it a ‘not so reliable’ test[46]. Thus, most of these methods would only provide a rough estimate of sodium consumption. As moderate salt restriction might make foods unappealing and affect overall nutrition, some strategies need to be adopted in order to ensure adequate nutrient intake. One of the strategies is to partially substitute sodium with potassium or other minerals, such as calcium or magnesium[47]. However, there are concerns about possible negative effects of such a replacement, such as hyperkalemia with potassium-based salt, especially in cirrhotic patients with renal impairment or those taking potassium sparing diuretics. Additionally, flavors and sensory experiences can be imparted using herbs, spices and yeast extract. When used as salt alternatives, they have demonstrated good customer acceptance[48].

CONCLUSION

Inconsistencies in the recommendations for salt intake and conflicting evidence regarding the effectiveness of salt restriction for controlling ascites in cirrhotic patients necessitate further research. Presently, the term ‘salt restriction’ for cirrhotic patients appears to be a misnomer, given that the salt recommendation for normal populations is also the same. However, it is necessary to carefully evaluate the efficacy of varied levels of salt intake at various stages of cirrhosis, including those who also have concurrent hyponatremia. Studies on salt restriction must consider the patients' salt sensitivity, nutritional status, volume status, sodium storage sites and hypochloremia risk. Innovative ideas in this area would be to evaluate the efficacy and safety of low-sodium salt substitutes (such as potassium-based salt) and find ways to make low-sodium foods more palatable (by utilizing herbs, spices and yeast extract, etc.) to ensure appropriate nutrition.

Until further data emerge, it seems appropriate for cirrhotic patients with ascites to consume 5–6 g of salt per day, which would mean avoiding foods with added salt. To increase adherence, prevent malnutrition and avoid harmful effects of excess salt consumption, it is crucial to educate patients about the recommended salt limit. A formal consultation with a nutritionist may be sought. It is necessary to set a lower limit for salt consumption as too much salt restriction has just as many negative effects as too much consumption. Finally, personalized salt management, depending on the sodium balance, nutritional status and volume status of the patient, may be required for some of these patients.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology & hepatology

Country/Territory of origin: India

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C, C, C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Ferrarese A, Italy; Laghmani K, France; Sato T, Japan S-Editor: Liu JH L-Editor: Webster JR P-Editor: Liu JH

References
1.  Bernal A, Zafra MA, Simón MJ, Mahía J. Sodium Homeostasis, a Balance Necessary for Life. Nutrients. 2023;15.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 4]  [Reference Citation Analysis (0)]
2.  Bie P. Mechanisms of sodium balance: total body sodium, surrogate variables, and renal sodium excretion. Am J Physiol Regul Integr Comp Physiol. 2018;315:R945-R962.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 19]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
3.  Cárdenas A, Arroyo V. Mechanisms of water and sodium retention in cirrhosis and the pathogenesis of ascites. Best Pract Res Clin Endocrinol Metab. 2003;17:607-622.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 51]  [Cited by in F6Publishing: 53]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
4.  Haberl J, Zollner G, Fickert P, Stadlbauer V. To salt or not to salt?-That is the question in cirrhosis. Liver Int. 2018;38:1148-1159.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 14]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
5.  Reynolds TB, Lieberman FL, Goodman AR. Advantages of treatment of ascites without sodium restriction and without complete removal of excess fluid. Gut. 1978;19:549-553.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 29]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
6.  Gauthier A, Levy VG, Quinton A, Michel H, Rueff B, Descos L, Durbec JP, Fermanian J, Lancrenon S. Salt or no salt in the treatment of cirrhotic ascites: a randomised study. Gut. 1986;27:705-709.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 57]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
7.  Gu XB, Yang XJ, Zhu HY, Xu BY. Effect of a diet with unrestricted sodium on ascites in patients with hepatic cirrhosis. Gut Liver. 2012;6:355-361.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 30]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
8.  European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397-417.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1125]  [Cited by in F6Publishing: 1102]  [Article Influence: 78.7]  [Reference Citation Analysis (0)]
9.  Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74:1014-1048.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 119]  [Cited by in F6Publishing: 349]  [Article Influence: 116.3]  [Reference Citation Analysis (0)]
10.  Aithal GP, Palaniyappan N, China L, Härmälä S, Macken L, Ryan JM, Wilkes EA, Moore K, Leithead JA, Hayes PC, O'Brien AJ, Verma S. Guidelines on the management of ascites in cirrhosis. Gut. 2021;70:9-29.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 139]  [Cited by in F6Publishing: 172]  [Article Influence: 57.3]  [Reference Citation Analysis (0)]
11.  Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, Jimenez W, Planas R, Arroyo V. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology. 2003;38:258-266.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 602]  [Cited by in F6Publishing: 567]  [Article Influence: 27.0]  [Reference Citation Analysis (0)]
12.  Bernardi M, Laffi G, Salvagnini M, Azzena G, Bonato S, Marra F, Trevisani F, Gasbarrini G, Naccarato R, Gentilini P. Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content. Liver. 1993;13:156-162.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 67]  [Cited by in F6Publishing: 67]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
13.  Sorrentino P, Castaldo G, Tarantino L, Bracigliano A, Perrella A, Perrella O, Fiorentino F, Vecchione R, D' Angelo S. Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis. J Gastroenterol Hepatol. 2012;27:813-822.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 33]  [Cited by in F6Publishing: 35]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
14.  Wong F, Liu P, Blendis L. Sodium homeostasis with chronic sodium loading in preascitic cirrhosis. Gut. 2001;49:847-851.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 25]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
15.  Jalan R, Hayes PC. Sodium handling in patients with well compensated cirrhosis is dependent on the severity of liver disease and portal pressure. Gut. 2000;46:527-533.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 21]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
16.  Ishimwe JA, Dola T, Ertuglu LA, Kirabo A. Bile acids and salt-sensitive hypertension: a role of the gut-liver axis. Am J Physiol Heart Circ Physiol. 2022;322:H636-H646.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 10]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
17.  van IJzendoorn M, van den Born J, Hijmans R, Bodde R, Buter H, Dam W, Kingma P, Maes G, van der Veen T, Zijlstra W, Dijkstra B, Navis G, Boerma C. An observational study on intracutaneous sodium storage in intensive care patients and controls. PLoS One. 2019;14:e0223100.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
18.  Descos L, Gauthier A, Levy VG, Michel H, Quinton A, Rueff B, Fermanian J, Fombonne E, Durbec JP. Comparison of six treatments of ascites in patients with liver cirrhosis. A clinical trial. Hepatogastroenterology. 1983;30:15-20.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Licata G, Tuttolomondo A, Licata A, Parrinello G, Di Raimondo D, Di Sciacca R, Cammà C, Craxì A, Paterna S, Pinto A. Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites. Aliment Pharmacol Ther. 2009;30:227-235.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 15]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
20.  Eghtesad S, Poustchi H, Malekzadeh R. Malnutrition in liver cirrhosis:the influence of protein and sodium. Middle East J Dig Dis. 2013;5:65-75.  [PubMed]  [DOI]  [Cited in This Article: ]
21.  Sam J, Nguyen GC. Protein-calorie malnutrition as a prognostic indicator of mortality among patients hospitalized with cirrhosis and portal hypertension. Liver Int. 2009;29:1396-1402.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 110]  [Cited by in F6Publishing: 120]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
22.  Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol. 2012;10:117-125.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 207]  [Cited by in F6Publishing: 228]  [Article Influence: 19.0]  [Reference Citation Analysis (0)]
23.  Kumar R, Prakash SS, Priyadarshi RN, Anand U. Sarcopenia in Chronic Liver Disease: A Metabolic Perspective. J Clin Transl Hepatol. 2022;10:1213-1222.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 7]  [Reference Citation Analysis (0)]
24.  Fordtran JS, Rector FC Jr, Carter NW. The mechanisms of sodium absorption in the human small intestine. J Clin Invest. 1968;47:884-900.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 241]  [Cited by in F6Publishing: 224]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
25.  Kwong EJL, Whiting S, Bunge AC, Leven Y, Breda J, Rakovac I, Cappuccio FP, Wickramasinghe K. Population-level salt intake in the WHO European Region in 2022: a systematic review. Public Health Nutr. 2022;1-14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 15]  [Article Influence: 15.0]  [Reference Citation Analysis (0)]
26.  Johnson C, Praveen D, Pope A, Raj TS, Pillai RN, Land MA, Neal B. Mean population salt consumption in India: a systematic review. J Hypertens. 2017;35:3-9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 35]  [Cited by in F6Publishing: 39]  [Article Influence: 5.6]  [Reference Citation Analysis (0)]
27.  Tan M, He FJ, Wang C, MacGregor GA. Twenty-Four-Hour Urinary Sodium and Potassium Excretion in China: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8:e012923.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 53]  [Cited by in F6Publishing: 85]  [Article Influence: 17.0]  [Reference Citation Analysis (2)]
28.  Morando F, Rosi S, Gola E, Nardi M, Piano S, Fasolato S, Stanco M, Cavallin M, Romano A, Sticca A, Caregaro L, Gatta A, Angeli P. Adherence to a moderate sodium restriction diet in outpatients with cirrhosis and ascites: a real-life cross-sectional study. Liver Int. 2015;35:1508-1515.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 53]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
29.  Sumarsono A, Wang J, Xie L, Chiang GC, Tielleman T, Messiah SE, Singal AG, Mufti A, Chen C, Leveno M. Prognostic Value of Hypochloremia in Critically Ill Patients With Decompensated Cirrhosis. Crit Care Med. 2020;48:e1054-e1061.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 7]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
30.  Ji Y, Li L. Lower serum chloride concentrations are associated with increased risk of mortality in critically ill cirrhotic patients: an analysis of the MIMIC-III database. BMC Gastroenterol. 2021;21:200.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
31.  Hanberg JS, Rao V, Ter Maaten JM, Laur O, Brisco MA, Perry Wilson F, Grodin JL, Assefa M, Samuel Broughton J, Planavsky NJ, Ahmad T, Bellumkonda L, Tang WH, Parikh CR, Testani JM. Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. Circ Heart Fail. 2016;9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 66]  [Cited by in F6Publishing: 88]  [Article Influence: 12.6]  [Reference Citation Analysis (0)]
32.  Kumar R, Kumar S, Prakash SS.   Compensated liver cirrhosis: Natural course and disease modifying strategies. World J Methodol 2023; 13: 179-193.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 3]  [Reference Citation Analysis (0)]
33.  Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, Escorsell A, Garcia-Pagan JC, Makuch R, Patch D, Matloff DS, Bosch J; Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133:481-488.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 747]  [Cited by in F6Publishing: 740]  [Article Influence: 43.5]  [Reference Citation Analysis (0)]
34.  Jindal A, Bhardwaj A, Kumar G, Sarin SK. Clinical Decompensation and Outcomes in Patients With Compensated Cirrhosis and a Hepatic Venous Pressure Gradient ≥20 mm Hg. Am J Gastroenterol. 2020;115:1624-1633.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 19]  [Article Influence: 4.8]  [Reference Citation Analysis (0)]
35.  Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev. 2005;85:679-715.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 472]  [Cited by in F6Publishing: 449]  [Article Influence: 23.6]  [Reference Citation Analysis (0)]
36.  Rosengren A. Salt: the sweet spot? Eur Heart J. 2022;43:2889-2891.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 4]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
37.  Sun M, Cui H, Liang M, Wang W, Wang Y, Liu X, Liu S, Cao L. Perceived dietary salt intake and the risk of primary liver cancer: a population-based prospective study. J Hum Nutr Diet. 2020;33:833-840.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
38.  Pashayee-Khamene F, Hajimohammadebrahim-Ketabforoush M, Saber-Firoozi M, Hatami B, Naseri K, Karimi S, Ahmadzadeh S, Kord H, Saadati S, Hekmatdoost A. Salt consumption and mortality risk in cirrhotic patients: results from a cohort study. J Nutr Sci. 2022;11:e99.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
39.  Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986;8:II127-II134.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 372]  [Cited by in F6Publishing: 433]  [Article Influence: 11.4]  [Reference Citation Analysis (0)]
40.  Mishra S, Ingole S, Jain R. Salt sensitivity and its implication in clinical practice. Indian Heart J. 2018;70:556-564.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 22]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
41.  Olde Engberink RHG, Selvarajah V, Vogt L. Clinical impact of tissue sodium storage. Pediatr Nephrol. 2020;35:1373-1380.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 16]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
42.  Titze J, Shakibaei M, Schafflhuber M, Schulze-Tanzil G, Porst M, Schwind KH, Dietsch P, Hilgers KF. Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin. Am J Physiol Heart Circ Physiol. 2004;287:H203-H208.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 220]  [Cited by in F6Publishing: 235]  [Article Influence: 11.8]  [Reference Citation Analysis (0)]
43.  Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park JK, Beck FX, Müller DN, Derer W, Goss J, Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A, Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D, Titze J. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009;15:545-552.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 690]  [Cited by in F6Publishing: 730]  [Article Influence: 48.7]  [Reference Citation Analysis (0)]
44.  Kumar R, Anand U, Priyadarshi RN. Lymphatic dysfunction in advanced cirrhosis: Contextual perspective and clinical implications. World J Hepatol. 2021;13:300-314.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 5]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
45.  McLean R, Cameron C, Butcher E, Cook NR, Woodward M, Campbell NRC. Comparison of 24-hour urine and 24-hour diet recall for estimating dietary sodium intake in populations: A systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2019;21:1753-1762.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 36]  [Article Influence: 7.2]  [Reference Citation Analysis (0)]
46.  Lucko AM, Doktorchik C, Woodward M, Cogswell M, Neal B, Rabi D, Anderson C, He FJ, MacGregor GA, L'Abbe M, Arcand J, Whelton PK, McLean R, Campbell NRC; TRUE Consortium. Percentage of ingested sodium excreted in 24-hour urine collections: A systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2018;20:1220-1229.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 50]  [Cited by in F6Publishing: 66]  [Article Influence: 11.0]  [Reference Citation Analysis (0)]
47.  Brand A, Visser ME, Schoonees A, Naude CE. Replacing salt with low-sodium salt substitutes (LSSS) for cardiovascular health in adults, children and pregnant women. Cochrane Database Syst Rev. 2022;8:CD015207.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 15]  [Article Influence: 7.5]  [Reference Citation Analysis (0)]
48.  Nurmilah S, Cahyana Y, Utama GL, Aït-Kaddour A. Strategies to Reduce Salt Content and Its Effect on Food Characteristics and Acceptance: A Review. Foods. 2022;11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 10]  [Reference Citation Analysis (0)]