Cirrhosis represents the terminal stage of chronic liver disease characterized by diffuse fibrosis and regenerative nodules, resulting in portal hypertension and hepatic insufficiency [1]. The development of ascites is a hallmark of decompensation and occurs in approximately 50–60% of patients within 10 years of diagnosis [2].

Ascites significantly worsens prognosis, with reported 1-year mortality rates of approximately 15–20% and 5-year survival dropping below 50% after its onset [3]. The pathophysiology involves portal hypertension, splanchnic vasodilation, activation of the renin–angiotensin–aldosterone system, and sodium-water retention [4].

Several complications frequently coexist with ascites, including spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and hepatic encephalopathy, all of which markedly increase mortality risk [5,6]. Prognostic models such as the Model for End-Stage Liver Disease (MELD) and Child–Pugh score are widely used; however, they may not fully account for complications specific to ascites [7,8].

Recent studies suggest that additional parameters such as serum sodium, inflammatory markers, and renal function indices may enhance mortality prediction [9]. Despite numerous individual studies, a comprehensive synthesis focusing specifically on cirrhosis with ascites remains limited.

METHODS

2.1 Study Design

This study was conducted in accordance with PRISMA guidelines [10].

2.2 Search Strategy

A comprehensive search was conducted in PubMed, Embase, Scopus, and Cochrane Library from database inception to January 2025 using predefined keywords [11].

2.3 Eligibility Criteria

• Adult patients with cirrhosis and ascites
• Observational studies reporting mortality predictors
• English-language full-text articles

2.4 Data Extraction and Quality Assessment

Two independent reviewers extracted data and assessed study quality using the Newcastle–Ottawa Scale [12].

2.5 Statistical Analysis

A random-effects model was applied. Heterogeneity was evaluated using I² statistics, and publication bias was assessed using funnel plots [13].

RESULTS

3.1 Study Selection

A total of 1,276 records were identified through database searching. After removing 312 duplicates, 964 articles underwent title and abstract screening. Of these, 87 full-text articles were assessed for eligibility, and 22 studies met the inclusion criteria.

Figure 1: PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This flow diagram illustrates the process of identification, screening, eligibility assessment, and inclusion of studies in the systematic review and meta-analysis. Reasons for exclusion at the full-text stage are detailed, and only studies meeting predefined inclusion criteria were included in the final analysis.

3.2 Study Characteristics

Table 1: Characteristics of Included Studies

The included studies comprised predominantly prospective cohort designs, with sample sizes ranging from 200 to 600 patients. The total pooled population was 6,845 patients [14–16].

3.3 Baseline Clinical Characteristics

Table 2: Baseline Patient Characteristics

Most patients presented with decompensated cirrhosis and moderate-to-severe ascites [16].

3.4 Narrative Analysis of Predictors

MELD Score

All 22 studies demonstrated a strong association between higher MELD scores and mortality. Patients with MELD ≥20 had significantly higher 3-month mortality rates (up to 35%) compared to those with lower scores [17].

Severity of Ascites

Severe ascites requiring repeated large-volume paracentesis was associated with increased mortality (HR 1.9, 95% CI 1.4–2.5) [18].

Hepatorenal Syndrome (HRS)

HRS was among the strongest predictors, with mortality rates exceeding 60% within 3 months [19].

Hyponatremia

Serum sodium <130 mmol/L was independently associated with increased mortality (HR 1.8) [20].

Spontaneous Bacterial Peritonitis (SBP)

Patients with SBP had nearly double the mortality risk compared to those without infection [5].

Hepatic Encephalopathy

Presence of hepatic encephalopathy increased mortality risk (HR 2.0), particularly in advanced grades [6].

3.5 Meta-analysis of Predictors

Table 3: Pooled Effect Sizes of Mortality Predictors

The strongest predictor identified was hepatorenal syndrome, followed by MELD score [19,20].

3.6 Subgroup Analysis

Table 4: Subgroup Analysis

Combining MELD score with serum sodium (MELD-Na) improved predictive accuracy significantly [21].

3.7 Publication Bias

Funnel plot analysis showed mild asymmetry, but Egger’s test was not statistically significant (p = 0.08), indicating low risk of publication bias.

Figure 2 Caption: Forest plot showing hazard ratios (HRs) with 95% confidence intervals for the association between MELD score and mortality across included studies. The vertical line at HR = 1 represents no effect.

Figure 3 Caption: Forest plot showing hazard ratios (HRs) with 95% confidence intervals for the association between hepatorenal syndrome and mortality in patients with cirrhosis and ascites. The vertical line at HR = 1 indicates no effect.

DISCUSSION

This systematic review and meta-analysis provides a comprehensive evaluation of predictors of mortality in patients with cirrhosis and ascites, highlighting the complex and multifactorial nature of disease progression. The findings demonstrate that mortality is driven not only by the severity of hepatic dysfunction but also by renal impairment, circulatory dysregulation, electrolyte imbalance, and infectious complications.

The MELD score emerged as a consistent and robust predictor of mortality across all included studies, reaffirming its central role in prognostication in cirrhosis [7,17]. Developed to predict survival in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), MELD has since been widely validated as an objective tool for risk stratification in end-stage liver disease [7]. In this analysis, higher MELD scores, particularly ≥20, were strongly associated with short-term mortality, consistent with prior studies demonstrating exponential increases in mortality risk with rising MELD values [17]. However, MELD alone may not fully capture the clinical complexity of patients with ascites, particularly in the presence of complications such as hyponatremia and HRS [9,21].

Renal dysfunction, particularly in the form of hepatorenal syndrome (HRS), was identified as the strongest predictor of mortality in this meta-analysis. HRS reflects advanced circulatory dysfunction characterized by splanchnic vasodilation, reduced effective arterial blood volume, and renal vasoconstriction [19]. The extremely high mortality associated with HRS—often exceeding 50–60% at 3 months—has been consistently reported in the literature and underscores its critical prognostic significance [19]. Our findings align with previous reports suggesting that renal failure is a more immediate determinant of survival than hepatic dysfunction alone in advanced cirrhosis [14,19]. This highlights the need for early identification and aggressive management, including vasoconstrictor therapy and consideration for liver transplantation.

Hyponatremia also emerged as an independent predictor of mortality, reflecting severe circulatory and renal dysfunction [20]. In cirrhosis, hyponatremia results from impaired free water excretion due to non-osmotic release of vasopressin and activation of neurohumoral pathways [4,20]. Multiple studies have demonstrated that serum sodium levels below 130 mmol/L are associated with increased mortality, independent of MELD score [20]. This has led to the development of the MELD-Na score, which incorporates serum sodium to improve predictive accuracy [21]. Our subgroup analysis further supports this, showing improved risk stratification when sodium levels are considered alongside MELD.

Infectious complications, particularly spontaneous bacterial peritonitis (SBP), significantly contribute to mortality in patients with ascites. SBP is a common and severe complication, occurring in up to 30% of hospitalized patients with cirrhosis and ascites [5]. It is associated with systemic inflammation, circulatory collapse, and a high risk of renal failure [5]. The increased mortality observed in patients with SBP in this analysis is consistent with previous studies reporting mortality rates of 20–40% despite appropriate antibiotic therapy [5]. These findings emphasize the importance of early diagnosis, prompt treatment, and prophylactic strategies in high-risk patients.

The presence of hepatic encephalopathy (HE) was also associated with significantly increased mortality. HE reflects advanced hepatic insufficiency and impaired detoxification of neurotoxins such as ammonia [6]. Its occurrence often indicates a critical stage of decompensation and is frequently associated with other complications such as infections and renal dysfunction [6]. Previous studies have demonstrated that recurrent or persistent HE is associated with poor long-term survival, which is consistent with the findings of this analysis [6].

Importantly, this meta-analysis highlights that the severity of ascites itself is an independent predictor of mortality, even after adjusting for MELD score and other variables [18]. Patients with refractory or grade 3 ascites requiring repeated large-volume paracentesis have significantly worse outcomes [18]. This finding reinforces the concept that clinical manifestations of portal hypertension provide important prognostic information beyond biochemical indices alone. It also supports current guidelines recommending early evaluation for liver transplantation in patients with refractory ascites.

Another important observation from this study is the interplay between systemic inflammation and circulatory dysfunction in driving disease progression. Emerging evidence suggests that bacterial translocation and chronic inflammation play a central role in the pathogenesis of complications such as SBP, HRS, and HE [14,15]. These processes contribute to worsening portal hypertension, endothelial dysfunction, and multiorgan failure, ultimately increasing mortality risk [14]. This highlights the need for a more integrated approach to prognostication that incorporates inflammatory markers and clinical parameters.

The findings of this study are consistent with previous large-scale analyses demonstrating that mortality in cirrhosis is determined by a combination of hepatic reserve, renal function, and systemic complications [3,14]. However, by specifically focusing on patients with ascites, this study provides a more targeted understanding of risk factors in this high-risk population. The results suggest that combining traditional scoring systems with clinical and biochemical parameters—such as sodium levels and presence of complications—can significantly improve risk stratification.

From a clinical perspective, these findings have important implications. Early identification of high-risk patients allows for timely interventions, including optimization of medical therapy, prevention of complications, and prioritization for liver transplantation [7,21]. The incorporation of dynamic variables such as renal function and sodium levels into prognostic models may further enhance decision-making and improve outcomes.

Despite its strengths, this study has several limitations. The included studies were predominantly observational, which may introduce bias and limit causal inference [13]. There was moderate heterogeneity in study populations, definitions of predictors, and follow-up durations, which may affect the generalizability of the findings. Additionally, most studies were conducted in tertiary care settings, potentially limiting applicability to community-based populations. Publication bias, although not statistically significant, cannot be entirely excluded.

Future research should focus on prospective multicenter studies to validate these findings and develop more comprehensive prognostic models incorporating clinical, biochemical, and inflammatory markers. The integration of machine learning and artificial intelligence may further enhance predictive accuracy and enable personalized risk assessment in patients with cirrhosis and ascites.

5. Limitations

• Moderate heterogeneity across studies
• Predominantly observational data
• Regional variability in healthcare settings
• Limited randomized controlled trials

CONCLUSION

Mortality in patients with cirrhosis and ascites is influenced by multiple interrelated factors, including hepatic dysfunction, renal impairment, electrolyte imbalance, and infectious complications. Early identification and comprehensive risk assessment are essential to improve patient outcomes.

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