Factors associated with refractory ascites and spontaneous bacterial peritonitis in a predominantly Hispanic population: A retrospective analysis

Abstract

BACKGROUND

Refractory ascites (RA) and spontaneous bacterial peritonitis (SBP) are severe complications of decompensated cirrhosis, contributing to high morbidity and mortality. RA develops when ascites persists despite maximum diuretic therapy, while SBP arises from bacterial translocation and immune dysfunction in cirrhotic patients with ascites. Identifying key risk factors associated with these conditions is crucial for early intervention and improved patient outcomes.

AIM

To assess clinical and biochemical predictors of RA and SBP in a cohort of hospitalized patients with cirrhotic ascites.

METHODS

A retrospective chart review was conducted on patients with cirrhotic ascites diagnosed with RA or SBP at University Medical Center, El Paso, from July 1, 2013 to December 31, 2023. Patient demographics, clinical history, laboratory parameters, ascitic fluid analysis, and cirrhosis severity scores [Model for End-Stage Liver Disease-Sodium (MELD-Na) and Child-Pugh] were recorded. Statistical analyses, including multivariate logistic regression, were performed to identify independent predictors of RA and SBP, with a significance threshold of P < 0.05.

RESULTS

A total of 179 patients were included, with a mean age of 59.08 ± 13.04 years, predominantly male (55.9%) and Hispanic (98.3%). The most common etiology of cirrhosis was alcohol-related liver disease (45.3%), and most patients had Grade III ascites (95.5%). Among them, 115 (64.2%) had RA, and 57 (31.8%) had SBP. RA was significantly associated with abnormal serum potassium levels [odds ratio (OR) = 2.27, 95%CI: 1.06–4.84, P = 0.034], while SBP was independently predicted by gastrointestinal bleeding (OR = 2.59, 95%CI: 1.18–5.64, P = 0.017) and thrombocytopenia (platelet count < 50000; OR = 3.27, 95%CI: 1.08–9.88, P = 0.035).

CONCLUSION

RA and SBP are major complications of cirrhosis, with electrolyte imbalances and coagulopathy playing key roles in their development. Our study confirms that abnormal potassium levels significantly predict RA, while gastrointestinal bleeding and thrombocytopenia are strong predictors of SBP. These findings emphasize the need for early risk stratification and targeted management strategies to improve outcomes in high-risk cirrhotic patients, particularly in minority populations with limited healthcare access. Further prospective studies are warranted to validate these results and explore potential interventions to reduce RA and SBP incidence.

Key Words: Refractory ascites; Spontaneous bacterial peritonitis; Hispanic population; Electrolyte abnormalities; Thrombocytopenia; Gastrointestinal bleeding

Core Tip: In this retrospective study of 179 cirrhotic patients with ascites, we identified key clinical predictors for refractory ascites (RA) and spontaneous bacterial peritonitis (SBP) in a predominantly Hispanic population. Abnormal serum potassium levels independently predicted RA, while gastrointestinal bleeding and thrombocytopenia (platelet count < 50000/µL) were significant predictors of SBP. These findings emphasize the critical role of electrolyte imbalance and coagulopathy in cirrhosis-related complications and highlight the importance of early risk stratification in vulnerable populations with limited healthcare access.

INTRODUCTION

Cirrhotic ascites accounts for over 75% of patients who are admitted to hospital with ascites, with the remaining 20% owing to malignancies (12%), cardiac failure (5%), tuberculosis (1%), pancreatitis (1%) or other rarer causes[1]. Splanchnic vasodilatation due to excessive vasodilator production from increased shear stress due to portal flow obstruction and gut bacterial dislocation is the most important factor in the pathogenesis of ascites formation[2]. Recurrent ascites is defined as a peritoneal effusion that recurs on at least three occasions within a 12-month period despite dietary sodium restriction and adequate diuretic doses[3]. This can be a precursor to a feared consequence of refractory ascites. Refractory ascites (RA) is defined as ascites that cannot be mobilized or recurs after large volume paracentesis (LVP) despite dietary sodium restriction and diuretic therapy. It can be classified in two types (A) diuretic resistant (i.e., persistent ascites despite maximal doses of diuretics) and (B) diuretic intractable, in which side effects of diuretics preclude the use of maximum doses[4]. RA is associated with an increased risk of further serious complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome. RA patients with older age, presence of hepatocellular carcinoma, diabetes and use of alcohol are associated with worse prognosis[5].

SBP is a frequent and severe complication in cirrhotic patients with ascites. The diagnosis is based on a polymorphonuclear cell count greater than or equal to 250/mm³ in ascitic fluid, in the absence of an intra-abdominal source of infection and other causes of elevated ascites neutrophil count, however cultures are negative in approximately 60% of cases[6]. SBP is usually caused by translocation of commensal gram-negative bacteria in the gut, however recently trends of increased infections with gram positive bacteria and multi drug resistant bacteria have been observed[7,8]. Presenting symptoms of patients with SBP can be abdominal tenderness and ileus, however cirrhotic patients may not demonstrate these symptoms, and it should be suspected when a patient deteriorates, particularly with encephalopathy, acute kidney injury, and/or jaundice[9]. Empirical antibiotic therapy with intravenous 3^rd generation cephalosporin for 7 days must be started when the neutrophil count is higher than 250/mm³ and before microbiologic results are obtained[10].

In this retrospective cohort study, we investigated factors associated with the development of RA and SBP in a tertiary county hospital.

MATERIALS AND METHODS

We conducted a retrospective chart review of patients with cirrhotic ascites (ICD 10 code K74.6), with either RA or SBP (ICD 10 code R18.8 and K65.2 respectively) who were admitted to University Medical Center, El Paso from July 1, 2013 to December 31, 2023. Ethics committee approval (#E24123) was obtained from the institutional review board at Texas Tech University Health Sciences Center, El Paso, Texas. We included RA patients in age group 18-89, with RA or SBP. A total of 179 patients were included in this study. Patients with incomplete information, lack of paracentesis fluid results and ascites secondary to other causes were excluded.

We collected baseline patient demographics (age, ethnicity, gender). Data regarding etiology of cirrhosis, severity of ascites, presence/absence of gastrointestinal bleeding (GIB), and hepatic encephalopathy (HE) was collected. Laboratory markers collected included platelet count, prothrombin time- international normalized ratio, serum sodium, serum potassium, serum blood urea nitrogen (BUN), serum creatinine, serum bilirubin and serum albumin along with ascitic fluid protein. Cirrhosis severity scores were recorded including Model for End-Stage Liver Disease-Sodium (MELD-Na) and Child Pugh score. Data regarding ascitic fluid culture, antibiotic treatment and recurrent SBP was collected in cases of SBP. Culture negative, neutrophilic ascites (> 250/mm³) was counted as SBP. We also recorded if the patient was on beta blocker or proton pump inhibitor. The primary outcome measures included factors associated with development of RA and SBP.

Statistical analysis

Descriptive statistics were used to summarize the study population’s demographic, clinical, and biochemical features. Statistical methods were used to identify predictors of RA and SBP, with a significance of P < 0.05. Statistical analyses were conducted to compare baseline characteristics between patients with and without RA and SBP, using appropriate tests such as the χ² test for categorical variables and the independent t-test for continuous variables. P values were calculated to determine the strength of associations between RA and SBP and clinical factors, with a threshold of P < 0.05 considered statistically significant. The statistical analysis was performed using STATA 17.0. To identify independent predictors of RA and SBP, a multivariate logistic regression model was employed, adjusting for potential confounders. The results were expressed as adjusted odds ratios (ORs) with corresponding 95%CI, and a P value < 0.05 was considered statistically significant.

RESULTS

A cohort of 179 patients was identified, the mean age was 59.08 ± 13.04 with a male predominance (55.9%). Majority of the patients were Hispanic (98.3%). The most common cause of cirrhosis was alcohol use (45.3%). Majority patients also had grade III ascites on presentation (95.5%). HE was less frequently seen (66.5% with no HE), whereas presence of GIB was more common (42.5%). Majority of the patients had moderately low platelet count (31.8%) and 25.7% patients had elevated international normalized ratio (INR). Most patients had elevated serum BUN (41.3%) with mean creatinine of 2.37 ± 2.39. We also observed elevated bilirubin (46.4%), low albumin (48.6%), normal serum sodium (62.0%), abnormal potassium levels (53.6%) and low ascitic fluid protein (60.9%) in most patients. This cohort consisted of patients with Child Class C (62.6%) and MELD-Na score more than 26 (44.7%). Overall, mortality was observed in 87 (48.60%) patients and 39 (21.79%) patients underwent liver transplant (Table 1). A comparison of baseline clinical and laboratory characteristics between survivors (n = 92) and non-survivors (n = 87) revealed that the CLIF-ACLF score was significantly higher in patients who died (63.77 ± 6.36 vs 49.57 ± 5.73, P < 0.001), indicating its strong predictive value for mortality. Additionally, the MELD-Na score was significantly associated with mortality (P = 0.02; Table 2).

Table 1 Descriptive characteristics of the whole cohort with 179 patients, n (%).

Variables		Total (n = 179)
	Mean age	59.08 ± 13.04
Gender	Male	100 (55.9)
	Female	79 (44.1)
Ethnicity	Hispanic or Latino	176 (98.3)
	Caucasian	2 (1.1)
	African American	1 (0.6)
Etiology of liver disease	Hepatitis (A, B, C, D)	23 (12.8)
	Congenital liver disease	3 (1.7)
	MASH	11 (6.1)
	Alcoholic liver disease	81 (45.3)
	Autoimmune hepatitis	26 (14.5)
	Others	26 (14.5)
	NA	9 (5.0)
Severity of ascites	Grade I	3 (1.7)
	Grade II	5 (2.8)
	Grade III	171 (95.5)
HE	None	119 (66.5)
	Grade I	4 (2.2)
	Grade II	40 (22.3)
	Grade III	13 (7.3)
	Grade IV	2 (1.1)
GI bleed		76 (42.5)
Serum BUN	< 25 mg/dL	71 (39.7)
	25-35 mg/dL	34 (19.0)
	> 35 mg/dL	74 (41.3)
Mean creatinine		2.37 ± 2.39
Platelet count	1.5-4.5 × 103	55 (30.7)
	1-1.49 × 103	47 (26.3)
	50000-99999	57 (31.8)
	< 500000	20 (11.2)
INR	< 1.7	77 (43.0)
	1.7-2.3	56 (31.3)
	> 2.3	46 (25.7)
Bilirubin	< 2 mg/dL	58 (32.4)
	2-3 mg/dL	38 (21.2)
	> 3 mg/dL	83 (46.4)
Albumin	> 3.5 g/dL	10 (5.6)
	2.8-3.5 g/dL	82 (45.8)
	< 2.8 g/dL	87 (48.6)
Sodium	136-145 mEq/L	38 (21.2)
	126-135 mEq/L	111 (62.0)
	< 125 mEq/L	27 (15.1)
	> 135 mEq/L	3 (1.7)
Serum potassium	3.5-5.5 mEq/L	83 (46.4)
	< 3.5 mEq/L	62 (34.6)
	> 5.5 mEq/L	34 (19)
Child Pugh score	Class A	8 (4.5)
	Class B	59 (33.0)
	Class C	112 (62.6)
MELD-Na score	6-15	26 (14.5)
	16-25	73 (40.8)
	26-35	64 (35.8)
	> 35	16 (8.9)
Ascitic fluid protein	Low	109 (60.9)
	High	70 (39.1)
Liver transplant	Yes	39 (21.79)
	No	140 (78.21)
Death	Yes	87 (48.60)
	No	92 (51.40)

MASH: Metabolic Dysfunction-Associated Steatohepatitis; HE: Hepatic encephalopathy; BUN: Blood urea nitrogen; INR: International normalized ratio; MELD-Na: Model for End-Stage Liver Disease-Sodium; NA: Not available.

Table 2 Factors associated with mortality.

Variables		Mortality		P value
		No (n = 92)	Yes (n = 87)
	Mean age	59.47 ± 13.56	58.67 ± 12.54	0.68
Gender	Male	49	51	0.47
	Female	43	36
Ethnicity	Hispanic or Latino	90	86	0.22
	Caucasian	2	0
	African American	0	1
Etiology of liver disease	Hepatitis (A, B, C, D)	11	12	0.61
	Congenital liver disease	0	3
	MASH	5	6
	Alcoholic liver disease	44	37
	Autoimmune hepatitis	15	11
	Others	12	14
	NA	5	4
Severity of ascites	Grade I	2	1	0.82
	Grade II	3	2
	Grade III	87	81
HE	None	60	59	0.43
	Grade I	1	3
	Grade II	23	17
	Grade III	6	7
	Grade IV	2	0
GI bleed		39	37	0.98
Serum BUN	< 25 mg/dL	36	35	0.78
	25-35 mg/dL	16	18
	> 35 mg/dL	40	34
Mean creatinine		2.33 ± 2.31	2.41 ± 2.48
CLIF-ACLF		49.57 ± 5.73	63.77 ± 6.36	< 0.001
Platelet count	1.5-4.5 × 103	30	25	0.87
	1-1.49 × 103	23	24
	50000-99999	30	27
	< 500000	9	11
INR	< 1.7	42	35	0.64
	1.7-2.3	26	30
	> 2.3	24	22
Bilirubin	< 2 mg/dL	25	33	0.30
	2-3 mg/dL	21	17
	> 3 mg/dL	46	37
Albumin	> 3.5 g/dL	4	6	0.30
	2.8-3.5 g/dL	40	42
	< 2.8 g/dL	48	39
Sodium	136-145 mEq/L	17	21	0.70
	126-135 mEq/L	59	52
	< 125 mEq/L	15	12
	> 135 mEq/L	1	2
Serum potassium	3.5-5.5 mEq/L	42	41	0.93
	< 3.5 mEq/L	33	29
	> 5.5 mEq/L	17	17
Child Pugh score	Class A	5	3	0.12
	Class B	24	35
	Class C	63	49
MELD-Na score	6-15	11	15	0.02
	16-25	34	39
	26-35	42	22
	> 35	5	11
Ascitic fluid protein	Low	55	54	0.75
	High	37	33

NA: Not available; MASH: Metabolic Dysfunction-Associated Steatohepatitis; HE: Hepatic encephalopathy; GI: Gastrointestinal; BUN: Blood urea nitroge; INR: International normalized ratio; MELD-Na: Model for End-Stage Liver Disease-Sodium.

Refractory ascites

A total of 115 RA patients were identified. RA patients had a higher mean age of 56.96 ± 12.40 years, with males comprising 56.5% of the RA group. Ethnicity was predominantly Hispanic or Latino (98.3%). Alcohol use was reported in 56.5% of patients with RA. Regarding liver disease etiology, alcoholic liver disease was the most common cause in both groups (48.7% vs 39.1%), followed by autoimmune hepatitis (17.4% vs 9.4%) and viral hepatitis (8.7% vs 20.3%). While viral hepatitis appeared more common in the non-RA group, the difference did not reach statistical significance (P = 0.09). The severity of ascites was predominantly Grade III in both groups, though slightly more frequent in the RA group (97.4% vs 92.2%, P = 0.26). HE distribution was also similar, with 66.1% of RA patients and 67.2% of non-RA patients having no HE (P = 0.67). However, a significantly higher proportion of patients with RA had a history of GIB (48.7% vs 31.3%, P = 0.02), suggesting a possible link between GIB and RA development.

Serum BUN levels were higher in RA patients, with 47% having BUN > 35 mg/dL compared to 31.3% in the non-RA group (P = 0.04). Mean creatinine levels were also significantly elevated in the RA group (2.79 ± 2.74 mg/dL vs 1.61 ± 1.29 mg/dL, P < 0.01). INR was higher in RA patients, with 33% having INR > 2.3 compared to 12.5% in the non-RA group (P < 0.01). Total bilirubin levels were also elevated in RA patients, with 52.2% having levels > 3 mg/dL compared to 35.9% in non-RA patients, although this difference did not reach statistical significance (P = 0.10). Albumin levels were similar between groups (P = 0.56), with most patients having values < 3.5 g/dL. Sodium levels did not differ significantly (P = 0.13), though severe hyponatremia (< 125 mEq/L) was more frequent in RA patients (18.3% vs 9.4%). Abnormal potassium levels were significantly more frequent in RA patients (63.4% vs 36%, P < 0.001). A significantly higher proportion of RA patients were classified as Child-Pugh Class C (69.6% vs 50.0%, P = 0.03) and had a higher MELD-Na score, with 41.7% scoring 26-35 compared to 25.0% in the non-RA group (P = 0.02). Finally, ascitic fluid protein levels were comparable between groups, with 60.0% of RA patients and 62.5% of non-RA patients having low protein levels (P = 0.87). The average CLIF-ACLF score in RA patients was 56.33 ± 9.49 (Table 3 and Figure 1).

Figure 1 Significant factors associated with refractory ascites. RA: Refractory ascites; MELD-Na: Model for End-Stage Liver Disease-Sodium; INR: International normalized ratio; BUN: Blood urea nitroge.

Table 3 Factors associated with refractory ascites, n (%).

Variables		Refractory ascites		P value
		Yes (n = 115)	No (n = 64)
	Mean age	56.96 ± 12.40	62.89 ± 13.39	< 0.01
Gender	Male	65 (56.5)	35 (54.7)	0.81
	Female	50 (43.5)	29 (45.3)
Ethnicity	Hispanic or Latino	114 (99.1)	62 (96.9)	0.36
	Caucasian	1 (0.9)	1 (1.6)
	African American	0 (0.0)	1 (1.6)
Etiology of liver disease	Hepatitis (A, B, C, D)	10 (8.7)	13 (20.3)	0.09
	Congenital liver disease	2 (1.7)	1 (1.6)
	MASH	7 (6.1)	4 (6.3)
	Alcoholic liver disease	56 (48.7)	25 (39.1)
	Autoimmune hepatitis	20 (17.4)	6 (9.4)
	Others	17 (14.8)	9 (14.1)
	NA	3 (2.6)	6 (9.4)
Severity of ascites	Grade I	1 (0.9)	2 (3.1)	0.26
	Grade II	2 (1.7)	3 (4.7)
	Grade III	112 (97.4)	59 (92.2)
HE	None	76 (66.1)	43 (67.2)	0.67
	Grade I	2 (1.7)	2 (3.1)
	Grade II	29 (25.2)	11 (17.2)
	Grade III	7 (6.1)	6 (9.4)
	Grade IV	1 (0.9)	1 (1.6)
GI bleed		56 (48.7)	20 (31.3)	0.02
Serum BUN	< 25 mg/dL	38 (33.0)	33 (51.6)	0.04
	25-35 mg/dL	23 (20.0)	11 (17.2)
	> 35 mg/dL	54 (47.0)	20 (31.3)
Mean creatinine		2.79 ± 2.74	1.61 ± 1.29	< 0.01
Platelet count	1.5-4.5 × 103	38 (33.0)	17 (26.6)	0.61
	1-1.49 × 103	27 (23.5)	20 (31.3)
	50000-99999	38 (33.0)	19 (29.7)
	< 500000	12 (10.4)	8 (12.5)
INR	< 1.7	42 (36.5)	35 (54.7)	< 0.01
	1.7-2.3	35 (30.4)	21 (32.8)
	> 2.3	38 (33.0)	8 (12.5)
Bilirubin	< 2 mg/dL	34 (29.6)	24 (37.5)	0.10
	2-3 mg/dL	21 (18.3)	17 (26.6)
	> 3 mg/dL	60 (52.2)	23 (35.9)
Albumin	> 3.5 g/dL	5 (4.3)	5 (7.8)	0.56
	2.8-3.5 g/dL	52 (45.2)	30 (46.9)
	< 2.8 g/dL	58 (50.4)	29 (45.3)
Sodium	136-145 mEq/L	19 (16.5)	19 (29.7)	0.13
	126-135 mEq/L	73 (63.5)	38 (59.4)
	< 125 mEq/L	21 (18.3)	6 (9.4)
	> 135 mEq/L	2 (1.7)	1 (1.6)
Serum potassium	3.5-5.5 mEq/L	42 (36.5)	41 (64.1)	< 0.001
	< 3.5 mEq/L	45 (39.1)	17 (26.6)
	> 5.5 mEq/L	28 (24.3)	6 (9.4)
Child Pugh score	Class A	4 (3.5)	4 (6.3)	0.03
	Class B	31 (27.0)	28 (43.8)
	Class C	80 (69.6)	32 (50.0)
MELD-Na score	6-15	14 (12.2)	12 (18.8)	0.02
	16-25	40 (34.8)	33 (51.6)
	26-35	48 (41.7)	16 (25.0)
	> 35	13 (11.3)	3 (4.7)
Ascitic fluid protein	Low	69 (60.0)	40 (62.5)	0.87
	High	46 (40.0)	24 (37.5)
CLIF-ACLF		56.33 ± 9.49	56.53 ± 9.29	0.89

NA: Not available; MASH: Metabolic Dysfunction-Associated Steatohepatitis; HE: Hepatic encephalopathy; GI: Gastrointestinal; BUN: Blood urea nitroge; INR: International normalized ratio; MELD-Na: Model for End-Stage Liver Disease-Sodium.

Multivariate logistic regression analysis identified one independent risk factors for RA. An abnormal serum potassium level emerged as a significant predictor, with an adjusted OR of 2.27 (95%CI: 1.06-4.84, P = 0.034). Other variables, including GIB, serum BUN > 25, creatinine level, INR > 1.7, and MELD-Na score did not demonstrate statistically significant associations with RA (Table 4). A Kaplan–Meier survival analysis was conducted to evaluate the time to development of RA in patients with cirrhosis. The cumulative RA-free survival declined sharply within the first 1000 days of follow-up, indicating that most RA cases occurred early in the disease course. Beyond this period, the survival function plateaued, suggesting a lower incidence of RA in long-term survivors. By the end of the follow-up period (approximately 4000 days), the RA-free survival rate stabilized at approximately 25%, reflecting a cumulative incidence of RA of around 75% (Figure 2).

Figure 2 Kaplan–Meier survival curve demonstrating time to development of refractory ascites. Censored observations are marked with plus signs.

Table 4 After doing multivariate logistic regression analysis, serum abnormal potassium level [adjusted odds ratio 2.27 (95%CI: 1.06-4.84)], was found to be associated with development of refractory ascites.

	P values	Odds ratio	95%CI for odds ratio
			Lower	Upper
GI bleed	0.392	1.394	0.651	2.988
Serum BUN > 25	0.506	1.342	0.564	3.191
Creatinine level	0.295	1.166	0.875	1.556
INR > 1.7	0.429	1.388	0.616	3.131
Serum potassium abnormal	0.034	2.270	1.064	4.845
MELD-Na score	0.956	1.016	0.575	1.797

BUN: Blood urea nitroge; INR: International normalized ratio; MELD-Na: Model for End-Stage Liver Disease-Sodium; GI: Gastrointestinal.

Spontaneous bacterial peritonitis

A total of 57 RA patients were identified. They had a mean age of 59.79 ± 10.53 years, with males representing 49.1% of the SBP group. Most participants in SBP group were Hispanic or Latino (98.2%). Alcohol use was prevalent in SBP group (56.1%). The etiology of liver disease was similar between SBP vs non-SBP groups, with alcoholic liver disease (ALD) being the most common cause (43.9% in SBP vs 45.9% in non-SBP), followed by autoimmune hepatitis (14.0% vs 14.8%) and viral hepatitis (12.3% vs 13.1%). No statistically significant differences were found in the underlying causes of liver disease (P = 0.77). Regarding ascites severity, almost all patients in both groups had Grade III ascites (96.5% in SBP). HE severity did not differ significantly between groups (P = 0.64), with about two-thirds of patients in both groups having no HE. However, GIB was significantly more prevalent in the SBP group compared with non-SBP group (57.9% vs 35.2%, P < 0.01).

Serum BUN were higher in SBP group (54.4% vs 35.2%, P = 0.05). Mean creatinine levels were higher in the SBP group (2.81 ± 1.44 vs 2.16 ± 2.34, P = 0.09). A higher proportion of SBP group had INR > 2.3 (33.3% vs 22.1%, P = 0.14), though the difference was not statistically significant. Serum bilirubin levels were elevated in the SBP group, with 56.1% having levels > 3 mg/dL compared to 41.8% in non-SBP patients (P = 0.14). Serum albumin levels were slightly lower in SBP group with 56.1% having values < 2.8 g/dL vs 45.1% in the non-SBP group (P = 0.37). Sodium levels were similar between both groups, severe hyponatremia (< 125 mEq/L) was slightly more frequent in SBP group (19.3% vs 13.1%, P = 0.40). Potassium abnormalities were more pronounced in SBP group, particularly hyperkalemia (> 5.5 mEq/L), which was seen in 26.3% compared to 15.6% of non-SBP group (P = 0.18). A greater proportion of SBP patients were classified as Child-Pugh Class C (71.9% vs 58.2%, P = 0.14). The MELD-Na score was significantly higher in the SBP group, compared to in the non-SBP group (52.6% vs 27.9%, P = 0.001). Finally, ascitic fluid protein levels were similar between groups, with 63.2% of SBP patients and 59.8% of non-SBP patients having low ascitic protein (P = 0.795). The average CLIF-ACLF score in SBP patients was 56.13 ± 9.04 (Table 5 and Figure 3).

Figure 3 Significant factors associated with spontaneous bacterial peritonitis. SBP: Spontaneous bacterial peritonitis; PC: Platelet count; MELD-Na: Model for End-Stage Liver Disease-Sodium.

Table 5 Factors associated with development of spontaneous bacterial peritonitis, n (%).

Variables		Yes (n = 57)	No (n = 122)	P value
	Mean age	59.79 ± 10.53	58.75 ± 14.09	0.61
Gender	Male	28 (49.1)	72 (59.0)	0.21
	Female	29 (50.9)	50 (41.0)
Ethnicity	Hispanic or Latino	56 (98.2)	120 (98.4)	0.68
	Caucasian	1 (1.8)	1 (0.8)
	African American	0 (0.0)	1 (0.8)
	Use of alcohol	32 (56.1)	68 (55.7)	0.96
Etiology of liver disease	Hepatitis (A, B, C, D)	7 (12.3)	16 (13.1)	0.77
	Congenital liver disease	0 (0.0)	3 (2.5)
	NASH	4 (7.0)	7 (5.7)
	ALD	25 (43.9)	56 (45.9)
	Autoimmune hepatitis	8 (14.0)	18 (14.8)
	Others	11 (19.3)	15 (12.3)
	NA	2 (3.5)	7 (5.7)
Severity of ascites	Grade I	0 (0.0)	3 (2.5)	0.45
	Grade II	2 (3.5)	3 (2.5)
	Grade III	55 (96.5)	116 (95.1)
HE	None	38 (66.7)	81 (66.4)	0.64
	Grade I	0 (0.0)	4 (3.3)
	Grade II	12 (21.1)	28 (23.0)
	Grade III	5 (8.8)	8 (6.6)
	Grade IV	1 (1.8)	1 (0.8)
GI bleed		33 (57.9)	43 (35.2)	< 0.01
Serum BUN	< 25 mg/dL	18 (31.6)	53 (43.4)	0.05
	25-35 mg/dL	8 (14.0)	26 (21.3)
	> 35 mg/dL	31 (54.4)	43 (35.2)
Mean creatinine		2.81 ± 1.44	2.16 ± 2.34	0.09
Platelet count	1.5-4.5 × 103/μL	17 (29.8)	38 (31.1)	0.02
	1-1.49 × 103/μL	15 (26.3)	32 (26.2)
	50000-99999/μL	13 (22.8)	44 (36.1)
	< 50000/μL	12 (21.1)	8 (6.6)
INR	< 1.7	25 (43.9)	52 (42.6)	0.14
	1.7-2.3	13 (22.8)	43 (35.2)
	> 2.3	19 (33.3)	27 (22.1)
Bilirubin	< 2 mg/dL	17 (29.8)	41 (33.6)	0.14
	2-3 mg/dL	8 (14.0)	30 (24.6)
	> 3 mg/dL	32 (56.1)	51 (41.8)
Albumin	> 3.5 g/dL	3 (5.3)	7 (5.7)	0.37
	2.8-3.5 g/dL	22 (38.6)	60 (49.2)
	< 2.8 g/dL	32 (56.1)	55 (45.1)
Sodium	136-145 mEq/L	10 (17.5)	28 (23.0)	0.40
	126-135 mEq/L	36 (63.2)	75 (61.5)
	< 125 mEq/L	11 (19.3)	16 (13.1)
	> 135 mEq/L	0 (0.0)	3 (2.5)
Serum potassium	3.5-5.5 mEq/L	26 (45.6)	57 (46.7)	0.18
	< 3.5 mEq/L	16 (28.1)	46 (37.7)
	> 5.5 mEq/L	15 (26.3)	19 (15.6)
Child Pugh score	Class A	3 (5.3)	5 (4.1)	0.14
	Class B	13 (22.8)	46 (37.7)
	Class C	41 (71.9)	71 (58.2)
MELD-Na score	6-15	10 (17.5)	16 (13.1)	0.001
	16-25	11 (19.3)	62 (50.8)
	26-35	30 (52.6)	34 (27.9)
	> 35	6 (10.5)	10 (8.2)
Ascitic fluid protein	Low	36 (63.2)	73 (59.8)	0.795
	High	21 (36.8)	49 (40.2)
CLIF-ACLF		56.13 ± 9.04	57.08 ± 9.86	0.51

NA: Not available; MASH: Metabolic Dysfunction-Associated Steatohepatitis; HE: Hepatic encephalopathy; GI: Gastrointestinal; BUN: Blood urea nitroge; INR: International normalized ratio; MELD-Na: Model for End-Stage Liver Disease-Sodium.

Multivariate logistic regression analysis identified two independent risk factors for SBP. The presence of GIB was strongly associated with SBP, with an adjusted OR of 2.59 (95%CI: 1.18–5.64, P = 0.017). Additionally, a platelet count < 50000 was significantly associated with SBP, with an adjusted OR of 3.27 (95%CI: 1.08-9.88, P = 0.035). Other factors, such as BUN > 35, MELD-Na > 25, and creatinine levels, were not significant independent predictors in the multivariate model (Table 6). A Kaplan–Meier survival analysis was performed to assess the time to development of SBP among patients with cirrhosis. The cumulative SBP-free survival declined sharply during the initial 1000 days of follow-up, indicating that the majority of SBP events occurred early in the disease course. After this period, the curve plateaued, suggesting a lower incidence of new SBP cases in long-term survivors. By the end of the follow-up period (approximately 4000 days), the SBP-free survival rate stabilized at around 60%, indicating a cumulative incidence of SBP of approximately 40% (Figure 4).

Figure 4 Kaplan–Meier survival curve demonstrating time to development of spontaneous bacterial peritonitis. Censored observations are marked with plus signs.

Table 6 After doing multivariate logistic regression analysis, presence of gastrointestinal bleed [adjusted odds ratio 2.59 (95%CI: 1.18-5.64)], platelet count < 50000 [adjusted odds ratio 3.27 (95%CI: 1.08-9.88)].

	P values	Odds ratio	95%CI for odds ratio
			Lower	Upper
GI bleed	0.017	2.591	1.188	5.648
Serum BUN > 35	0.425	1.522	0.542	4.271
Platelet count < 50000	0.035	3.275	1.085	9.883
MELD-Na score > 25	0.289	1.612	0.667	3.899
Creatinine absolute	0.495	0.931	0.758	1.143

BUN: Blood urea nitroge; MELD-Na: Model for End-Stage Liver Disease-Sodium; GI: Gastrointestinal.

DISCUSSION

The findings of this study highlight the significant clinical factors associated with the development of RA and SBP in patients with advanced liver disease. In this predominantly Hispanic cohort, our results demonstrate that RA is strongly linked to abnormal potassium levels, whereas SBP is independently associated with GIB and thrombocytopenia. These associations suggest that electrolyte imbalances and coagulopathy play a crucial role in the pathophysiology of RA and SBP, respectively. The predominance of ALD as the underlying etiology in both conditions aligns with existing literature, emphasizing the substantial burden of alcohol-related cirrhosis. Additionally, the high prevalence of severe ascites (Grade III) in both groups indicates that progressive portal hypertension and hepatic decompensation contribute to the development of these complications. The observed associations between higher MELD-Na scores and both RA and SBP further reinforce that worsening liver function predisposes patients to severe complications.

Cirrhosis management varies across racial groups due to healthcare barriers. Black and Hispanic patients often face delays in care, leading to more complications like ascites and HE. They are also less likely to receive timely liver transplants[11]. A recent study found that race and lower education levels had a significant on mortality in cirrhotic patients, with Hispanics facing mortality at an earlier stage as compared to other races[12]. American Gastroenterology Association currently recommends transjugular intrahepatic portosystemic shunt (TIPS) placement over LVP for control of RA, for patients with low MELD scores[13]. However, research shows that minority populations face barriers to liver transplants, TIPS and other procedures, which significantly impact survival outcomes[14]. As seen in our cohort, only 39 patients underwent liver transplants due to socioeconomic barriers.

Our results showed predominantly cause of cirrhosis as ALD, aligning with existing research. ALD disproportionately affects minority populations, particularly Hispanic and Black individuals. The prevalence of ALD is higher among Hispanics (9.3%) compared to Whites (4.1%) and Blacks (3.4%), likely influenced by social determinants of health, including higher alcohol outlet density, neighborhood disinvestment, and limited healthcare access[15]. Additionally, genetic factors such as the patatin-like phospholipase domain-containing-3 (PNPLA3) allele, more common in Hispanics, may contribute to increased ALD susceptibility[16]. Women are also at greater risk of ALD progression with lower alcohol consumption due to biological differences in alcohol metabolism. Cultural factors, including targeted alcohol marketing and shifting social norms, have contributed to rising alcohol use among women. This is reflected in increasing ALD prevalence, with NHANES data showing a doubling of ALD cases among women with significant fibrosis and a 50% rise in alcohol-associated cirrhosis from 2009 to 2015[17]. Our study consisted of 44.1% females. We also observed patients with higher MELD scores and Child class.

In our cohort, 115 patients with RA were identified (64.2%). As per current literature, RA can develop amongst 10% patients with cirrhosis and is associated with poor quality of life[18]. Previously, 1-year mortality with RA was 50%, newer studies show 1-year mortality is still exceeds 20%[19,20]. As cirrhosis progresses and portal hypertension worsens, fibrosis, stellate cell activation, and microthrombi increase intrahepatic resistance. Collateral vessel formation and splanchnic vasodilation further elevate portal flow, perpetuating hypertension[21]. Systemic vasodilation reduces effective arterial blood volume, triggering sodium and water retention, and excess fluid accumulates as ascites. Gut permeability rises due to venous congestion and angiogenesis, leading to bacterial translocation, systemic inflammation, and worsening fibrosis[22]. Renal circulation becomes increasingly vasoconstricted, causing hypoperfusion and chronic renal insufficiency, formerly termed type 2 hepatorenal syndrome. As a result, sodium retention intensifies, and ascites becomes refractory to diuretics[23].

We observed a higher mean age along with higher serum BUN, mean creatinine, serum INR, Child Pugh class, MELD score and abnormal serum potassium in our RA cohort. We also observed that patients with concurrent GIB developed RA. After logistic regression, abnormal potassium levels were significantly associated with RA development (OR = 2.270, 95%CI: 1.064-4.845, P = 0.034). The point to remember is that RA develops in patients who already have severe Grade III ascites and have been treated with the maximum tolerated doses of diuretics. At this stage, the persistent activation of sodium and water retention mechanisms leads to worsening fluid overload, while prolonged diuretic use causes significant electrolyte imbalances, including hypo- or hyperkalemia, depending on the type of diuretic administered. Loop diuretics, such as furosemide, contribute to hypokalemia, whereas potassium-sparing agents, like spironolactone, increase the risk of hyperkalemia. Evidence from previous studies supports the role of electrolyte disturbances, particularly abnormal potassium levels, in RA development. Angeli et al[24], Bernardi et al[25], and Seo et al[26] demonstrated that patients who fail to respond to diuretics tend to have lower serum sodium and higher potassium levels compared to those who achieve adequate ascites control. Furthermore, multiple reports suggest that serum potassium imbalances may directly contribute to the pathophysiology of RA[4,27]. Consistent with these findings, our study confirms that an abnormal serum potassium level is significantly associated with an increased risk of developing RA.

In our cohort, 57 patients with SBP were identified (31.8%). The incidence of SBP varies worldwide, with a recent metanalysis showed the global pooled prevalence to be 17.12%, highest in Africa (68.2%) and lowest in North America (10.8%)[28]. In addition to traditional SBP, three other types of SBP definitions exist. Culture-negative neutrocytic ascites (CNNA), monomicrobial bacterascites (MMB), and polymicrobial bacterascites (PMB) are distinct classifications of infected ascitic fluid. CNNA is diagnosed when the polymorphonuclear leukocyte (PMNL) count exceeds 250/mm³, but ascitic fluid cultures remain negative. MMB is identified when the PMNL count is below 250/mm³ with the growth of a single microorganism in ascitic fluid culture, whereas PMB is characterized by a PMNL count below 250/mm³ with multiple microorganisms present in culture[10]. When initially reported, the in-hospital mortality rate for SBP exceeded 90%. However, with early diagnosis and prompt antibiotic treatment, it has decreased to approximately 20%[29]. The pathogenesis of SBP involves gut dysbiosis, bacterial translocation, and immune dysfunction. In cirrhosis, increased gut permeability, altered motility, and dysbiosis promote bacterial overgrowth. Weakened mesenteric lymph nodes fail to contain bacteria, allowing systemic spread to ascitic fluid. Immune dysfunction, including impaired neutrophils, reduced complement activity, and low ascitic protein, further increases susceptibility to infection[30].

We observed a lower platelet count, higher MELD score and presence of GIB in our SBP cohort. Logistic regression revealed presence of GIB and thrombocytopenia (< 50000) as significant predictors of SBP (OR = 2.591, 95%CI: 1.188-5.648, P = 0.017 and OR = 3.275, 95%CI: 1.085-9.883, P = 0.035 respectively). Studies have identified key predictors of SBP, including low ascitic fluid protein, elevated bilirubin, and impaired renal function. Additionally, acute variceal bleeding, proton pump inhibitor use, and asymptomatic bacteriuria have been linked to increased susceptibility to SBP[31]. Conversely, nonselective beta blockers, particularly propranolol, have shown a protective effect against SBP development[32]. Recurrent SBP remains a significant concern, with studies reporting recurrence rates of 43% at six months, 69% at one year, and 74% at two years. Risk factors for recurrence include low serum albumin, low ascitic fluid protein, reduced prothrombin levels, and a history of prior SBP episodes[10]. Thrombocytopenia has been identified in several studies as well as an independent predictor of SBP, while some studies demonstrating platelet count < 98000 as predictor of first episode and another study demonstrating < 10000 as predictor of recurrence[33,34].

This study has some limitations. Being a retrospective study, it is subject to inherent biases, including potential missing data and confounding variables that may not have been accounted for. Additionally, the study population is primarily drawn from a single center, which may limit the generalizability of the findings to broader populations with different demographics or healthcare access. This study also has several strengths. It provides a comprehensive analysis of clinical and laboratory factors associated with RA and SBP, reinforcing the role of electrolyte imbalances and coagulopathy in their pathogenesis. The use of logistic regression strengthens the identification of independent predictors, adding to the robustness of the findings. We include a large and diverse cohort, primarily consisting of Hispanic patients, offering valuable insights into racial disparities in cirrhosis outcomes, an area often underrepresented in similar research.

CONCLUSION

In conclusion, this study highlights the significant clinical predictors of RA and SBP in patients with advanced cirrhosis, emphasizing the role of electrolyte imbalances and coagulopathy in disease progression. The findings reinforce the importance of careful monitoring and individualized management strategies, particularly in high-risk patients with abnormal potassium levels, gastrointestinal bleeding, and thrombocytopenia. Given the high burden of cirrhosis complications in minority populations, further prospective studies are needed to validate these findings and explore targeted interventions to improve outcomes in these vulnerable groups.