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  • Original Article
  • OPEN ACCESS

Global Prevalence, Temporal Trends, and Associated Mortality of Bacterial Infections in Patients with Liver Cirrhosis: A Meta-analysis

  • Yu-Xin Tian1,2,
  • Bai-Yun Wu1,2,
  • Qi An1,2,
  • Yin-Ping Wu1,2,
  • Jing Zuo1,2,
  • Yee Hui Yeo3 and
  • Yu-Chen Fan1,2,* 
 Author information 

Abstract

Background and Aims

Bacterial infections (BIs) are common and severe complications in patients with liver cirrhosis, but global data are limited. Here, we aimed to evaluate the global prevalence, temporal changes, and associated mortality risk of BIs in liver cirrhosis.

Methods

We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies published without language restrictions until 11 August 2025. A random-effects model was used for meta-analyses, meta-regression by study year, and pooling adjusted hazard ratios.

Results

Fifty-nine studies, including 1,191,421 patients with cirrhosis, were analyzed. The pooled prevalence of BIs (33 studies) was 35.1% (95% confidence interval (CI): 29.2–41.4). The prevalence of Escherichia coli and Streptococcus spp. was 3.8% (95% CI: 2.5–5.2) and 1.5% (95% CI: 0.8–2.6), respectively. The pooled prevalence of multidrug-resistant bacteria was 6.8% (95% CI: 4.0–11.3). The most common BI sites were the gastrointestinal tract, ascites fluid, and urinary tract. The highest prevalence of BIs was reported in Europe (38.2%; 95% CI: 24.8–53.6), followed by South America (37.5%; 95% CI: 29.7–46.1) and Asia (22.8%; 95% CI: 16.3–30.9). Patients with acute-on-chronic liver failure showed the highest prevalence of BIs (44.2%; 95% CI: 29.7–59.8). A modest increasing trend in BIs prevalence was observed over time. BIs were associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratios 2.22, 95% CI 1.33–3.71).

Conclusions

BIs are prevalent in cirrhosis, especially in acute-on-chronic liver failure, with a modest upward trend and increased mortality risk.

Graphical Abstract

Keywords

Cirrhosis, Acute-on-chronic liver failure, Bacterial infections, Prevalence, Global, Meta-analysis

Introduction

Bacterial infections (BIs) pose a substantial threat to public health, with severe illnesses and increasing mortality rates caused by antibiotic-resistant strains.1 These infections lead to serious complications, especially in vulnerable populations such as the elderly and immunocompromised individuals. Estimating hospital infection rates is difficult due to varying diagnostic criteria, under conditions ranging from the presence of asymptomatic cases to the complexity of healthcare settings. In addition, the Centers for Disease Control and Prevention in the United States and Europe have recommended different thresholds for the diagnosis of various BI infections.2,3 Therefore, accurate assessment is essential for the effective control of infection and improved outcomes for infected patients.

Cirrhosis is the end stage of various chronic liver diseases, including fatty liver disease, alcoholic liver disease, and hepatitis virus infection. BIs are frequent and serious complications in patients with cirrhosis, creating significant clinical challenges due to their high morbidity, high short-term mortality, and detrimental impact on long-term prognosis.4–7 Patients with cirrhosis are vulnerable to BIs due to various factors, including gut dysbiosis, compromised intestinal integrity, increased bacterial translocation across the gut wall, immune dysfunction associated with cirrhosis, and portal-systemic shunting.5,8 BIs cause systemic inflammation that leads to organ failure and acute-on-chronic liver failure (ACLF), resulting in a high risk of short-term mortality and potentially increasing the mortality rate fourfold.9 The diversity of bacterial pathogens and the variety of infection sites further complicate the management of these patients.10,11 Furthermore, the prevalence and types of BIs in patients with cirrhosis vary substantially across different countries and regions, reflecting differences in healthcare infrastructure, antimicrobial stewardship, local microbial ecology, and resistance landscapes.12 In addition, a major concern is the increasing prevalence of infections caused by multidrug-resistant (MDR) organisms. Patients infected with MDR bacteria present higher rates of septic shock, intensive care unit (ICU) admissions, mechanical ventilation, or renal replacement therapy compared with patients without MDR bacteria.7,10,12 Understanding the regional and global epidemiology of these infections is crucial for improving the management and outcomes of patients with cirrhosis.

While previous studies have focused on local or regional estimates, global evidence remains fragmented. Here, we conducted a meta-analysis to estimate the global prevalence of BIs in patients with liver cirrhosis, investigate temporal trends using meta-regression, and assess their association with mortality.

Methods

Search strategy and selection criteria

This meta-analysis was conducted following the updated PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (2020),13,14 and the protocol was registered on PROSPERO (CRD42024589916). We searched PubMed, Embase, Web of Science, and the Cochrane Library until August 11, 2025, without language restrictions, to identify relevant full-text studies reporting BIs in patients with cirrhosis. The search strategy included MeSH terms and keywords such as “Bacteria”, “Escherichia coli”, “Staphylococcus”, “Klebsiella”, “Streptococcus”, “Pseudomonas”, “Enterococcus”, “Acinetobacter”, “Proteus”, and conditions like “bacteremia”, “pneumonia”, and “sepsis”. These terms were combined with Boolean operators (“OR”, “AND”) and refined with liver cirrhosis-related terms such as “cirrhosis” and “cirrhotic” in the Keywords, Title, and Abstract fields. Supplementary Table 1 shows the search strategies for all included databases. We excluded letters, editorials, case reports, reviews, comments, and case series because of their insufficient methodology. Additionally, we searched for potential studies by manually reviewing the reference lists of the included studies and relevant reviews. Title and abstract screening for eligibility was independently conducted by TYX and WYP based on a predefined set of inclusion and exclusion criteria (Supplementary Table 2). Any discrepancies were resolved through consensus or by consulting ZJ or WBY.

Data extraction and quality assessment

A complete information list was extracted from the articles and entered into a Microsoft Excel worksheet. The following data were independently extracted by two reviewers (TYX and WYP): author names, publication year, period of conduct, study location, sample size, study design, sample characteristics, type of infection, infected sites, infected bacterial species, and prevalence estimates. In addition, for each study, we extracted the case definitions of BIs, including site-specific criteria and thresholds (Supplementary Table 3). For each included study, we extracted the ACLF definition that was explicitly stated or cited. We then classified each definition according to the European Association for the Study of the Liver (EASL)-Chronic Liver Failure Consortium (CLIF),15 Asian-Pacific Association for the Study of the Liver (APASL),16,17 Chinese Group on the Study of Severe Hepatitis B,18 North American Consortium for the Study of End-Stage Liver Disease,4 or other established criteria. When a study cited more than one set of criteria, the one designated as primary by the authors was used for classification. The authors were contacted to request additional data if the relevant data were not readily available. At least two authors independently evaluated the quality of the included studies (TYX, WYP, ZJ, and WBY) using the Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence Studies.19 Any disagreements were resolved by consensus or consultation with a third author (FYC).

Statistical analysis

The prevalence of BIs was calculated via a meta-analysis of single proportions by dividing the number of affected patients by the total study population.20 Prior to pooling the data for meta-analysis, the original proportions and the logit transformations were tested for normality, and the method that best approximated a normal distribution was selected based on the results.21 Quantitative variables are presented herein as the mean values ± standard deviations and median values with corresponding ranges. The significance level was set at 0.05, and differences with p-values below this threshold were considered statistically significant. A random-effects model was used for all analyses to account for between-study variability, as recommended in the Cochrane Handbook.22 Subgroup analyses were performed based on study characteristics, including study location, country’s economic status (categorized by the World Bank classification of high-, upper-middle-, and low-income countries),23 study design, study period, and patient populations. The significance threshold for subgroup differences was set at p < 0.05, with values below this threshold indicating significance. Publication bias was assessed qualitatively by visually inspecting funnel plot symmetry. A symmetric funnel plot suggests minimal publication bias, while asymmetry may indicate potential publication bias, heterogeneity, or small-study effects.21 We modeled temporal trends in BIs prevalence using random-effects meta-regression with the study mid-year as a continuous moderator, and results were visualized on the proportion scale via a bubble plot.24 Adjusted hazard ratios (HRs) for mortality associated with BIs were pooled using a random-effects model. The analysis was conducted in R v4.2.3 via meta-packages and metaprop functions.25

Results

Of the 31,002 articles identified through the search, 59 studies were included in the review (Fig. 1). These included studies involved 1,191,421 patients. Table 1 shows the characteristics of each study.4,6,7,10,12,26,27-79 These studies reported BIs in hospitalized, outpatient, ICU-admitted, and ACLF patients with cirrhosis. Thirty-three studies examined multiple BIs, and twenty-six studies examined specific BIs, such as bacteraemia, spontaneous bacterial peritonitis (SBP), and urinary tract infection (UTI). These studies were conducted in Asia (n = 24), Europe (n = 17), North America (n = 10), South America (n = 3), and Africa (n = 3), with two multicenter studies. Of the 59 studies, 30 were retrospective cohort studies, 22 were prospective cohort studies, five were case-control studies, and two were cross-sectional studies. The sample sizes of the included studies ranged from 45 to 742,391. According to the Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence Studies, 46 studies were rated low risk of bias, whereas 13 were rated moderate risk of bias (Supplementary Table 4).

PRISMA flow diagram of the search strategy.
Fig. 1  PRISMA flow diagram of the search strategy.
Table 1

Characteristics of the studies included in this meta-analysis

Authors (year)Country, period of conductStudy designNo. of patientsBI evaluated and criteriaPrevalence of BISite, mode of infectionBacteriological characteristics
Piano et al. 201912Multicenter, 2015–2016Prospective cohort1,302Multiple BI740/1,302NSMDR (n = 253)
Baijal et al. 201427India, 2013–2013Prospective cohort420Multiple BI93/420SBP (n = 33)E. coli (n = 18), Staphylococcus spp. (n = 15), Streptococcus spp. (n = 7), Klebsiella spp. (n = 6), Pseudomonas spp. (n = 2), MDR (n = 20)
Borzio et al. 200128Italy, 1995–1996Prospective cohort405Multiple BI150/405UTI (n = 62), SBP (n = 34), bacteraemia (n = 32), RTI (n = 26), others (n = 19)E. coli (n = 38), S. aureus (n = 19), Enterococcus spp. (n = 16), Streptococcus spp. (n = 12), Pseudomonas spp. (n = 5), Klebsiella spp. (n = 3), Proteus spp. (n = 2), others (n = 51)
Kremer et al. 202229Germany, 2019–2021Prospective cohort239Multiple BI151/239NSMDR (n = 7)
Mohan et al. 2011a30India, 2007–2008Case-control200SSTI21/200SSTI (n = 21)E. coli (n = 11), K. pneumoniae (n = 4), S. aureus (n = 2)
Fernández et al. 201210Spain, 2005–2007Prospective cohort1,578Multiple BI390/1,578SBP (n = 126), UTI (n = 98), cellulitis (n = 66), sepsis (n = 62), pneumonia (n = 46), bacteraemia (n = 30), purulent bronchitis (n = 27), catheter infection (n = 23), others (n = 29)MDR (n = 92)
Bajaj et al. 20144USA, NSProspective cohort507Multiple BI80/507NSNS
El-Amin et al. 201731Egypt, NSCross-sectional100Multiple BI54/100SBP (n = 24), UTI (n = 13), RTI (n = 12), GII (n = 3), SSTI (n = 1), sepsis (n = 1)Staphylococcus spp. (n = 27), Streptococcus spp. (n = 6), E. coli (n = 4), Enterococcus spp. (n = 2), Pseudomonas spp. (n = 1), Klebsiella spp. (n = 1), others (n = 5)
Bajaj et al. 201832USA, NSProspective cohort2,743Multiple BI918/2,743UTI (n = 297), SBP (n = 227), RTI (n = 136), bacteraemia (n = 121), SSTI (n = 95), others (n = 146)NS
Bartoletti et al. 201433Italy, 2008–2012Retrospective cohort8,874Bacteraemia146/8,874Bacteraemia (n = 146)E. coli (n = 43), Staphylococcus spp. (n = 21), K. pneumoniae (n = 29), E. faecium (n = 15), E. faecalis (n = 12), Pseudomonas spp. (n = 10), Acinetobacter spp. (n = 10), S. pneumoniae (n = 4), others (n = 28)
Li et al. 2015a34China, 2011–2013Retrospective cohort6,086SBP506/6,086SBP (n = 506)NS
Alexopoulou et al. 201335Greece, 2008–2011Retrospective cohort156SBP47/156SBP (n = 47)Streptococcus spp. (n = 10), Enterococcus spp. (n = 9), E. coli (n = 8), Staphylococcus spp. (n = 7), Klebsiella spp. (n = 5), Pseudomonas spp. (n = 2), MDR (n = 9), others (n = 6)
Dionigi et al. 201736USA, 2007–2008Retrospective cohort781Multiple BI200/781Bacteraemia (n = 73), SBP (n = 71), UTI (n = 37), pleural fluid (n = 9), others (n = 69)MDR (n = 46), GNB (n = 100), GPB (n = 139)
Bajaj et al. 201937USA, 2013–2014Prospective cohort2,864Multiple BI998/2,864UTI (n = 256), SBP (n = 218), RTI (n = 132), bacteraemia (n = 110), SSTI (n = 89)C. difficile (n = 65)
Caly et al. 199338Brazil, 1987–1990Prospective cohort170Multiple BI80/170SBP (n = 32), UTI (n = 26), pneumonia (n = 22), SSTI (n = 12), bacteraemia (n = 4), others (n = 7)E. coli (n = 12), Streptococcus spp. (n = 10), S. aureus (n = 8), K. pneumoniae (n = 4), Proteus spp. (n = 3), others (n = 10)
Santoiemma et al. 202039USA, 2006–2016Retrospective cohort2,159SBP314/2,159SBP (n = 314)NS
Evans et al. 200340USA, 1994–2000Prospective cohort427SBP23/427SBP (n = 23)S. viridans (n = 4), S. aureus (n = 3), Pseudomonas spp. (n = 1), others (n = 6)
Hung et al. 201541China, 2004–2004Retrospective cohort16,992SBP451/16,992SBP (n = 451)NS
D’Oliveira et al. 202242Brazil, 2012–2018Retrospective cohort784Multiple BI285/784NSNS
Tang et al. 202243China, 2020–2022Retrospective cohort1,271Multiple BI480/1,271SBP (n = 292), RTI (n = 82), UTI (n = 12), GII (n = 9), SSTI (n = 3), others (n = 83)NS
Liu et al. 202044China, 2016–2018Retrospective cohort974Multiple BI203/974SBP (n = 76), RTI (n = 54), UTI (n = 28), bacteraemia (n = 18), GII (n = 12), SSTI (n = 3), others (n = 12)NS
Cheng et al. 201745China, 2013–2016Retrospective cohort1,043Bacteraemia112/1,043Bacteraemia (n = 112)NS
Li et al. 2015b46China, 2010–2013Retrospective cohort419SBP82/419SBP (n = 82)NS
Choudhuri et al. 201847India, 2015–2017Retrospective cohort106Multiple BI23/106NSMDR (n = 23)
Ponzetto et al. 200048Italy, NSCase-control45GII40/45GII (n = 40)NS
Rahimkhani et al. 200849Pakistan, 2006–2008Case-control60GII39/60GII (n = 39)NS
TANDON et al. 20127USA, 2009–2010Retrospective cohort746Multiple BI115/746UTI (n = 37), SBP (n = 28), pneumonia (n = 22), bacteraemia (n = 10), cellulitis (n = 12), SBEM (n = 2), others (n = 4)E. coli (n = 15), K. pneumoniae (n = 16), S. aureus (n = 10), Streptococcus spp. (n = 4), P. aeruginosa (n = 2), P. mirabilis (n = 2), others (n = 21)
Siringo et al. 199750Italy, NSCase-control153GII117/153GII (n = 117)NS
Angeloni et al. 200851Italy, 2004–2006Retrospective cohort228SBP38SBP (n = 38)E. coli (n = 2), K. pneumoniae (n = 2), Enterococcus spp. (n = 2), S. aureus (n = 1), others (n = 2)
Chen et al. 201952China, 2015–2015Prospective cohort526GII104/526GII (n = 104)C. difficile (n = 104)
Zhao et al. 201853China, 2011–2017Retrospective cohort1,465Multiple BI635/1,465Bacteraemia (n = 199), RTI (n = 193), SBP (n = 191), UTI (n = 42), others (n = 10)MDR (n = 280)
Fernández et al. 201954Europe, 2011–2011Prospective cohort1,146Multiple BI455/1,146SBP (n = 130), UTI (n = 111), pneumonia (n = 85), SSTI (n = 44), bacteraemia (n = 28), others (n = 122)NS
Sargenti et al. 20156Sweden, 2001–2010Retrospective cohort633Multiple BI241/633UTI (n = 76), SBP (n = 61), pneumonia (n = 55), SSTI (n = 51), bacteraemia (n = 48), mixed infection (n = 19), others (n = 88)NS
Gunjača et al. 201055Croatia, 2006–2007Prospective cohort108SBP23/108SBP (n = 23)E. coli (n = 7), MRSA (n = 2), Acinetobacter spp. (n = 2), S. aureus (n = 1), Streptococcus spp. (n = 1), S.epidermidis (n = 1), E. faecalis (n = 1)
Singal et al. 201456USA, 1998–2007Retrospective cohort742,391Multiple BI168,654/742,391NSNS
Chu et al. 199557China, 1992–1992Retrospective cohort443SBP140/443SBP (n = 140)NS
Mohan et al. 2011b58USA, 2008–2009Prospective cohort110SBP7/110SBP (n = 7)E. coli (n = 1), Klebsiella spp. (n = 1), S. aureus (n = 1)
Cadranel et al. 199959France, 1994–1994Case-control244UTI38/244UTI (n = 38)NS
Zhu et al. 201260China, 2007–2010Retrospective cohort240Multiple BI60/240NSNS
Xing et al. 201461China, 2011–2013Retrospective cohort734Multiple BI79/734RTI (n = 50), UTI (n = 26), others (n = 4)NS
Makhlouf et al. 201262Egypt, 2010–2011Cross-sectional901SBEM16/901SBEM (n = 16)E. coli (n = 6), K. pneumoniae (n = 2), Streptococcus spp. (n = 2), P. aeruginosa (n = 1)
Xiol et al. 199663USA, 1988–1992Prospective cohort120SBEM16/120SBEM (n = 16)E. coli (n = 8), Streptococcus spp. (n = 5), Enterococcus spp. (n = 2), K. pneumoniae (n = 2), P. stutzeri (n = 1)
Syed et al. 200764Nepal, NSProspective cohort81SBP20/81SBP (n = 20)E. coli (n = 3), S. pneumoniae (n = 2), P. aeruginosa (n = 1), Acinetobacter spp. (n = 1)
Abu-Freha et al. 202165Israel, 1996–2020Retrospective cohort1,035SBP173/1,035SBP (n = 173)NS
Dia et al. 201466Senegal, 2010–2010Prospective cohort55SBP15/55SBP (n = 15)NS
Rubinstein et al. 200167Uruguay, 1998–2000Prospective cohort64SBP17/64SBP (n = 17)NS
Karvellas et al. 201068United Kingdom, 2003–2005Retrospective cohort184Bacteraemia67/184Bacteraemia (n = 67)NS
Mücke et al. 201869Germany, 2008–2015Retrospective cohort173Multiple BI80/173NSNS
Fernández et al. 201726Spain, NSProspective cohort407Multiple BI269/407SBP (n = 63), UTI (n = 52), pneumonia (n = 54), SSTI (n = 19), bacteraemia (n = 19), others (n = 62)NS
Katoonizadeh et al. 201070Belgium, 2002–2007Prospective cohort53Multiple BI31/53NSNS
Su et al. 202171China, 2014–2015Retrospective cohort609Bacteraemia63/609Bacteraemia (n = 63)E. coli (n = 23), Klebsiella spp. (n = 14), Acinetobacter spp. (n = 4), S. epidermidis (n = 4), Streptococcus spp. (n = 4), S. aureus (n = 3), Pseudomonas spp. (n = 1), E. faecium (n = 1), S. hominis (n = 1), MDR (n = 25), others (n = 8)
Moreau et al. 201372Europe, 2011–2011Prospective cohort303Multiple BI154/303NSNS
Shalimar et al. 201873India, 2011–2017Retrospective cohort417Multiple BI320/417NSNS
Cai et al. 201774China, 2008–2014Retrospective cohort389Multiple BI266/389NSNS
Cao et al. 202475Multicenter, 2021–2022Prospective cohort1,293Multiple BI1,293/4,238SBP (n = 391)E.coli (n = 145), K. pneumoniae (n = 35), Enterococcus spp.(n = 31), S. aureus(n = 22), Streptococcus spp.(n = 28), Pseudomonas spp.(n = 10), C.difficile (n = 8), MDR (n = 74)
Nakayama et al. 201876Japan , 2011–2014Retrospective cohort102Multiple BI26/102NSNS
Jeong et al. 202577South Korea 2009–2021Retrospective cohort381,691Multiple BI65,122/381,691NSNS
Hoshi et al. 202178Japan, 2012–2019Retrospective cohort285Multiple BI57/285NSNS
Park et al. 201579South Korea 2010-2012Retrospective cohort442Multiple BI110/442NSNS

C. difficile, Clostridioides difficile; E. coli, Escherichia coli; E. faecalis, Enterococcus faecalis; E. faecium, Enterococcus faecium; GNB, gram-negative bacteria; GPB, gram-positive bacteria; K. pneumoniae, Klebsiella pneumoniae; MDR, Multidrug-resistant; MRSA, methicillin-resistant Staphylococcus aureus; NS, not stated; P. aeruginosa, Pseudomonas aeruginosa; P. mirabilis, Proteus mirabilis; P. stutzeri, Pseudomonas stutzeri; RTI, respiratory tract infection; S. aureus, Staphylococcus aureus; S. epidermidis, Staphylococcus epidermidis; S. hominis, Staphylococcus hominis; S. pneumoniae, Streptococcus pneumoniae; S. viridans, Streptococcus viridans; SBEM, spontaneous bacterial empyema; SBP, spontaneous bacteria peritonitis; SSTI, skin and soft tissue infection; UTI, urinary tract infection.

Sample attributes

In 49 studies, all cases of cirrhosis were included in the denominator, whereas ACLF was included in 10 studies. The criteria for diagnosing cirrhosis included clinical, biochemical, ultrasonographic, and endoscopic assessments. Histopathology was used in 29 studies, ICD coding in four studies, APASL-ACLF criteria in four studies, and EASL-ACLF criteria in five studies, while 17 studies did not specify their criteria. The etiology of cirrhosis varies, with alcohol, viral hepatitis, and nonalcoholic fatty liver disease being the most common causes.

Description of BIs

Among 1,191,421 patients (59 studies), 180,132 had BIs. Escherichia coli (E. coli) was reported in 301 out of 8,592 patients (15 studies), Streptococcus spp. in 96 out of 8,709 patients (14 studies), Klebsiella spp. in 96 out of 8,484 patients (14 studies), Staphylococcus spp. in 124 out of 7,917 patients (13 studies), Pseudomonas spp. in 25 out of 8,002 patients (nine studies), Enterococcus spp. in 64 out of 5,964 patients (eight studies), Acinetobacter spp. in seven out of 798 patients (three studies), and Proteus spp. in seven out of 1,321 patients (three studies). Gram-negative bacteria were reported in 561 out of 9,253 patients (15 studies), and gram-positive bacteria were reported in 444 out of 9,253 patients (15 studies). The types of BIs included SBP, reported in 30 studies (3,853 out of 48,304 patients), UTI in 16 studies (1,211 out of 16,261 patients), bacteraemia in 16 studies (1,080 out of 24,622 patients), respiratory tract infection in 14 studies (996 out of 15,236 patients), skin and soft tissue infection in 10 studies (338 out of 10,508 patients), gastrointestinal infection (GII) in seven studies (324 out of 3,129 patients), pneumonia in six studies (284 out of 4,680 patients), spontaneous bacterial empyema in three studies (34 out of 1,767 patients), cellulitis in two studies (78 out of 2,324 patients), and sepsis in two studies (63 out of 1,678 patients).

Meta-analysis with subgroup analysis

On the basis of 59 studies that investigated both single and multiple BIs, the pooled overall prevalence of BIs in cirrhosis patients was 26.3% (95% confidence interval (CI): 20.9–32.5) (Fig. 2). This prevalence increased to 35.1% (95% CI: 29.2–41.4) when only the 33 studies focused on multiple BIs were pooled (Supplementary Fig. 1). Subgroup analysis revealed that the main sources of variation in overall BI estimates were the population studied, the geographic location, the study design, the country’s economic status, and the decade in which the study was conducted. Higher overall BI estimates were observed in studies that included patients with ACLF, patients admitted to the ICU, or outpatients as the denominator than in those involving all hospitalized patients (44.2%, 29.8%, 34.3%, and 21.7%, respectively; p = 0.0232) (Fig. 3). Furthermore, in a prespecified subgroup analysis stratified by ACLF definition, the pooled BI prevalence was 51.9% (95% CI: 33.4–69.8) for EASL-CLIF and 32.0% (95% CI: 14.2–57.2) for APASL. The unspecified definition category contained only one study, yielding 58.5% (95% CI: 44.1–71.9) (Supplementary Fig. 2). The prevalence of BIs varied across different regions of the world. The estimates from Europe (38.2%) were higher than those from South America (37.5%), Asia (22.8%), North America (17.0%), and Africa (16.4%), p = 0.0007 (Fig. 4). The studies with the highest prevalence pooled were from Pakistan (65.0%), Belgium (58.5%), and Germany (55.1%), p < 0.01 (Supplementary Fig. 3). Moreover, the prevalence in tropical zones (28.3%) was higher than in temperate zones (25.1%) (Supplementary Fig. 4). Additionally, estimates from lower-middle-income countries (27.2%) were higher than those from high-income (26.3%) and upper-middle-income countries (21.8%), p = 0.7479 (Supplementary Fig. 5). An increasing trend in the pooled estimates of overall BIs was observed over the last ten years, rising from 20.9% (95% CI: 15.4–27.6) to 30.5% (95% CI: 21.7–40.9), p = 0.0895 (Supplementary Fig. 6). Furthermore, the prevalence varied by study design, with case-control studies showing the highest prevalence at 49.9% (Supplementary Fig. 7).

Pooled overall prevalence of BIs in patients with cirrhosis in the included studies.
Fig. 2  Pooled overall prevalence of BIs in patients with cirrhosis in the included studies.

BIs, bacterial infections.

Forest plot demonstrating the pooled prevalence of BIs in patients with cirrhosis by subgroup: Clinical status.
Fig. 3  Forest plot demonstrating the pooled prevalence of BIs in patients with cirrhosis by subgroup: Clinical status.

BIs, bacterial infections.

Forest plot demonstrating the pooled prevalence of BIs in patients with cirrhosis by subgroup: Continent.
Fig. 4  Forest plot demonstrating the pooled prevalence of BIs in patients with cirrhosis by subgroup: Continent.

BIs, bacterial infections.

Types of BIs

The pooled prevalence of E. coli in patients with cirrhosis was 3.8% (95% CI: 2.5–5.2), that of Streptococcus spp. was 1.5% (95% CI: 0.8–2.6), that of Klebsiella spp. was 1.3% (95% CI: 0.9–1.8), that of Staphylococcus spp. was 2.0% (95% CI: 1.0–4.0), that of Pseudomonas spp. was 0.3% (95% CI: 0.2–0.6), that of Enterococcus spp. was 1.3% (95% CI: 0.6–2.8), that of Acinetobacter spp. was 0.9% (95% CI: 0.4–1.8), that of Proteus spp. was 0.6% (95% CI: 0.2–1.4), and the overall prevalence of gram-negative bacteria was 6.4% (95% CI: 4.3–9.3), that of gram-positive bacteria was 4.2% (95% CI: 2.1–8.3), and that of MDR bacteria was 6.8% (95% CI: 4.0–11.3) (Supplementary Figs. 8–19).

Sites of BIs

The site-specific pooled prevalence of BIs was highest for GII (18.4%), followed by SBP (12.4%), UTI (7.0%), respiratory tract infection (7.0%), bacteraemia (5.1%), skin and soft tissue infection (2.6%), and spontaneous bacterial empyema (1.9%) (Supplementary Figs. 20–26).

The temporal trends of BIs

After excluding studies without reported study years, 52 studies remained, spanning study mid-years 1988–2022. Random-effects meta-regression showed an upward temporal trend (β1 = 0.0176, SE 0.0221; p = 0.426), corresponding to an annual percent change of 1.78% (95% CI: −2.54–6.29). Predicted prevalence increased from 17.9% (95% CI: 7.8–36.1) in 1988 to 28.5% (95% CI: 16.9–43.8) in 2022 (Fig. 5).

The temporal trends of BIs in patients with cirrhosis from 1988 to 2022.
Fig. 5  The temporal trends of BIs in patients with cirrhosis from 1988 to 2022.

BIs, bacterial infections.

Association between BIs and mortality

Across six studies reporting adjusted HRs for mortality, BIs were associated with a higher risk of death, with pooled adjusted HRs of 2.22 (95% CI: 1.33–3.71). Between-study heterogeneity was extreme (I2 = 99.4%, τ2 = 0.233), and the 95% prediction interval was 0.58–8.55, indicating substantial variation in the true effects across settings (Fig. 6).

Forest plot for adjusted HRs for mortality associated with BIs in patients with cirrhosis.
Fig. 6  Forest plot for adjusted HRs for mortality associated with BIs in patients with cirrhosis.

BIs, bacterial infections; HR, hazard ratio.

Risk of bias

The funnel plot showed symmetry, indicating no significant evidence of publication bias (Supplementary Fig. 27).80 However, heterogeneity or small-study effects cannot be completely excluded. The substantial heterogeneity observed among individual studies was accounted for by applying a random-effects model to all calculations. Additionally, subgroup analyses were performed on the basis of various criteria, including the study location, study design, country’s economic status, and other characteristics.

Discussion

This review, which synthesizes studies from 21 countries across five continents, estimates the pooled prevalence of BIs in cirrhosis patients to be 35.1% (ranging from 29.2% to 41.4%). These studies focus on different patient populations, including hospitalized patients, ICU-admitted patients, ACLF patients, and outpatients, highlighting the significant burden and prevalence of BIs in these groups. This high prevalence translates into a significant annual burden on healthcare systems with respect to patient numbers and associated costs.81 These infections often lead to prolonged hospital stays, an increased need for intensive care, and a higher likelihood of complications, including sepsis and organ failure, all of which escalate healthcare costs.4,5 Furthermore, the recurrent nature of these infections contributes to repeated admissions and increased resource utilization, placing a considerable strain on healthcare systems.82

The meta-analysis revealed significant variations in BI prevalence across different sites in patients with cirrhosis. The most prevalent infections in patients with cirrhosis are GII (18.4%), SBP (12.4%), and UTI (7.0%). E. coli was the most prevalent pathogen, with an overall pooled prevalence of 3.8% (95% CI: 2.5–5.2, I2 = 87.5%). MDR bacteria (6.8%, 95% CI: 4.0–11.3, I2 = 98.5%) were particularly concerning, showing considerable variability across regions. Among gram-negative bacteria, Klebsiella spp. had a prevalence of 1.3% (95% CI: 0.9–1.8), whereas Pseudomonas spp. and Proteus spp. had lower prevalence rates of 0.3% and 0.6%, respectively. Gram-positive bacteria such as Staphylococcus spp. (2.0%, 95% CI: 1.0–4.0), with S. aureus (1.2%, 95% CI: 0.7–2.2) as the prominent species, also showed a notable presence. Overall, gram-negative bacteria (6.4%) were more prevalent than gram-positive bacteria (4.2%), reflecting the dominance of gram-negative pathogens. This may be attributable to intestinal dysbiosis, loss of gut-barrier integrity, increased bacterial translocation, immune dysfunction, and portosystemic shunting in cirrhosis, all of which promote the passage of enteric gram-negative bacteria and the development of infection.5,8 These findings emphasize the necessity of targeted antimicrobial strategies, especially given the high prevalence and resistance patterns of MDR organisms.12 The overall pooled prevalence may have been underestimated due to low bacterial culture positivity in patients with cirrhosis.8 This limitation, especially in cases involving fastidious organisms or prior antibiotic use, could have led to underreporting and obscuring of the true infection burden, potentially biasing the meta-analysis results.83 For instance, the relatively low pooled prevalence of E. coli (3.8%, 95% CI: 2.5–5.2) and other pathogens such as Klebsiella spp. (1.3%, 95% CI: 0.9–1.8) could reflect these diagnostic gaps. Moreover, variations in diagnostic criteria across studies, including differences in sampling methods, patient settings (e.g., ICU vs. non-ICU), and laboratory techniques, contribute to significant heterogeneity. Improved diagnostic techniques are essential to address this issue in future studies.

Europe ranks high in terms of the pooled prevalence of BIs among patients with cirrhosis (38.2%), which is comparable to that in South America (37.5%). This finding indicates that even in regions with well-developed healthcare systems, patients with cirrhosis remain susceptible to BIs. The wide CI (95% CI: 24.8–53.6) indicates significant variability between studies, reflecting the various study designs, patient populations, and healthcare settings across the different European countries. The pooled prevalence of BIs in patients with cirrhosis in North America is 17%, which is a moderate level. Countries such as the United States benefit from advanced healthcare systems, which allow for better infection control measures, timely diagnoses, and effective treatments. Notably, the pooled prevalence of BIs in cirrhosis patients in Africa was 16.4% (95% CI: 2.6–59.5), although the wide CI suggested considerable variability among the included studies. The lower overall infection rate might have been due to underreporting or smaller sample sizes, as well as the variability in healthcare access across different African countries. Asia has a moderately high pooled prevalence of BIs in cirrhosis, at 22.8% (95% CI: 16.3–30.9), which varies significantly among different countries, particularly between India (32.8%) and China (23.7%). The regional heterogeneity in Asia, with varying healthcare quality and practices, likely contributes to this rate.84 Countries with more advanced healthcare systems may have better infection control, whereas developing countries may still face significant challenges.85 The substantial regional variation observed in BI prevalence may be attributable to differences in case mix, patterns of healthcare exposure, antimicrobial usage, and methods of diagnosis. European cohorts often include a larger share of alcohol-related and more decompensated cirrhosis, which is associated with immune dysfunction and bacterial translocation, whereas many Asian cohorts include more hepatitis B-related disease with different risk profiles. Exposure to invasive procedures and devices, ICU admission, and a higher nosocomial proportion can also raise infection risk. Patterns of antibiotic prophylaxis and treatment, together with regional resistance ecology, may further shift observed prevalence.86 Finally, diagnostic intensity and access to culture and imaging vary across settings, which can inflate detection in well-resourced systems and depress it where testing is limited. Overall, these continental contrasts reflect biology and differences in diagnosis and testing, rather than geography alone.

In this meta-analysis, we showed that cirrhosis patients with ACLF (44.2%), as well as those in ICU (29.8%) or outpatient (34.3%) settings, present a significantly higher prevalence of BIs. Infections are key triggers for ACLF and are the most common cause. Among these, BIs are the main reason, with the resulting systemic inflammatory response syndrome leading to acute decompensation, multi-organ dysfunction, and failure in patients with cirrhosis. This chain reaction disrupts the balance of the immune system, worsens organ damage, and accelerates disease progression, ultimately increasing the risk of mortality in ACLF. Conversely, ACLF patients may exhibit an excessive systemic inflammatory response that leads to immune paralysis, thus increasing their risk for early infections.87 We further evaluated whether the high BI prevalence in ACLF varied by the definition used. In subgroup analyses stratified by ACLF definition, the pooled BI prevalence was 51.9% (95% CI, 33.4–69.8) in studies based on the EASL-CLIF criteria and 32.0% (95% CI, 14.2–57.2) in those based on the APASL criteria; one study with an unspecified definition reported 58.5% (95% CI, 44.1–71.9). Although between-definition differences were not statistically significant (p = 0.189), the higher point estimate with EASL-CLIF may reflect enrichment for extrahepatic organ failures and a more severely ill case mix. These observations underscore the need for consensus ACLF definitions in future epidemiological studies, given the impact of definitional choices on case selection, prevalence estimates, and generalizability.88 For patients with cirrhosis admitted to ICUs for care, BIs represent a serious clinical challenge due to various risk factors.26 These include invasive devices, immunosuppression, broad-spectrum antibiotics, and fungal colonization, which increase the risk of cross-infection and subsequent secondary infections.89 The compromised immunity, muscle weakness, and limited mobilization of patients with cirrhosis increase their susceptibility to infections.89 Treatment delays, environmental exposure, and limited preventive strategies are likely contributors to the higher infection rates among outpatients with cirrhosis.26 The difference in BI prevalence between ICU and outpatient settings warrants further consideration. ICU-based studies often focus on more severe infections, potentially underestimating the total burden of infections by excluding mild or subclinical cases. Furthermore, ICU settings typically have rigorous infection control measures, including strict hygiene protocols and early infection management, which may reduce the prevalence of infections compared to outpatient settings. In contrast, the higher prevalence of infections in outpatient settings may be influenced by underdiagnosis and delayed treatment. Outpatient populations may also include undiagnosed or poorly managed decompensated cirrhosis cases, increasing susceptibility to infections.

Interestingly, there appears to be a modest upward trend in the prevalence of BIs in patients with cirrhosis. Our meta-regression analysis revealed a rising pattern in predicted prevalence from 17.9% in 1988 to 28.5% in 2022. Subgroup analysis also suggested a higher prevalence of BIs in the last 10 years (30.5%) compared to earlier periods (20.9%). Several factors may underlie this temporal increase. Advances in the medical management of chronic liver disease have prolonged the survival of cirrhotic patients, inadvertently increasing their cumulative exposure to healthcare environments where nosocomial infections are more likely to occur, particularly in high-risk settings such as the ICU.83 Furthermore, the more frequent use of invasive procedures, including paracentesis, endoscopy, and catheterization, increases the degree of risk.90

Furthermore, our pooled analysis showed that BIs were significantly associated with increased mortality risk in patients with cirrhosis, with pooled HRs of 2.22 (95% CI: 1.33–3.71). This result highlights that infections not only occur frequently but also have a major impact on patient outcomes. The immunocompromised state of cirrhosis may predispose patients to rapid clinical decline following infection, often culminating in organ failure or the development of ACLF. These findings emphasize the critical need for early recognition, prompt antimicrobial intervention, and robust infection prevention strategies to reduce infection-related mortality in this vulnerable population.

The strengths of this review include its comprehensive analysis of global epidemiological trends in BIs among patients with cirrhosis and its investigation of variations in prevalence estimates. Although this meta-analysis provides valuable insights into the infection prevalence in patients with cirrhosis, several limitations should be considered. The heterogeneity observed across studies, in terms of population characteristics, diagnostic methods, and study quality, limits the generalizability of these results. The variability in infection prevalence may be influenced by differences in study quality, including sample size, methodological rigor, and consistency in reporting criteria. Additionally, the retrospective design of many studies may introduce selection bias, and the absence of standardized infection criteria may affect the reliability of pooled estimates. Furthermore, the variability in regional healthcare settings, including access to diagnostic tools and antimicrobial treatments, likely contributes to the underreporting of infection rates, particularly in lower-resource settings. Not all countries were represented, and several regions were informed by only a small number of studies, which limits geographic coverage and reduces the precision of regional estimates. A further methodological limitation arises from heterogeneous diagnostic criteria. A detailed inspection of the extracted criteria (Supplementary Table 3) confirms that the definition of each infection site varied across studies. For SBP, most studies defined cases by an ascitic polymorphonuclear neutrophil count of at least 250 cells/mm3, regardless of culture. However, some used 500 cells/mm3 or higher, and a few required a positive ascitic culture. For UTI, most studies combined compatible symptoms with pyuria, for example, more than 10–15 white blood cells per high-power field or more than 10 leukocytes per microliter, and/or a positive urine Gram stain or culture. Some studies explicitly required culture positivity, whereas a few accepted symptoms with pyuria without a mandatory culture. These definitional differences can bias prevalence in opposite directions because culture-dependent definitions tend to underestimate infections when prior antibiotics reduce yield or when the inoculum is low, whereas clinical or composite criteria may overestimate by capturing noninfectious presentations. The pooled estimates should therefore be read as averages across nonidentical constructs, which highlights the need for standardized site-specific definitions and transparent microbiological reporting to improve comparability and external validity. A recent multicenter study in China reported substantial differences in the clinical and microbiological profiles of BIs compared with global data, including a notably high prevalence of MDR organisms and a lower adherence to empirical antibiotic guidelines. These findings underscore the impact of regional practice variations on both diagnostic yield and treatment outcomes, reinforcing the necessity of internationally harmonized criteria and reporting standards.91 Another limitation is the insufficient data on clinical characteristics, such as decompensated versus compensated cirrhosis or cirrhosis etiology, limiting specific subgroup analyses. Moreover, our review did not specifically address the potential relationship between MDR and antibiotic usage (for instance, in hepatic encephalopathy or prophylaxis against SBP), which needs further investigation. Future studies should address these gaps to better understand infection risks and improve the applicability of findings. These findings underscore the need for improved diagnostic protocols, standardized infection criteria, and more uniform study designs in future research to provide clearer guidance for the clinical management of patients with cirrhosis.

Conclusions

BIs are common in patients with liver cirrhosis and show a modest upward trend over time, with the highest burdens observed in ACLF and notable regional variation. Gastrointestinal infections, SBP and UTI predominate, gram-negative organisms are more frequent than gram-positive organisms, and MDR pathogens are significant. Importantly, infections are associated with a higher mortality, underscoring the need for improved diagnostic approaches and standardized research frameworks to deliver clearer guidance for the clinical management of patients with liver cirrhosis.

Supporting information

Supplementary Table 1

Electronic search strategy.

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Supplementary Table 2

Inclusion and exclusion criteria for study selection.

(DOCX)

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Supplementary Table 3

Definitions of bacterial infections of the studies included in this meta-analysis.

(DOCX)

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Supplementary Table 4

Quality assessment of observational studies.

(DOCX)

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Supplementary Fig. 1

Forest plot comparing the prevalence of BIs in studies investigating both single and multiple infections.

BIs: bacterial infections, SSTI: skin and soft tissue infection, SBP: spontaneous bacteria peritonitis, UTI: urinary tract infection, GII: gastrointestinal tract, SBEM: spontaneous bacterial empyema.

(DOCX)

Click here for additional data file.

Supplementary Fig. 2

Forest plot showing the pooled prevalence of BIs in patients with cirrhosis, stratified by ACLF definitions.

ACLF: acute-on-chronic liver failure, APASL: Asian-Pacific Association for the Study of the Liver, BIs: bacterial infections, COSSH: Chinese Group on the Study of Severe Hepatitis B, EASL: European Association for the Study of the Liver, NACSELD: North American Consortium for the Study of End-Stage Liver Disease.

(DOCX)

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Supplementary Fig. 3

Forest plot of subgroup analysis for cirrhosis for different countries of BIs in patients with cirrhosis.

BIs: bacterial infections.

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Supplementary Fig. 4

Forest plot of subgroup analysis for cirrhosis for different climate zones of BIs in patients with cirrhosis.

BIs: bacterial infections.

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Supplementary Fig. 5

Forest plot demonstrating the pooled prevalence of BIs in patients with cirrhosis by subgroup: Country’s economic status.

BIs: bacterial infections.

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Supplementary Fig. 6

Forest plot of subgroup analysis for cirrhosis for decade of publication of BIs in patients with cirrhosis.

BIs: bacterial infections.

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Supplementary Fig. 7

Forest plot of subgroup analysis for cirrhosis for different study designs of BIs in patients with cirrhosis.

BIs: bacterial infections.

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Supplementary Fig. 8

Forest plot of the prevalence of E. coli in patients with cirrhosis.

E. coli: Escherichia coli.

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Supplementary Fig. 9

Forest plot of the prevalence of Streptococcus spp. in patients with cirrhosis.

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Supplementary Fig. 10

Forest plot of the prevalence of Klebsiella spp. in patients with cirrhosis.

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Supplementary Fig. 11

Forest plot of the prevalence of Staphylococcus spp. in patients with cirrhosis.

(DOCX)

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Supplementary Fig. 12

Forest plot of the prevalence of S.aureus in patients with cirrhosis.

S. aureus: Staphylococcus aureus.

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Supplementary Fig. 13

Forest plot of the prevalence of Pseudomonas spp. in patients with cirrhosis.

(DOCX)

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Supplementary Fig. 14

Forest plot of the prevalence of Enterococcus spp. in patients with cirrhosis.

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Supplementary Fig. 15

Forest plot of the prevalence of Acinetobacter spp. in patients with cirrhosis.

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Supplementary Fig. 16

Forest plot of the prevalence of Proteus spp. in patients with cirrhosis.

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Supplementary Fig. 17

Forest plot of the prevalence of Gram-positive bacteria in patients with cirrhosis.

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Supplementary Fig. 18

Forest plot of the prevalence of Gram-negative bacteria in patients with cirrhosis.

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Supplementary Fig. 19

Forest plot of the prevalence of MDR bacteria in patients with cirrhosis. MDR: multidrug-resistant.

(DOCX)

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Supplementary Fig. 20

Forest plot of the prevalence of BIs for GII in patients with cirrhosis.

BIs: bacterial infections, GII: gastrointestinal tract.

(DOCX)

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Supplementary Fig. 21

Forest plot of the prevalence of BIs for SBP in patients with cirrhosis.

BIs: bacterial infections, SBP: spontaneous bacteria peritonitis.

(DOCX)

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Supplementary Fig. 22

Forest plot of the prevalence of BIs for UTI in patients with cirrhosis.

BIs: bacterial infections, UTI: urinary tract infection.

(DOCX)

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Supplementary Fig. 23

Forest plot of the prevalence of BIs for RTI in patients with cirrhosis.

BIs: bacterial infections, RTI: respiratory tract infection.

(DOCX)

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Supplementary Fig. 24

Forest plot of the prevalence of BIs for bacteremia in patients with cirrhosis.

BIs: bacterial infections.

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Supplementary Fig. 25

Forest plot of the prevalence of BIs for SSTI in patients with cirrhosis.

BIs: bacterial infections, SSTI: skin and soft tissue infection.

(DOCX)

Click here for additional data file.

Supplementary Fig. 26

Forest plot of the prevalence of BIs for SBEM in patients with cirrhosis.

BIs: bacterial infections, SBEM: spontaneous bacterial empyema.

(DOCX)

Click here for additional data file.

Supplementary Fig. 27

Funnel plot for assessing publication bias.

(DOCX)

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Declarations

Funding

This work was supported by grants from the ECCM program of the Clinical Research Center of Shandong University (2021SDUCRCB006), the National Natural Science Foundation of China (82270631), and Young Taishan Scholars (tsqn202103169).

Conflict of interest

YCF has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication.

Authors’ contributions

Data analysis and interpretation, drafting of the manuscript (YXT, YPW), data collection (YXT, YPW, BYW, JZ, QA), critical comments and reading (YHY), study conception and design, revision of the manuscript, and leadership responsibility for the research (YCF). All authors have approved the final version and publication of the manuscript.

References

  1. de Nies L, Kobras CM, Stracy M. Antibiotic-induced collateral damage to the microbiota and associated infections. Nat Rev Microbiol 2023;21(12):789-804 View Article PubMed/NCBI
  2. Centers for Disease Control and Prevention. National Healthcare Safety Network (NHSN): patient safety component manual. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual_current.pdf
  3. European Centre for Disease Prevention and Control. Healthcare-associated infections acquired in intensive care units – annual epidemiological report for 2021. Available from: https://www.ecdc.europa.eu/en/publications-data/healthcare-associated-infections-acquired-intensive-care-units-annual
  4. Bajaj JS, O’Leary JG, Reddy KR, Wong F, Biggins SW, Patton H, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 2014;60(1):250-256 View Article PubMed/NCBI
  5. Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014;60(6):1310-1324 View Article PubMed/NCBI
  6. Sargenti K, Prytz H, Nilsson E, Kalaitzakis E. Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure. Scand J Gastroenterol 2015;50(7):875-883 View Article PubMed/NCBI
  7. Tandon P, Delisle A, Topal JE, Garcia-Tsao G. High prevalence of antibiotic-resistant bacterial infections among patients with cirrhosis at a US liver center. Clin Gastroenterol Hepatol 2012;10(11):1291-1298 View Article PubMed/NCBI
  8. Bajaj JS, Kamath PS, Reddy KR. The Evolving Challenge of Infections in Cirrhosis. N Engl J Med 2021;384(24):2317-2330 View Article PubMed/NCBI
  9. Arvaniti V, D’Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 2010;139(4):1246-1256.e5 View Article PubMed/NCBI
  10. Fernández J, Acevedo J, Castro M, Garcia O, de Lope CR, Roca D, et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology 2012;55(5):1551-1561 View Article PubMed/NCBI
  11. Bajaj JS, O’Leary JG, Reddy KR, Wong F, Olson JC, Subramanian RM, et al. Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology 2012;56(6):2328-2335 View Article PubMed/NCBI
  12. Piano S, Singh V, Caraceni P, Maiwall R, Alessandria C, Fernandez J, et al. Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide. Gastroenterology 2019;156(5):1368-1380.e10 View Article PubMed/NCBI
  13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71 View Article PubMed/NCBI
  14. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021;372:n160 View Article PubMed/NCBI
  15. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute-on-chronic liver failure. J Hepatol 2023;79(2):461-491 View Article PubMed/NCBI
  16. Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019;13(4):353-390 View Article PubMed/NCBI
  17. Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, et al. Acute-on-chronic liver failure (ACLF): the ‘Kyoto Consensus’-steps from Asia. Hepatol Int 2025;19(1):1-69 View Article PubMed/NCBI
  18. Wu T, Li J, Shao L, Xin J, Jiang L, Zhou Q, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut 2018;67(12):2181-2191 View Article PubMed/NCBI
  19. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc 2015;13(3):147-153 View Article PubMed/NCBI
  20. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health 2013;67(11):974-978 View Article PubMed/NCBI
  21. Barker TH, Migliavaca CB, Stein C, Colpani V, Falavigna M, Aromataris E, et al. Conducting proportional meta-analysis in different types of systematic reviews: a guide for synthesisers of evidence. BMC Med Res Methodol 2021;21(1):189 View Article PubMed/NCBI
  22. Cochrane. Chapter 10: Analysing data and undertaking meta-analyses. Cochrane Handbook for Systematic Reviews of Interventions. London: Cochrane; 2025
  23. World Bank country classifications by income level for 2024-2025. Available from: https://blogs.worldbank.org/zh/opendata/world-bank-country-classifications-by-income-level-for-2024-2025
  24. Vatcheva KP, Lee M, McCormick JB, Rahbar MH. Multicollinearity in Regression Analyses Conducted in Epidemiologic Studies. Epidemiology (Sunnyvale) 2016;6(2):227 View Article PubMed/NCBI
  25. The R Core Team. R: A language and environment for statistical computing. Vienna: R Core Team, 2026.
  26. Fernández J, Acevedo J, Wiest R, Gustot T, Amoros A, Deulofeu C, et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut 2018;67(10):1870-1880 View Article PubMed/NCBI
  27. Baijal R, Amarapurkar D, Praveen Kumar HR, Kulkarni S, Shah N, Doshi S, et al. A multicenter prospective study of infections related morbidity and mortality in cirrhosis of liver. Indian J Gastroenterol 2014;33(4):336-342 View Article PubMed/NCBI
  28. Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis 2001;33(1):41-48 View Article PubMed/NCBI
  29. Kremer WM, Gairing SJ, Kaps L, Ismail E, Kalampoka V, Hilscher M, et al. Characteristics of bacterial infections and prevalence of multidrug-resistant bacteria in hospitalized patients with liver cirrhosis in Germany. Ann Hepatol 2022;27(5):100719 View Article PubMed/NCBI
  30. Mohan P, Ramu B, Bhaskar E, Venkataraman J. Prevalence and risk factors for bacterial skin infection and mortality in cirrhosis. Ann Hepatol 2011;10(1):15-20 View Article PubMed/NCBI
  31. El-Amin H, Sabry AMM, Ahmed RE, Makhlouf NA. Types and microbiological spectrum of infections in patients with cirrhosis: A single-centre experience in Upper Egypt. Arab J Gastroenterol 2017;18(3):159-164 View Article PubMed/NCBI
  32. Bajaj JS, Reddy RK, Tandon P, Wong F, Kamath PS, Biggins SW, et al. Prediction of Fungal Infection Development and Their Impact on Survival Using the NACSELD Cohort. Am J Gastroenterol 2018;113(4):556-563 View Article PubMed/NCBI
  33. Bartoletti M, Giannella M, Caraceni P, Domenicali M, Ambretti S, Tedeschi S, et al. Epidemiology and outcomes of bloodstream infection in patients with cirrhosis. J Hepatol 2014;61(1):51-58 View Article PubMed/NCBI
  34. Li YT, Yu CB, Huang JR, Qin ZJ, Li LJ. Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients. World J Gastroenterol 2015;21(36):10409-10417 View Article PubMed/NCBI
  35. Alexopoulou A, Papadopoulos N, Eliopoulos DG, Alexaki A, Tsiriga A, Toutouza M, et al. Increasing frequency of gram-positive cocci and gram-negative multidrug-resistant bacteria in spontaneous bacterial peritonitis. Liver Int 2013;33(7):975-981 View Article PubMed/NCBI
  36. Dionigi E, Garcovich M, Borzio M, Leandro G, Majumdar A, Tsami A, et al. Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity. Am J Gastroenterol 2017;112(4):588-596 View Article PubMed/NCBI
  37. Bajaj JS, O'Leary JG, Tandon P, Wong F, Garcia-Tsao G, Kamath PS, et al. Nosocomial Infections Are Frequent and Negatively Impact Outcomes in Hospitalized Patients With Cirrhosis. Am J Gastroenterol 2019;114(7):1091-1100 View Article PubMed/NCBI
  38. Caly WR, Strauss E. A prospective study of bacterial infections in patients with cirrhosis. J Hepatol 1993;18(3):353-358 View Article PubMed/NCBI
  39. Santoiemma PP, Dakwar O, Angarone MP. A retrospective analysis of cases of Spontaneous Bacterial Peritonitis in cirrhosis patients. PLoS One 2020;15(9):e0239470 View Article PubMed/NCBI
  40. Evans LT, Kim WR, Poterucha JJ, Kamath PS. Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites. Hepatology 2003;37(4):897-901 View Article PubMed/NCBI
  41. Hung TH, Tsai CC, Hsieh YH, Tsai CC. The long-term mortality of spontaneous bacterial peritonitis in cirrhotic patients: A 3-year nationwide cohort study. Turk J Gastroenterol 2015;26(2):159-162 View Article PubMed/NCBI
  42. D’Oliveira RAC, Pereira LCD, Codes L, Rocha MS, Bittencourt PL. ANALYSIS OF HEALTHCARE ASSOCIATED AND HOSPITAL ACQUIRED INFECTIONS IN CRITICALLY ILL PATIENTS WITH CIRRHOSIS. Arq Gastroenterol 2022;59(1):102-109 View Article PubMed/NCBI
  43. Tang D, Maihebuba B, Sun XF, Lu XB. Analysis of pathogenic bacteria in cirrhotic patients complicated with bacterial infection in a tertiary hospital in Xinjiang. Zhonghua Gan Zang Bing Za Zhi 2022;30(8):885-888 View Article PubMed/NCBI
  44. Wu L, Hong H, Li WZ, Liu LL, Xue DY, Zhang J, et al. Clinical characteristics of bacterial infections in patients with liver cirrhosis. Chin J Infect Chemother 2020;20(6):601-606 View Article
  45. Cheng XL, Yang CJ, Liu K, Han LF. Clinical study of bloodstream infections in patients with decompensated cirrhosis. Chin J Nosocomiol 2017;27(19):4386-4388 View Article
  46. Li J, Hu ZB, Li YC, Hu WY, Luo HX, Zhou J, et al. Distribution and drug resistance of pathogens causing abdominal infections in liver cirrhosis patients. Chin J Nosocomiol 2015;25(17):3896-3898 View Article
  47. Choudhuri AH, Khurana P, Biswas PS, Uppal R. Epidemiology and risk factors for multidrug-resistant bacteria in critically ill patients with liver disease. Saudi J Anaesth 2018;12(3):389-394 View Article PubMed/NCBI
  48. Ponzetto A, Pellicano R, Leone N, Berrutti M, Turrini F, Rizzetto M. Helicobacter pylori seroprevalence in cirrhotic patients with hepatitis B virus infection. Neth J Med 2000;56(6):206-210 View Article PubMed/NCBI
  49. Rahimkhani M, Ghofrani H. Helicobacter Pylori and Peptic Ulcer in Cirrhotic Patients. Pak J Med Sci 2008;24(6):849-852
  50. Siringo S, Vaira D, Menegatti M, Piscaglia F, Sofia S, Gaetani M, et al. High prevalence of Helicobacter pylori in liver cirrhosis: relationship with clinical and endoscopic features and the risk of peptic ulcer. Dig Dis Sci 1997;42(10):2024-2030 View Article PubMed/NCBI
  51. Angeloni S, Leboffe C, Parente A, Venditti M, Giordano A, Merli M, et al. Efficacy of current guidelines for the treatment of spontaneous bacterial peritonitis in the clinical practice. World J Gastroenterol 2008;14(17):2757-2762 View Article PubMed/NCBI
  52. Chen Y, Gu H, Lv T, Yan D, Xu Q, Gu S, et al. Longitudinal investigation of carriage rates and genotypes of toxigenic Clostridium difficile in hepatic cirrhosis patients. Epidemiol Infect 2019;147:e166 View Article PubMed/NCBI
  53. Zhao R, Ma J, Li P, Fang H, Sun S, Wu W, et al. Multidrug-resistant bacterial infections in cirrhotic patients: an epidemiological study. Expert Rev Gastroenterol Hepatol 2018;12(11):1167-1174 View Article PubMed/NCBI
  54. Fernández J, Prado V, Trebicka J, Amoros A, Gustot T, Wiest R, et al. Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe. J Hepatol 2019;70(3):398-411 View Article PubMed/NCBI
  55. Gunjaca I, Francetić I. Prevalence and clinical outcome of spontaneous bacterial peritonitis in hospitalized patients with liver cirrhosis: a prospective observational study in central part of Croatia. Acta Clin Croat 2010;49(1):11-18 View Article PubMed/NCBI
  56. Singal AK, Salameh H, Kamath PS. Prevalence and in-hospital mortality trends of infections among patients with cirrhosis: a nationwide study of hospitalised patients in the United States. Aliment Pharmacol Ther 2014;40(1):105-112 View Article PubMed/NCBI
  57. Chu CM, Chang KY, Liaw YF. Prevalence and prognostic significance of bacterascites in cirrhosis with ascites. Dig Dis Sci 1995;40(3):561-565 View Article PubMed/NCBI
  58. Mohan P, Venkataraman J. Prevalence and risk factors for unsuspected spontaneous ascitic fluid infection in cirrhotics undergoing therapeutic paracentesis in an outpatient clinic. Indian J Gastroenterol 2011;30(5):221-224 View Article PubMed/NCBI
  59. Cadranel JF, Denis J, Pauwels A, Barbare JC, Eugène C, di Martino V, et al. Prevalence and risk factors of bacteriuria in cirrhotic patients: a prospective case-control multicenter study in 244 patients. J Hepatol 1999;31(3):464-468 View Article PubMed/NCBI
  60. Zhu JH. Related factors for nosocomial infections in cirrhosis patients during decompensated period. Chin J Nosocomiol 2012;22(5):975-977
  61. Xing YM, Feng D, Zhou RJ. Risk factors of nosocomial infections in patients with cirrhosis. Chin J Nosocomiol 2014;24(16):4041-4042+4045
  62. Makhlouf HA, Morsy KH, Makhlouf NA, Eldin EN, Khairy M. Spontaneous bacterial empyema in patients with liver cirrhosis in Upper Egypt: prevalence and causative organisms. Hepatol Int 2013;7(1):274-279 View Article PubMed/NCBI
  63. Xiol X, Castellví JM, Guardiola J, Sesé E, Castellote J, Perelló A, et al. Spontaneous bacterial empyema in cirrhotic patients: a prospective study. Hepatology 1996;23(4):719-723 View Article PubMed/NCBI
  64. Syed VA, Ansari JA, Karki P, Regmi M, Khanal B. Spontaneous bacterial peritonitis (SBP) in cirrhotic ascites: a prospective study in a tertiary care hospital, Nepal. Kathmandu Univ Med J (KUMJ) 2007;5(1):48-59 PubMed/NCBI
  65. Abu-Freha N, Michael T, Poupko L, Estis-Deaton A, Aasla M, Abu-Freha O, et al. Spontaneous Bacterial Peritonitis among Cirrhotic Patients: Prevalence, Clinical Characteristics, and Outcomes. J Clin Med 2021;11(1):227 View Article PubMed/NCBI
  66. Dia D, Serme YK, Bassène ML, Halim A, Diallo S, Thioubou MA, et al. Infection spontanée du liquide d’ascite à Dakar, Sénégal : étude de cinquante-cinq patients cirrhotiques [Spontaneous bacterial peritonitis in Dakar, Senegal: study of 55 patients with cirrhosis]. Med Sante Trop 2014;24(1):55-57 View Article PubMed/NCBI
  67. Rubinstein P, Morales M, Pandiani A, Bagattini JC. Peritonitis bacteriana espontánea en cirrosis hepática con ascitis: incidencia, bacteriología y mortalidad en Uruguay [Spontaneous bacterial peritonitis in hepatic cirrhosis with ascites: incidence, bacteriology and mortality in Uruguay]. Acta Gastroenterol Latinoam 2001;31(4):307-312 View Article PubMed/NCBI
  68. Karvellas CJ, Pink F, McPhail M, Austin M, Auzinger G, Bernal W, et al. Bacteremia, acute physiology and chronic health evaluation II and modified end stage liver disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure. Crit Care Med 2010;38(1):121-126 View Article PubMed/NCBI
  69. Mücke MM, Rumyantseva T, Mücke VT, Schwarzkopf K, Joshi S, Kempf VAJ, et al. Bacterial infection-triggered acute-on-chronic liver failure is associated with increased mortality. Liver Int 2018;38(4):645-653 View Article PubMed/NCBI
  70. Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, et al. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010;59(11):1561-1569 View Article PubMed/NCBI
  71. Su H, Tong J, Liu X, Li C, Chen J, Xu X, et al. Characteristics and outcome of nosocomial bloodstream infection in patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol 2021;33(1):83-88 View Article PubMed/NCBI
  72. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144(7):1426-1437.e14379 View Article PubMed/NCBI
  73. Rout G, Jadaun SS, Ranjan G, Kedia S, Gunjan D, Shalimar, et al. Prevalence, predictors and impact of bacterial infection in acute on chronic liver failure patients. Dig Liver Dis 2018;50(11):1225-1231 View Article PubMed/NCBI
  74. Cai JJ, Zhang MC, Han T, Jiang HQ. Characteristics of infection and its impact on short-term outcome in patients with acute-on-chronic liver failure. Medicine (Baltimore) 2017;96(37):e8057 View Article PubMed/NCBI
  75. Cao Z, Wong F, Choudhury AK, Kamath PS, Topazian M, Torre A, et al. Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium. Lancet Gastroenterol Hepatol 2024;9(11):997-1009 View Article PubMed/NCBI
  76. Nakayama N, Uemura H, Uchida Y, Tomiya T, Ido A, Inoue K, et al. A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan. Hepatol Res 2018;48(4):303-312 View Article PubMed/NCBI
  77. Jeong JY, Cho JY, Kang D, Kim JH, Park SJ, Joo EJ, et al. Impact of serious infection on mortality of patients with chronic liver disease: a nationwide population-based cohort study. Clin Gastroenterol Hepatol 2025 View Article PubMed/NCBI
  78. Hoshi H, Chu PS, Yoshida A, Taniki N, Morikawa R, Yamataka K, et al. Vulnerability to recurrent episodes of acute decompensation/acute-on-chronic liver failure characterizes those triggered by indeterminate precipitants in patients with liver cirrhosis. PLoS One 2021;16(4):e0250062 View Article PubMed/NCBI
  79. Park JK, Lee CH, Kim IH, Kim SM, Jang JW, Kim SH, et al. Clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease. J Korean Med Sci 2015;30(5):598-605 View Article PubMed/NCBI
  80. Lin L, Chu H. Quantifying publication bias in meta-analysis. Biometrics 2018;74(3):785-794 View Article PubMed/NCBI
  81. Allen AM, Kim WR, Moriarty JP, Shah ND, Larson JJ, Kamath PS. Time trends in the health care burden and mortality of acute on chronic liver failure in the United States. Hepatology 2016;64(6):2165-2172 View Article PubMed/NCBI
  82. Piano S, Bunchorntavakul C, Marciano S, Rajender Reddy K. Infections in cirrhosis. Lancet Gastroenterol Hepatol 2024;9(8):745-757 View Article PubMed/NCBI
  83. Bakhit M, Hoffmann T, Scott AM, Beller E, Rathbone J, Del Mar C. Resistance decay in individuals after antibiotic exposure in primary care: a systematic review and meta-analysis. BMC Med 2018;16(1):126 View Article PubMed/NCBI
  84. Liu YB, Chen MK. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022;28(41):5910-5930 View Article PubMed/NCBI
  85. Allaire M, Cadranel JF, Nguyen TTN, Garioud A, Zougmore H, Heng R, et al. Management of infections in patients with cirrhosis in the context of increasing therapeutic resistance: A systematic review. Clin Res Hepatol Gastroenterol 2020;44(3):264-274 View Article PubMed/NCBI
  86. Fernández J, Piano S, Bartoletti M, Wey EQ. Management of bacterial and fungal infections in cirrhosis: The MDRO challenge. J Hepatol 2021;75(Suppl 1):S101-S117 View Article PubMed/NCBI
  87. Arroyo V, Moreau R, Jalan R. Acute-on-Chronic Liver Failure. N Engl J Med 2020;382(22):2137-2145 View Article PubMed/NCBI
  88. Xu Z, Zhang X, Chen J, Shi Y, Ji S. Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management. J Clin Transl Hepatol 2024;12(7):667-676 View Article PubMed/NCBI
  89. Fernández J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol 2012;56(Suppl 1):S1-12 View Article PubMed/NCBI
  90. Tapper EB, Parikh ND. Diagnosis and Management of Cirrhosis and Its Complications: A Review. JAMA 2023;329(18):1589-1602 View Article PubMed/NCBI
  91. Zhang X, Weng H, Deng Q, Deng M, Wu X, Huang Z, et al. Clinical, Microbiological, and Antibiotic Treatment Characteristics of Bacterial Infections in Patients with Liver Cirrhosis in China: A Multicenter Study. J Clin Transl Hepatol 2025;13(8):644-654 View Article PubMed/NCBI
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Tian YX, Wu BY, An Q, Wu YP, Zuo J, Yeo YH, et al. Global Prevalence, Temporal Trends, and Associated Mortality of Bacterial Infections in Patients with Liver Cirrhosis: A Meta-analysis. J Clin Transl Hepatol. Published online: Oct 27, 2025. doi: 10.14218/JCTH.2025.00260.
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Article History
Received Revised Accepted Published
June 1, 2025 September 14, 2025 September 26, 2025 October 27, 2025
DOI http://dx.doi.org/10.14218/JCTH.2025.00260
  • Journal of Clinical and Translational Hepatology
  • pISSN 2225-0719
  • eISSN 2310-8819
  • © 2025 Xia & He Publishing Inc.
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Global Prevalence, Temporal Trends, and Associated Mortality of Bacterial Infections in Patients with Liver Cirrhosis: A Meta-analysis

Yu-Xin Tian, Bai-Yun Wu, Qi An, Yin-Ping Wu, Jing Zuo, Yee Hui Yeo, Yu-Chen Fan
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