In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors\' proposals on the use of NSBBs concerning the severity of liver disease and the patient\'s performance status.

BACKGROUND: Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker.
OBJECTIVE: Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD.
METHODS: We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients.
RESULTS: A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation.
CONCLUSIONS: Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with advanced cirrhosis. Prophylactic Norfloxacin used to be considered effective in SBP prevention, but in recent years its efficacy has been partially compromised by increasing quinolone-resistant bacteria. However, whether the effects of alternative prophylactic regimens are superior to norfloxacin remains controversial. The goal of this study is to compare the effects of norfloxacin with other antibiotics in SBP prophylaxis for cirrhotic patients.
METHODS: We systematically searched Pubmed, Embase, and Cochrane Library Databases. Two reviewers independently identified relevant random control trials (RCTs) comparing the role of norfloxacin and other antibiotics in SBP prevention.
RESULTS: Eight studies comprising 1043 cirrhotic patients were included in this study. Norfloxacin and alternative antibiotics displayed comparable effects in SBP prophylaxis, survival benefit, overall infection prevention, and safety. Subgroup analyses revealed that rifaximin prophylaxis could reduce the recurrence of SBP with fewer adverse events but failed to improve overall survival compared with norfloxacin.
CONCLUSIONS: Other antibiotics are a reasonable alternative to norfloxacin in the prophylaxis of SBP. Rifaximin prophylaxis could be an alternative choose of antibiotic for SBP prevention because of its better protective effect and safety.

Background and Aim: Spontaneous bacterial peritonitis (SBP) is a common infection in liver cirrhosis. This systematic review and meta-analysis provide detailed information on the prevalence of SBP among hepatitis B virus (HBV) and hepatitis C virus (HCV)-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV and HCV-related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV-associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7−21.0%; I2 = 96.13%; p < 0.001)], followed by SBP in HCV-associated liver cirrhosis [4.0% (95% CI, 1.3%−11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1−66.3%), the USA (50.0%, CI: 34.6−65.4%), and Holland (31.1%, CI: 21.6−42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV + HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P < 0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed a rise in the incidence of SBP in viral hepatitis over the last decade. The latter indicates a possible future rise in the global prevalence of SBP among HBV and HCV-related liver cirrhosis.

BACKGROUND: Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial.
METHODS: EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
RESULTS: Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding.
CONCLUSIONS: Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored.

BACKGROUND: Spontaneous bacterial empyema (SBE) occurs when a hepatic hydrothorax becomes infected and runs a course similar to spontaneous bacterial peritonitis (SBP). It remains underdiagnosed as patients with cirrhosis do not routinely undergo diagnostic thoracentesis. Current understanding is limited by small cohorts, while studies reporting its association with ascites/SBP are conflicting.
OBJECTIVE: To explore the incidence of SBE, to determine its association with ascites, and to summarize what is known regarding treatment and outcomes for patients with SBE.
METHODS: Major databases were searched until June 2021. Outcomes include the incidence of SBE in pleural effusions, SBP in peritoneal fluid, and SBE in patients without ascites within our cohort of patients with cirrhosis. We performed a meta-analysis using a random-effects model with pooled proportions and 95% confidence intervals (CI). We assessed heterogeneity using I 2 and classic fail-safe to determine bias.
RESULTS: Eight studies with 8899 cirrhosis patients were included. The median age ranged between 41.2 to 69.7 years. The majority of the patients were Child-Pugh B and C. Mean MELD score was 18.6 ± 8.09. A total of 1334 patients had pleural effusions and the pooled incidence of SBE was 15.6% (CI 12.6-19; I 2 50). Amongst patients diagnosed with SBE, the most common locations included right (202), left (64), and bilateral (8). Amongst our cohort, a total of 2636 patients had ascites with a pooled incidence of SBP of 22.2% (CI 9.9-42.7; I 2 97.8). The pooled incidence of SBE in patients with cirrhosis but without concomitant ascites was 9.5% (CI 3.6-22.8; I 2 82.5).
CONCLUSIONS: SBE frequently occurs with concurrent ascites/SBP; our results suggest high incidence rates of SBE even in the absence of ascites. The pleura can be an unrecognized nidus and our findings support the use of diagnostic thoracentesis in patients with decompensated cirrhosis after exclusion of other causes of pleural effusion. Thoracentesis should be considered particularly in patients without ascites and when there is a high suspicion of infection. The need for diagnostic thoracentesis will continue to be important as rates of multi-drug resistant bacterial infections increase and antibiotic susceptibility information is required for adequate treatment.

Spontaneous bacterial peritonitis (SBP) is one of the most common complications in patients with end-stage liver disease (ESLD), which increases the risk of short-term mortality. Proton pump inhibitors (PPIs) are frequently used in patients with ESLD, in which controversies about the risk of PPI treatment in the occurrence of SBP are largely raised and the pathogenic mechanism of PPI-associated SBP remains unclear. We conducted a systematic literature search through PubMed/MEDLINE for publications mainly from 1 January 2000 to 1 January 2021. Our narrative review summarized the adverse effect of specific PPI therapy on the occurrence and prognosis of SBP in cirrhotic patients, described the potential mechanisms by which PPI induces the development of SBP, and discussed the risk factors associated with the development of SBP and the strategy of PPI therapy in cirrhotic patients. Although controversy regarding the association between PPI use and the occurrence of SBP exists, PPIs use should be restricted to patients with clear benefit indications, and be cautious for elderly patients with severe liver damage.

UNASSIGNED: Spontaneous bacterial peritonitis (SBP) is a bacterial infection associated with a high mortality rate in cirrhotic patients. The gold standard for the detection of SBP is a manual cell count from ascitic fluid; however, alternative screening methods are under investigation. In particular, leukocyte esterase reagent strips (LERS) has been studied as an alternative method to detect SBP with a low cost and instant turnaround time. Therefore, this study aims to evaluate the performance of LERS in the detection of SBP.
UNASSIGNED: A literature search was performed for studies evaluating LERS for the detection of SBP on PubMed, Embase, Scopus, Cochrane, and clinical trial registries. Summary sensitivity, specificity, log diagnostic odds ratio (LDOR), and the area under the summary receiver operating curve (AUC) were calculated according to the respective manufacturer.
UNASSIGNED: In total, 31 studies were evaluated. The summary sensitivity of Aution Sticks, Combur, Multistix, Periscreen reagent strips was 0.962 (95% confidence interval [CI] 0.926, 0.998), 0.892 (95% CI 0.846, 0.938), 0.806 (95% CI 0.738, 0.874), and 0.939 (95% CI 0.900, 0.979), respectively. The summary specificity of Aution Sticks, Combur, Multistix, and Periscreen reagent strips was 0.940 (95% CI 0.904, 0.976), 0.922 (95% CI 0.874, 0.970), 0.974 (95% CI 0.962, 0.985), and 0.672 (95% CI 0.381, 0.963), respectively.
UNASSIGNED: LERS appears to have a notable overall performance for the detection of SBP. LERS appeared to be an acceptable alternative to diagnose SBP in facilities without ability to perform cell count. However, there were significant differences in performance between each manufacturer.

UNASSIGNED: Hemorrhagic ascites is characterized as red blood cell count greater than 10,000/mm3. In cirrhosis, ascites is an event of decompensation, and associated with poor prognosis. However, significance of hemorrhagic ascites is unclear. We conducted a systematic review and meta-analysis to evaluate the significance of hemorrhagic ascites in cirrhotic patients.
UNASSIGNED: We conducted a systematic search in Embase, MEDLINE, Cochrane Central Register of Controlled Trials, the World Health Organization (WHO) International Clinical Trial Registry, and Web of Science Core Collection to identify studies till March 2021, which, in patients with cirrhosis, compared outcomes amongst those with hemorrhagic ascites to those with non-hemorrhagic ascites. The primary outcome was 3-year mortality, and secondary outcomes were acute kidney injury (AKI), hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP) and portal vein thrombosis (PVT).
UNASSIGNED: Four studies, with 2,058 cirrhosis patients, were included. Among these, 1,488 patients had non-hemorrhagic ascites and 570 had hemorrhagic ascites. We observed no significant differences in AKI (odds ratio (OR) = 2.55; confidence interval (CI): 0.58 - 11.24), HE (OR = 2.52; CI: 0.70 - 9.05), SBP (OR = 1.66; CI: 0.12 - 22.83) and PVT (OR = 0.99; CI: 0.71 - 1.39). Intensive care unit (ICU) stay was significantly higher in patients with hemorrhagic ascites compared to those with non-hemorrhagic ascites (OR = 1.79; CI: 1.37 - 2.36; I2 = 56%). Pooled 3-year mortality was significantly higher in those with hemorrhagic (72.5% (CI: 68.2-76.4%)) when compared to non-hemorrhagic ascites (57.9% (CI: 55.2-60.6%)) (OR = 2.17; CI: 1.71 - 2.74) with low heterogeneity (I2 = 15%).
UNASSIGNED: In patients with cirrhosis, hemorrhagic ascites is a poor prognostic marker, which is associated with increased ICU stay and mortality. Prospective studies are needed to further evaluate significance of hemorrhagic ascites in patients with cirrhosis.

BACKGROUND: Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles.
METHODS: A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died.
CONCLUSIONS: Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.