Patients with cirrhosis are susceptible to infections due to abnormalities in humoral and cell-mediated immunity. Fungal infections are associated with delayed diagnosis and high mortality rates, emphasizing the importance of performing fungal cultures and maintaining elevated levels of suspicion in this patient population.

This retrospective cohort study analyzes cirrhotic patients readmitted with bacterial and fungal infections and investigates outcomes, including in-hospital mortality and hospital resource utilization. Data was acquired from the Nationwide Readmission Database (NRD) from 2016 to 2020. Total hospital costs were calculated using HCUP Cost-to-Charge Ratio files and adjusted for inflation based on the Consumer Price Index (CPI) for medical care services in the U.S., with 2020 as the reference year. The NRD dataset lacks details like ascitic fluid cell counts, antifungal/antibacterial drugs used, and treatment responses, limiting the clinical insights that can be derived.

The study analyzed 393,195 index hospitalizations. Among these, 102,505 account for 30-day and 157,079 account for 90-day readmissions. The 30-day and 90-day readmissions for spontaneous bacterial peritonitis (SBP) are 8478 and 15,690 respectively. The 30-day and 90-day readmissions for spontaneous fungal peritonitis (SFP) are 3106 and 5798 respectively. The mean age of patients was 57.9 years (standard deviation between 57.7 and 58.1). The mean length of stay (LOS) for SBP at 30 days is 9.4 days, while SFP has ranged from 14.9 to 32.3 days for various fungal infections. Aspergilloses have the longest LOS among SFP. There is an increased rate of mortality as well as hospital charges with SFP compared to SBP (P < 0.001). The 30-day index admission total charges for SBP are $42,258 and SFP are $51,739. The 30-day readmission total charges for SBP are 64, 266 and for SFP 89,913.

There is increased mortality, LOS, and hospital costs for SFP compared to SBP. It is important to consider SFP in the diagnostic workup for patients who do not respond to antibiotics. Early recognition and administration of antifungals can be associated with improved outcomes.

Cirrhosis is a major global health concern due to its progressive nature and high risk of complications, including spontaneous bacterial peritonitis (SBP), which significantly increases mortality. Quinolone antibiotics, especially norfloxacin, are commonly used for SBP prophylaxis in high-risk cirrhotic patients, but the long-term impact on overall mortality remains uncertain. The purpose of this meta-analysis and systematic review is to evaluate how quinolone prophylaxis affects the SBP incidence, mortality, and non-SBP infections in cirrhosis patients.

A comprehensive search of Web of Science, Embase, and PubMed identified research evaluating quinolone prophylaxis on the risk of spontaneous bacterial peritonitis (SBP) and mortality in cirrhotic patients. Inclusion criteria included randomized controlled trials reporting risk ratios for patients on quinolone prophylaxis versus controls. A random-effects meta-analysis pooled the results, with heterogeneity assessed by the I2 statistic. Sensitivity analyses were performed for robustness.

The search screened 1754 items and identified 6 relevant studies. Quinolone prophylaxis was associated with a significantly lower risk of spontaneous bacterial peritonitis (SBP), non-SBP infections, and mortality in cirrhotic patients, with a pooled relative risk (RR) for SBP of 0.47 (95% CI: 0.22-1.01), for non-SBP infections of 0.79 (95% CI: 0.66-0.94), and for mortality of 0.67 (95% CI: 0.52-0.86). Sensitivity analysis confirmed the robustness of these findings.

This meta-analysis reveals that quinolone prophylaxis significantly lowers the risk of spontaneous bacterial peritonitis (SBP), other infections, and mortality in high-risk cirrhotic patients. The results support incorporating quinolone prophylaxis in cirrhosis management to improve outcomes, with future studies needed to refine treatment duration and patient-specific strategies.

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that develops naturally, without being triggered by any surgical conditions or procedures, and is a common complication of cirrhosis. With a potential mortality rate of 40 ​%, accurate diagnosis and prompt initiation of appropriate antibiotic therapy are crucial for optimizing patient outcomes and preventing life-threatening complications. This study aimed to expand the use of computational models to improve the diagnostic accuracy of SBP in cirrhotic patients by incorporating a broader range of data, including clinical variables and laboratory values.

We employed 5 machine learning classification methods - Decision Tree, Support Vector Machine, Naive Bayes, K-Nearest Neighbor, and Random Forest, utilizing a variety of demographic, clinical, and laboratory features and biomarkers.

Ascitic fluid markers, including white blood cell (WBC) count, lactate dehydrogenase (LDH), total protein, and polymorphonuclear cells (PMN), significantly differentiated between SBP and non-SBP patients. The Random Forest model demonstrated the highest overall accuracy at 86 ​%, while the Naive Bayes model achieved the highest sensitivity at 72 ​%. Utilizing 10 key features instead of the full feature set improved model performance, notably enhancing specificity and accuracy.

Our analysis highlights the potential of machine learning to enhance the accuracy of SBP diagnosis in cirrhotic patients. Integrating these models into clinical workflows could substantially improve patient outcomes. To achieve this, ongoing multidisciplinary research is crucial. Ensuring model interpretability, continuous monitoring, and rigorous validation will be essential for the successful implementation of real-time clinical decision support systems.

Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.

Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.

Bacterial infections are a leading cause of hospitalization and mortality in patients with decompensated cirrhosis. Antibiotic prophylaxis in cirrhotic patients has demonstrated significant short-term reductions in bacterial infections in randomized controlled trials, but at the cost of drug resistance and with uncertain survival benefits.

This review examines antibiotic use in cirrhosis, focusing on patients most likely to benefit from antibiotic prophylaxis, management strategies for infections through risk-based antibiotic selection and timely treatment initiation, challenges posed by the emergence of multidrug-resistant organisms, and principles of antimicrobial stewardship.

The efficacy of prophylaxis has decreased over time, and current registry data have questioned its use, emphasizing the need for better risk-based individualized strategies. When bacterial infections occur, the efficacy of antimicrobial therapies depends heavily on local epidemiological patterns and individual patient risk factors, necessitating tailored antibiotic selection based on regional resistance data and specific clinical scenarios. Nosocomial infections, colonization with multidrug-resistant organisms, and prior exposure to systemic antibiotics are key risk factors that should guide empirical therapy selection. Until evidence-based algorithms are available, clinicians should continue to adopt individualized approaches, guided by available evidence, local specificities, and antimicrobial stewardship principles to optimize patient outcomes.

Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling.

This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects.

The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1-5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87-3.51), 1.86 (1.34-2.59), and 1.83 1.29-2.59).

The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients' prognoses.

Psoriasis is a chronic, inflammatory dermatosis characterized by thickened, reddened, and scaly skin lesions. Norfloxacin is a fluoroquinolone antibiotic with enhanced antioxidant, anti-inflammatory, and immunomodulatory bioactivities. The aim of this study was to figure out the possible impact of topical norfloxacin on an imiquimod-induced model of psoriasis in mice. Thirty albino-type mice were split into five distinct groups of six animals each. The control group included healthy mice that had not received any treatment. The induction group was given the vehicle 2 h after the topical imiquimod, once daily for 8 days. Two hours after receiving topical imiquimod, the treatment groups including calcipotriol, norfloxacin 2.5%, and norfloxacin 5% were given topical ointments containing calcipotriol 0.005%, norfloxacin 2.5%, and norfloxacin 5%, for 8 days. Topical norfloxacin ointment significantly reduced the severity of imiquimod-exacerbated psoriatic lesions including erythema, shiny-white scaling, and acanthosis and fixed histological abnormalities. Furthermore, imiquimod-subjected mice treated with a higher concentration of norfloxacin ointment exhibited dramatically lower skin levels of inflammation-related biomarkers like IFN-γ, TNF-α, IL-6, IL-17A, IL-23, and TGF-β but higher levels of IL-10. They also demonstrated a notable decrease in angiogenesis parameters such as VEGF and IL-8, a substantial reduction in oxidative indicators like MDA and MPO, and a considerable rise in antioxidant enzymes like SOD and CAT. This study offers novel evidence that norfloxacin may assist in controlling inflammatory dermatoses like psoriasis by minimizing the severity of psoriatic plaques, correcting histological alterations, and diminishing the production of inflammatory, oxidative, and angiogenetic parameters.

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.

Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.

Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC).

The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC.

This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1 : 1 into two groups. Group A received oral midodrine (5 mg/8 h) and rifaximin (550 mg/12 h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period.

In the study group, there was a significant reduction in Child-Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (P < 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (P < 0.05). Survival rates demonstrated a noteworthy improvement (P = 0.014), substantiated by evidence in both univariate and multivariate regression analyses.

Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.

There are many options for the reduction of portal hypertension (pH) in cirrhotic patients, but all the current ones have side effects. Probiotics are a new approach for ameliorating the hyperdynamic circulation of cirrhotic patients. The aim of this study is to measure the effect of probiotics on pH in cirrhosis for the first time.

A search was conducted across four electronic databases (PubMed, Scopus, Web of Science, Cochrane) for English-language records evaluating probiotic effects on pH in cirrhotic patients. Quality assessment used the Cochrane Collaboration's tool, employing a random-effects model in statistical analysis with Stata software version 1.

A search yielded 1,251 articles, which were narrowed down to 5 through screening. These studies, involving 158 participants across Canada, India, Spain, and Russia, focused on probiotic interventions in cirrhotic patients. Meta-analysis of two RCTs (66 participants) indicated a significant decrease in hepatic venous pressure gradient (HVPG) (SMD: -0.60 [-1.09, -0.12]). In single-arm analysis, four studies (58 participants) showed a substantial reduction in HVPG with probiotic use compared to the control (SMD: -2.55 [-3.42, -1.68]).

In summary, it showcased a notable reduction in HVPG compared to the control group, indicating a potential advantage of probiotics in decreasing pH in cirrhotic patients. Further research with larger samples and robust designs is warranted.

Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive "cure" for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.

Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.

Hepatorenal syndrome (HRS) is a critical and potentially life-threatening complication of advanced liver disease, including cirrhosis. It is characterized by the development of renal dysfunction in the absence of underlying structural kidney pathology. The pathophysiology of HRS involves complex interactions between systemic and renal hemodynamics, neurohormonal imbalances, and the intricate role of vasoconstrictor substances. Understanding these mechanisms is crucial for the timely identification and management of HRS. The diagnosis of HRS is primarily clinical and relies on specific criteria that consider the exclusion of other causes of renal dysfunction. The management of HRS comprises two main approaches: vasoconstrictor therapy and albumin infusion, which aim to improve renal perfusion and mitigate the hyperdynamic circulation often seen in advanced liver disease. Additionally, strategies such as liver transplantation and renal replacement therapy are essential considerations based on individual patient characteristics and disease severity. This review article provides a comprehensive overview of hepatorenal syndrome, focusing on its pathophysiology, diagnostic criteria, and current management strategies.

Regardless of etiology, complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46% according to the most recent data. Due to frequent episodes of bacterial infection and repetitive antibiotic treatment, most often with broad-spectrum gram negative coverage, patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria, and this raises concern. In such patients, extended-spectrum beta-lactamase and AmpC-producing Enterobacterales, methicillin- or vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, carbapenem-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii, all of which are difficult to treat, are the most common. That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed. At the same time, our knowledge of resistance mechanisms is constantly updated. This review summarizes the current situation regarding the burden of antibiotic resistance, including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Objective To investigate predictive biomarkers correlated with the onset of hepatorenal syndrome (HRS) in individuals with alcoholic liver cirrhosis using various factors, including age, sex, and laboratory indicators such as serum sodium, bilirubin, PT/INR, and albumin levels. Additionally, we sought to establish a correlation between the occurrence of hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and the model for end-stage liver disease (MELD) score at the time of diagnosis and the development of HRS in cirrhotic patients. Methods This cross-sectional study spanned 12 months and included a total of 83 patients as its sample size. This study was conducted at the Department of Internal Medicine, a tertiary care hospital situated in Mumbai, India. Two distinct groups were formed: one consisted of patients diagnosed with HRS, and the other group comprised patients with alcoholic liver cirrhosis but without HRS. This study aimed to investigate potential relationships with the suggested risk factors. To discern statistically meaningful distinctions among categorical variables, the chi-square test was employed, whereas for continuous variables, analysis of variance (ANOVA) was used. Only patients who provided written informed consent were included in this study. Results No correlation was found between patients with and without HRS with respect to age (p=0.056) and sex (p=0.067). The presence of HE (p<0.001), SBP (p=0.021), hyponatremia (p=0.0001), hypoalbuminemia (p<0.0001), higher PT/INR (p=0.03), and higher MELD score (p=0.0002) were found to be correlated with an increased risk of developing HRS. Hyperbilirubinemia was not correlated with an increased risk of developing HRS (p=0.157). Conclusions HRS is a severe and potentially avoidable complication associated with advanced liver cirrhosis, characterized by a notably high mortality rate. By closely monitoring key biomarkers, such as serum sodium, PT/INR, and albumin levels, in addition to assessing the presence of SBP and HE during the initial presentation of patients with alcoholic cirrhosis, medical professionals may be able to identify those at a heightened risk of developing HRS. This, in turn, enables the swift diagnosis and implementation of aggressive treatment strategies. Such measures not only hold the potential to reverse HRS but also enhance survival rates among individuals with alcoholic liver cirrhosis, thereby increasing the pool of candidates eligible for liver transplantation, which remains the cornerstone of treatment.

Patients with cirrhosis are susceptible to infections, especially by multidrug-resistant organisms (MDROs). There are limited data on the incidence of culture-positive infections and the validity of Sepsis 3-criteria in patients with cirrhosis admitted to the intensive care unit (ICU) in India, which we aimed to assess.

In this prospective study, we included consecutive patients with cirrhosis admitted to the ICU between November 1, 2021, and April 30, 2022. The primary objective was to compare the outcomes of patients with microbiologically proven infections with those without proven infections. The secondary objective was to assess the predictors of infections and mortality and the impact of drug-resistant organisms.

A total of 298 patients (9.4% women) were included. The incidence of microbiologically proven infection was 34% (101/298; 95%CI=27.6-41.2). Most patients (61%) had healthcare-associated infections, Gram-negative organisms accounted for 75.3%, and bacteremia was the commonest site. Drug-resistant organisms accounted for 52.5% (53/101; 95%CI=39.3-68.7), of which 39.6% were multidrug-resistant (MDR) and 12.8% were extensively drug-resistant (XDR). Mortality was significantly higher in patients with proven infections than those without (61.4% vs. 44.2%; P=0.007). The sequential organ failure assessment (SOFA) score (OR=1.91; 95%CI=1.04-3.52; P<0.001) and presence of fever and/or positive quick SOFA (qSOFA; OR=1.91;1.04-3.52; P=0.03) were associated with an increased risk of infections. The SOFA score (OR=1.06;95%CI=1.002-1.12; P=0.04), MELD NA score (OR=1.08;95%CI=1.05-1.12; P<0.001), and presence of fever and/or positive qSOFA (OR=2.19; 95%CI=1.27-3.76; P=0.005) predicted mortality.

One-third of the patients with cirrhosis admitted to the ICU had microbiologically proven infection, and the mortality rate in such patients was high. SOFA, qSOFA, and fever can predict microbiologically proven infections and mortality in patients with cirrhosis.

Impairments in liver function lead to different complications. As chronic liver disease progresses (CLD), hypoalbuminemia and alterations in bile acid compositions lead to changes in gut microbiota and, therefore, in the host-microbiome interaction, leading to a proinflammatory state. Alterations in gut microbiota composition and permeability, known as gut dysbiosis, have important implications in CLD; alterations in the gut-liver axis are a consequence of liver disease, but also a cause of CLD. Furthermore, gut dysbiosis plays an important role in the progression of liver cirrhosis and decompensation, particularly with complications such as hepatic encephalopathy and spontaneous bacterial peritonitis. In relation to this, antibiotics play an important role in treating CLD. While certain antibiotics have specific indications, others have been subjected to continued study to determine whether or not they have a modulatory effect on gut microbiota. In contrast, the rational use of antibiotics is important, not only because of their disrupting effects on gut microbiota, but also in the context of multidrug-resistant organisms. The aim of this review is to illustrate the role of gut microbiota alterations in CLD, the use and impact of antibiotics in liver cirrhosis, and their harmful and beneficial effects.

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.

Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death.

This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries.

Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Absolute polymorphonuclear leukocyte (PMN) count (PMN-C) ≥250 cells/mm 3 in ascites is the diagnostic hallmark of spontaneous bacterial peritonitis (SBP) and is associated with high morbidity and mortality. However, the clinical significance of ascitic PMN percentage (PMN-%) and PMN-C in the absence of SBP as additional biomarkers for mortality and future incidence of SBP has not been determined.

This retrospective cohort included adults with cirrhosis undergoing first-recorded paracentesis with initial PMN-C < 250 cells/mm 3 at 2 tertiary medical centers between 2015 and 2020. Patients with prior SBP were excluded. Outcomes were death and SBP development. Cox regression estimated hazard ratios (HRs) for risk of death and SBP development and Akaike information criterion to compare model fit.

Three hundred eighty-four adults (73% male, median age 58 years, 67% with alcohol-associated cirrhosis, median PMN-C 14 cells/mm 3 [interquartile range 5-34], and median PMN-% 10% [interquartile range 4-20]) were included in this study. Univariate risk of death increased 10% per 25-unit increase in PMN-C (95% confidence interval 1.01-1.21, P = 0.03) and 19% per 10-unit increase in PMN-% (95% confidence interval 1.06-1.33, P = 0.003) with PMN-% demonstrating better model fit in assessing mortality risk (Akaike information criterion: 1,044 vs 1,048, respectively). In models adjusted for age, chronic hepatitis C virus infection, and Model for End-Stage Liver Disease-Sodium, PMN-% was associated with risk of death (PMN-% 10%-29%, HR 1.17, P = 0.50; PMN-% ≥ 30% group, HR 1.94, P = 0.03; vs PMN-% < 10%) and SBP development (PMN-% 10%-29%, HR 1.68, P = 0.07; PMN-% ≥ 30%, HR 3.48, P < 0.001; vs PMN-% < 10%).

Our results suggest PMN-% at first paracentesis represents a better biomarker compared with PMN-C for assessing risk of death and future SBP development in patients with PMN-C < 250 cells/mm 3 .

Hepatorenal syndrome is a complication of liver cirrhosis with ascites that results from the complex interplay of many pathogenetic mechanisms. Advanced cirrhosis is characterized by the development of hemodynamic changes of splanchnic and systemic arterial vasodilatation, with paradoxical renal vasoconstriction and renal hypoperfusion. Cirrhosis is also an inflammatory state. The inflammatory cascade is initiated by a portal hypertension-induced increased translocation of bacteria, bacterial products, and endotoxins from the gut to the splanchnic and then to the systemic circulation. The inflammation, whether sterile or related to infection, is responsible for renal microcirculatory dysfunction, microthrombi formation, renal tubular oxidative stress, and tubular damage. Of course, many of the bacterial products also have vasodilatory properties, potentially exaggerating the state of vasodilatation and worsening the hemodynamic instability in these patients. The presence of cardiac dysfunction, related to cirrhotic cardiomyopathy, with its associated systolic incompetence, can aggravate the mismatch between the circulatory capacitance and the circulation volume, worsening the extent of the effective arterial underfilling, with lower renal perfusion pressure, contributing to renal hypoperfusion and increasing the risk for development of acute kidney injury. The presence of tense ascites can exert an intra-abdominal compartmental syndrome effect on the renal circulation, causing renal congestion and hampering glomerular filtration. Other contributing factors to renal dysfunction include the tubular damaging effects of cholestasis and adrenal dysfunction. Future developments include the use of metabolomics to identify metabolic pathways that can lead to the development of renal dysfunction, with the potential of identifying biomarkers for early diagnosis of renal dysfunction and the development of treatment strategies.

In 2015 the International Club of Ascites gave an accurate, exact and new definition of acute renal injury in cirrhotic patient, identifying objective criteria of severity and recoding hepatorenal syndrome as a particular form of renal dysfunction for which excessive renal vasoconstriction is one of the main, but not the only, pathophysiological mechanisms. In this review we tried to outline new pathophysiological and therapeutic insights, and to summarize the most recent recommendations. Vasopressor such as terlipressin and norepinephrine, in combination with albumin, still represent the first line therapy. However, the new discoveries in the pathophysiology of the disease have led the search for new pharmacological approaches, although, to date, the only definitive remedy is represented by liver (or simultaneous liver-kidney) transplantation.

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.

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.

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.

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.

Bacterial infections (BIs) are the most common precipitating event of acute-on-chronic liver failure (ACLF) and a frequent complication of ACLF. BIs aggravate the course of the syndrome and are associated with higher mortality rates. For this reason, BIs should be promptly diagnosed and treated in all patients with ACLF. The administration of an appropriate empirical antibiotic therapy improves survival in patients with BIs and ACLF and is the cornerstone of treatment. Due to the spread of antibiotic resistance worldwide, the empirical treatment should cover multi-drug-resistant organisms. Herein we reviewed the current evidence about the management of BIs in ACLF.

Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.

Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit.

Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX.

Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this condition.

This paper evaluates key evidence-based updates concerning SBP for the emergency clinician.

SBP is commonly due to Gram-negative bacteria, but infections due to Gram-positive bacteria and multidrug resistant bacteria are increasing. The typical presentation of SBP includes abdominal pain, worsening ascites, fever, or altered mental status in a patient with known liver disease; however, some patients may be asymptomatic or present with only mild symptoms. Paracentesis is the diagnostic modality of choice and should be performed in any patient with ascites and concern for SBP or upper gastrointestinal bleeding, or in those being admitted for a complication of cirrhosis. Ultrasound should be used to optimize the procedure. An ascites absolute neutrophil count (ANC) ≥ 250 cells/mm³ is diagnostic of SBP. Ascitic fluid should be placed in blood culture bottles to improve the culture yield. Leukocyte esterase reagent strips can be used for rapid diagnosis if available. While many patients will demonstrate coagulation panel abnormalities, routine transfusion is not recommended. Management traditionally includes a third-generation cephalosporin, but specific patient populations may require more broad-spectrum coverage with a carbapenem or piperacillin-tazobactam. Albumin infusion is associated with reduced risk of renal impairment and mortality.

An understanding of literature updates can improve the care of patients with suspected SBP.

Acute-on-chronic-liver failure (ACLF) refers to a phenomenon in which patients with chronic liver disease develop multiple organ failure due to acute exacerbation of underlying liver disease. More than 10 definitions of ACLF are extant around the world, and there is lack of consensus on whether extrahepatic organ failure is a main component or a consequence of ACLF. Asian and European consortiums have their own definitions of ACLF. The Asian Pacific Association for the Study of the Liver ACLF Research Consortium does not consider kidney failure as a diagnostic criterion for ACLF. Meanwhile, the European Association for the Study of the Liver Chronic Liver Failure and the North American Consortium for the Study of End-stage Liver Disease do consider kidney failure as an important factor in diagnosing and assessing the severity of ACLF. When kidney failure occurs in ACLF patients, treatment varies depending on the presence and stage of acute kidney injury (AKI). In general, the diagnosis of AKI in cirrhotic patients is based on the International Club of Ascites criteria: an increase of 0.3 mg/dL or more within 48 hours or a serum creatinine increase of 50% or more within one week. This study underscores the importance of kidney failure or AKI in patients with ACLF by reviewing its pathophysiology, prevention methods, and treatment approaches.

Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites. Currently, the accuracy of the model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) as prognostic scores in this cohort is unclear. This study aimed to evaluate and compare the accuracy of MELD and MELD-Na for predicting 90-day mortality and determine whether the mortality risk estimates they provide accurately reflect the poor prognosis of patients with SBP Methods: Patients with cirrhosis and SBP were retrospectively identified from ascitic fluid samples sent for microscopy, culture and sensitivity analysis (1/1/18-31/12/20) and a previous audit. MELD and MELD-Na scores at diagnosis were calculated and associations with 90-day mortality were assessed using univariate analysis. Receiver operator characteristic curves were compared, and standardised mortality ratios (SMRs) were calculated by comparing the number of deaths observed to the number predicted by MELD and MELD-Na.

Of the 567 patients identified, 15 patients with cirrhosis and SBP were included. The 90-day mortality rate was 66.7% (10/15). Only concurrent hyponatremia (<135mmol/L) was associated with mortality (6/10 non-survivors vs 0/5 survivors, p=0.04). The difference in MELD and MELD-Na's C-statistic was not significant: 0.66 (95% Cl:0.35-0.98) vs 0.74 (95% Cl:0.47-1.0) respectively (p=0.72). Patients with a MELD-Na >18.5 had significantly higher 90-day mortality than patients with MELD-Na ≤18.5 (88.9% (8/9) vs. 33.3% (2/6), p=0.05). The SMR (95% Cl) for each MELD decile evaluated was 33.3 (0-79.5), 11.1 (0.2-22.0) and 3.4 (0-7.0) for scores ≤9,10-19 and 20-29 respectively. For each MELD-Na tertile, these were: 25 (0-59.6), 5.2 (0.1-10.3) and 2.7 (0.1-8.1) for scores <17,17-26, ≥27 respectively.

In a small cohort of patients with cirrhosis and SBP, the MELD's accuracy in predicting 90-day mortality was limited. MELD-Na's accuracy was higher but not significantly. Both scores consistently underestimated participants' mortality, therefore future studies could evaluate the accuracy of alternative prognostic scores in this patient group.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.