Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1-G3) showing distinct microbial patterns. G1 (n = 39) displayed lowest diversity and highest Enterococcus abundance, G2 (n = 24) was dominated by Bifidobacteria, G3 (n = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n = 33; 86.8%), had highest plasma-levels of Zonulin (p = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections (p = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.

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.

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.

This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage.

After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days.

Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B ( P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B ( P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B ( P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B ( P < 0.001).

After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay.

Bleeding events are feared complications in patients with advanced liver diseases and are associated with morbidity and mortality. In this context, gastrointestinal bleeding, particularly upper gastrointestinal bleeding, has a special clinical importance. In addition to endoscopic measures for hemostasis, reducing portal pressure in particular is a key component of treatment. Although the standard coagulation parameters are often altered in patients with liver diseases, optimizing coagulation plays a secondary role. Typically, a bundle of measures are employed in patients with portal hypertensive bleeding, which nowadays in most cases can halt the bleeding and stabilize the situation. The measures include endoscopy, antibiotic treatment, vasopressor treatment and, if necessary, shunt placement (transjugular intrahepatic portosystemic shunt).

Chronic liver disease occurs throughout the world irrespective of region, age, sex, or race, and it is caused by a variety of liver conditions. One of the most frequent infectious complications in liver cirrhosis that severely reduces the median survival is spontaneous bacterial peritonitis. Current guidelines recommend a paracentesis before starting an antibiotic prophylaxis for this complication.

Selective intestinal decontamination significantly lowers the rate of first or recurrent SBP in cirrhotic patients, so in this study we aimed to investigate and quantify the intestinal integrity of patients with liver cirrhosis and correlate a pathologically increased permeability with the incidence of SPB. We included 14 patients who met the inclusion criteria. No patient was excluded. For the CLE investigation, we use probe based confocal laser endomicroscopy techniques from Mauna Kea (Cellvizio), enabling in vivo surface imaging. The images (optical biopsies) were analyzed for functional and structural barrier defects after the procedure using Mauna Kea software (version 1.0.09).

Because of the small number of included patients and healthy controls, most results are lacking statistical relevance. We found that the CLE investigation showed an increased intestinal permeability in patients with liver cirrhosis, in concordance with previous published data, based on other assessment methods.

This study confirms that previously published permeability scores can be applied for patients with liver cirrhosis and is, to our knowledge, the first to investigate the intestinal permeability in vivo in patients with liver cirrhosis. Further data are needed to identify patients at risk and help develop new and less invasive diagnostic criteria for cirrhotic patients who may profit from a prophylactic antibiotic treatment.

Acute upper gastrointestinal bleeding (UGIB) is a common emergency requiring hospital-based care. Advances in care across pre-endoscopic, endoscopic and post-endoscopic phases have led to improvements in clinical outcomes.

To provide a detailed, evidence-based update on major aspects of care across pre-endoscopic, endoscopic and post-endoscopic phases.

We performed a structured bibliographic database search for each topic. If a recent high-quality meta-analysis was not available, we performed a meta-analysis with random effects methods and odds ratios with 95% confidence intervals.

Pre-endoscopic management of UGIB includes risk stratification, a restrictive red blood cell transfusion policy unless the patient has cardiovascular disease, and pharmacologic therapy with erythromycin and a proton pump inhibitor. Patients with cirrhosis should be treated with prophylactic antibiotics and vasoactive medications. Tranexamic acid should not be used. Endoscopic management of UGIB depends on the aetiology. For peptic ulcer disease (PUD) with high-risk stigmata, endoscopic therapy, including over-the-scope clips (OTSCs) and TC-325 powder spray, should be performed. For variceal bleeding, treatment should be customised by severity and anatomic location. Post-endoscopic management includes early enteral feeding for all UGIB patients. For high-risk PUD, PPI should be continued for 72 h, and rebleeding should initially be evaluated with a repeat endoscopy. For variceal bleeding, high-risk patients or those with further bleeding, a transjugular intrahepatic portosystemic shunt can be considered.

Management of acute UGIB should include treatment plans for pre-endoscopic, endoscopic and post-endoscopic phases of care, and customise treatment decisions based on aetiology and severity of bleeding.

Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are 2 distinct gastric vascular abnormalities that may present with acute or chronic blood loss. PHG requires the presence of portal hypertension and is typically associated with chronic liver disease, whereas there is controversy about the association of GAVE with chronic liver disease and/or portal hypertension. Distinguishing between GAVE and PHG is crucial because their treatment strategies differ. This review highlights characteristic endoscopic appearances and the clinical features of PHG and GAVE, which, in turn, aid in their appropriate management.

Upper gastrointestinal bleeding (UGIB) continues to be an important cause for emergency room visits and carries significant morbidity and mortality. Early resuscitative measures form the basis of the management of patients presenting with UGIB and can improve the outcomes of such patients including lowering mortality. In this review, using an evidence-based approach, we discuss the initial assessment and resuscitation of patients presenting with UGIB including identifying clues from history and physical examination to confirm UGIB, preendoscopic risk assessment tools, the role of early fluid resuscitation, utilization of blood products, use of pharmacologic interventions, and the optimal timing of endoscopy.

Over the past decade, significant advancements in pharmacological, endoscopic, and radiographic treatments have emerged in the management of patients with cirrhosis and esophagogastric varices or variceal hemorrhage. These advances have been in several areas, including the role of screening and primary prophylaxis (preventing an initial variceal bleed), evaluation and management of acute esophagogastric variceal hemorrhage, and in preventing variceal rebleeding. Therefore, we believe there is a need for an updated, evidence-based "narrative review" on this important clinical topic that will be relevant for internists, hospitalists, intensive care unit physicians, and those in training. We believe the guidance presented in this narrative review will enhance daily medical practice of health care professionals and has the potential to improve quality of care for these complex patients.

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.

Upper gastrointestinal bleeding (UGIB) in children has many causes, with its prevalence varying by age. Often presenting as hematemesis or melena, the initial treatment is stabilization of the patient, including protection of the airway, fluid resuscitation, and a transfusion hemoglobin threshold of 7 g/L. Endoscopy should be performed with the goal of using combinations of therapies to treat a bleeding lesion, generally involving epinephrine injection along with either cautery, hemoclips, or hemospray. This review discusses the diagnosis and treatment of variceal and non-variceal gastrointestinal bleeding in children with a focus on current advances in the treatment of severe UGIB.

Upper gastrointestinal bleeding is a relatively common and life-threatening condition encountered by critical care transport crews. It is of paramount importance that transport crews understand the underlying pathophysiology of variceal and nonvariceal gastrointestinal bleeding as well as the nuanced management of this patient population. This article reviews the current clinical evidence on initial resuscitation, medical management, and advanced invasive therapies (such as balloon tamponade devices) that transport crews should be familiar with to manage these patients. In addition, we present a novel method of continuous balloon pressure monitoring of balloon tamponade devices that is applicable to the transport environment.

Ascites is the most common complication of cirrhosis, with 5-year mortality reaching 30%. Complications of ascites (ie, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent/refractory ascites, and hepatic hydrothorax) further worsen survival. The development of ascites is driven by portal hypertension, systemic inflammation, and splanchnic arterial vasodilation. Etiologic treatment and nonselective beta-blockers can prevent ascites in compensated cirrhosis. The treatment of ascites is currently based on the management of fluid overload (eg, diuretics, sodium restriction, and/or paracenteses). In selected patients, long-term albumin use, norfloxacin prophylaxis, and transjugular intrahepatic portosystemic shunt reduce the risk of further decompensation and improve survival.

Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.

To evaluate the effect of different prophylactic antibiotic treatments for cirrhosis patients with upper gastrointestinal bleeding (UGIB) and to investigate whether prophylactic antibiotics are equally beneficial to reducing the risk of adverse outcomes in A/B with low Child-Pugh scores.

Relevant studies were searched via PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet (CNKI), Wanfang, and VIP databases up to July 16, 2021. The heterogeneity test was conducted for each outcome measuring by I2 statistics. Subgroup analysis was performed regarding antibiotic types. Relative risk (RR) and 95% confidence interval (CI) were used to evaluate prophylactic antibiotics on the risk of adverse outcomes in cirrhosis patients with UGIB.

Twenty-six studies involving 12,440 participants fulfilled our inclusion criteria. Antibiotic prophylaxis was associated with a reduced overall mortality (RR: 0.691, 95%CI: 0.518 to 0.923), mortality due to bacterial infections (RR: 0.329, 95%CI: 0.144 to 0.754), bacterial infections (RR: 0.389, 95%CI: 0.340 to 0.444), rebleeding (RR: 0.577, 95%CI: 0.433 to 0.767) and length of hospitalization [weighted mean difference (WMD): -3.854, 95%CI: -6.165 to -1.543] among patients with UGIB. Nevertheless, prophylactic antibiotics may not benefit to A/B population with low Child-Pugh scores. In our subgroup analysis, quinolone, beta-lactams alone or in combination reduced adverse outcomes in cirrhosis patients with UGIB.

Administration of antibiotics was associated with a reduction in mortality, bacterial infections, rebleeding, and length of hospitalization. Quinolone, beta-lactams alone or in combination can be used in cirrhosis patients with UGIB. Nevertheless, targeted efforts are needed to promote the appropriate use of antibiotics among patients with cirrhosis and UGIB.

The guidelines are intended to provide practical information for the correct use of antibiotics for intra-abdominal infections in Korea. With the aim of realizing evidence-based treatment, these guidelines for the use of antibiotics were written to help clinicians find answers to key clinical questions that arise in the course of patient care, using the latest research results based on systematic literature review. The guidelines were prepared in consideration of the data on the causative pathogens of intra-abdominal infections in Korea, the antibiotic susceptibility of the causative pathogens, and the antibiotics available in Korea.

1: ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI < 30 kg/m2] nonalcoholic steatohepatitis) and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] > 10 mmHg and/or liver stiffness by transient elastography > 25 kPa) should receive, if no contraindications, nonselective beta blocker (NSBB) therapy (preferably carvedilol) to prevent the development of variceal bleeding.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in those patients unable to receive NSBB therapy with a screening upper gastrointestinal (GI) endoscopy that demonstrates high risk esophageal varices, endoscopic band ligation (EBL) is the endoscopic prophylactic treatment of choice. EBL should be repeated every 2-4 weeks until variceal eradication is achieved. Thereafter, surveillance EGD should be performed every 3-6 months in the first year following eradication.Strong recommendation, moderate quality evidence. 3: ESGE recommends, in hemodynamically stable patients with acute upper GI hemorrhage (UGIH) and no history of cardiovascular disease, a restrictive red blood cell (RBC) transfusion strategy, with a hemoglobin threshold of ≤ 70 g/L prompting RBC transfusion. A post-transfusion target hemoglobin of 70-90 g/L is desired.Strong recommendation, moderate quality evidence. 4 : ESGE recommends that patients with ACLD presenting with suspected acute variceal bleeding be risk stratified according to the Child-Pugh score and MELD score, and by documentation of active/inactive bleeding at the time of upper GI endoscopy.Strong recommendation, high quality of evidence. 5 : ESGE recommends the vasoactive agents terlipressin, octreotide, or somatostatin be initiated at the time of presentation in patients with suspected acute variceal bleeding and be continued for a duration of up to 5 days.Strong recommendation, high quality evidence. 6 : ESGE recommends antibiotic prophylaxis using ceftriaxone 1 g/day for up to 7 days for all patients with ACLD presenting with acute variceal hemorrhage, or in accordance with local antibiotic resistance and patient allergies.Strong recommendation, high quality evidence. 7 : ESGE recommends, in the absence of contraindications, intravenous erythromycin 250 mg be given 30-120 minutes prior to upper GI endoscopy in patients with suspected acute variceal hemorrhage.Strong recommendation, high quality evidence. 8 : ESGE recommends that, in patients with suspected variceal hemorrhage, endoscopic evaluation should take place within 12 hours from the time of patient presentation provided the patient has been hemodynamically resuscitated.Strong recommendation, moderate quality evidence. 9 : ESGE recommends EBL for the treatment of acute esophageal variceal hemorrhage (EVH).Strong recommendation, high quality evidence. 10 : ESGE recommends that, in patients at high risk for recurrent esophageal variceal bleeding following successful endoscopic hemostasis (Child-Pugh C  ≤ 13 or Child-Pugh B > 7 with active EVH at the time of endoscopy despite vasoactive agents, or HVPG > 20 mmHg), pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) within 72 hours (preferably within 24 hours) must be considered.Strong recommendation, high quality evidence. 11 : ESGE recommends that, for persistent esophageal variceal bleeding despite vasoactive pharmacological and endoscopic hemostasis therapy, urgent rescue TIPS should be considered (where available).Strong recommendation, moderate quality evidence. 12 : ESGE recommends endoscopic cyanoacrylate injection for acute gastric (cardiofundal) variceal (GOV2, IGV1) hemorrhage.Strong recommendation, high quality evidence. 13: ESGE recommends endoscopic cyanoacrylate injection or EBL in patients with GOV1-specific bleeding.Strong recommendations, moderate quality evidence. 14: ESGE suggests urgent rescue TIPS or balloon-occluded retrograde transvenous obliteration (BRTO) for gastric variceal bleeding when there is a failure of endoscopic hemostasis or early recurrent bleeding.Weak recommendation, low quality evidence. 15: ESGE recommends that patients who have undergone EBL for acute EVH should be scheduled for follow-up EBLs at 1- to 4-weekly intervals to eradicate esophageal varices (secondary prophylaxis).Strong recommendation, moderate quality evidence. 16: ESGE recommends the use of NSBBs (propranolol or carvedilol) in combination with endoscopic therapy for secondary prophylaxis in EVH in patients with ACLD.Strong recommendation, high quality evidence.

Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.

Pharmacotherapy has become more focused on the personalized treatment of patients with various diseases. This field of pharmacology and pharmacogenomics focuses on developing drug delivery systems designed to address the unique characteristics of individual patients. Three-dimensional printing technology can be used to fabricate personalized drug delivery systems with desired release properties according to patient needs. Norfloxacin (NOR)-loaded micropellets (MPs) were fabricated and filled inside a stereolithography (SLA) 3D printing technology-mediated hollow capsular device in accordance with a standard size of 09 (8.4 mm length × 2.70 mm diameter). The prepared 3D-printed hollow capsular device filled with pristine NOR and NOR-loaded MPs were characterized in terms of both in vitro and in vivo means. MPs with the particle size distribution of 1540.0 ± 26 µm showed 95.63 ± 2.0% NOR content with pellet-shaped surface morphology. The in vitro release profile showed an initial lag phase of approximately 30 min, followed by the sustained release of NOR from MPs from the 3D-printed hollow capsular device. The pharmacokinetic profile showed prolonged T_max, AUC, and evidence of good RBA of NOR compared to pure NOR after a single oral administration in the experimental animal model. The overall results confirm the feasibility of SLA-mediated 3D printing technology for preparing customized solid oral unit dosage carriers that can be filled with pure NOR- and NOR-loaded MPs with controlled-release delivery features.

Cirrhosis consists of two main stages: compensated (asymptomatic) and decompensated, the latter with a higher mortality. Variceal hemorrhage, together with ascites or encephalopathy, or both, are events that define cirrhosis decompensation and are driven by portal hypertension. The approach and management of patients with compensated cirrhosis has been mostly focused on preventing variceal hemorrhage in those who have high-risk varices on endoscopy. Recent studies suggest a paradigm shift aimed at preventing all decompensating events, not only variceal hemorrhage, in patients with cirrhosis and clinically significant portal hypertension identified via noninvasive measures such as liver stiffness and platelet count. In these patients, nonselective beta-blockers have been shown to prevent ascites (the most common decompensating event) and variceal growth. Variceal hemorrhage has a high mortality rate and even though advances in diagnostic approach and standard of care over the past decades have led to a decrease in mortality, it is still high with a 6-week mortality rate of 15-20%. Survival has improved with the preemptive placement of the transjugular intrahepatic portosystemic shunt in patients at high risk of failing standard therapy. In this review, we provide an overview of the pathophysiology and bases for therapy of portal hypertension and varices, the diagnostic approach and management of compensated cirrhosis with clinically significant portal hypertension, and the management of acute variceal hemorrhage as well as prevention strategies for variceal hemorrhage recurrence.

The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy.

Portal hypertensive bleeding is a major complication of portal hypertension (PHT) with high morbidity and mortality. A lot of advances have been made in our understanding of screening, risk stratification, and management strategies for portal hypertensive bleeding including acute variceal bleeding leading to improved overall outcomes in patients with PHT. A number of guidelines on variceal bleeding have been published by various societies in the past few years. The Indian Society of Gastroenterology (ISG) Task Force on Upper Gastrointestinal Bleeding (UGIB) felt that it was necessary to bring out a standard practice guidance document for the use of Indian health care providers especially physicians, gastroenterologists, and hepatologists. For this purpose, an expert group meeting was convened by the ISG Task Force to deliberate on this matter and write a consensus guidance document for Indian practice. The delegates including gastroenterologists, hepatologists, radiologists, and surgeons from different parts of the country participated in the consensus development meeting at Coorg in 2018. A core group was constituted which reviewed all published literature on portal hypertensive UGIB with special reference to the Indian scenario and prepared unambiguous statements on different aspects for voting and consensus in the whole group. This consensus was produced through a modified Delphi process and reflects our current understanding and recommendations for the diagnosis and management of portal hypertensive UGIB in Indians. Intended for use by the health care providers especially gastroenterologists and hepatologists, these consensus statements provide an evidence-based approach to risk stratification, diagnosis, and management of patients with portal hypertensive bleeding.

Bacterial infection represents a turning point in the natural history of cirrhosis, causing the development of acute-on-chronic liver failure. It significantly affects the outcome of patients listed for liver transplantation. We report the case of a 57-year-old man who had been regularly treated for hepatitis B virus, alcoholic liver cirrhosis, and hepatic failure. The patient was hospitalized again due to variceal bleeding and hepatic coma. He visited the emergency room with painful anal swelling, dysuria, icteric sclera, and serious abdominal distension. The painful anal swelling and necrosis progressed; thus, he was diagnosed with Fournier's gangrene. Enterococcus faecium and Candida albicans were detected in the blood. Gangrene wound debris was studied extensively. Despite appropriate antibiotic treatment, vancomycin-resistant enterococcus and C. albicans were continuously present in the blood. Wide debridement of the wound and T-colostomy were performed. After this, norepinephrine and vasopressin were used to maintain stable vital signs. It was difficult to establish a liver transplant operation. Despite repeated bleeding, bacterial infections improved with additional antibiotics. Finally, selected deceased donor liver transplantation in controlled Fournier's gangrene was successfully performed. Controlled infections may be allowed in transplantation surgery.

China is regarded as the "leader in liver diseases" because that one-fifth of the population was affected by some forms of liver diseases in this developing country. In addition to common infectious liver diseases (such as viral hepatitis and parasitic liver diseases), non-infectious liver diseases such as fatty liver diseases (FLD), drug-induced liver injury (DILI), alcoholic liver diseases (ALD), autoimmune liver diseases (AILD), vessel-related liver diseases, genetic metabolic liver diseases and liver masses are present. In recent years, an increasing number of liver diseases have been reported in special populations, including childhood liver diseases, pregnancy-related liver diseases and liver transplant-associated diseases and so on. Absence of characteristic symptoms and signs coupled with a lack of medical knowledge, patients with chronic liver diseases seek medical treatment without a reliable model, which resulted to the chaotic consult medical status in China mainland. This article aims to describe the current seek medical status of chronic liver diseases and discuss a stage-based consulting medical model for chronic liver diseases in China mainland, which would contribute to make rational use of limited medical resources and help to address National Health China 2030 strategy initiated by the Chinese government.

Varices are a frequent complication of liver cirrhosis and a major cause of mortality in patients with liver cirrhosis. Patients with decompensated cirrhosis complications have a poor prognosis and require careful management. Portal hypertension is the most common complication of liver cirrhosis, which is the key determinant for varices development. Increased intrahepatic vascular resistance to portal flow leads to the development of portal hypertension. Collateral vessels develop at the communication site between the systemic and portal circulation with the progression of portal hypertension. Varices are the representative collaterals, develop gradually with the progression of portal hypertension and may eventually rupture. Variceal bleeding is a major consequence of portal hypertension and causes the death of cirrhotic patients. The present paper reviews the latest knowledge regarding the diagnosis and management of esophageal and gastric variceal bleeding.

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Antibiotic prophylaxis is effective but can lead to an increased incidence of Clostridioides difficile infection (CDI). The aim of this study was to evaluate the incidence of CDI and the risk factors in cirrhotic patients with a previous episode of SBP receiving norfloxacin as secondary prophylaxis. Materials and Methods: We performed a prospective, cohort study including patients with liver cirrhosis and SBP, successfully treated over a 2-year period in a tertiary university hospital. All the patients received secondary prophylaxis for SBP with norfloxacin 400 mg/day. Results: There were 122 patients with liver cirrhosis and SBP included (mean age 57.5 ± 10.8 years, 65.5% males). Alcoholic cirrhosis was the major etiology accounting for 63.1% of cases. The mean MELD score was 19.7 ± 6.1. Twenty-three (18.8%) of all patients developed CDI during follow-up, corresponding to an incidence of 24.8 cases per 10,000 person-years. The multivariate Cox regression analysis demonstrated that alcoholic LC etiology (HR 1.40, 95% CI 1.104-2.441, p = 0.029) and Child-Pugh C class (HR 2.50, 95% CI 1.257-3.850, p = 0.034) were independent risk factors for CDI development during norfloxacin secondary prophylaxis. The development of CDI did not influence the mortality rates in cirrhotic patients with SBP receiving norfloxacin. Conclusions: Cirrhotic patients with SBP and Child-Pugh C class and alcoholic liver cirrhosis had a higher risk of developing Clostridioides difficile infection during norfloxacin secondary prophylaxis. In patients with alcoholic Child-Pugh C class liver cirrhosis, alternative prophylaxis should be evaluated as SBP secondary prophylaxis.

Patients with cirrhosis show an increased susceptibility to infection due to disease-related immune-dysfunction. Bacterial infection therefore represents a common, often detrimental event in patients with advanced liver disease, since it can worsen portal hypertension and impair the function of hepatic and extra-hepatic organs. Among pharmacological strategies to prevent infection, antibiotic prophylaxis remains the first-choice, especially in high-risk groups, such as patients with acute variceal bleeding, low ascitic fluid proteins, and prior episodes of spontaneous bacterial peritonitis. Nevertheless, antibiotic prophylaxis has to deal with the changing bacterial epidemiology in cirrhosis, with increased rates of gram-positive bacteria and multidrug resistant rods, warnings about quinolones-related side effects, and low prescription adherence. Short-term antibiotic prophylaxis is applied in many other settings during hospitalization, such as before interventional or surgical procedures, but often without knowledge of local bacterial epidemiology and without strict adherence to antimicrobial stewardship. This paper offers a detailed overview on the application of antibiotic prophylaxis in cirrhosis, according to the current evidence.

Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis.

A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.

A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9).

Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Patients with cirrhosis are susceptible to develop infections because of immune dysfunction, changes in microbiome and increase in bacterial translocation from the gut to systemic circulation. Bacterial infections can worse the clinical course of the disease, triggering the development of complications such as acute kidney injury, hepatic encephalopathy, organ failures and acute on chronic liver failure. In recent years, the spread of multi drug resistant bacteria made more challenging the management of infections in patients with cirrhosis. Hence, the mortality rate associated to sepsis is increasing in these patients. Therefore, the optimization of the management of infections has a high priority in cirrhosis. Herein we reviewed the recent changes in the epidemiology and the management of bacterial infections in patients with liver cirrhosis.