Study Of Bacterial/Fungal Infections in Hospitalized Patients With Liver Cirrhosis in China

Study Overview
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Brief Summary
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This is a national, investigator-initiated, multicenter, prospective, observational, web-based registry in hospitalized patients with cirrhosis across China. The overarching aim of this study is to investigate the epidemiology and clinical impact of bacterial/fungal infections in hospitalized patients with liver cirrhosis in China within the collaborative network. We also aimed to build up the national prospective cohort of hospitalized cirrhosis in China to stand in the future for the backbone of various research programs focused on infection, other complications of cirrhosis, organ failure, the ACLF syndrome, end-stage liver disease and beyond.

Detailed Description
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Patients with cirrhosis are prone to infections due to the abnormal bacterial translocation and immune dysfunction. Infections are more common when these patients are admitted into the hospital. Infections are life-threatening complications of cirrhosis which can precipitate hepatic encephalopathy, acute kidney injury, and the acute-on-chronic liver failure (ACLF) syndrome. The survival rate is significantly decreased once infections set in, especially when the first-line empirical antibiotic therapy is insufficient or inappropriate. Moreover, the prevalence of multi-drug-resistant organism (MDRO) is naturally increasing across the world due to the overuse of antibiotics. Patients with cirrhosis, especially those at the decompensated stage are at high risk of developing MDRO due to recurrent hospitalizations and repeatedly exposed to antibiotics either for treatment or prophylactic purposes. Empiric antibiotic therapy could be very difficult without understanding the profile of antibiotic resistance and could be varied significantly among different areas. The issue of infection in patients with cirrhosis has been recently highlighted by International Club of Ascites with its GLOBAL study (ILC2018, GS-001) showing that the global prevalence of MDRO across the world was 34% (95% CI=31-37%). The prevalence of MDRO varies across the world with the highest in India followed by South America and other Asian countries. The source of acquisition (Community acquire, health-care related or nosocomial origin), site of infection (Spontaneous bacterial peritonitis, urinary tract, blood, respiratory tract, etc.) and category of the organism (Gram negative or positive) had an influence on the prevalence of MDRO and response to empirical antibiotic treatment. The results highlight the need to develop different empirical antibiotic strategies across different continents and countries, although China was not included in this study. Epidemiology data and investigation on the role of bacterial/fungal infection in patients with cirrhosis from China is therefore urgently needed. The overarching aim of this study is to investigate the epidemiology and clinical impact of bacterial/fungal infections in hospitalized patients with liver cirrhosis in China within the collaborative network. We also aimed to build up the national prospective cohort of hospitalized cirrhosis in China to stand in the future for the backbone of various research programs focused on infection, other complications of cirrhosis, organ failure, the ACLF syndrome, end-stage liver disease and beyond.

Official Title
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Prospective, Non-interventional, Multicenter Observational Study of Bacterial/Fungal Infections in Hospitalized Patients With Liver Cirrhosis in China

Conditions
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Cirrhosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inpatient with cirrhosis as confirmed either by the histological scoring system, imaging technique (abdominal Ultrasound, CT or MRI), endoscopic findings or a combination of biochemical and clinical manifestation. Admitted for at least one of the following reasons: Bacterial infection/fungal infection Overt Ascites (Grade II-III) Gastrointestinal bleeding Hepatic encephalopathy Jaundice (Total bilirubin ≥5 mg/dL) with coagulation dysfunction (INR ≥1.5) Exclusion Criteria: 1. Age below 16 or over 80 years 2. Lactation/ Pregnancy women 3. HIV infection 4. Admitted for scheduled procedures (e.g., band ligation, splenectomy, transjugular intrahepatic portosystemic shunting, liver biopsy) or re-examination or multidisciplinary consultation) 5. Hepatocellular carcinoma (HCC) outside Milan criteria or other disseminated malignancies 6. Previous liver transplantation 7. With previously known severe extra-hepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe heart disease; severe chronic pulmonary disease, psychiatric disorders) 8. Taking immunosuppressive or anticoagulation drugs for the treatment of extra-hepatic disease. 9. Patient' s refusal to participation 10. Failure to provide prior informed consent or with documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infection<br>Patients admitted or developed bacterial/fungal infection while hospitalization | |
| Non-infection<br>Patients without bacterial/fungal infection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day transplantation-free Survival | Survival at 28-day follow-up without liver transplantation | From admission to 28-day post-admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristics of bacterial/fungal infection including the prevalence of infection, the source of acquisition, type of infection, multidrug resistance rate, antibiotic treatment efficiency and efficacy in relation to disease course and outcome | Characteristics of bacterial/fungal infection including the prevalence of infection, the source of acquisition, type of infection, multidrug resistance rate, antibiotic treatment efficiency and efficacy in relation to disease course and outcome | From admission to discharge, an average of 28-day | 
| Association between bacterial/fungal infection between other complications of cirrhosis、organ failure、AKI or ACLF. | Association between bacterial/fungal infection between other complications of cirrhosis、organ failure、AKI or ACLF. | From admission to discharge, an average of 28-day | 
| Difference in type of organ failure between bacterial/fungal infection and other precipitating events. | Difference in type of organ failure between bacterial/fungal infection and other precipitating events. | From admission to discharge, an average of 28-day | 
| ACLF and each sub-type organ failure development at 28-day | ACLF defined as per EASL CLIF-C or NACSELD definition Organ failure defined as per CLIF-C OF criteria, including Liver, coagulation, kidney, brain, respiratory and circulatory. | From admission to discharge, an average of 28-day | 
| Transplantation-free Survival at 90-day | Survival at 90-day follow-up without liver transplantation | From admission to 90 day post-admission | 
| Overall survival at 28-、90-day | Overall survival at 28-、90-day | From admission to 90 day post-admission | 
| Readmission and further decompensations rate at 90-day post discharge | Readmission and further decompensations rate at 90-day post discharge | From admission to 90 day post-discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial infection, Fungal infection, Cirrhosis, Multi-drug resistance, Antibiotic treatment, Clinical outcome, Organ failure, Acute-on-chronic liver failure, Decompensated cirrhosis, Complications of cirrhosis, Acute kidney injury