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

• Conditions: Cirrhosis

• Registration Number: NCT03676777
• Lead Sponsor: Ruijin Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-09-17
• Study First Submitted QC: 2018-09-17
• Study First Posted: 2018-09-19
• Study Start: 2018-11-07
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-17
• Last Update Posted: 2019-11-19
• Primary Completion: 2019-12
• Study Completion: 2020-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1232

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:

  1. Bacterial infection/fungal infection
  2. Overt Ascites (Grade II-III)
  3. Gastrointestinal bleeding
  4. Hepatic encephalopathy
  5. 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
28-day transplantation-free Survival	From admission to 28-day post-admission	Survival at 28-day follow-up without liver transplantation

Secondary Outcome Measures

Name	Time	Method
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	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
Difference in type of organ failure between bacterial/fungal infection and other precipitating events.	From admission to discharge, an average of 28-day	Difference in type of organ failure between bacterial/fungal infection and other precipitating events.
Overall survival at 28-、90-day	From admission to 90 day post-admission	Overall survival at 28-、90-day
Readmission and further decompensations rate at 90-day post discharge	From admission to 90 day post-discharge	Readmission and further decompensations rate at 90-day post discharge
Association between bacterial/fungal infection between other complications of cirrhosis、organ failure、AKI or ACLF.	From admission to discharge, an average of 28-day	Association between bacterial/fungal infection between other complications of cirrhosis、organ failure、AKI or ACLF.
ACLF and each sub-type organ failure development at 28-day	From admission to discharge, an average of 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.
Transplantation-free Survival at 90-day	From admission to 90 day post-admission	Survival at 90-day follow-up without liver transplantation

Trial Locations

Locations (23)

Second Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

First Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

Xiamen Hospital of Traditional Chinese Medicine; 🇨🇳 Xiamen, Fujian, China

Ningbo no.2 Hospital; 🇨🇳 Ningbo, Zhejiang, China

Department of Infectious Disease, The First Hospital of Lanzhou University; 🇨🇳 Lanzhou, Gansu, China

Department of Critical Care Medicine of Liver Disease, Beijing You'an Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Department of severe Liver Diseases, Fuzhou Municipal Infectious Disease Hospital, Mengchao Hepatobiliary Hospital of Fujian Medical University,; 🇨🇳 Fuzhou, Fujian, China

The First People's Hospital of Lanzhou City; 🇨🇳 Lanzhou, Gansu, China

The Third People's Hospital of Guilin; 🇨🇳 Guilin, Guangxi, China

Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University; 🇨🇳 Shijiazhuang, Hebei, China

Department of Liver Diseases, The Third People's Hospital of Changzhou; 🇨🇳 Changzhou, Jiangsu, China

Department of Infectious Disease, The First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China

Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine; 🇨🇳 Shanghai, Shanghai, China

Department of Infectious Diseases, the Fifth People's Hospital of Suzhou; 🇨🇳 Suzhou, Jiangsu, China

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

The Fifth People's Hospital of Wuxi, Affiliated to Jiangnan University; 🇨🇳 Wuxi, Jiangsu, China

Shengjing Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

Department of Infectious Diseases , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China

Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University.; 🇨🇳 Xi'an, Shanxi, China

The first Hospital of Jiaxing; 🇨🇳 Jiaxing, Zhejiang, China

First Affiliated Hospital, Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China

Department of Infectious Diseases, Zhejiang Provincial People's Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Department of Hepatology and Infection, Tongren Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China