On September 4, Dr. Qing Xie's team from Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, published a research paper titled Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium in The Lancet Gastroenterology & Hepatology. Dr. Qing Xie and Dr. Jasmohan S. Bajaj from Virginia Commonwealth University served as co-corresponding authors, while the first author was Zhujun Cao, an attending physician and researcher at Ruijin Hospital's Infectious Diseases Department.Infection is the most common non-liver-related cause of hospitalization in cirrhosis patients. The global burden of infections and antimicrobial resistance is increasing, with significant regional differences in infection prevention, control, access to antibiotics, and resistance patterns. To address this, Qing Xie and Zhujun Cao led a research team in China, collaborating with the CLEARED research alliance to conduct the CLEARED-Infection study. This study provides critical insights into the global and regional burden and characteristics of infections in cirrhosis patients, offering scientific data for shaping effective management strategies.
The study analyzed 4,238 hospitalized cirrhosis patients from 98 centers across 26 countries or regions. Results showed that 32% of patients in the global cirrhosis cohort were diagnosed with an infection upon admission or within 48 hours of hospitalization. The most common infections were spontaneous bacterial peritonitis, respiratory infections, and urinary tract infections. Only 40.6% of infected patients had microbiologically confirmed pathogens, with Gram-negative bacteria being the most common, followed by Gram-positive bacteria and fungi. The top three pathogens were Escherichia coli, Klebsiella pneumoniae, and Enterococcus species.
The overall antibiotic resistance rate among patients with positive cultures was 40%. Broad-spectrum antibiotics, such as beta-lactams combined with beta-lactamase inhibitors and carbapenems, were frequently used empirically. Alarmingly, 75.5% of empirical antibiotic treatments were not adjusted afterward, with “de-escalation therapy” only accounting for 20% of antibiotic adjustments.
In terms of outcomes, patients with infections upon admission had higher rates of in-hospital mortality or referrals to palliative care. After adjusting for demographic factors, economic classification of countries or regions, and cirrhosis severity, infections increased the risk of in-hospital mortality or palliative care referral by 1.75 times.
There were significant regional differences in infection prevalence, types, pathogen detection rates, resistance rates, and empirical antibiotic usage and adjustments. Low- and lower-middle-income countries had higher infection rates compared to upper-middle- and high-income countries. Patients in higher-income countries had higher rates of resistant bacteria detection, more frequent use of broad-spectrum antibiotics, higher rates of pathogen detection, and more Gram-positive infections, with the lowest mortality risks.
This large-scale, prospective global cohort study highlights the high burden of infections and mortality among hospitalized cirrhosis patients, particularly in low- and lower-middle-income countries. There are significant regional differences in pathogen detection rates, resistance, and treatment patterns, which result in delays in adjusting empirical antibiotic therapy and lower de-escalation rates, contributing to further resistance. The findings underscore the need for global strategies to address regional differences in infection diagnosis and antibiotic use, especially in resource-limited settings, to reduce disease burden and regional disparities.
The journal included a commentary praising the study: “The findings of this study have important implications for various healthcare stakeholders. Policymakers can use these data to allocate resources more effectively, including funding advanced diagnostic laboratories, implementing infection control policies, and strengthening public health strategies. Healthcare providers should follow guidelines tailored to regional infection types and resistance patterns to optimize antibiotic use. Researchers can prioritize studies on multidrug resistance, develop rapid diagnostic tools, and create personalized therapeutic interventions.”
About Cirrhosis and the CLEARED Consortium
Cirrhosis ranks as the 11th leading cause of death globally, becoming an increasingly significant public health issue. However, the relationship between cirrhosis and its clinical characteristics, management, and prognosis varies across regions, especially between different income levels. In 2021, Qing Xie, along with Jasmohan S. Bajaj and Ashok Choudhury from the Institute of Liver and Biliary Sciences, India, and other global experts in cirrhosis, formed the Academic Committee for Research on Disease Progression in Hospitalized Patients with Chronic Liver Disease. This led to the creation of the global CLEARED research consortium, comprising nearly 100 centers in over 20 countries, covering six continents and ten key regions (the US and Canada, Mexico, South America, Europe, Africa, Australia, Turkey, mainland China, India, and other parts of Asia). Qing Xie serves as the leading PI in mainland China, overseeing 24 centers involved in the research.
The CLEARED consortium analyzes global data on hospitalized cirrhosis patients, revealing significant differences in clinical characteristics, management, and disease outcomes between regions with varying levels of economic development. This includes disparities in infection complications, microbiological diagnosis, drug therapy, intensive care, palliative care, and access to liver transplantation, all of which significantly impact clinical outcomes in cirrhosis patients (as reported in The Lancet Gastroenterology & Hepatology, 2023 and 2024)
