Bacterial infections in acute-on-chronic liver failure: Epidemiology, diagnosis, pathogenesis, and management

Acute-on-chronic liver failure (ACLF) is a critical and often fatal syndrome characterized by a sudden exacerbation of chronic liver disease, leading to multi-organ failure and high short-term mortality. Among the various triggers for ACLF, bacterial infections (BIs) stand out as one of the most frequent and severe, significantly influencing the clinical course and prognosis of the disease. This review provides an updated analysis of the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF, emphasizing their role in the progression and outcome of this complex condition.

Epidemiology

The prevalence of bacterial infections in ACLF patients is notably high, ranging from 55.7% to 81.2%, with substantial variations across different regions and patient populations. Notably, infections tend to increase with the severity of ACLF, with higher prevalence in patients with advanced stages of the syndrome. The review highlights the global variation in infection types, with spontaneous bacterial peritonitis (SBP) being most common in Asia, while urinary tract infections (UTIs) are more prevalent in Europe and America. The review also notes the rising incidence of multidrug-resistant (MDR) bacteria, particularly in the Indian subcontinent, where the prevalence of MDR strains is alarmingly high.

Microbiology

The microbiological profile of BIs in ACLF patients varies significantly by region and time. Gram-negative bacteria remain the dominant pathogens globally, although gram-positive bacteria are more prevalent in certain regions like North America. The review discusses the increasing prevalence of MDR and extensively drug-resistant (XDR) bacteria, such as ESBL-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), which pose significant challenges to effective treatment. The review emphasizes the importance of local epidemiological knowledge in guiding appropriate antibiotic use.

Impact of Bacterial Infections on ACLF Outcome

Bacterial infections in ACLF are associated with significantly worse outcomes, including higher mortality rates. The review underscores the role of specific infections, such as SBP and bacteremia, in increasing the severity of ACLF and leading to poorer survival rates. Infections caused by MDR bacteria are particularly concerning, as they are more likely to contribute to the development of ACLF and are associated with higher rates of septic shock and mortality.

Diagnosis

Diagnosing bacterial infections in ACLF patients remains challenging due to the complexities of distinguishing between colonization and true infection, particularly in respiratory infections. The review highlights the need for new diagnostic biomarkers and technologies to improve the accuracy and speed of BI diagnosis in ACLF. Promising developments include the use of ascitic fluid lactoferrin and calprotectin for diagnosing SBP and advanced molecular techniques such as droplet digital PCR for detecting bacterial DNA.

Pathogenesis

The review delves into the pathogenesis of BIs in ACLF, exploring how systemic inflammation and compensatory anti-inflammatory responses contribute to increased susceptibility to infections. The overactivation of the innate immune system, coupled with the suppression of the adaptive immune system, leads to a paradoxical state where ACLF patients, despite heightened inflammation, are more prone to infections. The review also discusses the role of pathogen-associated molecular patterns (PAMPs) in triggering excessive inflammatory responses, leading to organ failure and exacerbating ACLF.

Prophylaxis

The review discusses both antibiotic and non-antibiotic prophylactic strategies for preventing BIs in ACLF patients. While antibiotics like norfloxacin and rifaximin are effective in reducing the incidence of BIs, their use is complicated by the emergence of MDR bacteria. Non-antibiotic approaches, such as albumin infusion and non-selective beta-blockers, also show promise in reducing the risk of infections, although their efficacy needs further validation.

Treatment

Prompt and appropriate antibiotic therapy is critical in managing BIs in ACLF patients. The review emphasizes the importance of tailoring antibiotic treatment based on local microbiological data and the clinical setting, with a focus on early de-escalation to prevent the development of antibiotic resistance. Specific treatment recommendations are provided for managing SBP and non-SBP infections, including the use of broad-spectrum antibiotics and adjunctive therapies like albumin infusion.

Conclusions

Bacterial infections are a significant threat to ACLF patients, impacting both the onset and progression of the disease. The review highlights the need for continued research into the pathogenesis, diagnosis, and treatment of BIs in ACLF, particularly in the face of rising MDR bacteria. New therapeutic strategies, including immunomodulatory agents and novel antibiotics, are urgently needed to improve outcomes for ACLF patients.

Full text

https://www.xiahepublishing.com/2310-8819/JCTH-2024-00137

The study was recently published in the Journal of Clinical and Translational Hepatology.

The Journal of Clinical and Translational Hepatology (JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study’s novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.

Follow us on X: @xiahepublishing

Follow us on LinkedIn: Xia & He Publishing Inc.