MASLD Associated with Greater Risk of Serious Bacterial Infection Requiring Hospitalization

Giovanni Targher, MD

Credit: ResearchGate

New research is calling attention to a significant association between metabolic dysfunction-associated steatotic liver disease (MASLD) and increased risk of serious bacterial infections requiring in-hospital or emergency department care.¹

The meta-analysis included aggregate data on more than 26 million adults from 8 observational studies, with results suggesting the importance of clinician vigilance regarding infection in their patients with MASLD and the need for preventive measures in this patient population.¹

A growing body of epidemiological evidence suggests MASLD is linked to complications extending beyond the liver, including extrahepatic cancers, new-onset type 2 diabetes, cardiovascular events, and adverse renal outcomes.²

“Among the least investigated MASLD-related extrahepatic complications, an ever-increasing number of observational cross-sectional and prospective studies have assessed the association between MASLD and the risk of severe bacterial infections, such as pneumonia, meningitis, sepsis, gastrointestinal/abdominal infections or other bacterial infections requiring hospital admission,” Giovanni Targher, MD, a full professor of endocrinology and diabetes at the University of Verona in Italy, and colleagues wrote.¹ “However, the magnitude of this risk and whether the risk varies with the severity of MASLD remain uncertain.”

To determine the association between MASLD and serious bacterial infections requiring hospital admission, investigators conducted a systematic review and meta-analysis of relevant observational studies. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis Of Observational Studies in Epidemiology (MOSE) guidelines and included a search of PubMed, Scopus, Web of Science, and Embase from database inception until April 1, 2024, using predefined keywords to identify studies examining the risk of serious bacterial infections among individuals with and without MASLD.

Studies were required to meet the following inclusion criteria:

• Observational studies examining the risk of serious bacterial infections requiring hospital admission among adult patients with and without MASLD
• Studies that reported odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (CI) values for the outcome of interest
• The diagnosis of MASLD was based on liver biopsy, imaging techniques, blood-based biomarkers/scores, or International Classification of Diseases (ICD) codes, in the absence of significant alcohol consumption (usually defined as <20 g/day for women and <30 g/day for men) or other competing causes of hepatic steatosis
• The diagnosis of serious bacterial infections, such as pneumonia, meningitis, sepsis, gastrointestinal/abdominal infections, or other severe bacterial infections requiring hospital admission was based on hospital charts, electronic medical records, or ICD-9/ICD-10 codes

The primary outcome measure of the meta-analysis was the presence of serious bacterial infections requiring hospital admission for cross-sectional studies or the risk of developing incident serious bacterial infections requiring hospital admission over the follow-up for longitudinal studies.

Investigators identified 8 unique observational studies for inclusion in the meta-analysis, including 6 cross-sectional and 2 prospective cohort studies with aggregate data on approximately 26.6 million individuals. The 6 cross-sectional hospital-based studies included 26,434,377 individuals, 43.6% of whom were male with a mean age of 60 years, who were hospitalized for serious bacterial infections. The 2 eligible prospective cohort studies included 221,663 individuals, 52% of whom were male with a mean age of 55 years, who were followed for a median period of 14.1 and 5.3 years, respectively.

Upon analysis of the cross-sectional studies, MASLD was significantly associated with increased odds of serious bacterial infections (pooled random-effects OR, 1.93; 95% CI, 1.44–2.58; I2 = 93%). Additional meta-analysis of the prospective cohort studies again showed MASLD was associated with an increased risk of developing serious bacterial infections (pooled random-effects HR, 1.80; 95% CI, 1.62–2.0; I2 = 89%), with risk increasing as the severity of MASLD and fibrosis increased (pooled random-effects HR, 2.42; 95% CI, 1.89–2.29; I2 = 92%).

Of note, these results remained significant after adjusting for age; sex; obesity; diabetes; and other potential confounders. Investigators pointed out sensitivity analyses did not modify these findings, and the funnel plot did not reveal any significant publication bias (P = .336).

Investigators outlined multiple limitations to these findings, some of which included the inability to establish a causal association between MASLD and serious bacterial infections requiring hospital admission due to the design of the included studies; the possibility of residual confounding by unmeasured factors; and the medium-high heterogeneity for the pooled primary analysis of cross-sectional studies and the moderate overall quality of the studies.

“This comprehensive meta-analysis provides evidence of a significant association between MASLD and an increased risk of serious bacterial infections requiring hospital admission (such as pneumonia, meningitis, urinary tract infections, gastrointestinal/abdominal infections or sepsis),” investigators concluded.¹ “Future well-designed large prospective cohort studies from different countries (including Asian populations and low-income countries) are needed to further corroborate these results, and mechanistic studies are also required to better decipher the complex molecular pathways linking MASLD with increased susceptibility to developing serious bacterial infections requiring hospital admission.”

References

1. ^{Mantovani A, Morandin R, Fiorio V, et al. Association between MASLD and increased risk of serious bacterial infections requiring hospital admission: A meta-analysis. Liver International. https://doi.org/10.1111/liv.16101}
2. ^{Tomeno W, Imajo K, Takayanagi T, et al. Complications of Non-Alcoholic Fatty Liver Disease in Extrahepatic Organs. Diagnostics (Basel). 2020;10(11):912. Published 2020 Nov 7. doi:10.3390/diagnostics10110912}