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Type of Infection Is Associated with Prognosis in Acute-on-Chronic Liver Failure: A National Veterans Health Administration Study

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Abstract

Background

Acute-on-chronic liver failure (ACLF) is a syndrome in patients with cirrhosis with high short-term mortality. Infection is a frequent precipitant of ACLF; however, it is unclear if prognosis varies by difference infectious sources. To address this knowledge gap, we utilized a large national database of patients with cirrhosis.

Methods

This was a retrospective cohort study of patients with cirrhosis in the Veterans Health Administration between 2008 and 2016. First ACLF hospitalizations were identified and infections were classified using validated algorithms, categorized as bacteremia, fungal, spontaneous bacterial peritonitis (SBP), pyelonephritis/urinary tract infection, or skin and soft tissue/musculoskeletal infection (SST/MSK). Inverse probability treatment weighing for infection-associated ACLF followed by multivariable logistic regression was used to evaluate the association between infection type and 90-day mortality.

Results

A total 22,589 ACLF hospitalizations were included, 3998 (17.7%) of which had ACLF grade 3. Infection was associated with 12,405 (54.9%) of ACLF hospitalizations. In regression models, SBP was associated with a 1.79-fold increased odds of 90-day mortality vs. no infection (95% confidence interval [CI] 1.58–2.02, p < 0.001), whereas SST/MSK infections had a lower relative odds of mortality (odds ratio 0.48, 95% CI 0.42–0.53, p < 0.001). There was a significant interaction between infection category and ACLF grade on the outcome of 90-day mortality (p < 0.001).

Conclusions

The impact of infection on short-term mortality in ACLF varies depending on the source of infection. This has relevance for ACLF prognostication and challenges previous notions that bacterial infection invariably worsens prognosis among all patients with ACLF.

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Abbreviations

ACLF:

Acute–on-chronic liver failure

AD:

Acute decompensation

ALD:

Alcohol-related liver disease

BMI:

Body mass index

CI:

Confidence interval

EASL:

European Association for the Study of the Liver

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

INR:

International normalized ratio

IPTW:

Inverse probability treatment weighting

IQR:

Interquartile range

MELD:

Model for end-stage liver disease

MELD-Na:

Model for end-stage liver disease-sodium

NAFLD:

Nonalcoholic fatty liver disease

OF:

Organ failure

OR:

Odds ratio

PNA:

Pneumonia

PS:

Propensity score

SBP:

Spontaneous bacterial peritonitis

SIRS:

Systemic inflammatory response syndrome

SST/MSK:

Skin and soft tissue infection/musculoskeletal infection

TIPS:

Transjugular intrahepatic portosystemic shunt

UTI:

Urinary tract infection

VHA:

Veterans Health Administration

VOCAL:

Veterans Outcomes and Costs Associated with Liver Disease

WBC:

White blood cell

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Funding

Nadim Mahmud is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (Grant No. K08-DK124577). David E. Kaplan has received support from Gilead, Glycotest and Bayer unrelated to the topic of this manuscript. He is also supported by VA Merit Grants (Grant Nos. I01-CX-001933, I01-CX-002010).

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nadim Mahmud, K. Rajender Reddy & David E. Kaplan

  2. Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA

    Nadim Mahmud & David E. Kaplan

  3. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nadim Mahmud

  4. Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Nadim Mahmud

  5. Division of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA

    Tamar H. Taddei

  6. VA Connecticut Healthcare System, West Haven, CT, USA

    Tamar H. Taddei

Authors
  1. Nadim Mahmud
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  2. K. Rajender Reddy
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  3. Tamar H. Taddei
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  4. David E. Kaplan
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Correspondence to Nadim Mahmud.

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Mahmud, N., Reddy, K.R., Taddei, T.H. et al. Type of Infection Is Associated with Prognosis in Acute-on-Chronic Liver Failure: A National Veterans Health Administration Study. Dig Dis Sci 68, 1632–1640 (2023). https://doi.org/10.1007/s10620-022-07680-9

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