Infections increase the risk of decompensation and death in patients with early alcohol-related liver disease
Stine Johansen,
Simon Langkjær,
Ditlev Nytoft Rasmussen,
Mads Israelsen,
Nikolaj Torp,
Katrine Lindvig,
Maria Kjærgaard,
Johanne Kragh Hansen,
Camilla Dalby Hansen,
Katrine Thorhauge,
Peter Andersen,
Sönke Detlefsen,
Helene Bæk Juel,
Ulrik Stenz Justesen,
Torben Hansen,
Aleksander Krag,
Maja Thiele,
Ema Anastasiadou,
Manimozhian Arumugam,
Peer Bork,
Torben Hansen,
Jenny Presto,
Hans Israelsen,
Morten Karsdal,
Cristina Legido-Quigley,
Hans Olav Melberg,
Maja Thiele,
Jonel Trebicka,
Aleksander Krag,
Peer Bork,
Mathias Mann,
Jelle Matthijnssens,
Aleksander Krag,
Torben Hansen
Affiliations
Stine Johansen
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Simon Langkjær
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Ditlev Nytoft Rasmussen
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Mads Israelsen
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Nikolaj Torp
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Katrine Lindvig
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Maria Kjærgaard
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Johanne Kragh Hansen
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Camilla Dalby Hansen
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Katrine Thorhauge
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Peter Andersen
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
Sönke Detlefsen
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark
Helene Bæk Juel
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark
Ulrik Stenz Justesen
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
Torben Hansen
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark
Aleksander Krag
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Corresponding author. Address: Center for Liver Research, Kloevervaenget 10, entrance 112, 11th floor, Odense University Hospital, Denmark
Maja Thiele
Fibrosis, fatty liver and steatohepatitis research center Odense (FLASH), Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Background & Aims: Infections are frequent in patients with cirrhosis and worsen prognosis. We evaluated the incidence of infections and their impact on decompensation and death in patients with early alcohol-related liver disease (ALD) during long-term follow-up. Methods: We performed a prospective cohort study of patients in secondary care with a history of excess alcohol intake, no prior decompensation, and with liver biopsies along with clinical investigations conducted at baseline. During follow-up, we reviewed the patients’ electronic healthcare records for cases of infections, hospitalizations, transient elastography measurements, decompensations, all-cause mortality, and alcohol intake. Results: We included 461 patients with a mean age of 56±10 years (76% males; fibrosis stage F0-1/F2/F3-4 = 259/107/93 [56%/23%/20%]). During a median follow-up of 4.5 years (IQR 2.9-6.3), 134 patients (29%) developed a total of 312 infections, most frequently pneumonia (106/312, 34%) and urinary tract infections (57/312, 18%). Excessive alcohol intake during follow-up, smoking ≥30 pack years, MELD score and elevated liver stiffness during follow-up were independent predictors of infections. Patients who developed at least one infection had a significantly increased risk of subsequent decompensation (hazard ratio 4.98, 95% CI 2.47-10.03) and death (hazard ratio 8.24, 95% CI 4.65-14.59). Infections increased the risk of decompensation and death independently of baseline fibrosis stage, age, gender, and MELD score. Conclusions: Almost one-third of patients with early ALD develop an infection, which worsens their prognosis by increasing the risk of decompensation and death. The risk of infections increases with liver disease severity and ongoing harmful use of alcohol. Impact and implications: This study reveals that infections significantly worsen the prognosis of patients with early alcohol-related liver disease (ALD), increasing the likelihood of decompensation and death by up to eight times. These findings, pertinent to healthcare providers, researchers, and policymakers, emphasize the importance of early prevention and management of infections in patients with ALD, even those in early stages who may be asymptomatic. It was observed that nearly one-third of patients with early-stage ALD developed infections over 4.5 years, with risk factors including alcohol overuse, smoking, and higher MELD scores. The research underscores the critical need to incorporate these insights into clinical practice and public health policies to improve patient outcomes and mitigate the impact of infections in patients with ALD.