Infections increase the risk of decompensation and death in patients with early alcohol-related liver disease

Abstract

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.

Keywords: Alcoholic liver disease; Cirrhosis; Decompensation; Fibrosis; Prognosis.

Graphical abstract

Fig. 1

Cumulative incidence of infections and severe infections. (A) Cumulative incidence of infections. (B) Cumulative incidence of severe infections.

Fig. 2

Risk of death and decompensation in patients developing infections. (A) Risk of death in patients developing infections (Simon & Makuch plot). (B) Risk of decompensation in patients developing infections (Simon & Makuch plot). Between-group comparisons for survival data with a time-dependent covariate was performed using the Mantel-Byar test.

Fig. 3

Cumulative incidence of infections. (A) Cumulative incidence of infections stratified by Kleiner fibrosis stage. (B) Cumulative incidence of infections stratified by liver stiffness; The cumulative incidence plot is based on 447 patients as liver stiffness measurements are missing in 14 patients. (C) Cumulative incidence of infections stratified by excessive alcohol use during follow-up; The cumulative incidence plot is based on 403 patients as data on alcohol intake was not available in 58 patients.