Risk of infections and their role on subsequent mortality in biopsy‐proven alcohol‐related liver disease

Abstract

Background and Aims The risk for infection in alcohol‐related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital‐based infections in a nationwide cohort of biopsy‐proven ALD, and the subsequent risk of death. Methods Population‐based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals. Results Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person‐years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85–3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36–3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89–4.78) were linked to subsequent death. Conclusions Individuals with biopsy‐proven ALD have a three‐fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.

The Liverpool alcohol‐related liver disease algorithm identifies twice as many emergency admissions compared to standard methods when applied to Hospital Episode Statistics for England

“… 14 Several studies have combined this with the Swedish histopathology cohort to demonstrate higher rates of infections, mortality and cancer compared to matched controls after a biopsy‐proven diagnosis of ArLD. 15 , 16 , 17 However, these data do not document hospital admissions and only report the subset of patients with biopsy‐proven disease. Furthermore, the use of the K70 ICD‐10 codes as the primary diagnosis only may miss those with alternative coding patterns.…”

“…Sweden's National Patient Register has a 91% positive predictive value for the ICD‐10 code ‘K703: alcoholic cirrhosis of the liver’ when coded as an inpatient 14 . Several studies have combined this with the Swedish histopathology cohort to demonstrate higher rates of infections, mortality and cancer compared to matched controls after a biopsy‐proven diagnosis of ArLD 15–17 . However, these data do not document hospital admissions and only report the subset of patients with biopsy‐proven disease.…”

Global prevalence, incidence, and outcomes of alcohol related liver diseases: a systematic review and meta-analysis

“…ARLD caused by long-term heavy drinking included the whole disease spectrum from liver steatosis to liver cirrhosis and even liver cancer [ 237 ]. The constituent ratio of alcoholic cirrhosis in ARLD population was the highest, up to 32.9% (95% CI: 27.3–38.7) (Table 2 ) got from 147 articles [ 16 , 19 , 25 – 27 , 31 , 36 , 46 , 64 , 66 , 80 , 81 , 84 , 86 , 91 , 92 , 98 , 100 – 102 , 111 , 113 , 117 , 119 , 121 – 124 , 145 , 148 , 149 , 152 , 153 , 157 , 159 – 162 , 165 , 170 , 173 – 176 , 187 , 193 , 194 , 197 , 199 , 208 , 219 , 221 – 223 , 225 , 227 , 229 – 234 , 236 , 238 – 321 ]. A total of 121 datasets [ 25 , 26 , 30 , 43 , 47 , 113 , 115 , 116 , 122 , 125 , 126 ...…”

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

“…A recent registry-based Swedish study investigated the risk of infections in patients who underwent liver biopsy and had an ICD-code of ALD compared to matched controls from the general population. 5 In that study, patients with ALD had a 3-fold higher risk of infections, and patients with alcohol-related liver fibrosis, but not cirrhosis, still had a 2-fold higher risk of infections. While the study included patients from the entire spectrum of liver disease, nearly 60% of patients had cirrhosis and 30% were decompensated prior to inclusion.…”