Effectiveness of influenza vaccines in adults with chronic liver disease: a systematic review and meta-analysis

Abstract

Objectives: Patients with liver disease frequently require hospitalisation with infection often the trigger. Influenza vaccination is an effective infection prevention strategy in healthy and elderly but is often perceived less beneficial in patients with liver disease. We investigated whether influenza vaccination triggered serological response and prevented hospitalisation and death in liver disease.

Design: Systematic review and meta-analysis.

Data sources: MEDLINE, EMBASE, PubMed and CENTRAL up to January 2019.

Eligibility criteria: Randomised or observational studies of the effects of influenza vaccine in adults with liver disease.

Data extraction and synthesis: Two reviewers screened studies, extracted data and assessed risk of bias and quality of evidence. Primary outcomes were all-cause hospitalisation and mortality. Secondary outcomes were cause-specific hospitalisation and mortality, and serological vaccine response. Random-effects meta-analysis was used to estimate pooled effects of vaccination.

Results: We found 10 041 unique records, 286 were eligible for full-text review and 12 were included. Most patients had viral liver disease. All studies were of very low quality. Liver patients both with and without cirrhosis mounted an antibody response to influenza vaccination, and vaccination was associated with a reduction in risk of hospital admission from 205/1000 to 149/1000 (risk difference -0.06, 95% CI -0.07 to 0.04) in patients with viral liver disease. Vaccinated patients were 27% less likely to be admitted to hospital compared with unvaccinated patients (risk ratio 0.73, 95% CI 0.66 to 0.80). No effect against all-cause or cause-specific mortality or cause-specific hospitalisation was found.

Conclusions: The low quantity and quality of the evidence means that the protective vaccine effect may be uncertain. Considering the high risk of serious health outcomes from influenza infection in patients with liver disease and the safety and low cost of vaccination, overall, the potential benefits of seasonal vaccination both to patients and the healthcare systems are likely to outweigh the costs and risks associated with vaccination.

Prospero registration number: CRD42017067277.

Keywords: cirrhosis; hospitalisation; influenza vaccine; liver disease; seroprotection; vaccine effectiveness.

Figure 1

Study selection. ILI, influenza-like illness.

Figure 2

Serological response to influenza vaccination: mean difference in log haemagglutinisation inhibition (HI) antibody geometric mean titres (GMTs) before and after vaccination. Sayyad et al (2012a) includes patients with cirrhosis and Sayyad et al (2012b) includes patients without cirrhosis.

Figure 3

Serological response to influenza vaccination: seroconversion rate after vaccination. Sayyad et al (2012a) includes patients with cirrhosis and Sayyad et al (2012b) includes patients without cirrhosis. ES=effect size.

Figure 4

Serological response to influenza vaccination: seroprotection rate after vaccination. Sayyad et al (2012a) includes patients with cirrhosis and Sayyad et al (2012b) includes patients without cirrhosis. ES=effect size.

Figure 5

Effect of influenza vaccine on clinical outcomes: all-cause hospitalisation in vaccinated compared with unvaccinated patients with liver disease. Ohfuji et al investigated the effect of pandemic (monovalent) vaccine and SU et al investigated the effect of seasonal vaccine (against three or more virus subtypes).

Figure 6

Effect of influenza vaccine on clinical outcomes: all-cause mortality in vaccinated compared with unvaccinated patients with liver disease.