The Effect of Diffuse Liver Diseases on the Occurrence of Liver Metastases in Cancer Patients: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Diffuse liver diseases have a high incidence among the general population and even higher in patients with a solid cancer. Since many patients with a solid tumor die of liver metastases, the aim of this systematic review of the literature was to explore the correlation between diffuse liver diseases and the risk of having liver metastases at diagnosis or during follow-up. To summarize the results of included studies, a meta-analysis was also conducted. The results of our systematic review should encourage the research community to further investigate the complex relationship between the liver’s microscopic environment and metastases, which may also affect prognosis and response to therapy. ABSTRACT: This systematic review with meta-analysis aimed to assess the effect of diffuse liver diseases (DLD) on the risk of synchronous (S-) or metachronous (M-) liver metastases (LMs) in patients with solid neoplasms. Relevant databases were searched for systematic reviews and cross-sectional or cohort studies published since 1990 comparing the risk of LMs in patients with and without DLD (steatosis, viral hepatitis, cirrhosis, fibrosis) in non-liver solid cancer patients. Outcomes were prevalence of S-LMs, cumulative risk of M-LMs and LM-free survival. Risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale. We report the pooled relative risks (RR) for S-LMs and hazard ratios (HR) for M-LMs. Subgroup analyses included DLD, primary site and continent. Nineteen studies were included (n = 37,591 patients), the majority on colorectal cancer. ROB appraisal results were mixed. Patients with DLD had a lower risk of S-LMs (RR 0.50, 95% CI 0.34–0.76), with a higher effect for cirrhosis and a slightly higher risk of M-LMs (HR 1.11 95% CI, 1.03–1.19), despite a lower risk of M-LMs in patients with vs without viral hepatitis (HR 0.57, 95% CI 0.40–0.82). There may have been a publication bias in favor of studies reporting a lower risk for patients with DLD. DLD are protective against S-LMs and slightly protective against M-LMs for viral hepatitis only.