Previous studies regarding the association between schizophrenia and the subsequent risk of liver cancer have shown inconsistent results. We aimed to perform a systematic review and meta-analysis to evaluate the association between schizophrenia and liver cancer incidence. We systematically searched the PubMed and Embase electronic databases for cohort studies reporting the standardized incidence ratio (SIR) for the risk of liver cancer in patents with schizophrenia as compared with the general population. A random-effects model was used to analyze the data. Stratified analyses were performed according to the gender of the patients. Seven studies comprising 312,834 patients with schizophrenia were included. During follow-up, 581 liver cancer cases were confirmed. The meta-analysis results showed that schizophrenia was associated with a trend of a lower liver cancer incidence (SIR: 0.83, 95% confidence interval [CI]: 0.66-1.04, p = 0.10) with significant heterogeneity (I2 = 81%). Sensitivity analysis of five cohorts of patients with cancer events before the diagnosis of schizophrenia indicated that schizophrenia was associated with a significantly lower incidence of liver cancer (SIR: 0.76, 95% CI: 0.61-0.96, p = 0.02; I2 = 84%). The reduction of a subsequent incidence of liver cancer was significant in male patients with schizophrenia (SIR: 0.71, p = 0.005), and a trend of a reduced risk of liver cancer was also detected in female patients (SIR: 0.83, p = 0.12). Significant publication bias was detected. However, "trim and fill" analyses by including the imputed unpublished studies showed similar results. In summary, schizophrenia may be protective against the incidence of liver cancer.
Keywords: cohort study; incidence; liver cancer; schizophrenia; systematic review.