No medications have been approved for managing nonalcoholic fatty liver disease (NAFLD). Lifestyle intervention is the mainstay for its treatment. Hyperferritinemia, which appears to be associated with the severity of liver injury and insulin resistance, is frequently observed in patients with NAFLD.

We conducted a systematic review and meta-analysis of the outcomes of four interventional trials regarding the effect of phlebotomy in patients with NAFLD versus the outcomes of NAFLD patients who did not undergo phlebotomy. Primary outcome was the pooled mean difference (MD) of the homeostasis model assessment of insulin resistance (HOMA-IR). The secondary outcomes were the changes in liver enzymes and the lipid profile.

Four interventional studies involving 438 participants were included in the meta-analysis. HOMA-IR was lower in patients who underwent phlebotomy, with an MD of 0.84 [95% confidence interval (CI) 0.01 to 1.67, I2 = 72%]. Phlebotomy also significantly reduced the alanine aminotransferase (MD = 10.05, 95% CI 7.19-12.92, I2 = 34%) and triglyceride (MD = 9.89, 95% CI 4.96-14.83, I2 = 22%) levels and increased the high-density cholesterol level (MD = 3.48, 95% CI 2.03-4.92, I2 = 18%).

Phlebotomy decreased insulin resistance and liver transaminase levels in patients with NAFLD. In addition, it improved their lipid profile.