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Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects throughout the viral lifecycle, with hepatic steatosis frequently observed in patients with chronic HCV infection. Hepatic steatosis is most common in patients infected with genotype 3 viruses, possibly due to direct effects of genotype 3 viral proteins. Hepatic steatosis in patients infected with other genotypes is thought to be mostly due to changes in host metabolism, involving insulin resistance in particular. Specific effects of the HCV genotype 3 core proteins have been observed in cellular models in vitro: mechanisms linked with a decrease in microsomal triglyceride transfer protein activity, decreases in the levels of peroxisome proliferator-activating receptors, increases in the levels of sterol regulatory element-binding proteins, and phosphatase and tensin homologue downregulation. Functional differences between the core proteins of genotype 3 viruses and viruses of other genotypes may reflect differences in amino acid sequences. However, bioclinical studies have failed to identify specific ‘steatogenic’ sequences in HCV isolates from patients with hepatic steatosis. It is therefore difficult to distinguish between viral and metabolic steatosis unambiguously, and host and viral factors are probably involved in both HCV genotype 3 and nongenotype 3 steatosis.