• Shingo Nakamoto, Fumio Imazeki, Tatsuo Kanda, Shuang Wu, Masato Nakamura, Shin Yasui, Akinobu Tawada, Rintaro Mikata, Tetsuhiro Chiba, Makoto Arai, Osamu Yokosuka, and Hiroshi Shirasawa.
• Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan.
• Int J Med Sci. 2017 Jan 1; 14 (11): 108810931088-1093.

BackgroundGenetic variation near the interferon lambda 3 (IFNL3) is known to be associated with response to pegylated interferon (pegIFN) and ribavirin combination therapy in patients with chronic hepatitis C virus (HCV) infection which is often accompanied by hepatic steatosis.AimsWe examined whether this genetic variation is associated with host lipids and treatment response.MethodsA total of 101 Japanese patients who had underwent liver biopsy before treatment with pegIFN and ribavirin for HCV genotype 1b infection were retrospectively analyzed for association between IFNL3 genotypes (rs8099917) and clinical factors including histopathological features of the liver. The presence of >5% steatosis in the liver specimen was defined as hepatic steatosis.ResultsForty patients (40%) had liver steatosis before therapy. Patients with IFNL3 minor genotype (non-TT) showed lower low-density lipoprotein cholesterol level (p=0.0045), higher γ-glutamyl transpeptidase level (p=0.0003) and higher prevalence of hepatic steatosis (p=0.0002). Advanced fibrosis [odds ratio (OR) 4.63, p=0.03] and IFNL3 major genotype (OR 0.13, p=0.001) were 2 independent factors for determining the presence of hepatic steatosis. Among the factors associated with sustained virological response, IFNL3 genotype was the most significant predictor, as per multivariate analysis.ConclusionsOur results confirmed that IFNL3 genotype is associated with hepatic steatosis as well as IFN response.

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