Abstract
BackgroundDespite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies.MethodsThis cross-sectional study enrolled 365 treatment-naïve patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C > T) and PNPLA3 (rs738409 c.444C > G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome.ResultsIn HCV subjects, the frequencies of TM6SF2 CC and CT + TT were 89% and 11%, while PNPLA3 frequencies of CC and CG + GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT + TT genotype in HCV was associated with significant liver fibrosis (p = 0.047; OR 1.953; 95% CI 1.009–3.788). In comparison to the CT + TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p = 0.002), higher frequency of arterial hypertension (p = 0.032), obesity (p = 0.030), metabolic syndrome (p = 0.014) and lower total cholesterol levels (p = 0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p = 0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis.ConclusionIn this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV.
Highlights
Despite the growing body of knowledge about Transmembrane 6 Superfamily Member 2 (TM6SF2) and Patatin-like Phospholipase-3 (PNPLA3) polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of hepatitis C virus (HCV) liver disease is not yet fully defined
The aim of this study is to describe the prevalence of TM6SF2 and PNPLA3 polymorphisms in Brazilian patients with chronic hepatitis C naïve for antiviral therapy, and to evaluate their association with liver fibrosis, steatosis, and other components of the metabolic syndrome
All stages of liver fibrosis were represented in this cohort, with cirrhosis predominating (30.5%)
Summary
Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Chronic hepatitis C virus (HCV) infection affects about 1% of the world population and remains one of the main causes of liver disease worldwide [1]. Between 55 and 85% of patients exposed to the virus develop chronic liver disease, and 15 to 20% of these will reach the stage of cirrhosis [3]. HCV is the leading cause of death among viral hepatitis in Brazil, and it remains a public health problem: in 2019, it was estimated that 22,747 individuals were infected with HCV [4]. Liver disease progression with accelerated fibrosis and cirrhosis is associated with other factors, such as insulin resistance, obesity, non-alcoholic fatty liver disease (NAFLD), alcohol consumption, and coinfections with HIV or hepatitis B virus [6]. Liver steatosis is another frequent complication in HCVinfected patients, affecting 50 to 72% of this population [8]
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