| Part one Association of chronic kidney disease with PNPLA3 and TM6SF2 gene variants in chronic HCV infectionAims:Patients with chronic hepatitis C virus(HCV)infections differ in their risk for metabolic disorders and chronic kidney disease(CKD).The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients.Methods:Patients with chronic non-genotype 3 HCV infection with or without CKD were examined.PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing.The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients.Univariate and multivariate analyses were used to identify factors associated with CKD.Results:There were 1022 patients with chronic HCV infection,226 with CKD and 796 without CKD.The CKD group had more severe metabolic disorders,and also had higher prevalences of liver steatosis,the PNPLA3 rs738409 non-CC genotype,and the TM6SF2 rs58542926 CC genotype(all P<0.05).Relative to patients with the PNPLA3 rs73 8409 CC genotype,patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD(CKD G45).Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype.Multivariable analysis indicated that multiple metabolic abnormalities,including liver steatosis and the PNPLA3 rs738409 C>G variant,increased the risk of CKD,but the TM6SF2 rs58542926 C>T variant decreased the risk of CKD.Conclusion:Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of kidney injury.Part two The effect of DA A treatment on the prognosis of kidney injury and its relationship with PNPLA3 and TM6SF2 gene variantsAims:To explore the factors influencing kidney injury outcomes after achieving SVR48 with DAA treatment in chronic HCV-infected patients with CKD.Methods:A total of 372 patients with chronic HCV infection(143 with CKD and 229 without CKD)from four liver disease centers in Northeast China were enrolled and followed up after the completion of DAA antiviral therapy.In addition to observing the antiviral efficacy of DAA in patients with kidney injury,we focused on exploring the renal function prognosis after achieving SVR48,especially its relationship with the single nucleotide polymorphisms of PNPLA3 and TM6SF2 genes at rs738409 and rs58542926 respectively,which is closely related to lipid metabolism.Results:DAA antiviral therapy resulted in high response rates in chronic HCV-infected patients,with or without CKD.There was no difference in response rates to DAA among those with different CKD categories;the rate of kidney injury improvement in patients achieving SVR48 could be as high as 38.5%,and was not lower than the average(38.8%)among those with CKD G3-G5.There was a higher rate of kidney injury progression and a lower rate of kidney injury improvement in patients with PNPLA3 non-CC than those with CC genotype,while patients with TM6SF2 nonCC genotypes had a lower rate of kidney injury progression and a higher rate of kidney injury improvement compared with CC-types.The prevalence of PNPLA3 rs738409 CC genotypes and TM6SF2 rs58542926 non-CC genotypes was higher in those with significant kidney injury improvement compared with those with no significant renal injury improvement.Multivariable analysis indicated that HOMAR≥2.5,total cholesterol level,liver steatosis,and PNPLA3 rs738409 C>G and TM6SF2 rs58542926 C>T were important influencing factors for the prognosis of kidney injury after DAA antiviral therapy.Conclusion:After obtaining a sustained virological response,the kidney injury in chronic HCV-infected patients with CKD can be largely reversed.Multiple metabolic abnormalities,especially PNPLA3 rs738409 and TM6SF2 rs58542926 SNPs closely related to lipid metabolism,could affect the outcome of kidney injury. |
