Correlation Between PNPLA3 And IFNLR1 Gene Polymorphisms And Response To Antiviral Therapy In Patients With Hepatitis B Cirrhosis

Objective: To explore the significance of gene polymorphisms at three sites of PNPLA3(rs2294919)and IFNLR1(rs4649203,rs7525481)in antiviral therapy of hepatitis B cirrhosis nucleotide analogs,This study was set to research the correlation among the genetic polymorphisms of PNPLA3(rs2294919)and IFNLR1(rs4649203,rs7525481)and nucleotide drugs(lamivudine,adefovir dipivoxil,entecavir,telbivudine)in the efficacy of antiviral therapy in hepatitis with sclerosis;And the environmental influencing factors of antiviral therapy for patients with hepatitis B cirrhosis and the interaction between gene-gene and gene-environment were analyzed to provide basis for individualized treatment of hepatitis B cirrhosis in China.Method: A total of 134 eligible patients with hepatitis B cirrhosis were selected and the general conditions of the subjects were collected by questionnaire.After the nucleotide drug antiviral treatment,according to the virological response,the study subjects were divided into a DNA response group(HBV-DNA ? minimum detection value,minimum detection value 500IU/m L),and a poor DNA response group(HBV-DNA decline>2log10,but still>500IU/m L),of which 51 were in the DNA response group in patients with liver cirrhosis,83 cases in the poor response group;Single-factor analysis was used to analyze the relationship between the gender,age,smoking,alcohol consumption,HBV-DNA baseline,HBe Ag,ALT baseline,gene PNPLA3-rs2294919,IFNLR1-rs4649203,rs7525481 with drug response;The relationship between PNPLA3-rs2294919,IFNLR1-rs4649203,rs7525481 and drug response was analyzed by multi-factor analysis;The interactions between gene-gene and gene-environment were analyzed by logistic regression analysis and multi-factor dimension reduction(MDR).P?0.05 was considered statistically significant.Results:1.General situation of the research objectThe average age of the DNA response group of patients with hepatitis B cirrhosis was 52.490 years old,with 64.7% males,29.4% smokers and 25.3% drinkers.The average age of the group with poor DNA responses was 51.650 years,with 69.9% of men,22.9% of smokers and 21.7% of drinkers.There were no significant differences between the two groups in age,sex,smoking,drinking and ALT baseline(P>0.05).2.Influencing factors related to antiviral treatment effect of hepatitis B cirrhosisHigh HBV-DNA load and HBe Ag-positive were independent risk factors for DNA response.The poor DNA response of patients with HBV-DNA>20000IU/ml was 9.540 times higher than that of patients with HBV-DNA ? 20000IU/ml(OR=9.540,95%CI : 2.150-42.330,P=0.003).HBe Ag-positive hepatitis B cirrhosis patients were 9.722 times more likely to poor DNA response than HBe Ag-positive patients(OR=9.722,95%CI:3.296-28.677,P=0.001).PNPLA3-rs2294919 and IFNLR1-rs7525481 were both associated with DNA response.The risk of poor DNA response in hepatitis B cirrhosis patients carrying the PNPLA3-rs2294919 TC genotype was 9.393 times to that of those carrying the PNPLA3-rs2294919 TT genotype(OR=9.393,95%CI:2.795-31.566,P=0.001);The risk of poor DNA response in hepatitis B cirrhosis patients carrying the IFNLR-rs7525481 CT genotype was 5.333 times to that of those carrying the IFNLR-rs7525481 CC genotype(OR=5.333,95%CI:1.763-16.129,P=0.003);IFNLR1-rs4649203 has not been found to be associated with DNA responses to antiviral therapy in patients with hepatitis B cirrhosis.3.Effects of gene-gene and gene-environment interactions on antiviral treatment of hepatitis B cirrhosisThe best model combinations for gene-gene interaction were the 3-factor models of PNPLA3-rs2294919,IFNLR1-rs4649203 and IFNLR1-rs7525481.The risk of poor DNA response was 5.611 times that of the low-risk combinations(OR=5.611,95%CI:2.616-12.034);The best model combination of gene-environment interaction was the 3-factor model of the initial state of HBe Ag,HBV-DNA baseline level and PNPLA3-rs2294919,and the poor DNA response of the high-risk combination was 21.273 times that of the low-risk combination(OR=21.273,95%CI:8.595-52.649).The interaction between IFNLR1-rs4649203 and IFNLR1-rs7525481 was statistically significant,and the analysis showed that patients with both the IFNLR1-rs4649203 GG genotype and the IFNLR1-rs7525481 CT genotype had a significantly higher risk of poor DNA response than patients with one genotype(OR=103.987,95%CI:4.762-2270.584,P=0.003);The interactions between PNPLA3-rs2294919,IFNLR1-rs7525481 and HBV-DNA baseline levels were statistically significant,patients with high HBV-DNA load of the PNPLA3-rs2294919 TC genotype and IFNLR1-rs7525481 CT genotype had a higher risk of poor DNA response than patients with low HBV-DNA load(OR=5.955,95%CI:2.102-16.871,P=0.001;OR=5.333,95%CI:1.763-16.129,P=0.003).Conclusion:1 HBV-DNA baseline level and initial HBe Ag status may be independent risk factors for antiviral treatment with nucleotide drugs in patients with hepatitis B cirrhosis.There was a positive interaction between PNPLA3-rs2294919 TC,IFNLR1-rs7525481 CT and HBV-DNA baseline,which reduced the antiviral efficacy in patients with hepatitis B cirrhosis.2 PNPLA3-rs2294919 TC and IFNLR1-rs7525481 CT may be risk factors for DNA response in patients with hepatitis B cirrhosis.It was not found that IFNLR1-rs4649203 was associated with DNA response to antiviral therapy in patients with hepatitis B cirrhosis,but its interaction with PNPLA3-rs2294919 and IFNLR1-rs7525481 reduced the antiviral efficacy in patients with hepatitis B cirrhosis.