Analysis Of Influencing Factors Of Virological Breakthrough And Virological Response In Patients With Chronic Hepatitis B

OBJECTIVEChronic hepatitis B significantly increases the risk of developing cirrhosis or liver cancer if it is not treated promptly and effectively.At present,nucleos(t)ide analogues can effectively reduce viral load,but patients need long-term continuous drug use,which makes patients prone to virological breakthrough.Clinical studies have shown that virological breakthroughs and virological responses are related to demographic characteristics,virology and biochemical indicators,adherence,and initial antiviral treatment regimens,but the findings are controversial.Therefore,in order to reduce the virological breakthrough rate of CHB patients and improve the virological response rate during the treatment,this study used the information database of a liver disease specialist hospital in Guangzhou to explore the influencing factors related to virological breakthrough in patients with CHB.At the same time,the factors affecting the virological response of CHB patients without virological breakthrough were analyzed.METHODSThe study used a information system of a liver disease specialist hospital in Guangzhou to establish a retrospective cohort.A nested case-control study was conducted to select 1035 patients with CHB patients who were treated from January 1,2008 to December 31,2016.Patients who had virological breakthrough during follow-up were included in the breakthrough group,and the control group was selected according to the ratio of age,sex,and observation time according to the ratio of 1:1.By collecting data from two groups of subjects,a conditional logistic model was used to explore the relationship between antiviral drugs,baseline HBV DNA,baseline HBeAg,baseline ALT levels,early virological response,type of medical insurance,adherence,and virological breakthrough.Then,patients with CHB who did not have virological breakthrough were selected and divided into response group and non-response group to see if virological response occurred.Unconditional logistic models were used to investigate the factors affecting the virological response in CHB patients who did not have virological breakthrough.RESULTS1.Virological breakthrough after treatment with nucleos(t)ide analogues:The virological breakthrough rate increased with the prolongation of antiviral treatment time in CHB patients(P<0.001).The virological breakthrough rates of different antiviral drugs were different,and the difference was statistically significant.The cumulative virological breakthrough rates ofentecavir,telbivudine,adefovir dipivoxil,andlamivudinetreatment at 5 and 8 years were 1.25%vs.21.34%vs.13.51%vs.53.39%and 1.46%vs.24.16%vs.20.08%vs.60.17%,with the lowest ETV group and the highest LAM group.2.Influencing factors of virological breakthrough in CHB naive patients:This study showed that antiviral drugs,baseline HBeAg and adherence were the influencing factors of virological breakthrough.Compared with the LAM group,the ETV,LdT,and ADV groups were less likely to have virological breakthroughs with OR values of 0.002,0.110,and 0.088,respectively.Therisk of virological breakthrough in baseline HBeAg-negative patients was 0.252 times higher than baseline HBeAg-positive.Patients with poor adherence had a higher probability of virological breakthrough than patients with good adherence,with an OR of 2.419.There was no statistically significant correlation between baseline HBV DNA,baseline ALT,early virological response,payment methods,and virological breakthrough.3.Influencing factors of virological response in CHB patients without virological breakthrough:Single factor results showed that age,antiviral drugs,baseline HBeAg,baseline HBV DNA levels,and baseline ALT levels were factors influencing the virological response in CHB naive patients.After multi-factor adjustment,the possibility of virological response of ETV and LdT was higher than that of LAM group,the OR values were 6.679,2.799,respectively,and the P values were less than0.05.Patients with a high viral load at baseline had a lower probability of virological response(OR=0.327,P<0.001).For patients with baseline HBeAg negative,the probability of virological response was 3.969 times higher than baseline HBeAg positive.Patients with CHB with baseline ALT levels of 80-200 U/L and greater than 200 U/L may have a virological response of 2.050 and 2.306 times,respectively,for patients less than or equal to 80 U/L.CONCLUSION1.Nucleos(t)ide analogues can effectively inhibit viral replication in CHB naive patients,but the virological breakthrough rate increases with the prolonged administration time.2.Patients with LAM,baseline HBeAg-positive,and poor adherence with CHB are more likely to have virological breakthroughs.3.CHB patients with ETV,baseline HBV DNA levels?10~7copies/mL,baseline HBeAg-negative,and high baseline ALT levels are more likely to have a virological response.4.It is recommended that patients with CHB prefer nucleos(t)ide analogues with fast,high-efficiency and high-resistance barriers to improve the virological response rate and reduce the occurrence of virological breakthroughs.