Optimal Cut-off Value Of ALT To Intiate Antiviral Monotherapy For Chronic Hepatitis B Virus Infection:a Retrospective Study

Background:Monotherapy with interferon（IFN）or nucleos（t）ide analogue（NA）is generally recommended for chronic hepatitis B virus（HBV）infection.International clinical practice guidelines differ on the cut-offs for treatment initiation:serum HBV DNA of 20000 IU/mL or above,or 2000IU/mL or above;and serum ALT above the upper limit of normal,or more than two-times the upper limit of normal.The definition of the upper limit of normal for ALT also differs,ranging from 33 U/L for men and 25 U/L for women to 40 U/L for both men and women.So,the cut-off value of ALT to initiate antiviral therapy is remains to determine.Objective:To explore the optimal cut-off value of ALT to initiate antiviral monotherapy with chronic hepatitis B virus infection.Methods:This retrospective real-world study involving chronic hepatitis B virus（HBV）infection patients with high levels of HBV DNA（>2000 IU/mL）.According to whether or not to receive antiviral monotherapy,they were divided into treatment group and non-treatment group.The independent samples t-test was used for comparison of measurement data（age,biochemical parameters）and the chi-square test was used for comparison of count data（gender,previous treatment,HBeAg qualitation,treatment strategies）.Kaplan-Meier curves were used to illustrate and compare the cumulative incidence of undetectable HBV DNA,ALT normalisation,and hepatitis e surface antigen（HBeAg）seroclearance between the two groups,log-rank test to evaluate the differences among these outcomes.Landmark analysis was used to analyze the cumulative incidence of clinical outcomes at different period.Binary logistic regression model was established to explore the optimal ALT cutoff value for initiation of antiviral monotherapy.The patients in the treatment group were further divided by the old and new cut-off values.Kaplan-Meier curve and log-rank test were used to analyze the cumulative incidence of clinical outcomes in patients with different ALT ranges.Results:The total number of subjects was 131,including 87 males and44 females.There were 81 HBeAg positive patients and 50 HBeAg negative patients.Of these,92 received antiviral therapy and 39 did not receive treatment.There was no significant difference in the ratio of male to female in the treatment group and the non-treatment group.The age of the patients in the treatment group was older than that in the non-treatment group（P<0.05）,and the ALT level in the treatment group were significantly higher than those in the non-treatment group（P<0.05）.By analysis,the cumulative incidence of HBV DNA suppress to undetectable level（χ²=60.834,P=0.000）and HBeAg seroclearance（χ²=9.536,P=0.002）in the treatment group were both higner than non-treatment group,and the difference was statistically significant,but there was no statistically significant difference in the cumulative incidence of ALT normalisation（χ²=0.010,P=0.992）.For the patients with ALT below 80 U/L,antiviral therapy also contribute to higher cumulative incidence of HBV DNA suppress to undetectable levels（χ²=55.759,P=0.000）.There was no significant difference in the cumulative incidence of ALT normalisation（χ²=0.006,P=0.936）and HBeAg seroclearance（χ²=2.519,P=0.113）between the two groups.Landmark analysis of the incidence of HBeAg seroclearance at different period showed that the cumulative incidence of HBeAg seroclearance in the treatment group was higher than that in the non-treatment group（χ²=7.013,P=0.008）before60^th month of follow-up,but the difference was not statistically significant after 60^th month（χ²=0.250,P=0.617）.HBV DNA was selected as the main indicator for evaluating clinical outcomes,establish a binary logistic regression model,and the results of binary logistic regression model show that when the ALT cutoff value changes between 30 U/L and 80 U/L,the partial regression coefficient B and the OR value continue to change.When the ALT cut-off value equal to 43 U/L,the B and OR values are the largest.That is to say,when ALT above 43 U/L,the difference of clinical outcome between treatment group and non-treatment group is most significant.For the treatment group,there was no statistically significant difference in the cumulative incidence of undetectable HBV DNA（χ²=1.180,P=0.276）,ALT normalisation（χ²=0.380,P=0.538）and HBeAg clearance（χ²=2.604,P=1.107）in patients with ALT levels between 43 U/L and 80 U/L versus above 80 U/L.Conclusions:When HBV DNA>2000IU/ml,antiviral therapy can effectively suppress HBV DNA to undetectable levels and is also effective in patients with baseline ALT levels below 80 U/L.And the optimal cut-off value of ALT for initiating antiviral monotherapy might be 43U/L.