Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity

Background and Aims:Direct evidence on the outcomes of hepatitis B e antigen(HBeAg)-negative chronic hepatitis(CHB)patients with normal alanine transaminase after long-term antiviral treatment is lacking.Methods:HBeAg-nega-tive patients with normal ALT and positive HBV DNA(≥20 IU/mL)were retrospectively enrolled.The endpoints included virological response(HBV DNA<100 IU/mL),changes in as-partate aminotransferase to platelet ratio index(APRI)and fibrosis-4 index(FIB-4),and the incidence of liver nodules,cirrhosis,and hepatocellular carcinoma(HCC).Results:This.cohort(n=194)was divided into three subgroups,untreated(n=67),treatment-continued(n=87),and treatment-dis-continued patients(n=40),with a median follow-up of 54 months.The treatment-continued group achieved 100%(95%CI:94.7-100)virological response,and significantly reduced APRI and FIB-4 scores(both p<0.001).The risk of liver nodules and cirrhosis in that group was reduced by 76%(HR:0.24,95%CI:0.11-0.54,p<0.001)and 89%(HR:0.11,95%CI:0.14-0.91,p=0.041)vs.the untreated group and by 77%(HR:0.23,95%CI:0.10-0.49,p<0.001)and 95%(HR:0.05,95%CI:0.01-0.44,p=0.006)vs.the treat-ment-discontinued group.For patients with HBV DNA≥2,000 IU/mL,adherence to treatment lowered the risks of liver cirrhosis by 92%(95%CI:0.01-0.67)and 93%(95%CI:0.01-0.53)vs.the untreated and treatment-discontinued patients,respectively.No patient adhering to treatment de-veloped HCC,but one in each of the remaining groups did.Conclusions:Continuous nucleos(t)ide analog(NA)treat-ment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase,especially in those with HBV DNA22,000 IU/mL.