| BackgroundHepatitis B is a systemic infectious disease caused by hepatitis B virus infection that causes liver parenchymal lesions.The number of patients with chronic HBV infections in the world has reached about 296 million.Patients without antiviral treatment may be more likely develop into liver cirrhosis and liver cancer,and their quality of life and survival time will be affected.At present,there are still controversies about when to start antiviral treatment and the ALT threshold for starting treatment for people with normal ALT(that means ALT≤ULN,at the following will be described as"ALT≤ULN"),which need to be further explored.ObjectiveTo understand the clinical characteristics of patients with chronic HBV infection and ALT≤ULN in different stages of liver fibrosis,and to explore the clinical efficacy of using nucleos(t)ide analogues for antiviral treatment in patients with chronic HBV infection and ALT≤ULN in stages F2-F3,so as to provide reference for clinicians to make better antiviral treatment decisions.Methods1.Select patients who accept two-dimensional real-time shear wave elastography to detect liver stiffness and had ALT≤ULN in Qingyuan People’s Hospital in 2019 as the research subjects,collect their gender,age,and liver function,hepatitis B two pairs and half quantitative,HBV DNA,LSM,liver ultrasound and imaging examination reports.2.For chronic HBV infected patients with ALT≤ULN in F2-F3 stage indicated by 2D-SWE test results,divide them into antiviral treatment group and non-antiviral treatment group according to their willingness to accept antiviral treatment,and observe the changes of various clinical indicators in the past 3 years.Results1.2D-SWE application implementation and baseline situation:In 2019,the total number of 2D-SWE tests in our hospital was 2,503,and 2,405test results were obtained,with a success rate of 96.1%.The age span of these patients was 5～85 years old,distribution proportion of each age group shows that most of the patients were 30～50 years old,with 32.92%(31～40 Y)and 27.77%(41～50 Y).The 2D-SWE detection value indicates that there are 1343 peoples who had chronic HBV infection with ALT≤ULN in the F0-F4 stage of liver fibrosis,and their constituent ratios in each fibrosis stage(the internal composition ratio is not the composition ratio in the whole,so the addition is not equal to 100%.The subsequent composition ratio of this study also uses the same method)were 87.2%in F0-F1,73.9%in F2-F3,and 55.7%in F4,showing a decreasing trend with the increase of fibrosis stage(?~2=129.885,P<0.001).The group composition ratio of male patients in each stage was F0-F1 57.9%,F2-F3 75.2%,F4 80.9%,showing an increasing trend with the increase of fibrosis stage(?~2=53.336,P<0.001).In terms of age difference,patients older than 30accounted for a relatively high proportion(?~2=24.120,P<0.001),and the composition ratio within the group was 87.5%in stage F0-F1,92.5%in stage F2-F3,and 99.4%in stage F4.Among patients with ALT≤ULN,there were 200 peoples had HBe Ag positive(20.5%of F0-F1 stage,4.9%of F2-F3 stage,13.4%of stage F4),and 1143peoples had HBe Ag negative(79.5%of F0-F1 stage,95.1%of F2-F3 stage,86.6%of F4 stage),?~2=52.222,P<0.001.The constituent ratios of patients with HBV DNA>20IU/ml were 64.0%in stage F0-F1,56.9%in stage F2-F3,59.9%in stage F4,and the difference was not statistically significant(?~2=5.820,P=0.054).2.Clinical characteristics of patients with ALT≤ULN in different fibrosis stage:In this study,patients with HBVDNA>20 IU/ml and ALT≤ULN in phase F0-F3(n=632)were divided into groups with ALT threshold 30 U/L for male and 19 U/L for female.The results showed that both male and female with high-normal height ALT had higher LSM and HBV DNA than those with low-normal ALT(P<0.001).In this study,572 HBe Ag negative patients from the above population were grouped with a cut-off value of 20 U/L to obtain similar research results.The ALT>20U/L group had higher LSM,HBV DNA,and male patient ratios(P<0.001).This study included 91 patients with F0-F1 stage ALT≤ULN who did not initiate antiviral therapy for 3 consecutive years.The results showed that there was no significant change in ALT and LSM compared to baseline in the third year(P>0.05),and HBV DNA decreased compared to baseline in the third year(P<0.001).The median values of HBV DNA(log10IU/ml)in 2019 and 2022 were 3.5 and 3.2,respectively;No patients experienced cirrhosis or liver cancer during the observation period.3.Cohort study of patients with ALT≤ULN and chronic HBV infection in stage F2-F3:(the antiviral treated group in this study took ETV or TDF 1 tablet/day orally for antiviral treatment)(1)The changes of ALT:the antiviral treatment group showed a decrease in ALT levels in the first,second,and third years,with a statistically significant difference compared to baseline ALT levels,P<0.001.The group without antiviral treatment showed no statistically significant difference in ALT levels compared to baseline at the first,second,and third years,P>0.05.(2)The changes of HBV DNA:the baseline median levels of HBV DNA(log10IU/ml)in the antiviral treatment group and the non antiviral treatment group were 5.1 and 4.1,respectively,with P=0.110.With 20 IU/ml as the lower limit of HBV DNA detection,the virology response rates of the antiviral treatment group in2020,2021 and 2022 were 75%,82%and 87.5%respectively.(3)The changes of LSM(k Pa):when the observation period was 1 year,the changes of LSM in the antiviral treated group was(8.17±1.66)VS(7.42±1.67),t=4.223,P<0.001,and the decrease of LSM was 9.2%.The change of LSM in the non-antiviral treated group was(7.71±1.51)VS(7.04±1.61),t=4.034,P<0.001,and the decrease of LSM was 8.6%.When the observation period was 2 years,the change of LSM in the antiviral treated group was(8.53±1.65)VS(7.19±1.54),t=6.259,P<0.001,and the decrease of LSM was 15.7%.The change of LSM in the non-antiviral treated group was(7.85±1.25)VS(6.73±1.59),t=5.027,P<0.001,and the decrease of LSM was 14.3%.When the observation period was 3 years,the changes of LSM in the antiviral treated group was(8.89±1.20)VS(7.02±1.21),t=7.451,P<0.001,and the decrease in LSM was 21.0%.The change of LSM in the non-antiviral treated group was(8.29±0.91)VS(7.22±1.66),t=3.828,P<0.001,the decrease of LSM was 12.9%.In summary,both groups showed a decrease of LSM,and the decline in the antiviral treated group increased year by year,while the non-antiviral treated group fluctuated.Further analysis found that by the third years,70%(28/40)of patients in the antiviral treated group had their LSM decrease from F2-F3 to F0-F1,and 54.5%(18/33)in the non-antiviral treated group,but there was no difference.Statistically significant(?~2=1.853,P=0.173).(4)Regarding the difference in the outcome of the observation endpoint(2022),4 patients(6.6%)in the antiviral treated group developed liver cirrhosis,and 3patients in the non-antiviral treated group,?~2=0.972,P=0.324,the difference was not statistically significant.No patients in the two groups developed liver cancer,no serious adverse reactions related to antiviral drugs occurred in the antiviral treated group.Conclusion1.As the degree of liver fibrosis increased from F0 to F4,the proportion of chronic HBV infection patients with ALT≤ULN showed a decreasing trend,but the proportion of male patients showed an increasing trend.2.Among chronic HBV infected patients with ALT≤ULN and HBe Ag negative,the patients with ALT>20 U/L had higher LSM,HBV DNA and male ratio.Showing to be a potential antiviral indication group,more attention should be given to their long-term management.3.Patients with chronic HBV infection and ALT≤ULN can get decrease of ALT and viral suppression after antiviral treatment. |
PDF Full Text Request