Long-term Prognosis Of Chronic Hepatitis B Patients With Normal ALT

ObjectiveTo study the pathological characteristics of hepatitis B infection with normal alanine aminotransferase(Alanine aminotransferase,ALT)and the effect of antiviral therapy on the longterm prognosis of hepatitis B infection with normal ALT.MethodsPatients with chronic hepatitis B virus(Hepatitis B virus,HBV)infection who underwent liver biopsy in the third people’s Hospital affiliated to Jiangsu University from January 2005 to July 2022 were collected.Patients were screened according to the inclusion exclusion criteria,and baseline clinical and pathological data were collected and clinical data at the end of followup were collected,which was the date of the clinical outcome(liver cirrhosis,liver cancer or death)or the date of the last follow-up.According to the GS score system to evaluate the degree of liver inflammation and fibrosis,G≥2 is considered to have significant inflammation,S≥2 is considered to have significant fibrosis.Liver cirrhosis was judged by ultrasound,FIB-4 index or aspartate aminotransferase-platelet ratio index.Hepatocellular carcinoma was diagnosed by pathology or imaging.Univariate and multivariate analysis of significant hepatic inflammation and fibrosis were performed by logistic regression.ROC curve was used to analyze the predictive probability of significant hepatic inflammation and fibrosis.Cox proportional hazard regression was used to analyze univariate and multivariate analysis of liver cancer and liver cirrhosis.Kaplan-Meier survival analysis was used to evaluate the risk of liver cancer and liver cirrhosis.Results1.A total of 227 patients with normal ALT hepatitis B infection were included in this study,and the median follow-up time of the whole cohort was 72.00(35.50,133.00)months,of which42(18.50%)people had significant liver inflammation,75(33.03%)people had significant fibrosis in the liver,and patients with obvious liver inflammation had higher age(P=0.010),ALT(P=0.024),AST(P=0.007),ALP(P=0.026),GGT(P<0.001),AFP(P<0.001)values,balloon degeneration ratio(P=0.015)and lower PLT values(P<0.001);Patients with significant fibrosis had higher age(P=0.002),ALT(P=0.004),AST(P=0.003),ALP(P=0.041),GGT(P<0.001),AFP(P<0.001),proportion of balloon degeneration(P=0.030),and lower PLT(P<0.001)。GGT(P=0.009)and PLT(P=0.008)were possible independent predictors of significant liver inflammation,while age(P=0.013)and PLT(P<0.001)were possible independent predictors of significant liver fibrosis.The AUC cut-off for age associated with a diagnosis of significant fibrosis in patients with hepatitis B with consistently normal ALT is 37 years and 25 U/L for ALT.2.In patients with chronic HBV infection with normal ALT,antiviral therapy had no significant effect on the risk of liver cancer(log-rank,P>0.05),but patients with significant liver inflammation had an increased risk of liver cancer(log-rank,P=0.003).Univariate analysis showed that significant liver inflammation(P=0.015),ALT(P=0.040),AFP(P=0.032)were associated with the occurrence of liver cancer.3.In patients with chronic HBV infection with normal ALT and liver pathology<G2S2,after matching,the risk of cirrhosis diagnosed by ultrasound in the non-antiviral group was increased(log-rank,P=0.034).The risk of liver cancer was not significantly increased(log-rank,P>0.05).Ballooning degeneration significantly increased the risk of cirrhosis diagnosed by ultrasound(log-rank,P<0.001).4.In patients with normal ALT and non-cirrhotic chronic HBV infection,after matching,patients in the non-antiviral group had an increased risk of ultrasonic diagnosis of liver cirrhosis(log-rank,P=0.019).significant liver inflammation(log-rank,P<0.001),significant liver fibrosis(log-rank,P<0.001)and balloon degeneration(log-rank,P<0.001).Multivariate analysis showed that age(P=0.019),significant hepatic fibrosis(P=0.020)and AFP(P<0.001)were independent risk factors for liver cirrhosis diagnosed by ultrasound.5.Compared with patients with normal ALT and low level,the patients with high level had a higher proportion of significant liver fibrosis(P<0.023)and a higher proportion of males(P<0.001).Different antiviral drugs had no significant effect on the risk of liver cancer(log-rank,P>0.05).Antiviral therapy could significantly increase the proportion of the last HBV-DNA lower than the detected value(P<0.001)and the proportion of normal ALT(P=0.001),but there was no significant difference in the negative conversion rate of the last HBs Ag between patients who received antivirus and those who did not receive antivirus(P>0.05).Conclusion1.In hepatitis B patients with normal ALT,some patients have significant inflammation or fibrosis of liver tissue,GGT,PLT are independent risk factors for significant liver inflammation,age and PLT are independent risk factors for obvious liver fibrosis,the AUC cut-off value of age associated with significant fibrosis diagnosis of hepatitis B patients with normal ALT is 37 years old,and the AUC cut-off value of ALT is 25U/L;2.Antiviral therapy is recommended for hepatitis B patients with normal ALT according to liver histological characteristics.Antiviral therapy helps to maintain normal ALT and low levels of hepatitis B virus,and can reduce the risk of liver cirrhosis;3.Ballooning degeneration in the liver,significant liver inflammation and significant liver fibrosis significantly increase the risk of liver cirrhosis in non-cirrhotic hepatitis B patients with normal ALT.Age,significant liver fibrosis and AFP are independent risk factors for cirrhosis in non-cirrhotic hepatitis B patients with normal ALT.4.The proportion of significant liver fibrosis is higher in the group with normal high level of ALT,and liver biopsy is more urgently needed.