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...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.展开更多
Background and Aims:Chronic hepatitis B is the main cause of liver cancer.However,the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase(ALT).People have te...Background and Aims:Chronic hepatitis B is the main cause of liver cancer.However,the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase(ALT).People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment.However,the truth is not as optimistic as we thought.We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients.Methods:Medline,Embase,and Cochrane Library were searched up to January 10th 2020,to identify studies of these patients with liver biopsy.The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis.Potential heterogeneity was explored by subgroup analysis and meta-regression.Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis.The secondary outcome was to find the risk factors of significant histological changes.Results:Nineteen eligible studies,with 2,771 participants,were included.The pooled proportion of significant inflammation or fibrosis was 35%[95%confidence interval(CI):27 to 43]and 30%(95%CI:25 to 36),respectively.The pooled proportion of cirrhosis was 3%[95%CI:1 to 5,(12 studies;1,755 participants)].In subgroup analysis,old age[vs.young(<40 years-old),44%vs.26%,p=0.012]was significantly associated with higher fibrosis stage as well as cirrhosis[vs.young(<40 years-old),4.8%vs.1.8%,p<0.001].Conclusions:About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes,and some even have cirrhosis.展开更多
With the improved efficacy and accessibility of antiviral agents as well as the concerns about disease progression,there is a hot discussion on whether HBeAg-negative chronic hepatitis B(CHB)patients with normal alani...With the improved efficacy and accessibility of antiviral agents as well as the concerns about disease progression,there is a hot discussion on whether HBeAg-negative chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and positive HBV DNA should be treated.According to the international guidelines on the stages of the natural history of HBV infection,HBeAgnegative CHB patients with normal ALT and positive HBV DNA can be divided into two groups:one is the well-known“inactive carrier phase”,which is defined as serum HBV DNA<2000 IU/ml and no significant liver inflammation;and the other is the“indeterminate phase”,which is defined as serum HBV DNA≥2000 IU/mL regardless of the pathological changes in liver tissue,or HBV DNA<2000 IU/mL but accompanied by significant pathological changes in the liver.In this minireview,we will expound the disease characteristics,disease progression,and clinical management status of these two groups.Based on the analysis,we propose that HBeAg-negative patients with normal ALT but detectable serum HBV DNA should be treated,regardless of their age,family history of hepatocellular carcinoma(HCC)or the severity of liver necroinflammation.Expanding the indications of antiviral therapy will help improve the survival and quality of life of patients by preventing disease progression,and consequently reduce the risk of HCC development.展开更多
We present a new nonparametric predictive inference(NPI)method using a power-normal model for accelerated life testing(ALT).Combined with the accelerating link function and imprecise probability theory,the proposed me...We present a new nonparametric predictive inference(NPI)method using a power-normal model for accelerated life testing(ALT).Combined with the accelerating link function and imprecise probability theory,the proposed method is a feasible way to predict the life of the product using ALT failure data.To validate the method,we run a series of simulations and conduct accelerated life tests with real products.The NPI lower and upper survival functions show the robustness of our method for life prediction.This is a continuous research,and some progresses have been made by updating the link function between different stress levels.We also explain how to renew and apply our model.Moreover,discussions have been made about the performance.展开更多
基金approved by the Institutional Review Board of the West China Hospital of Sichuan University(ChiC-TR2100050064).
文摘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.
基金This study was supported by the China Mega-Project for Infectious Diseases(Grant Nos.2017ZX10203202 and 2013ZX10002005)the China Mega-Project for Innovative Drugs(Grant No.2016ZX09101065).
文摘Background and Aims:Chronic hepatitis B is the main cause of liver cancer.However,the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase(ALT).People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment.However,the truth is not as optimistic as we thought.We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients.Methods:Medline,Embase,and Cochrane Library were searched up to January 10th 2020,to identify studies of these patients with liver biopsy.The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis.Potential heterogeneity was explored by subgroup analysis and meta-regression.Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis.The secondary outcome was to find the risk factors of significant histological changes.Results:Nineteen eligible studies,with 2,771 participants,were included.The pooled proportion of significant inflammation or fibrosis was 35%[95%confidence interval(CI):27 to 43]and 30%(95%CI:25 to 36),respectively.The pooled proportion of cirrhosis was 3%[95%CI:1 to 5,(12 studies;1,755 participants)].In subgroup analysis,old age[vs.young(<40 years-old),44%vs.26%,p=0.012]was significantly associated with higher fibrosis stage as well as cirrhosis[vs.young(<40 years-old),4.8%vs.1.8%,p<0.001].Conclusions:About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes,and some even have cirrhosis.
基金supported by the National Natural Science Fundation of China(Grant No.30972622)the Clinical Research Incubation Project of West China Hospital of Sichuan University(Grant No.2022HXFH013).
文摘With the improved efficacy and accessibility of antiviral agents as well as the concerns about disease progression,there is a hot discussion on whether HBeAg-negative chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and positive HBV DNA should be treated.According to the international guidelines on the stages of the natural history of HBV infection,HBeAgnegative CHB patients with normal ALT and positive HBV DNA can be divided into two groups:one is the well-known“inactive carrier phase”,which is defined as serum HBV DNA<2000 IU/ml and no significant liver inflammation;and the other is the“indeterminate phase”,which is defined as serum HBV DNA≥2000 IU/mL regardless of the pathological changes in liver tissue,or HBV DNA<2000 IU/mL but accompanied by significant pathological changes in the liver.In this minireview,we will expound the disease characteristics,disease progression,and clinical management status of these two groups.Based on the analysis,we propose that HBeAg-negative patients with normal ALT but detectable serum HBV DNA should be treated,regardless of their age,family history of hepatocellular carcinoma(HCC)or the severity of liver necroinflammation.Expanding the indications of antiviral therapy will help improve the survival and quality of life of patients by preventing disease progression,and consequently reduce the risk of HCC development.
基金the National Natural Science Foundation of China(No.11272082)the China Scholarship Council State Scholarship Fund(No.201506070017)
文摘We present a new nonparametric predictive inference(NPI)method using a power-normal model for accelerated life testing(ALT).Combined with the accelerating link function and imprecise probability theory,the proposed method is a feasible way to predict the life of the product using ALT failure data.To validate the method,we run a series of simulations and conduct accelerated life tests with real products.The NPI lower and upper survival functions show the robustness of our method for life prediction.This is a continuous research,and some progresses have been made by updating the link function between different stress levels.We also explain how to renew and apply our model.Moreover,discussions have been made about the performance.
