On May 21, 2022, the second session of “The 4th Chronic Hepatitis B Clinical Cure Summit and China School Summit Forum” will be online It was successfully held, and more than 20 top clinical experts and scientific researchers in the field of liver disease in my country focused on the hot issues of clinical cure of chronic hepatitis B and the treatment of special populations There was a great discussion.
/span>Professor Wu Chao from the Drum Tower Hospital Affiliated to Nanjing University School of Medicine gave a wonderful speech on the topic of “Cure or Not Treat Chronic Hepatitis B Patients in Uncertain Period” , Yimaitong summarizes the main content, and now presents it to you as follows.
content0content” responsive” sizes=”(min-width: 320px) 320px, 100vw” src=”https://mmbiz.qpic.cn/mmbiz_png/7QRTvkK2qC5lnflAURO42ibicr3c4ia4MlqxgTmsEO8oB8TxoopY2IXAly4RXPKKCI3zZWt4FtniaibEWKD5LAJ6XdQ/640″ width=”600″> >Professor Wu Chao
Nanjing University Medicine Vice President, Chief Physician, Professor, Doctoral Supervisor of Drum Tower Hospital Affiliated to the Hospital
Chairman of Infectious Diseases Branch of Jiangsu Medical Association
Member of Infectious Diseases Branch of Chinese Medical Association p>
Member of the Liver Disease Branch of the Chinese Medical Association
Institute of Viruses and Infectious Diseases, Nanjing University Director
Member of the American and European Society of Liver Diseases (AASLD) (EASL)
Member of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID)
Published more than 130 academic papers as the first and corresponding author, Among them, more than 100 papers are included in SCI; the cumulative impact factor is >400, and the highest impact factor is 25.071, including 2 papers with IF>20 points, 9 papers with IF>10 points, and 17 papers with IF>5 points, including Lancet Infect DisHepatology >, J Hepatol and other authoritative magazines
Three patents for invention, three monographs published
Editors and special reviewers for more than 10 Chinese journals and several SCI journals
span>
I. Definition and distribution of chronic HBV infection in uncertain period
Chronic indefinite periodHepatitis B virus (HBV) infection means: the HBV DNA and alanine aminotransferase (ALT) patterns of newly treated chronic HBV infection patients were followed up for 1 year, and their HBV DNA and alanine aminotransferase (ALT) patterns were different from the four traditional chronic HBV infection stages.
The latest edition of Chronic Hepatitis B (Chronic Hepatitis B ( CHB) diagnosis and treatment guidelines or guidance, which divides HBV infection into 4 stages: (1) immune tolerance stage; (2) immune active stage or immune clearance stage; (3) ) period of inactivity or low replication; (4) period of reactivity.
However, clinically, the condition of CHB patients is more complicated, and a considerable proportion of CHB patients do not meet the above-mentioned 4-stage diagnostic criteria and cannot be directly classified.in it. Taking the 2018 AASLD guidelines as an example, about 40% of patients could not be clearly classified as stage 4 (Table 1).
Table 1 2018 AASLD-guided staging and patients who do not meet the diagnostic criteria for stage 4
Multiple studies have shown that chronic indefinite periodHBV infection A high percentage of . In 2021, a study by our team included 4759 patients with hepatitis B, of which 27.78% of those with chronic HBV infection were in indeterminate period (an estimated 19 million patients with indeterminate period chronic HBV infection in my country); another study in the United States included 3366 patients Hepatitis B patients, 38.7% of them with chronic HBV infection are in indeterminate period.
“immune tolerance period”and strong>“Inactive Period”Indefinite PeriodCHB The proportion of patientsis also high. A study in 2021 analyzed the histopathological analysis of liver biopsy from 179 patients with HBeAg positive, high HBV DNA level, and persistently normal ALT (≤40 U/L) in the “immune tolerance stage” HBV infection, and the patients in the uncertain stage accounted for 57.5%. (103/179), HBV DNA≤107 IU/ml group accounted for 81.8% (18/22) of patients with indeterminate period, which was significantly higher than that of HBV DNA> 107 IU/ml group (54.1%, 85/157); for 327 patients with negative HBeAg, relatively low level of HBV DNA, and continuous normal ALT (40 U/L) ) Histopathological analysis of liver biopsy in patients with “inactive” HBV infection, patients with indeterminate stage accounted for 59.0% (193/327), and HBV DNA≥103 IU/ The proportion of patients with indeterminate period in the ml group was 74.5% (79/106), which was significantly higher than that in the HBV DNA<103 IU/ml group (51.6%, 114/221 ).
791 patients were followed up for 6 months to detect ALT (ULN>40 U/L) twice or more and underwent liver biopsy HBeAg positive or negative chronic HBV infection was evaluated, and the results of staging according to Chinese guidelines showed that patients in immune tolerance stage, immune clearance stage, immune control stage, reactivation stage and uncertain stage >9.6% (76/791), 24.9% (197/791), 17.0% (134/791), 11.1% (87/791) and 37.4% (296/791).
Second, the prognosis of patients with chronic HBV infection in uncertain stage
A study in Spain in 2018 included HBeAg-negative, HBeAb-positive, HBV DNA<20000 IU/ml, ALT<80 U/L HBV-infected patients, with a median follow-up of 8.2 (5-19) years, the results showed that only Eighteen (6.3%) "grey zone" (GZ) patients converted to HBeAg-negative CHB, and none developed cirrhosis or severe fibrosis. The proportion of spontaneous HBsAg clearance in patients with chronic HBV infection in indeterminate period was higher, and age >40 years and male gender were independent predictors of HBsAg clearance in patients with chronic HBV infection in indeterminate period. This result is far from the current cognition, and the research conclusions reveal the impact of HBV genotype on the prognosis of patients in uncertain period:
All patients with HBsAg clearance were HBV genotype A/D, and none of HBV genotype B/C had HBsAg clearance;
Patients with genotype B/C are more prone to ALT fluctuations (>80 U/L) and HBV DNA fluctuations (>20000 IU/ml);
span>
An Asian patient with HBV genotype C GZ developed hepatocellular carcinoma (HCC) (without liver cirrhosis).
Multiple studies have shown that periods of uncertainty CHB patients have a higher risk of developing HCC. A 2016 American study followed 1465 HBV-infected patients for 6.3 years. The cumulative incidence of HCC in patients with immune tolerance, active, inactive, and indeterminate stages of CHB was 0 (0/10) and 21% (21%), respectively. 96/457), 3% (3/112) and 9% (80/886), patients with CHB in indeterminate stage were significantly higher than those in immune tolerance stage and inactive stage; a 2019 Korean study showed that HBV DNA >2000 IU/ml, HBeAg-negative chronic HBV-infected patients with ALT
Figure 1 Incidence of chronic HBV infection and death/HCC in different subgroups Transplantation rate
Table 2 Comparison of 10-year HCC incidence in patients with indeterminate baseline status and inactive HBsAg carriers p>
Table 3 Comparison of inactive patients with indeterminate status at baseline and at the end of follow-up 10-year HCC incidence in HBsAg carriers
3, no, no Management of definite chronic HBV infection
indefinite chronic whether HBV infected The need for antiviral therapy is still controversial. Anna S. Lok, the former chairman of AASLD, believes that patients with chronic HBV infection in the uncertain period should be closely followed up, and if necessary, liver puncture and non-invasive detection of liver fibrosis should be performed. If there are significant liver tissue lesions, active antiviral treatment is required.
Guided by the 2018 AASLD, the management of patients with chronic HBV infection in uncertain periods can be divided into two categories: E antigen positive and E antigen negative.
Figure 2 Management of chronic HBV E antigen-positive patients in uncertain period span>
Management of chronic HBV antigen-negative patients with indeterminate stage Figure 3
With the “Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition)” and “Experts in Expanding Antiviral Treatment of Chronic Hepatitis B” Opinions” as a guide, the management of chronic HBV infection in uncertain period is shown in the figure below.
Management of chronic HBV infection /span>
IV. Summary
For newly-treated HBV-infected patients One-year follow-up showed that the HBV DNA and ALT patterns were different from the four traditional disease stages, and it was chronic HBV infection of indeterminate stage; CHBApproximately40% of patients, but it is dynamic strong>, need regular follow-up; if not receiving antiviral treatment, indefinite periodCHB Patients with have a significantly higher risk of HCC than inactive patients, especially≥ 40 years oldpatient; should be more active Antiviral therapy for CHB patients in uncertain period should be considered, but the timing, regimen, course of treatment, efficacy and its impact on long-term prognosis still need further research.