The Study on Optimal Treatment and Clinical Outcome of Chronic Hepatitis B Patients With Inactive Hypoviremia

The Clinical Outcome of Inactive HBsAg Carrier Patients With Low HBV DNA Levels and Normal ALT by Antiviral Therapy

Chronic hepatitis B seriously endangers the health of our people, especially the occurrence of HCC, which brings huge economic burden and life threat to our people. 84% - 92% of HCC in China is related to chronic HBV infection. How to further reduce the risk of liver cancer is an urgent problem to be solved in clinical research and an important direction. Although NAs treatment can make patients achieve the negative transformation of virus, it can not effectively reduce the level of virus antigen, and it also lacks the ability to improve the immune clearance of virus. As a result, the incidence of liver cancer in patients with long-term NA treatment is still 4.5% - 10.5%, and the incidence of HCC in patients with hypoviremia in Na treatment is higher. In current clinical practice, nearly 1 / 3 of patients treated with NAs can not reach the detection line of highly sensitive reagent. It is an important measure to make the patients with hypoviremia and inactive low virus replication treated by NAs below the detection line of highly sensitive reagent and further reduce the risk of HCC. However, it is still not enough to minimize the risk of HCC to achieve a complete viral response only through NA treatment. The long-term follow-up showed that the incidence of HBsAg disappeared by only 2.0% - 0.0% regardless of the long-term treatment of HBsAg. Therefore, the most important measure to minimize the occurrence of HCC is to optimize the treatment of NA treated patients with low virus replication and inactive patients with low virus replication to achieve complete virus response and clinical cure. The purpose of this study is to explore the optimal treatment scheme for chronic hepatitis B NA treated patients with hypoviremia and natural low virus replication patients to significantly reduce the risk of HCC.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: PEG-IFN

Detailed Description

Chronic hepatitis B seriously endangers the health of our people, especially the occurrence of liver cancer, which brings huge economic burden and life threat to our people. 84% - 92% of hepatocellular carcinoma (HCC) in China is related to chronic HBV infection. How to further reduce the risk of liver cancer is an urgent problem to be solved in clinical research and an important direction. Although NAs treatment can make patients achieve the negative transformation of virus, it can not effectively reduce the level of virus antigen, and it also lacks the ability to improve the immune clearance of virus. As a result, the incidence of liver cancer in patients with long-term NA treatment is still 4.5% - 10.5%, and the incidence of HCC in patients with hypoviremia in Na treatment is higher. In current clinical practice, nearly 1 / 3 of patients treated with NAs can not reach the detection line of highly sensitive reagent. It is an important measure to make the patients with hypoviremia and inactive low virus replication treated by NAs below the detection line of highly sensitive reagent and further reduce the risk of HCC. However, it is still not enough to minimize the risk of HCC to achieve a complete viral response only through NA treatment. The long-term follow-up showed that the incidence of HBsAg disappeared by only 2.0% - 0.0% regardless of the long-term treatment of HBsAg. Therefore, the most important measure to minimize the occurrence of HCC is to optimize the treatment of NA treated patients with low virus replication and inactive patients with low virus replication to achieve complete virus response and clinical cure. The purpose of this study is to explore the optimal treatment scheme for chronic hepatitis B Na treated patients with hypoviremia and natural low virus replication patients to significantly reduce the risk of liver cancer.

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

• Study Contact: Name: Yao Xie, Doctor; Phone Number: 8610-84322200; Email: xieyao00120184@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100015
      • Recruiting
      • Department of Hepatology Division 2, Beijing Ditan Hospital
      • Contact: Yao Xie, Doctor; Phone Number: 2489 8610-84322200; Email: xieyao00120184@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Chronic Hepatitis B patients With Inactive Hypoviremia

Description

Inclusion Criteria:

• Aged from 16 to 60;
• The positive time of HBsAg was 6 months,
• 48 weeks of treatment with ETV, TDF or TAF, including HBeAg positive and negative patients;
• High sensitive reagent was used to confirm that the low level of serum HBV DNA was 20 IU / ml-2000 IU / ml.
• Good compliance and sign informed consent.

Exclusion Criteria:

1. Patients with decompensated liver cirrhosis or previous decompensated liver cirrhosis;
2. Those who have used interferon within 6 months;
3. at the same time, it is associated with other virus infections, such as hepatitis A virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, AIDS virus, etc;
4. in addition to hepatitis B, there are other serious physical and mental diseases, including uncontrolled primary kidney, heart, lung, vascular, neurological, digestive, severe metabolic diseases (such as uncontrolled hyperthyroidism, serious complications of diabetes and adrenal diseases), immune deficiency diseases, and severe infections;
5. Active or suspected malignant tumor or history of malignant tumor;
6. 6 months before enrollment or currently receiving corticosteroids, immunosuppressants and chemotherapeutic drugs;
7. Complicated with alcoholic liver disease, autoimmune liver disease and other liver diseases;
8. HBV resistant patients;
9. Other situations that the researcher believes are not suitable for inclusion.

PegIFN α Treatment contraindications:

1. Prohibited for known pairs α- Patients who are allergic to interferon, E. coli products, polyethylene glycol or any component of this product;
2. It is forbidden to be used in patients with autoimmune hepatitis;
3. Pregnant and lactating women;
4. Central nervous system diseases, mental diseases, uncontrolled epilepsy, non withdrawal of alcohol / drug abuse, decompensated liver cirrhosis, symptomatic heart disease, uncontrolled autoimmune diseases and severe thyroid function diseases;
5. Absolute neutrophil count before treatment ≤ 1.0 × 109 / L, platelet ≤ 80 × 109/L。

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment intervention group; NA (TDF or TAF) combined with PEG-IFN was used. PEG-IFN was injected subcutaneously once a week and a personalized course of 24 weeks was used.	Drug: PEG-IFN; PEG-IFN 180 or 135 micrograms, subcutaneously injected once a week, with a personalized treatment course of 24 weeks
Non therapeutic intervention observation group; patients do not receive treatment and are observed and followed up regularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of HCC during the project study	Once the hepatitis attack (HBV DNA > 2000 IU / ml, ALT >40 U / L) is reached during the observation of inactive low virus replication HBsAg carriers, the researchers will communicate with the patients and take antiviral treatment, and continue to follow-up observation. All enrolled patients were included in the continuous follow-up cohort during the study period and after the end of the project.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The negative conversion rate of HBV DNA after 48 weeks of treatment was optimized (below the detection line of highly sensitive detection reagent)	Once the hepatitis attack (HBV DNA > 2000 IU / ml, ALT >40 U / L) is reached during the observation of inactive low virus replication HBsAg carriers, the researchers will communicate with the patients and take antiviral treatment, and continue to follow-up observation. All enrolled patients were included in the continuous follow-up cohort during the study period and after the end of the project.	48 weeks
The incidence of HBsAg disappearance during the study period;	Once the hepatitis attack (HBV DNA >2000 IU / ml, ALT > 40 U / L) is reached during the observation of inactive low virus replication HBsAg carriers, the researchers will communicate with the patients and take antiviral treatment, and continue to follow-up observation. All enrolled patients were included in the continuous follow-up cohort during the study period and after the end of the project.	48 weeks
HBeAg seroconversion rate in HBeAg positive patients;	Once the hepatitis attack (HBV DNA > 2000 IU / ml, ALT> 40 U / L) is reached during the observation of inactive low virus replication HBsAg carriers, the researchers will communicate with the patients and take antiviral treatment, and continue to follow-up observation. All enrolled patients were included in the continuous follow-up cohort during the study period and after the end of the project.	48 weeks
Incidence of chronic hepatitis B during the study period	Once the hepatitis attack (HBV DNA > 2000 IU / ml, ALT >40 U / L) is reached during the observation of inactive low virus replication HBsAg carriers, the researchers will communicate with the patients and take antiviral treatment, and continue to follow-up observation. All enrolled patients were included in the continuous follow-up cohort during the study period and after the end of the project.	48 weeks
To study the incidence of complications such as cirrhotic ascites and upper gastrointestinal bleeding during long-term follow-up.	Once the hepatitis attack (HBV DNA > 2000 IU / ml, ALT > 40 U / L) is reached during the observation of inactive low virus replication HBsAg carriers, the researchers will communicate with the patients and take antiviral treatment, and continue to follow-up observation. All enrolled patients were included in the continuous follow-up cohort during the study period and after the end of the project.	48 weeks

Collaborators and Investigators

• Sponsor: Beijing Ditan Hospital
• Collaborators: Beijing YouAn Hospital; Beijing 302 Hospital/5th Medical Center of Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Clinical Outcome; Chronic Hepatitis B infection; Nucleoside analogues; Inactive HBsAg Carrier
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: CFH2022-1-2172-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No