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

Recruiting

• Conditions: Chronic Hepatitis B
• Interventions: Drug: PEG-IFN

• Registration Number: NCT05357183
• Lead Sponsor: Beijing Ditan Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2022-04-27
• Study First Submitted QC: 2022-04-27
• Status Verified: 2022-05
• Study First Posted: 2022-05-02
• Last Update Submitted: 2022-05-09
• Last Update Posted: 2022-05-12
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1200

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; Active or suspected malignant tumor or history of malignant tumor;
5. 6 months before enrollment or currently receiving corticosteroids, immunosuppressants and chemotherapeutic drugs;
6. Complicated with alcoholic liver disease, autoimmune liver disease and other liver diseases;
7. HBV resistant patients;
8. 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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PEG-IFN optimized treatment group	PEG-IFN	Patients received optimized treatment of NAs (ETV + TDF or ETV + TAF) combined with PEG-IFN ETV 0.5 mg, TDF 300 mg or TAF 25 mg, oral once a day, PEG-IFN 180 or 135 micrograms, subcutaneous injection once a week, with a personalized course of treatment of 24 weeks.

Primary Outcome Measures

Name	Time	Method
Incidence of HCC during the project study	48 weeks	In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.

Secondary Outcome Measures

Name	Time	Method
The incidence of HBsAg disappearance during the study period;	48 weeks	In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
The negative conversion rate of HBV DNA after 48 weeks of treatment was optimized (below the detection line of highly sensitive detection reagent)	48 weeks	In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
HBeAg seroconversion rate in HBeAg positive patients;	48 weeks	In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
Incidence of chronic hepatitis B during the study period	48 weeks	In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
To study the incidence of complications such as cirrhotic ascites and upper gastrointestinal bleeding during long-term follow-up.	48 weeks	In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.

Trial Locations

Locations (1)

Department of Hepatology Division 2, Beijing Ditan Hospital; 🇨🇳 Beijing, Beijing, China