PILOT: Clinical Outcomes of HBeAg-negative CHB Patients With Indeterminate Phase

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)

Overall Status

Recruiting

CT.gov ID

NCT05661786

Collaborator

(none)

4,500

Enrollment

Locations

Anticipated Duration (Months)

900

Patients Per Site

13.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic hepatitis B virus (HBV) infection remains a global public health burden around the world. Investigating the disease process of chronic hepatitis B (CHB) is essential to individual management in clinical practice. According to American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidance, CHB can be classified into four phases: immune-tolerant CHB, HBeAg-positive immune active CHB, inactive CHB and hepatitis B e antigen (HBeAg)-negative immune active CHB. Antiviral therapy is recommended in patients with HBeAg-positive or -negative immune active CHB patients to reduce the incidence of liver cirrhosis and hepatocellular carcinoma, while periodic monitoring is recommended for inactive carrier and immune-tolerant CHB patients. However, a substantial proportion of patients fall into an indeterminate phase whose serum HBV DNA and alanine aminotransferase levels do not fit well into these well-described phases. Most of CHB patients with indeterminate phase are HBeAg negative. However, the clinical outcomes of these patients remain unclear. Therefore, the purpose of this study is to investigate the clinical outcomes of HBeAg-negative chronic hepatitis B patients with indeterminate phase.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b	Other: Observation Other: Antiviral treatment

Study Design

Study Type:

Observational

Anticipated Enrollment :

4500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Clinical Outcomes of HBeAg-negative Chronic Hepatitis B Patients With Indeterminate Phase: a Multi-center, Prospective, Observational Cohort Study (PILOT)

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2028

Anticipated Study Completion Date :

May 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Observation cohort	Other: Observation Monitor every 6 months
Treatment cohort	Other: Antiviral treatment Receive first-line antiviral treatment, including entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, tenofovir amibufenamide or peginterferon

Arm

Intervention/Treatment

Observation cohort

Other: Observation

Monitor every 6 months

Treatment cohort

Other: Antiviral treatment

Receive first-line antiviral treatment, including entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, tenofovir amibufenamide or peginterferon

Outcome Measures

Primary Outcome Measures

The incidence of hepatocellular carcinoma at 240 weeks [240 weeks]
The HBsAg clearance rate at 240 weeks [240 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Hepatitis B surface antigen (HBsAg) positive over 6 months
Age ≥18 years
Treatment-naïve
HBeAg negative, anti-HBe positive
HBV DNA >2000 IU/mL
Persistently normal alanine transaminase (ALT)
Liver inflammation <G2 or A2 and liver fibrosis <S2 or F2 before enrollment, or liver stiffness >8 kilopascals (kPa)
No family history of liver cirrhosis or hepatocellular carcinoma

Exclusion Criteria:

Coinfection with hepatitis A virus, hepatitis C virus, hepatitis D virus, hepatitis E virus or human immunodeficiency virus;
Coexisting of hepatocellular carcinoma and other malignancy, or alpha-fetoprotein

upper limit of normal at enrollment;

Presence of liver cirrhosis;
Alcohol abuse within the last year (ethanol: male >40 g/d, female >20 g/d; or heavy drinking within 2 weeks before enrollment: ethanol >80 g/d), or history of drug abuse;
Participating in other clinical trials in the last 3 months;
Coexisting of autoimmune liver diseases;
Pregnant or planned pregnancy in a short term or lactation patients;
History of severe heart disease, mental disease;
Uncontrolled diabetes, hypertension, thyroid dysfunction, retinopathy, autoimmune diseases;
Neutrophil count <2×10^{9/L and/or platelet count <100×10}9/L;
History of organ transplantation or preparing for organ transplantation;
Using immunosuppressive drugs;
Undergone organ transplantation or preparing for organ transplantation;
Receiving immunosuppressive agents;
Patients thought by the investigators not suitable to participate in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Third Hospital of Changzhou	Changzhou	Jiangsu	China	213001
2	Huai'an No.4 People's Hospital	Huai'an	Jiangsu	China	223300
3	Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu	China	210008
4	Suqian People's Hospital	Suqian	Jiangsu	China	223800
5	The Fifth People's Hospital of Suzhou	Suzhou	Jiangsu	China	215007