Clinical trial NCT05661786: Clinical Outcomes of HBeAg-negative CHB Patients With Indeterminate Phase
Official title: Clinical Outcomes of HBeAg-negative Chronic Hepatitis B Patients With Indeterminate Phase: a Multi-center, Prospective, Observational Cohort Study (PILOT)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Hepatitis b
Keywords: Chronic hepatitis b
Indeterminate phase
hepatitis B surface antigen clearance
Hepatocellular carcinoma
Antiviral treatment
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2022-12-22
Enrollment: 4500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: HBeAg-negative chronic hepatitis B patients with indeterminate phase

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Coinfection with hepatitis A virus, hepatitis C virus, hepatitis D virus, hepatitis E virus or human immunodeficiency virus;
2. Coexisting of hepatocellular carcinoma and other malignancy, or alpha-fetoprotein \>upper limit of normal at enrollment;
3. Presence of liver cirrhosis;
4. 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;
5. Participating in other clinical trials in the last 3 months;
6. Coexisting of autoimmune liver diseases;
7. Pregnant or planned pregnancy in a short term or lactation patients;
8. History of severe heart disease, mental disease;
9. Uncontrolled diabetes, hypertension, thyroid dysfunction, retinopathy, autoimmune diseases;
10. Neutrophil count \<2×10\^9/L and/or platelet count \<100×10\^9/L;
11. History of organ transplantation or preparing for organ transplantation;
12. Using immunosuppressive drugs;
13. Undergone organ transplantation or preparing for organ transplantation;
14. Receiving immunosuppressive agents;
15. Patients thought by the investigators not suitable to participate in this study.

Primary outcomes:
measure: The incidence of hepatocellular carcinoma at 240 weeks
timeFrame: 240 weeks
measure: The HBsAg clearance rate at 240 weeks
timeFrame: 240 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Changzhou
country: China
facility: The Third Hospital of Changzhou
state: Jiangsu
city: Huai'an
country: China
facility: Huai'an No.4 People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Suqian
country: China
facility: Suqian People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
state: Jiangsu
Study officials:
References:
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