Clinical Outcomes of HBeAg-negative CHB Patients With Indeterminate Phase

Chronic Hepatitis b Clinical Trial

— PILOT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05661786
• Other study ID #: NJDTID-2201
• Status: Recruiting
• Start date: December 2022
• Est. completion date: May 2028

Study information

• Verified date: December 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Chao Wu, M.D., Ph.D
• Phone: 86-25-83105890
• Email: dr.wu[@]nju.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4500
• Est. completion date: May 2028
• Est. primary completion date: February 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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

Locations

Country	Name	City	State
China	The Third Hospital of Changzhou	Changzhou	Jiangsu
China	Huai'an No.4 People's Hospital	Huai'an	Jiangsu
China	Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	Suqian People's Hospital	Suqian	Jiangsu
China	The Fifth People's Hospital of Suzhou	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

References & Publications (8)

Bonacci M, Lens S, Marino Z, Londono MC, Rodriguez-Tajes S, Mas A, Garcia-Lopez M, Perez-Del-Pulgar S, Sanchez-Tapias JM, Forns X. Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg-negative Caucasian patients in the Grey Zo — View Citation

Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65. — View Citation

Choi GH, Kim GA, Choi J, Han S, Lim YS. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Aliment Pharmacol Ther. 2019 Jul;50(2):215-226. doi: 10.1111/apt.15311. Ep — View Citation

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67 — View Citation

Huang DQ, Li X, Le MH, Le AK, Yeo YH, Trinh HN, Zhang J, Li J, Wong C, Wong C, Cheung RC, Yang HI, Nguyen MH. Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients With Indeterminate Phase. Clin Gastroenterol Hepatol. — View Citation

Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ. 2019 Mar 1;97(3):230-238. doi: 10.2471/BLT.18.219469. Epub 2019 Jan 28. — View Citation

Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep — View Citation

Yao K, Liu J, Wang J, Yan X, Xia J, Yang Y, Wu W, Liu Y, Chen Y, Zhang Z, Li J, Huang R, Wu C. Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone. J Viral Hepat. 2021 Jul;28(7):1025-1033. doi: 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of hepatocellular carcinoma at 240 weeks		240 weeks
Primary	The HBsAg clearance rate at 240 weeks		240 weeks