A Non-invasive Model to Predict Antiviral Therapy in Gray Zone of Chronic Hepatitis B

Hepatitis B, Chronic Clinical Trial

Official title:

A Non-invasive Model to Predict Antiviral Therapy in Patients With Gray Zone of Chronic Hepatitis B: a Multi-center, Retrospective Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06041022
• Other study ID #: KYLL-202301-030
• Status: Not yet recruiting
• Start date: October 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2023
• Source: Qilu Hospital of Shandong University
• Contact: Yu-Chen Fan, MD,PhD
• Phone: 18560082065
• Email: fanyuchen[@]sdu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Establishment and validation of the non-invasive model to predict antiviral therapy in the gray zone of chronic hepatitis B

Description:

Chronic hepatitis B virus (HBV) infection continues to be a major public health problem worldwide today. According to statistics, the prevalence of chronic HBV infection assessed globally in 2016 was 3.5%, or 257 million people with chronic infection. In China, it is estimated that about 70 million people are chronically infected with HBV in 2019, including about 20-30 million people with chronic hepatitis B (CHB). CHB is a major risk factor for cirrhosis, and hepatocellular carcinoma (HCC). 12-20% of patients with chronic hepatitis B will develop cirrhosis, and of these, around 20% will further develop decompensated cirrhosis and 6-15% will develop HCC, with hepatitis B accounting for approximately 50% of HCC cases worldwide. Therefore, strongly and exact management of chronic hepatitis B is extremely important for the control of HBV progression. Current domestic and international clinical guidelines generally divide the natural history of chronic hepatitis B into four immune phases based on HBV DNA levels, liver injury, and HBeAg status: immune active, immune tolerant, inactive HBsAg carriers, and reactive stage. The guidelines of American Association for the Study of Liver Diseases (AASLD) recommend the use of antiviral therapy for patients in the immune active and reactive phases, and also provide a detailed follow-up plan for patients in other phases. However, a significant number of patients with chronic hepatitis B cannot be classified in any of these four phases, who falls into a gray area with uncertainty of formal management. According to the 2018 AASLD Hepatitis B Guidelines criteria for antiviral therapy, patients in the gray zone still do not have clarity on the need for antiviral therapy based only on clinical indicators. A recent study showed that nearly 40% of patients with chronic hepatitis B were in the indeterminate stage. At long-term follow-up assessment, half of these patients were still in the indeterminate phase and one-fifth had transitioned to the immune active phase. Patients in the indeterminate phase were 14 times more likely to develop HCC than those with inactive hepatitis B. Therefore, the management of antiviral therapy in patients with CHB in the "gray zone" is crucial and should be demonstrated. The aim of the investigators is to investigate the clinical characteristics of patients with uncertain treatment in the "gray zone" of CHB and to develop a non-invasive predictive model for the indication of antiviral therapy. This will provide guidance for the clinical management of patients in the "gray zone" of CHB, thereby reducing the incidence of cirrhosis and liver cancer and improving their quality of life.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

Inclusion Criteria:

• HBeAg positive, normal serum alanine aminotransferase(ALT) level,HBVDNA=10^6 IU/ml

• HBeAg positive, elevated serum ALT, HBVDNA=2*10^4 IU/ml

• HBeAg negative, elevated serum ALT, HBVDNA=2*10^3 IU/ml

• HBeAg negative, normal serum ALT, HBVDNA=2*10^3 IU/ml

Normal upper limit of ALT is 35 U/L for male and 25 U/L for female.

Exclusion Criteria:

• Concurrent with other liver diseases such as autoimmune hepatitis, Hepatitis C virus infectious, liver cirrhosis, HCC, or unexplained liver function abnormalities

• Patients with incomplete clinical data

Related Conditions & MeSH terms

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

Intervention

Other:
• Exposure factors
Including demographical data, laboratory features and liver histological indicators.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Qilu Hospital of Shandong University	First Affiliated Hospital of Wenzhou Medical University, First Affiliated Hospital of Zhejiang University, First Affiliated Hospital Xi'an Jiaotong University, Linyi People's Hospital, Sir Run Run Shaw Hospital, Third Affiliated Hospital, Sun Yat-Sen University

References & Publications (4)

Huang DQ, Lim SG. Hepatitis B: Who to treat? A critical review of international guidelines. Liver Int. 2020 Feb;40 Suppl 1:5-14. doi: 10.1111/liv.14365. — View Citation

Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 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.29800. No abstract available. — View Citation

Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol. 2021 Oct 28;9(5):769-791. doi: 10.14218/JCTH.2021.00209. Epub 2021 Sep 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with the antiviral therapy as assessed by AASLD guideline	The criteria of antiviral therapy: Immune-active CHB: an elevation of ALT=2 the upper limit of normal (ULN)plus elevated HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive).; Immune-active CHB and cirrhosis if HBV DNA is >2,000 IU/mL.; Immune-active CHB with ALT < 2 the ULN and HBV DNA below thresholds (less than 2,000 IU/mL if HBeAg negative or less than 20,000 IU/mL if HBeAg positive) are as follows: 1) Age: older age (>40 years). 2) Family history of cirrhosis or HCC. 3) Previous treatment history. 4) Presence of extrahepatic manifestations. 5) Presence of cirrhosis.; Immune tolerance CHB with the moderate-to-severe necroinflammation or fibrosis on a liver biopsy specimen.	From Jan 1st,2010 to Aug 31,2023
Primary	Number of participants with significant liver histology as assessed by Metavia scoring system	Significant liver histology showing significant hepatic inflammation =G2 and/or fibrosis =S2 as assessed by Metavir scoring system; The fibrosis score is used to describe the amount of inflammation (the intensity of inflammation/breakdown of tissue) in the liver: F0: No fibrosis F1: Portal fibrosis without septa F2: Portal fibrosis with few septa F3: Numerous septa without cirrhosis F4: Cirrhosis; The activity score is a prediction about how rapidly the degree of fibrosis is progressing: G0: No activity G1: Mild activity G2: Moderate activity G3: Severe activity	From Jan 1st,2010 to Aug 31,2023