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

Sponsor

Qilu Hospital of Shandong University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06041022

Collaborator

Linyi People's Hospital (Other), First Affiliated Hospital Xi'an Jiaotong University (Other), First Affiliated Hospital of Wenzhou Medical University (Other), Third Affiliated Hospital, Sun Yat-Sen University (Other), Sir Run Run Shaw Hospital (Other), First Affiliated Hospital of Zhejiang University (Other)

1,000

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Other: Exposure factors

Detailed 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Case-Only

Time Perspective:

Retrospective

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Outcome Measures

Primary Outcome Measures

Number of participants with the antiviral therapy as assessed by AASLD guideline [From Jan 1st,2010 to Aug 31,2023]
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.
Number of participants with significant liver histology as assessed by Metavia scoring system [From Jan 1st,2010 to Aug 31,2023]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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