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The 2022 edition of the Guidelines for the Prevention and Treatment of Chronic Hepatitis B points out that patients in the indeterminate phase (GZ) still have a relatively higher risk of disease progression than those in the immunotolerant and inactive phases, and antiviral is recommended**. Previous studies have also shown that patients with indeterminate phase have a significantly higher risk of disease progression than patients with HBEAg negative chronic HBV infection. Therefore, it is also particularly important for disease progression** and HCC risk stratification in patients with uncertain phases.
Previous studies published by Professor Gao Jiahong's team at the National Taiwan University School of Medicine showed that HBCRA Ping can stratify the risk of liver cancer in patients with chronic hepatitis B in the indefinite HBEAG negative stage. Based on this, the team recently published the study in JHEP ReportsestablishedhbeagA model of liver cancer risk** in patients with chronic hepatitis B in the negative indeterminate period.
Research Methods:
Establish two according to the AASLD definitionhbeagPatients in the negative indeterminate periodRetrospective cohorts were deduced and validated (Taiwan Eradicate-B study, n = 911;Japanese cohort, n = 806). All patients were non-cirrhosis at baseline, andNot received during the follow-up period**。The primary endpoint was liver cancer development.
Patient baseline
Patients in the derivation cohort were younger than those in the validation cohort (median age 41.).8 years old vs 43.5 years old). In contrast, in the validation cohort, there were more patients with HBCRAG < 10,000 U mL (54.)8% vs. 80.5%）。The dominant virus strain in the derivation cohort was type B (84.)9%), and type C (53.) in the validation cohort4%）。
Findings:
The cumulative incidence of HCC in patients with chronic hepatitis B in the Taiwan cohort was significantly higher than that in the Japanese cohort
The median follow-up time for the derivation and validation cohorts was 15., respectively5 years and 81 year (p < 0001）。Compared to the validation queue,The derivation cohort had a higher cumulative incidence of liver cancer（p = 0.014）。Liver cancer occurred in 85 patients in the derivation cohort and 28 in the validation cohort.
To establish a liver cancer risk model for patients with chronic hepatitis B in the indefinite HBEAG-negative stage
Analytical findingshbcragLevels are the only viral factor associated with HCC progression。Therefore, it will include:Age, gender,althbcragand platelet countwere included in the multivariate COX proportional hazards model.
The GZ-HCC scoring rules are as follows, and the scoring range is 0 - 20 points.
At 10 and 15 years of follow-up, the incidence of liver cancer in patients with each score of GZ-HCC was detailed.
At the 10-year and 15-year follow-up of the derivation cohort, the GZ-HCC score** AUROC for HCC development was 0., respectively86（95% ci：0.81 - 0.91) and 083（95% ci：0.79 - 0.88）。The performance was better than at both time pointsreach-bwithgagScoring（p < 0.001）。
At 10 and 15 years of follow-up in the validation cohort, the GZ-HCC score** AUROC for HCC development was 0., respectively92（95% ci：0.88 - 0.97) and 090（95% ci：0.83 - 0.97）。**Performance is always betterreach-bgagwithcu-hccScoring
The risk of HCC in the low-risk and high-risk groups of GZ-HCC was similar to that of the inactive HBsAg carrier group and the immunologically active patients, respectively
In the derivation cohort, the relationship between GZ-HCC score and the risk of HCC was evaluated using a restrictive cubic spline regression with the lowest AIC value, and the results showed that the risk of HCC began to increase at 8 points and increased rapidly after 13 points.
Thus, 3 cut-off values were tested in patients in the indeterminate phase, including (71.)5% <10) and 13 (920% <13）。It was found thatuseThe risk of liver cancer in the low-risk group was close to that of inactivehbsagCarrying status。However, there is no such low risk when using 10 or 13 as cut-off values. In addition,The risk of liver cancer in patients was also similar to that of immunoactive patients
Compared with the inactive HBsAg carrier population, the HR of patients in the indeterminate phase and immunologically active patients with scores of < 8 (n = 459) and 8 (n = 452) were 1., respectively09（95% ci：0.49 - 2.40) and（95% ci：5.20 - 15.31) and 935（95% ci：5.01 - 17.45）。
The cut-off value of 8 points was used to stratify the risk of liver cancer in the Japanese validation cohort, which was reconfirmedThe risk of developing liver cancer in the low-risk and high-risk groups was compared with inactivity, respectivelyhbsagCarriers are similar to immunoactive patients.
Liver Linjun has something to sayA recent meta-analysis showed a high incidence of liver cancer in patients with an indeterminate phase, especially in HBEAg-negative and Asian populations. This study also found that the cumulative incidence of liver cancer in patients with chronic hepatitis B in the indefinite stage in the Taiwan cohort was significantly higher than that in the Japanese cohort. The GZ-HCC model based on HBCRA can effectively reduce the risk of HCC in patients with chronic hepatitis B in the indefinite HBEAG-negative stage, and the risk of HCC in the low-risk and high-risk groups of GZ-HCC is similar to that of the inactive HBSAG-carrier population and immunoactive patients, respectively.
Several studies have shown that antiviral** in patients with indeterminate phase can effectively reduce the risk of liver cancer, so antiviral** should be considered more actively in patients with chronic hepatitis B in indeterminate phase. At present, a multi-center prospective cohort study initiated by the Liver Health Promotion Center of China United Province and led by the First People's Hospital of Yunnan Province - "Qihang" project is also underway, aiming to evaluate the ** effect of different antiviral regimens on patients with immune tolerance and HBEAG-negative indeterminate period. Data from previous pilot studies have shown that patients with HBEAG-negative indeterminate phase have a good effect on receiving PEG IFN-2B in combination with TDF**.
References:
tseng tc, hosaka t, liu cj, et al. hbcrag-based risk score performs better than the hbv dna-based scores for hcc prediction in grey zone patients who are hbeag-negative[j]. jhep rep, 2024, 6(1): 100956.
Hepatitis B antiviral