The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection
Abstract
:1. Introduction
2. Methods
2.1. Patient Enrollment
2.2. Classification of the Patients into Different Phases of Chronic HBV Infection
2.3. Characterization of the Grey-Zone Patients
2.4. Impact of Different ALT ULN Values on the Proportion of Patients in the Grey Zone
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Proportion of the Patients in the Grey Zone as Per the AASLD 2018 and the CSH/CSID 2022
3.3. Characteristics of the Grey Zone Patients as Per the AASLD 2018 and the CSH/CSID 2022
3.4. Changes in the Proportions in Grey Zone Patients with Varying ALT ULN Values as Per the AASLD 2018 and the CSH/CSID 2022
3.5. Subgroup Analyses by Age and Sex
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Phase 1 | Phase 2 | Phase 3 | Phase 4 | Grey Zone | |
---|---|---|---|---|---|
Terminology | |||||
CSH/CSID 2022 | HBeAg-positive chronic HBV infection | HBeAg-positive chronic hepatitis B | HBeAg-negative chronic HBV infection | HBeAg-negative chronic hepatitis B | Grey Zone/Indeterminate phase |
AASLD 2018 | Immune tolerant | HBeAg-positive immune active | Inactive | HBeAg-negative immune active | |
HBsAg | |||||
CSH/CSID 2022 | >1 × 104 a | Detectable | <1 × 103 a | Detectable | |
AASLD 2018 | Present for ≥ 6 months | ||||
HBeAg | Positive | Positive | Negative | Negative | Patients who do not fit into any of the criteria of phases 1~4 were deemed grey zone. |
HBV DNA, IU/mL | |||||
CSH/CSID 2022 | >2 × 107 | Detectable | Undetectable | Detectable | |
AASLD 2018 | >106 | >2 × 104 | <2 × 103 | ≥2 × 103 | |
ALT, U/L | |||||
CSH/CSID 2022 b | <1 × ULN | ≥1 × ULN | <1 × ULN | ≥1 × ULN | |
AASLD 2018 c | <1 × ULN | ≥2 × ULN | <1 × ULN | ≥2 × ULN |
AASLD 2018 N = 1971 | CSH/CSID 2022 N = 1444 | p Value | |
---|---|---|---|
Age | 42.0 (32.9, 51.6) | 44.2 (35.0, 52.4) | 0.001 |
% Male | 1267 (64.3) | 835 (57.8) | 0.000 |
% HBeAg-positive | 966 (49.0) | 563 (39.0) | <0.0001 |
PLT (×109/L) | 187.0 (141.0, 228.0) | 188.0 (145.0, 228.0) | 0.778 |
ALT (U/L) | 37.0 (25.0, 50.0) | 26.0 (20.0, 35.0) | <0.0001 |
AST (U/L) | 29.4 (23.4, 40.0) | 25.0 (21.0, 33.0) | <0.0001 |
Alb (g/L) | 44.0 (40.5, 46.6) | 44.0 (40.8, 46.6) | 0.844 |
TBil (μmol/L) | 15.1 (11.4, 21.2) | 14.6 (11.0, 20.4) | 0.059 |
HBV DNA (log10 IU/mL) | 3.9 (2.9, 5.2) | 3.6 (2.0, 4.5) | <0.0001 |
APRI | 0.4 (0.3, 0.7) | 0.3 (0.3, 0.5) | <0.0001 |
% APRI ≥ 1.5 | 224 (11.4) | 114 (7.9) | 0.001 |
FIB-4, Median | 1.1 (0.7, 2.1) | 1.2 (0.8, 2.0) | 0.218 |
% FIB-4 ≥ 3.25 | 278 (14.1) | 188 (13.0) | 0.389 |
AASLD 2018 (N = 1971) | CSH/CSID 2022 (N = 1444) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Age < 30 N = 338 n (%) | Age ≥ 30 N = 1633 n (%) | p Value | Male N = 1267 n (%) | Female N = 704 n (%) | p Value | Age < 30 N = 199 n (%) | Age ≥ 30 N = 1245 n (%) | p Value | Male N = 835 n (%) | Female N = 609 n (%) | p Value | |
FIB-4 ≥ 3.25 | 10 (3.0) | 268 (16.4) | <0.001 | 190 (15.0) | 88 (12.5) | 0.145 | 7 (3.5) | 181 (14.5) | <0.001 | 125 (15.0) | 63 (10.3) | 0.012 |
APRI ≥ 1.5 | 25 (7.4) | 199 (12.2) | 0.015 | 167 (13.2) | 57 (8.1) | 0.001 | 11 (5.5) | 103 (8.3) | 0.233 | 81 (9.7) | 33 (5.4) | 0.004 |
ALT ≥ 40 U/L | 178 (52.7) | 697 (42.7) | 0.001 | 717 (54.6) | 158 (22.4) | <0.001 | 33 (16.6) | 185 (14.9) | 0.600 | 162 (19.4) | 56 (9.2) | <0.001 |
PLT < 150 × 109/L | 65 (19.2) | 516 (31.6) | <0.001 | 406 (32.0) | 175 (24.9) | 0.001 | 38 (19.1) | 359 (28.8) | 0.006 | 253 (30.3) | 144 (23.7) | 0.006 |
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Xu, X.; Wang, H.; Shan, S.; Sun, Y.; Xu, X.; You, H.; Jia, J.; Zhuang, H.; Kong, Y.; on behalf of the China Registry of Hepatitis B (CR-HepB) Group. The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection. Viruses 2023, 15, 1212. https://doi.org/10.3390/v15051212
Xu X, Wang H, Shan S, Sun Y, Xu X, You H, Jia J, Zhuang H, Kong Y, on behalf of the China Registry of Hepatitis B (CR-HepB) Group. The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection. Viruses. 2023; 15(5):1212. https://doi.org/10.3390/v15051212
Chicago/Turabian StyleXu, Xiaoqian, Hao Wang, Shan Shan, Yameng Sun, Xiaoyuan Xu, Hong You, Jidong Jia, Hui Zhuang, Yuanyuan Kong, and on behalf of the China Registry of Hepatitis B (CR-HepB) Group. 2023. "The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection" Viruses 15, no. 5: 1212. https://doi.org/10.3390/v15051212