Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment
Abstract Longitudinal serological proteomic dynamics during antiviral therapy (AVT) in chronic hepatitis B (CHB) patients with liver fibrosis remain poorly characterized. Here, using four-dimensional data-independent acquisition mass spectrometry (4D-DIA-MS), paired liver biopsy (LBx)-proven serum s...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63006-z |
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| author | Mengyang Zhang Shuyan Chen Xiaoning Wu Jialing Zhou Bingqiong Wang Tongtong Meng Rongxuan Hua Yameng Sun Hong You Wei Chen |
| author_facet | Mengyang Zhang Shuyan Chen Xiaoning Wu Jialing Zhou Bingqiong Wang Tongtong Meng Rongxuan Hua Yameng Sun Hong You Wei Chen |
| author_sort | Mengyang Zhang |
| collection | DOAJ |
| description | Abstract Longitudinal serological proteomic dynamics during antiviral therapy (AVT) in chronic hepatitis B (CHB) patients with liver fibrosis remain poorly characterized. Here, using four-dimensional data-independent acquisition mass spectrometry (4D-DIA-MS), paired liver biopsy (LBx)-proven serum samples from 130 CHB liver fibrosis patients undergoing short-term (78 weeks) or long-term (260 weeks) AVT are analyzed. Our findings show that prolonged AVT drives progressive serological proteomic remodeling in fibrosis regressors, characterized by a temporal inversion in the activation of the complement and coagulation cascades. Using machine learning algorithms trained on the 4D-DIA-MS discovery cohort, we develop a logistic regression model incorporating a seven-protein panel for short-term AVT and a three-protein panel for long-term AVT, respectively, both of which demonstrate moderate discriminatory capabilities for fibrosis regression. Subsequent external validation in an independent cohort (n = 54) with serial LBx assessments at baseline, 78 weeks, and 260 weeks, where serological proteins are quantified using parallel reaction monitoring mass spectrometry (PRM-MS), further confirms their generalizability. Furthermore, our longitudinal trajectory analysis highlights that the long-term proteomic signature exhibits greater stability compared to the short-term panel. This study proposes and validates duration-adapted serological proteomic panels as non-invasive tools for monitoring histological fibrosis regression in on-treatment CHB patients. |
| format | Article |
| id | doaj-art-0e90d749dcc7466eac22cde96e46b4fa |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0e90d749dcc7466eac22cde96e46b4fa2025-08-24T11:36:36ZengNature PortfolioNature Communications2041-17232025-08-0116111510.1038/s41467-025-63006-zSerological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatmentMengyang Zhang0Shuyan Chen1Xiaoning Wu2Jialing Zhou3Bingqiong Wang4Tongtong Meng5Rongxuan Hua6Yameng Sun7Hong You8Wei Chen9Liver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityLiver Research Center, Beijing Friendship Hospital, Capital Medical UniversityState Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical UniversityAbstract Longitudinal serological proteomic dynamics during antiviral therapy (AVT) in chronic hepatitis B (CHB) patients with liver fibrosis remain poorly characterized. Here, using four-dimensional data-independent acquisition mass spectrometry (4D-DIA-MS), paired liver biopsy (LBx)-proven serum samples from 130 CHB liver fibrosis patients undergoing short-term (78 weeks) or long-term (260 weeks) AVT are analyzed. Our findings show that prolonged AVT drives progressive serological proteomic remodeling in fibrosis regressors, characterized by a temporal inversion in the activation of the complement and coagulation cascades. Using machine learning algorithms trained on the 4D-DIA-MS discovery cohort, we develop a logistic regression model incorporating a seven-protein panel for short-term AVT and a three-protein panel for long-term AVT, respectively, both of which demonstrate moderate discriminatory capabilities for fibrosis regression. Subsequent external validation in an independent cohort (n = 54) with serial LBx assessments at baseline, 78 weeks, and 260 weeks, where serological proteins are quantified using parallel reaction monitoring mass spectrometry (PRM-MS), further confirms their generalizability. Furthermore, our longitudinal trajectory analysis highlights that the long-term proteomic signature exhibits greater stability compared to the short-term panel. This study proposes and validates duration-adapted serological proteomic panels as non-invasive tools for monitoring histological fibrosis regression in on-treatment CHB patients.https://doi.org/10.1038/s41467-025-63006-z |
| spellingShingle | Mengyang Zhang Shuyan Chen Xiaoning Wu Jialing Zhou Bingqiong Wang Tongtong Meng Rongxuan Hua Yameng Sun Hong You Wei Chen Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment Nature Communications |
| title | Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment |
| title_full | Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment |
| title_fullStr | Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment |
| title_full_unstemmed | Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment |
| title_short | Serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis B patients on treatment |
| title_sort | serological proteomic characterization for monitoring liver fibrosis regression in chronic hepatitis b patients on treatment |
| url | https://doi.org/10.1038/s41467-025-63006-z |
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