1.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
2.Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B.
Man-Ting HOU ; Kai-Xin DING ; Ting-Ting HE ; Yan YANG ; Zhao-Fang BAI ; Xiao-He XIAO
China Journal of Chinese Materia Medica 2022;47(1):224-234
The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.
Drugs, Chinese Herbal/adverse effects*
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Hepatitis B, Chronic/drug therapy*
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Humans
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Liver Cirrhosis/drug therapy*
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Tablets
3. Effect of Li-Zhong-Tang on gastric ulcer in rats based on Raf/MEK/ERK signaling pathway and its mechanism
Hou-Pan SONG ; Xiao-Juan CHEN ; Xin-Yi CHEN ; Jing-Yue QIU ; Man-Ting WU ; Hou-Pan SONG ; Xiao-Juan CHEN ; Xin-Yi CHEN ; Jing-Yue QIU ; Man-Ting WU ; Hou-Pan SONG ; Qing-Hua PENG ; Mei-Yan ZENG
Chinese Pharmacological Bulletin 2021;37(9):1291-1298
Aim To investigate the effect of Li-Zhong-Tang (LZT) in the treatment of gastric ulcer (GU) with pattern of spleen-stomach vacuity cold in rats based on Raf/MEK/ERK signaling pathway and the underlying molecular mechanism. Methods SD rats were randomly divided into normal group, GU model group, esomeprazole (ESO) group, LZT low dose and high dose groups. The morphological changes of gastric mucosa were observed by naked eyes and HE staining. The activities of gastric acid and pepsin were measured. The contents of prostaglandin E
4. Prediction of T cell and B cell epitopes of the 22-, 47-, 56-, and 58-kDa proteins of Orientia tsutsugamushi
Li-Na NIU ; Ting-Ting FU ; Yu-Ying DONG ; Zi-Hao WANG ; Si-Qi WANG ; Xuan ZHAO ; Nai-Xu HOU ; Qiang WU ; Qian CHEN ; Man-Ling CHEN ; Jin-Chun TU ; Li-Na NIU ; Qiang WU
Asian Pacific Journal of Tropical Biomedicine 2019;9(10):443-448
Objective: To predict B cell and T cell epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins. Methods: The sequences of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA, DNAstar, Bcepred, ABCpred, NetMHC, NetMHC II and IEDB. The 58-kDa tertiary structure model was built by MODELLER9.17. Results: The 22-kDa B-cell epitopes were located at positions 194-200, 20-26 and 143-154, whereas the T-cell epitopes were located at positions 154-174, 95-107, 17-25 and 57-65. The 47-kDa protein B-cell epitopes were at positions 413-434, 150-161 and 283-322, whereas the T-cell epitopes were located at positions 129-147, 259-267, 412-420 and 80-88. The 56-kDa protein B-cell epitopes were at positions 167-173, 410-419 and 101-108, whereas the T-cell epitopes were located at positions 88-104, 429-439, 232-240 and 194-202. The 58-kDa protein B-cell epitopes were at positions 312-317, 540-548 and 35-55, whereas the T-cell epitopes were located at positions 415-434, 66-84 and 214-230. Conclusions: We identified candidate epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins from Orientia tsutsugamushi. In the case of 58-kDa, the dominant antigen is displayed on tertiary structure by homology modeling. Our findings will help target additional recombinant antigens with strong specificity, high sensitivity, and stable expression and will aid in their isolation and purification.