1.Molecular mechanisms of traditional Chinese medicine in reversing liver fibrosis
Xiaoling GUO ; Zhansheng JIA ; Jing ZHANG
Journal of Clinical Hepatology 2025;41(1):170-175
Liver fibrosis is the intermediate stage in the progression of many chronic liver diseases to liver cirrhosis, and although there is still a lack of widely accepted and effective chemical or biological agents for reversing liver fibrosis, significant progress has been made in the treatment of liver fibrosis with traditional Chinese medicine. This article elaborates on the molecular mechanisms of different herbal extracts, a single Chinese herb, and Chinese patent drugs in reversing liver fibrosis, such as inhibiting liver inflammation, exerting an effect on lipid peroxidation damage, inhibiting the activation and proliferation of hepatic stellate cells, regulating the synthesis and secretion of pro-fibrogenic factors, and regulating the synthesis and degradation of extracellular matrix, in order to provide more precise options for the treatment of liver fibrosis in the future.
2.Predictive value of TgAb for disease status in differentiated thyroid cancer patients with stimulated Tg<1 μg/L during postoperative assessment
Si ZHOU ; Ruping LI ; Lijun WANG ; Kai CHEN ; Xianmin DING ; Sen WANG ; Zhansheng ZHANG ; Jianmin JIA ; Hui YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(9):540-543
Objective:To analyze the association between thyroglobulin antibody (TgAb) and differentiated thyroid cancer (DTC) metastases detected by post-radioactive iodine (RAI) therapy scan, when stimulated thyroglobulin (sTg) <1 μg/L.Methods:A total of 314 (68 males, 246 females, age (44.5±12.5) years) post-thyroidectomy DTC patients whose sTg <1 μg/L between March 2013 and May 2017 in Henan Cancer Hospital were enrolled retrospectively. Patients underwent 131I whole-body planar imaging ( 131I-WBS) and SPECT/CT imaging 5 d after 131I administration. Iodine avid metastases were compared between TgAb-positive group and TgAb-negative (TgAb<4 kU/L) group. Logistic regression analysis was conducted to assess odds ratio ( OR) for iodine avid metastases in each subgroup (Q1: 4 kU/L≤TgAb≤9.27 kU/L; Q2: 9.27 kU/L
3. A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection
Yinghui GAO ; Guangming LI ; Qinglong JIN ; Yingren ZHAO ; Zhansheng JIA ; Xiaorong MAO ; Yongfeng YANG ; Jia SHANG ; Gongchen WANG ; Wen XIE ; Shanming WU ; Mingxiang ZHANG ; Jinlin HOU ; Dongliang LI ; Yuemin NAN ; Yujuan GUAN ; Chunxia ZHU ; Yangzhou YUAN ; Lai WEI
Chinese Journal of Hepatology 2019;27(5):352-357
Objective:
To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.
Methods:
Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.
Results:
132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.
Conclusion
Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.
4.Efficacy and safety of yimitasvir phospha combined with sofosbuvir in patients with chronic hepatitis C virus infection
Bifen LUO ; Jinglan JIN ; Huiying RAO ; Qin NING ; Jinlin HOU ; Lang BAI ; Yongfeng YANG ; Sujun ZHENG ; Xiaorong MAO ; Jun10 QUAN ; Dongliang YANG ; Lunli ZHANG ; Caiyan ZHAO ; Zhansheng JIA ; Fuchun ZHANG ; Zuojiong GONG ; Feng LIN ; Guiqiang WANG ; Lin LUO ; Li DENG ; Hongming XIE ; Jing LI ; Yingjun ZHANG ; Lai WEI
Chinese Journal of Infectious Diseases 2019;37(7):420-429
Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127/129), with 98.4%(63/64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64/65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 =0.000 2, P=0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24/24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15/129) patients had baseline NS5A Y93H/Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2/129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.
5.Research advances in the clinical effect of tenofovir alafenamide in treatment of chronic hepatitis B
Suna WANG ; Jianqi LIAN ; Zhansheng JIA
Journal of Clinical Hepatology 2019;35(8):1828-1833
Tenofovir alafenamide (TAF) is a novel nucleoside reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV) infection and chronic hepatitis B virus (HBV) infection. Compared with tenofovir disoproxil fumarate, TAF has better plasma stability and stronger liver-targeting ability and can significantly reduce the adverse events of renal injury and reduced bone mineral density. This article summarizes the research advances in the pharmacological characteristics, metabolic pathways, drug interactions, drug resistance, and renal safety of TAF and its role in patients with chronic HBV infection.
6. Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis
Lai WEI ; Guiqiang WANG ; Kopecky-Bromberg SARAH ; Jun CHENG ; Qing XIE ; Maorong WANG ; Min XU ; Zhongping DUAN ; Jinlin HOU ; Mingxiang ZHANG ; Yuexin ZHANG ; Hong TANG ; Wei ZHAO ; Shumei LIN ; Zhansheng JIA ; Junqi NIU ; Zhiliang GAO ; Hong YUAN ; Minghua LIN ; Xinmin ZHOU ; Yan LUO ; Fredrick LINDA ; Mobashery NILOUFAR ; Ye WANG ; Jidong JIA
Chinese Journal of Hepatology 2018;26(5):353-358
Objective:
To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis.
Methods:
An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs.
Results:
A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal.
Conclusion
Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.
7.Retrospect and reflection: the past 30 years of research on hepatitis C prophylaxis and treatment
Journal of Clinical Hepatology 2015;31(11):1803-1806
The research on prophylaxis and treatment of hepatitis C has been performed for more than 30 years, with outstanding achievements. The discovery and confirmation of hepatitis C virus (HCV) was a milestone for how humans discovered new life. Emphasis on HCV molecular biology, infection immunity, and pathogenesis is the basic rule for scientific research on infectious diseases. PEG-IFN combined with ribavirin as the standardized antiviral treatment has been a great success; this combination therapy achieves a sustained viral response more than 80% in Chinese people, which is a typical example for successful clinical application of cytokines. Direct-acting antiviral agent(DAA) or combined application has made it possible to cure all patients infected with hepatitis C, which is the most successful example for reference. Persistent viral infection and maintenance of immune homeostasis under certain conditions are the results of the interaction between the host and the virus, and the development of vaccines will be continued.
8.Progress in treatment of hypersplenism in patients with post-hepatitis cirrhosis
Yan LIANG ; Wenjing YI ; Zhansheng JIA
Journal of Clinical Hepatology 2015;31(11):1924-1927
Hypersplenism is a common complication of post-hepatitis cirrhosis, and may not need to be treated. The treatment of hypersplenism is not considered if it is not proven clinically beneficial to patients. However, there are still some patients with hypersplenism who should be treated for some reasons. This article reviews the latest progress in the therapies for hypersplenism, including splenectomy, splenic artery embolization, splenic radiofrequency ablation, liver transplantation, medication, and transjugular intrahepatic portosystemic shunt. It is demonstrated that all the above treatments have advantages and disadvantages. Minimally invasive methods, through currently preferred for hypersplenism, have not yet been clinically applied for a long period, and remain to be technically improved and supported by relevant evidence for standardization.
9.Persistent hepatitis virus infection and immune homeostasis
Yun ZHOU ; Jianqi LIAN ; Zhansheng JIA
Journal of Clinical Hepatology 2014;30(9):851-854
Homeostasis between the host and viruses is naturally maintained.On the one hand,the immune system activates the immune re-sponse to kill or eliminate viruses;on the other hand,the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance.Long-term coexistence of the host and viruses is the process involving various immune cells and molecules and is the result of homeostasis maintenance in antiviral immune response.The immune homeostasis maintained during persis-tent infections with hepatitis viruses is analyzed by the cellular and molecular mechanisms.
10.Improving understanding of liver immune function and enhancing research on cell therapy for liver diseases
Journal of Clinical Hepatology 2014;30(9):839-841
As an important immune organ,the liver has a unique immune microenvironment,and is one of the important places for innate immunity and adaptive immunity.The liver is closely connected with the immune system through the gut-liver axis and is also the target or-gan of immune injury.However,the defensive role of the liver for Hepadnaviridae remains unclear.Cell therapy for liver diseases includes input of liver cells or stem cells for functional replacement,therapy by immune cells for antiviral and antitumor purposes,and genetic therapy for hereditary hepatopathy with cells as the carrier.The features of mesenchymal stem cells,multi-directional differentiation potential and immunomodulatory property,become the hot spots of cell therapy for liver diseases,and efficient in vitro amplification of cells makes it possi-ble for the use of NK cells in the treatment of hepatocellular carcinoma.

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