1.Research progress in the regulation of pathogenesis and the transformation of chronic liver disease by short-chain fatty acids
Qianqian JIN ; Shusheng LIAO ; Yue QIN ; Xiaoguang DOU ; Chong ZHANG
Chinese Journal of Hepatology 2024;32(3):268-272
Short-chain fatty acids are metabolites of the intestinal flora and serve as the main energy source for intestinal epithelial cells. At the same time, as important signaling molecules, it regulate a variety of cellular inflammatory responses and homeostatic proliferation through receptor-dependent and independent pathways. Short-chain fatty acids regulate the gut-liver axis and thereby directly act on the liver, participating in the pathogenesis and transformation of various liver diseases, including alcoholic liver disease, metabolic dysfunction-related liver disease, autoimmune liver disease, liver fibrosis, and hepatocellular carcinoma. In addition, short-chain fatty acids can inhibit HBV DNA replication. This article reviews the research progress on the role of short-chain fatty acids in aspects of the pathogenesis and transformation of chronic liver diseases.
2.Strategies for hepatitis B virus-infected patients in the immune-tolerant phase: complete therapy at the last mile
Yang DING ; Qiuju SHENG ; Xiaoguang DOU
Chinese Journal of Hepatology 2024;32(5):399-401
Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease’s characteristics and antiviral treatment strategies, are discussed here.
3.Therapeutic strategies, practice, and prospect of a clinical cure for chronic hepatitis B in China
Zhishuo MO ; Dongying XIE ; Bingliang LIN ; Xiaoguang DOU ; Mobin WAN ; Jiaji JIANG ; Yingren ZHAO ; Hong TANG ; Hui ZHUANG ; Zhiliang GAO
Chinese Journal of Hepatology 2024;32(5):411-417
Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.
4.Establishment and evaluation of anterior cervical discectomy fusion model in small-tailed Han sheep model
Xinyu DOU ; Yu LIU ; Xiao LIU ; Bin ZHU ; Fei JIA ; Linbang WANG ; Gong JIN ; Fei SHEN ; Xiaoguang LIU
Acta Laboratorium Animalis Scientia Sinica 2024;32(2):139-150
Objective Cervical disc herniation(CDH)is one of the common orthopaedic diseases.With the in-depth study of it and the development of cervical implants,the establishment of cervical fusion animal models has become an indispensable part.Notably however,studies of the establishment and evaluation of cervical fusion animal models in China are currently lacking.This study aimed to provide a suitable animal model and evaluation scheme for implants for cervical spine-related research.Methods Small-tailed Han sheep were chosen for anterior cervical discectomy fusion(ACDF)after modified surgery,and a polyetheretherketone(PEEK)interbody fusion cage(Cage)(control group),3D-printed Ti6Al4V Cage(group 1),and new method Ti6Al4V Cage(group 2)were implanted in different cervical segments(C2/3~C4/5)in each sheep,respectively.Hematology and histopathological analyses were carried out after surgery to evaluate recovery of sheep and the biosafety of the materials.Bone in-growth and bone fusion were assessed by X-ray,computed tomography(CT),Micro-CT and quantitative analysis,hard tissue section staining,and biomechanical tests.Results The modified ACDF ovine model was established successfully.There were no significant differences in important hematology indexes(P>0.05)and histopathological analysis showed no pathological changes,such as inflammatory cell infiltration.The implants had good biosafety.Furthermore,X-ray and CT examinations showed that the position of internal fixation and the interbody fusion were good.Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group,the bone volume/total volume and trabecular number were significantly increased(P<0.01)while the trabecular spacing was significantly decreased in the new method Ti6Al4V and 3D-printed Ti6Al4V groups compared with the PEEK Cage group(P<0.01).Moreover,the new method new method Ti6Al4V Cage group had more bone growth(P<0.01).Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and relatively dense pores in the new method Ti6Al4V and 3D-printed Ti6Al4V groups,and the combination was slightly better than that of PEEK Cage.Biomechanical evaluation indicated that the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extension,lateral bending,and axial rotation(P<0.05)compared with the PEEK cage,as well as enhancing the stability of the cervical vertebra,and the new method Ti6Al4 V Cage was more advantageous(P<0.05).Conclusions After the establishment of the modified ACDF ovine model,reasonable and effective assessment method were used to demonstrate the suitability and effectiveness of the model and the good biosecurity of all three Cage materials.Compared with the PEEK Cage,the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cages showed better performances in terms of bone growth and bone fusion,which could enhance the stability of the cervical vertebrae.The new method Ti6Al4V Cage was particularly advantageous.
5.Focus on the timing and strategies of antiviral therapy for special populations with chronic hepatitis B
Journal of Clinical Hepatology 2024;40(5):861-865
Several factors need to be considered for special populations with chronic hepatitis B(CHB),such as the family history of liver cirrhosis and liver cancer,age,disease stage,and antiviral response.It is necessary to select the appropriate timing of antiviral therapy and timely adjust antiviral strategies for CHB populations,which plays an important role in delaying disease progression and reducing the development of liver cirrhosis and hepatocellular carcinoma.This article elaborates on the timing and strategies for antiviral therapy in the special populations such as patients with chronic HBV infection who have an age of≤30 years and a normal alanine aminotransferase(ALT)level,pregnant women with chronic HBV infection who have an age of>30 years and a normal ALT level,children with chronic HBV infection,and treatment-experienced HBeAg-positive CHB patients with low-level viremia,so as to help clinicians choose a better timing of antiviral therapy and optimize the strategies of antiviral therapy for special CHB populations.
6.Expanding the indications for antiviral therapy for chronic hepatitis B: Advantages and disadvantages
Journal of Clinical Hepatology 2023;39(1):22-26
Chronic hepatitis B (CHB) is a chronic progressive disease caused by hepatitis B virus (HBV), and without timely and effective antiviral therapy, it will eventually develop into liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). Early initiation of antiviral therapy can prevent or delay disease progression and greatly reduce the incidence rates of liver cirrhosis, liver failure, and HCC. Due to the limited efficacy of current antiviral drugs, the indications for antiviral therapy are mainly applicable to patients with positive HBV DNA and persistent ALT abnormality and some special populations with HBV infection. However, some patients who cannot reach the criteria for antiviral therapy may have insidious disease progression, leading to adverse clinical outcomes. Therefore, the guidelines and consensus statements in China and globally are constantly expanding the indications for antiviral therapy for CHB, so as to bring benefits to more patients.
7.Antiviral therapy for chronic hepatitis B: the imperative to move from scaling-up treatment to full treatment
Chinese Journal of Hepatology 2023;31(3):225-227
Timely and effective antiviral therapy can prevent or delay the progression of the disease to cirrhosis, liver failure, or hepatocellular carcinoma in patients with chronic hepatitis B. Antiviral therapy indications are constantly expanding, and eventually it will be manageable to treat viral positives based on the new understanding of the disease progression and the changes in the definition of abnormal values in liver function tests.
8.Clinical efficacy analysis of TMF for the treatment of hyperviremia HBeAg-positive chronic hepatitis B patients with incomplete response to first-line oral antiviral nucleos(t)ide analogues
Qiuju SHENG ; Chao HAN ; Yanwei LI ; Chong ZHANG ; Xiaoguang DOU ; Yang DING
Chinese Journal of Hepatology 2023;31(3):252-257
Objective:To prospectively explore the treatment strategies for clinical difficulties in patients with hyperviremia HBeAg-positive chronic hepatitis B with incomplete response to first-line nucleos(t)ide analogues (NAs).Methods:Patients with hyperviremia HBeAg-positive chronic hepatitis B were treated with first-line NAs, including entecavir, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) for 48 weeks or more. Tenofovir amibufenamide (TMF) or TAF therapy was changed when HBV DNA remained positive and then divided into a TMF group and a TAF group. Clinical efficacy of treatment was evaluated at 24 and 48 weeks, including HBV DNA undetectable rates and virological and serological responses in both patient groups.Results:In the TMF group and the TAF groups, 30 and 26 cases completed 24-week follow-up, while 18 and 12 cases completed 48-week follow-up. There were no statistically significant differences in baseline HBV DNA, HBsAg, and HBeAg levels between the two groups before switching to TMF/TAF therapy ( P > 0.05). At 24 weeks of treatment, 19 (19/30, 63.33%) cases in the TMF group had HBV DNA negative conversion, while 14 (14/26, 53.85%) cases in the TAF group had HBV DNA negative conversion ( P > 0.05). Among the patients who completed 48 weeks of follow-up, 15 (15/18, 83.33%) cases in the TMF group and 7 (7/12, 58.33%) cases in the TAF group had negative HBV DNA tests ( P > 0.05). The changes in HBsAg and HBeAg levels between the two groups of patients at 24 and 48 weeks of treatment were not statistically significant compared to baseline ( P > 0.05). Conclusion:TMF is effective in treating patients with hyperviremia HBeAg-positive CHB with an incomplete response to first-line NAs treatment, but there is no significant difference compared to TAF.
9.Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease.
Yanwei LI ; Yunrui LU ; Mozuo NIAN ; Qiuju SHENG ; Chong ZHANG ; Chao HAN ; Xiaoguang DOU ; Yang DING
Chinese Journal of Natural Medicines (English Ed.) 2023;21(9):643-657
Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.
Humans
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Drugs, Chinese Herbal/therapeutic use*
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Fibrosis
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Liver Diseases/drug therapy*
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Treatment Outcome
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Liver Cirrhosis/drug therapy*
10.Focus on the special population with hepatitis B virus infection: Early diagnosis, early treatment, and early benefits
Journal of Clinical Hepatology 2022;38(11):2441-2443
Hepatitis B virus (HBV) infection is a major public health problem worldwide. With the extensive prophylactic vaccination with hepatitis B vaccine for neonates and an increasing number of patients receiving antiviral treatment, remarkable achievements have been made in HBV infection among Chinese children. However at present, there is still a high HBsAg-positive rate among the adults in China, and with more and more special populations, it is necessary to perform timely screening and diagnosis and give antiviral therapy as early as possible, so as to prevent or delay the progression to liver cirrhosis, liver failure, and hepatocellular carcinoma after HBV infection. The selection of treatment timing and drugs should not only focus on HBV virology and liver function, but also consider chronic underlying diseases, mother-to-child transmission, and reactivation of HBV in patients receiving chemotherapy and immunosuppressants, thereby realizing the timely screening, diagnosis, and treatment of the population at a high risk of HBV and special populations and bringing more benefits to patients.

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