1.Expert consensus on MRI diagnosis of liver fibrosis in chronic hepatitis B (version 2023).
Chinese Journal of Hepatology 2023;31(10):1009-1017
Chronic hepatitis B is a common chronic inflammatory disease of the liver in China that frequently results in sustained damage to the liver parenchyma, followed by liver fibrosis, and ultimately progresses to unfavorable outcomes such as cirrhosis, liver failure, and liver cancer. Liver fibrosis reversal can be achieved through early and effective intervention. Therefore, timely and accurate assessment of the degree of liver fibrosis is of great clinical significance for the treatment and prognosis assessment of patients with chronic hepatitis B. MRI plays a crucial role in the early assessment and monitoring of the therapeutic efficacy of liver fibrosis in chronic hepatitis B. Currently, there is a lack of uniform consensus on MRI scanning protocols and related diagnostic thresholds for liver fibrosis in chronic hepatitis B, which is not conducive to practical clinical evaluation and application. This expert consensus is based on a full review of relevant domestic and international literature and the formulation of methodologies based on evidence-based medical guidelines and standards to develop recommendations for MRI scanning techniques and the diagnosis of liver fibrosis in chronic hepatitis B, with a view to providing a clear basis for the clinical diagnosis.
Humans
;
Hepatitis B, Chronic/drug therapy*
;
Consensus
;
Liver Cirrhosis/diagnosis*
;
Liver/diagnostic imaging*
;
Magnetic Resonance Imaging/methods*
2.Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B.
Chuan JIANG ; Jinqing LIU ; Ronghua LI ; Keyu CHEN ; Wenting PENG ; Lei FU ; Shifang PENG
Journal of Central South University(Medical Sciences) 2023;48(5):698-706
OBJECTIVES:
Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).
METHODS:
This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.
RESULTS:
Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).
CONCLUSIONS
The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans
;
Hepatitis B, Chronic/complications*
;
Hepatitis B e Antigens/therapeutic use*
;
Alkaline Phosphatase
;
DNA, Viral
;
Retrospective Studies
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Fibrosis
;
Hepatitis B virus/genetics*
;
Liver Cirrhosis/etiology*
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Inflammation/drug therapy*
;
Antiviral Agents/therapeutic use*
;
Alanine Transaminase
3.Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022).
Hong YOU ; Ya Meng SUN ; Meng Yang ZHANG ; Yue Min NAN ; Xiao Yuan XU ; Tai Sheng LI ; Gui Qiang WANG ; Jin Lin HOU ; Zhongping DUAN ; Lai WEI ; Fu Sheng WANG ; Ji Dong JIA ; Hui ZHUANG
Chinese Journal of Hepatology 2023;31(4):385-388
Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.
Humans
;
Hepatitis B, Chronic/drug therapy*
;
Hepatitis B/drug therapy*
;
Hepatitis B virus
;
Antiviral Agents/therapeutic use*
;
Gastroenterology
4.Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection.
Wen Ping ZHAO ; Li Min WANG ; Jing Yue WANG ; Si XIE ; Jie Hua JIN ; Yuan HUANG
Chinese Journal of Hepatology 2023;31(5):489-494
Objective:b> To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods:b> Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results:b> 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion:b> The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.
Humans
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Male
;
Female
;
Hepatitis B, Chronic/drug therapy*
;
Liver Cirrhosis/pathology*
;
Elasticity Imaging Techniques
;
Antiviral Agents/therapeutic use*
;
Liver/pathology*
5.A conceptual framework for dynamics of cccDNA in hepatitis B virus.
Chinese Journal of Hepatology 2023;31(5):545-550
The resolution of the hepatitis C issue has raised expectations for a chronic hepatitis B cure, driving the industry to expand investment in research and development efforts to strengthen functional cure strategies. These strategies have a wide variety of types, and the published research findings are heterogeneous. The theoretical analysis of these strategies is of great significance for determining prioritized research orientations as well as sensibly allocating research and development resources. However, due to a paucity of necessary conceptual models, current theoretical analysis has not been able to unify various therapeutic strategies into a proper theoretical framework. In view of the fact that the decrease in the quantity of cccDNA is an inevitable core event accompanied by the process of functional cure, this paper intends to analyze several chronic hepatitis B cure strategies using cccDNA dynamics as a framework. Furthermore, there are currently few studies on the dynamics of the cccDNA field, hoping that this article can promote recognition and research in this field.
Humans
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Hepatitis B virus/genetics*
;
Hepatitis B, Chronic/drug therapy*
;
Antiviral Agents/therapeutic use*
;
Virus Replication
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DNA, Circular/therapeutic use*
;
DNA, Viral/genetics*
;
Hepatitis B/drug therapy*
6.Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome.
Dan Ying CHENG ; Peng GUO ; Feng Xia SUN ; Xiao Jing WANG ; Wei LI ; Qin CHEN ; Gui Qin ZHOU ; Rong Bing WANG ; Hui Chun XING
Chinese Journal of Hepatology 2023;31(6):608-613
Objective:b> To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods:b> Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results:b> After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion:b> Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.
Humans
;
Antiviral Agents/therapeutic use*
;
Hepatitis B, Chronic/drug therapy*
;
Liver Cirrhosis/drug therapy*
;
Prospective Studies
;
Treatment Outcome
8.Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy.
Ting ZHANG ; You DENG ; Hai Yan KANG ; Hui Ling XIANG ; Yue Min NAN ; Jin Hua HU ; Qing Hua MENG ; Ji Lian FANG ; Jie XU ; Xiao Ming WANG ; Hong ZHAO ; Calvin Q PAN ; Ji Dong JIA ; Xiao Yuan XU ; Wen XIE
Chinese Journal of Hepatology 2023;31(7):692-697
Objective:b> To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods:b> Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results:b> 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion:b> Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans
;
Hepatitis B virus/genetics*
;
Hepatitis B, Chronic/drug therapy*
;
Antiviral Agents/adverse effects*
;
Esophageal and Gastric Varices/complications*
;
Liver Cirrhosis/complications*
;
Treatment Outcome
;
Gastrointestinal Hemorrhage/complications*
;
Hepatitis B/drug therapy*
9.Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study.
Xiao Qian XU ; Hao WANG ; Shan SHAN ; Hong YOU ; Yue Min NAN ; Xiao Yuan XU ; Zhong Ping DUAN ; Lai WEI ; Jin Lin HOU ; Hui ZHUANG ; Ji Dong JIA ; Yuan Yuan KONG
Chinese Journal of Hepatology 2023;31(7):698-704
Objective:b> To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods:b> Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results:b> A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion:b> The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.
Humans
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Male
;
Female
;
Adult
;
Aged, 80 and over
;
Antiviral Agents/therapeutic use*
;
Hepatitis B, Chronic/epidemiology*
;
Hepatitis B e Antigens
;
Hepatitis B/drug therapy*
;
Hepatitis B Surface Antigens
;
Hepatitis A
;
Liver Cirrhosis/drug therapy*
;
China/epidemiology*
;
Registries
;
Hepatitis B virus/genetics*
;
DNA, Viral
10.Anti-hepatitis B virus activities of natural products and their antiviral mechanisms.
Wanyu DENG ; Fu CHEN ; Yue ZHAO ; Ming ZHOU ; Min GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):803-811
Chronic hepatitis B (CHB) infections caused by the hepatitis B virus (HBV) continue to pose a significant global public health challenge. Currently, the approved treatments for CHB are limited to interferon and nucleos(t)ide analogs, both of which have their limitations, and achieving a complete cure remains an elusive goal. Therefore, the identification of new therapeutic targets and the development of novel antiviral strategies are of utmost importance. Natural products (NPs) constitute a class of substances known for their diverse chemical structures, wide-ranging biological activities, and low toxicity profiles. They have shown promise as potential candidates for combating various diseases, with a substantial number demonstrating anti-HBV properties. This comprehensive review focuses on the current applications of NPs in the fight against HBV and provides a summary of their antiviral mechanisms, considering their impact on the viral life cycle and host hepatocytes. By offering insights into the world of anti-HBV NPs, this review aims to furnish valuable information to support the future development of antiviral drugs.
Humans
;
Hepatitis B virus
;
Hepatitis B, Chronic/drug therapy*
;
Antiviral Agents/therapeutic use*
;
Biological Products/therapeutic use*
;
Hepatocytes

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