1.Comparison of the population covered by the 2024 version of the WHO's hepatitis B prevention and treatment guidelines and the Chinese antiviral treatment guidelines
Bingqiong WANG ; Shan SHAN ; Yuanyuan KONG ; Xiaoning WU ; Jialing ZHOU ; Yameng SUN ; Shuyan CHEN ; Hao WANG ; Xiaoqian XU ; Shuai XIA ; Jidong JIA ; Hong YOU
Chinese Journal of Hepatology 2024;32(6):525-531
		                        		
		                        			
		                        			Objective:This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB).Methods:The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications.Results:A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines.Conclusion:The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.
		                        		
		                        		
		                        		
		                        	
2.Expanding initial anti-HBV therapy for chronic hepatitis B: Reducing the treatment threshold of alanine aminotransferase
Jiayi ZHANG ; Shuyan CHEN ; Hong YOU
Journal of Clinical Hepatology 2023;39(1):27-30
		                        		
		                        			
		                        			 In order to achieve the global goal of eliminating viral hepatitis as a public health threat by 2030 proposed by the World Health Organization, it is of great importance to expand the treatment of chronic hepatitis B patients. Recent studies have shown that alanine aminotransferase (ALT) is associated with liver inflammation, fibrosis, hepatocellular carcinoma, and outcome events of liver disease. Besides, as a strategy for expanding antiviral therapy, reducing the treatment threshold of ALT can reduce the occurrence of liver cirrhosis, hepatocellular carcinoma, and liver-related death. In the Expert opinion on expanding antiviral therapy for chronic hepatitis B published in China in 2022, the treatment indication for chronic hepatitis B patients was updated to positive serum HBV DNA and ALT above the treatment threshold (30 U/L for male and 19 U/L for female), with the exclusion of other causes. 
		                        		
		                        		
		                        		
		                        	
3.Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients
Xiaoning WU ; Xiaoqian XU ; Jialing ZHOU ; YaMeng SUN ; Huiguo DING ; Wen XIE ; Guofeng CHEN ; Anlin MA ; HongXin PIAO ; Bingqiong WANG ; Shuyan CHEN ; Tongtong MENG ; Xiaojuan OU ; Hwai-I YANG ; Jidong JIA ; Yuanyuan KONG ; Hong YOU
Clinical and Molecular Hepatology 2023;29(3):747-762
		                        		
		                        			 Background/Aims:
		                        			Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). 
		                        		
		                        			Methods:
		                        			Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. 
		                        		
		                        			Results:
		                        			The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. 
		                        		
		                        			Conclusions
		                        			The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted. 
		                        		
		                        		
		                        		
		                        	
4.Different treatment strategies in patients with HBeAg-positive and negative chronic hepatitis B
Mengyang ZHANG ; Shuyan CHEN ; Yameng SUN ; Hong YOU
Chinese Journal of Hepatology 2023;31(3):238-241
		                        		
		                        			
		                        			Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.
		                        		
		                        		
		                        		
		                        	
5.Reversal of hepatic fibrosis: more evidence and more challenges
Jiayi ZHANG ; Yameng SUN ; Shuyan CHEN ; Hong YOU
Chinese Journal of Hepatology 2022;30(6):569-571
		                        		
		                        			
		                        			Hepatic fibrosis is a response to various types of hepatic injury, which can lead to cirrhosis and its complications. In recent years, in patients with viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, autoimmune liver disease and others the fibrosis or even early cirrhosis can be regressed if the etiology are controlled. Liver biopsy is still the gold standard for assessing fibrosis reversal, but non-invasive methods such as transient elastography hold great promise due to the ease to use for dynamic monitoring. Mechanisms of hepatic fibrosis reversal include extracellular matrix degradation, hepatocyte regeneration, and vascular remodeling. Presently, novel agents targeting the steps of fibrosis are urgently need for achieving regression of liver fibrosis.
		                        		
		                        		
		                        		
		                        	
6.Histological regression and clinical benefits in patients with liver cirrhosis after long-term anti-HBV treatment
Shuyan CHEN ; Yameng SUN ; Jialing ZHOU ; Xiaoning WU ; Tongtong MENG ; Bingqiong WANG ; Hui LIU ; Tailing WANG ; Chen SHAO ; Xinyu ZHAO ; Xiaoqian XU ; Yuanyuan KONG ; Xiaojuan OU ; Jidong JIA ; Hong YOU
Chinese Journal of Hepatology 2022;30(6):583-590
		                        		
		                        			
		                        			Objective:Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients.Methods:Treatment-na?ve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis.Results:Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably ( P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression ( OR=0.887, 95% CI: 0.802-0.981, P=0.020). Conclusions:After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.
		                        		
		                        		
		                        		
		                        	
7.Analysis of change in esophageal varices and clinical characteristics in hepatitis B virus-related cirrhosis after antiviral therapy
Bingqiong WANG ; Xiaoning WU ; Jialing ZHOU ; Yameng SUN ; Tongtong MENG ; Shuyan CHEN ; Qiushuang GUAN ; Zhiying HE ; Shanshan WU ; Yuanyuan KONG ; Xiaojuan OU ; Jidong JIA ; Hong YOU
Chinese Journal of Hepatology 2022;30(6):591-597
		                        		
		                        			
		                        			Objective:To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis.Methods:Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data.Results:All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% ( χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices ( χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion:After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.
		                        		
		                        		
		                        		
		                        	
8.Diagnosis and management of primary biliary cholangitis with osteoporosis
Wen ZHANG ; Shuyan CHEN ; Tingting LYU ; Hong YOU
Journal of Clinical Hepatology 2021;37(10):2272-2276
		                        		
		                        			
		                        			 Primary biliary cholangitis (PBC) is a chronic progressive cholestatic liver disease often observed in the middle-aged and elderly women and it can eventually lead to liver cirrhosis or liver failure. Osteoporosis is one of the common complications in PBC patients and is characterized by decreased bone mass and increased susceptibility to fractures. Osteoporosis and fractures caused by osteoporosis seriously affect the quality of life of PBC patients, and with the improvement of PBC treatment strategies and the increase in life expectancy, early diagnosis, prevention, and treatment of PBC with osteoporosis is of particular importance. This article briefly summarizes the epidemiology, pathogenesis, and diagnosis and treatment of patients with PBC and osteoporosis and proposes current challenges and future research directions. 
		                        		
		                        		
		                        		
		                        	
9. Clinical characteristics and diagnosis of early hydatidiform mole
Lanzhou JIAO ; Shuyan YOU ; Yaping WANG ; Chenggong ZHU ; Jiyong JIANG
Chinese Journal of Obstetrics and Gynecology 2019;54(11):756-762
		                        		
		                        			 Objective:
		                        			To evaluate the clinical characteristics and diagnostic strategies of early hydatidiform mole.
		                        		
		                        			Methods:
		                        			A retrospective cohort study was conducted of 526 women with hydatidiform mole who underwent suction curettage and were confirmed by histopathology in Dalian Maternal and ChildHealth Care Hospital from Feb. 2013 to Feb. 2018, including 484 women with gestational age less than or equal to 12 weeks (the early group) and 42 women with gestational age greater than 12 weeks (the late group). The clinical characteristics between the two groups were compared, and the pathological diagnosis and pre-evacuation ultrasound examination of the early group were further discussed.
		                        		
		                        			Results:
		                        			Compared with the late group, the clinical characteristics of the early group tended to be atypical, and the incidence of vaginal bleeding, excessive uterine size, theca lutein cysts (>6 cm) and pregnancy complications decreased significantly (all 
		                        		
		                        	
10. Prenatal ultrasound characteristics of fetal congenital absence of the ductus venosus and follow-up analysis of the prognosis
Yanqing YIN ; Chunli JING ; Shuyan YOU
Chinese Journal of Postgraduates of Medicine 2018;41(8):746-749,759
		                        		
		                        			 Objective:
		                        			To investigate the sonographic findings of fetal congenital absence of the ductus venosus (ADV) and its effect on the prognosis of fetus.
		                        		
		                        			Methods:
		                        			The ultrasonographic features of 11cases of fetal ADV deficiency diagnosed from December 2013 to June 2017 were retrospectively analyzed, and the fetal prognosis was followed up.
		                        		
		                        			Results:
		                        			Of the 11 cases, umbilical vein flew directly back to the right atrium in 7 cases; umbilical vein connected with the inferior vena cava in 1 case; umbilical vein directly flowed into the iliac vein in 1 case; umbilical vein and portal vein connection in the other 2 cases. Of the 11 cases, 4 cases were solitary and had no abnormality after birth; 5 cases were complicated with abnormal structure of intracardiac and extracardiac system; 2 cases were only followed with abnormal extracardiac system. Of the 5 complicated cases, 1 case was double chorionic twin amniotic membrane pregnancy (the second fetuse had no obvious abnormality) and died after birth; the other 4 cases were terminated before 28 weeks of gestation. Of the 2 complicated cases, 1 case was followed with severe digestive tract abnormalities and died after birth, and the other one was followed with single umbilical artery and hydramnion.
		                        		
		                        			Conclusions
		                        			Color Doppler ultrasonography is an important means for prenatal screening of fetal ADV.The prognosis of patients with solitary ADV without fetal cardiac dysfunction is good.The prognosis is poor to patients with severe intracardiac and extracardiac abnormality. There is a correlation between the ADV and fetal chromosomal abnormalities. If pregnancy is necessary, fetal chromosome examination should be recommended first and cardiac function should be followed up closely by ultrasound. 
		                        		
		                        		
		                        		
		                        	
            
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