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By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV 1 /FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate OR s and 95% CI s for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95% CI ) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P <0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

Objective: To evaluate the level of psychological distress among Chinese children and adolescents and analyze its lifestyle influencing factors. Methods: Data were obtained from the 2019 Chinese National Survey on Students' Constitution and Health. A lotal of 120 285 Han Chinese children and adolescents aged 9-18 years with complete information on the psychological distress scale and lifestyle factors were selected, including 58 432 boys and 61 853 girls. The Kessler Psychological Distress Scale (K10) measured psychological distress, and lifestyles such as physical activity, sedentary behavior, diet, and sleep were also investigated. K10 scores of different genders were compared using the t -test, and the levels of psychological distress were compared using the χ 2 The average K10 score for Han Chinese children and adolescents aged 9-18 years was 21.25±7.35, with girls (21.43±7.35) scoring higher than boys (21.06±7.36), the difference was statistically significant ( Results: The average K10 score for Han Chinese children and adolescents aged 9-18 years was 21.25±7.35, with girls (21.43±7.35) scoring higher than boys (21.06±7.36), the difference was statistically significant ( t =8.72, P <0.001). The rate of high psychological distress was 29.81%, with girls (31.08%) reporting higher rates than boys (28.46%), the difference was statistically significant ( χ 2 =98.54, P <0.001). 56.10% of children and adolescents have unhealthy lifestyles, with girls (58.77%) reporting higher rates than boys (53.27%), the difference was statistically significant ( χ 2 =368.53, P <0.001). Except for insufficient outdoor activities for girls ( P =0.128), lifestyles such as insufficient physical activity, insufficient muscle-and-bone exercises, long screen time, not eating breakfast, eggs and dairy products every day, drinking sugary beverages once or more per day, and not having enough sleep are all risk factors for high psychological distress (all P <0.001). For every additional healthy lifestyle score, the K10 score decreased by 0.98 [ β =-0.98 (95% CI The prevalence of psychological distress and unhealthy lifestyle in Chinese children and adolescents are high and interrelated. Compared those with healthy lifestyles, children and adolescents with unhealthy lifestyles are at greater risk of high psychological distress. Therefore, promoting healthy lifestyles for children and adolescents may be one of the important ways to improve their mental health.P <0.001). K10 scores in each region negatively correlate with lifestyle scores (all P <0.001). Among them, the K10 score in the eastern region showed the slightest decrease as the lifestyle score increased, while the western region showed the most decrease. Conclusions: The prevalence of psychological distress and unhealthy lifestyle in Chinese children and adolescents are high and interrelated. Compared those with healthy lifestyles, children and adolescents with unhealthy lifestyles are at greater risk of high psychological distress. Therefore, promoting healthy lifestyles for children and adolescents may be one of the important ways to improve their mental health.

Objective: To analyze the association between exposure to ambient PM 2.5 and its components [sulfate (SO 4 2- ), nitrate (NO 3 - Based on data from the 2019 Chinese National Survey on Students' Constitution and Health, 130 808 children and adolescents aged 9 to 18 years were included. Scoring and determination of higher psychological distress were based on the Kessler Psychological Distress Scale (K10), and annual average exposure data for air pollution were matched by survey location and time. We used a restricted cubic spline approach based on logistic regression to fit the associations between PM 4 + ), organic matter (OM), and black carbon (BC)] and psychological distress among school children and adolescents aged 9 to 18 years in China. Methods: Based on data from the 2019 Chinese National Survey on Students' Constitution and Health, 130 808 children and adolescents aged 9 to 18 years were included. Scoring and determination of higher psychological distress were based on the Kessler Psychological Distress Scale (K10), and annual average exposure data for air pollution were matched by survey location and time. We used a restricted cubic spline approach based on logistic regression to fit the associations between PM 2.5 , SO 4 2- , NO 3 - , NH 4 + , organic matter, black carbon concentrations, and psychological distress. Logistic regression models were used to analyse different age, gender, BMI and physical activity subgroups to estimate the association between exposure to high levels of pollution and high levels of psychological distress in different subgroups. Results: The proportion of children and adolescents with high levels of psychological distress in China was 30.4%, with girls being higher than boys at 31.6% and 29.1%, respectively ( P <0.05). A non-linear positive association existed between exposure to PM 2.5 , SO 4 2- , NO 3 - and organic matter concentrations and higher psychological distress. As PM 2.5 , NO 3 - , NH 4 + , organic matter, and black carbon concentrations continued to rise, the increase in the risk of higher psychological distress slowed, while SO 4 2- showed little change in the OR of psychological distress at lower concentrations but continued to rise at higher concentrations. PM 2.5 and its components were statistically associated with psychological distress in the physically inactive group but not in the physically active group. The association between high levels of pollutants and high psychological distress was stronger among students aged 9 to 12 years compared with students aged 13 to 15 years and 16 to 18 years. Conclusions: The ambient pollutant PM 2.5 and its components are associated with psychological distress in children and adolescents aged 9 to 18 years in China. High pollutant exposure is a risk factor for high psychological distress among physically inactive children and adolescents, and there are age differences in the association between PM 2.5 and components and psychological distress.

Objective: To analyze the association between the occurrence of spermarche and menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years. Methods: Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and a total of 54 438 boys aged 11 to 18 years and 76 376 girls aged 9 to 18 years with psychological distress, spermarche/menarche records were included in the final analysis. The occurrence of spermarche/menarche was recorded by physicians, and psychological distress was classified according to the Kessler Psychological Distress Scale scores. The chi-square test was used to compare the difference between groups in the occurrence of spermarche/menarche, and the multinomial logistic regression model and stratification analysis was established to analyze the association between psychological distress and spermarche/menarche. Results: The incidence of spermarche/menarche in 2019 ranged from 6.3% to 96.5% for eight age groups of Chinese boys and 2.8% to 99.0% for ten age groups of girls. The rates of high psychological distress among boys and girls were 32.5% and 32.7%. Among boys aged 11 to 18 years, the rate of high psychological distress increased with age, with a trend test P <0.001, and the difference in the rate of high psychological distress between those who had and had not had their spermarche was not statistically significant in all age groups. Among girls aged 9 to 18 years, the rate of high psychological distress increased with age, with a trend P <0.001; the rate of high psychological distress was higher in the group with menarche at age 10 and 12 than in the group without menarche (all P <0.05). High psychological distress was positively correlated with spermarche among boys aged 13-15 years living in urban areas and hight level economic development areas ( OR =1.11, 95% CI : 1.02-1.21; OR =1.18, 95% CI : 1.06-1.32). Overall, high psychological distress was positively correlated with menarche in girls aged 9-12 and 13-15 years ( OR =1.33, 95% CI : 1.25-1.42; OR =1.22, 95% CI : 1.07-1.39). High psychological distress was positively correlated with menarche among girls aged 9-12 years living in different regions except for the Northeast region, in areas with different levels of economic development, and in urban and rural areas, in girls aged 13-15 years living in urban, central, and western regions, and in girls aged 16-18 years residing in the central region. Conclusions: This study found an association between the occurrence of spermarche/menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years in 2019, which was particularly significant among girls aged 9 to 12 years and boys aged 13 to 15 years living in areas with higher levels of socioeconomic development.

Objective: To describe the status of physical fitness of children and adolescents aged 13-18 years in China in 2019 and analyze its association with psychological distress. Methods: Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and 90 633 Han children and adolescents aged 13-18 years were included. Physical fitness was evaluated by "National Students Constitutional Health Standards" (2014 revised edition). Psychological distress was classified according to the scores of the Kessler Psychological Distress Scale: ≤19, 20-24, 25-29, and ≥30 scores indicated no, mild, moderate, and severe psychological distress, respectively, with moderate and severe psychological distress collectively referred to as high psychological distress. The χ 2 test was used to compare the distribution differences between boys and girls, the Cochran-Armitage test was used to analyze the trend, and the multinomial logistic regression in the mixed effect model was established to analyze the association between physical fitness and psychological distress. Results: In 2019, the unqualified rate of physical fitness among children and adolescents aged 13-18 years in China was 17.2%, and the prevalence of excellent and good physical fitness was 18.2%, which was lower among boys (15.9%) than girls (20.5%) with a statistically significant difference ( P <0.05). The excellent and good physical fitness rate showed a significantly decreasing trend with age (trend test P <0.05). The rate of high psychological distress among children and adolescents aged 13-18 years in China in 2019 was 39.3%, with boys (37.0%) having a lower prevalence than girls (41.6%), supported by a statistically significant difference ( P <0.05), and a decreasing trend with the degree of physical fitness was observed both in boys and girls (trend test P <0.05). The multinomial logistic regression model showed that the prevalence of moderate ( OR =0.83, 95% CI : 0.79-0.88, P <0.001) and severe ( OR =0.81, 95% CI : 0.77-0.86, P The status of physical fitness and psychological distress of Chinese children and adolescents aged 13-18 in 2019 was not optimistic, with physical fitness showing a significantly negative association with psychological distress.Conclusion: The status of physical fitness and psychological distress of Chinese children and adolescents aged 13-18 in 2019 was not optimistic, with physical fitness showing a significantly negative association with psychological distress.

Objective: To describe the prevalence of psychological distress and to analyze its influencing factors among Chinese children and adolescents aged 9-18 years in 2019. Methods: Data was from the 2019 Chinese National Survey on Students' Constitution and Health, and 148 892 children and adolescents were included. Psychological distress was measured using the Kessler Psychological Distress Scale (K10): scores ≤19 were defined as no psychological distress, scores between 20-24 were defined as mild psychological distress, scores between 25-29 were defined as moderate psychological distress, and scores ≥30 were defined as severe psychological distress (moderate to severe psychological distress were defined as high psychological distress). The ANOVA, t test, and χ 2 test were used to compare the differences in K10 scores and high psychological distress rates among children and adolescents with different characteristics. The ANOVA and trend χ The K10 scores for Chinese children and adolescents aged 9-18 years in 2019 was 21.5±9.2, and their rate of high psychological distress was 31.6%. The rates of high psychological distress among children and adolescents aged 9-12, 13-15, and 16-18 years were 22.3%, 35.9%, and 38.8%. K10 scores and rates of high psychological distress showed an increasing trend as age increased (trends test all 2 test were used to analyze the trends. Modified-Poisson regression models were used to determine influencing factors of high psychological distress. Results: The K10 scores for Chinese children and adolescents aged 9-18 years in 2019 was 21.5±9.2, and their rate of high psychological distress was 31.6%. The rates of high psychological distress among children and adolescents aged 9-12, 13-15, and 16-18 years were 22.3%, 35.9%, and 38.8%. K10 scores and rates of high psychological distress showed an increasing trend as age increased (trends test all P <0.001). K10 scores and rates of high psychological distress were higher among children and adolescents who were older, female, rural, in areas with medium to low GDP per capita level, and with lower parental education (all P <0.001). Multifactorial modified-Poisson regression analysis showed that children and adolescents aged 13-15 years, 16-18 years, female, rural, and in areas with low to moderate GDP per capita level were at higher risk of high psychological distress (all P <0.05), with a OR (95% CI ) of 1.55 (1.52-1.58), 1.66 (1.63-1.69), 1.07 (1.05-1.09), 1.02 (1.01-1.04), 1.10 (1.07-1.12). Children and adolescents in areas with medium to high GDP per capita level, whose father had a secondary or high school degree, whose father had a college degree or above, whose mother had a secondary or high school degree, and whose mother had a college degree or above were at lower risk of high psychological distress (all P <0.05), with a OR The prevalence of psychological distress was high among Chinese children and adolescents aged 9-18 years in 2019, which is a vital problem. Mental health interventions need to be implemented among children and adolescents that were older, girls, rural, live in areas with lower economic levels, and whose parents have a lower education level.CI ) of 0.96 (0.94-0.98), 0.92 (0.90-0.93), 0.84 (0.82-0.86), 0.95 (0.93-0.97), 0.86 (0.83-0.88). Conclusions: The prevalence of psychological distress was high among Chinese children and adolescents aged 9-18 years in 2019, which is a vital problem. Mental health interventions need to be implemented among children and adolescents that were older, girls, rural, live in areas with lower economic levels, and whose parents have a lower education level.

Objective: To analyze the association between overweight and obesity, psychological distress, and the influence of physical exercise among Chinese children and adolescents. Methods: The study used data from the 2019 Chinese National Survey on Students' Constitution and Health. A total of 95 280 Han Chinese children and adolescents aged 13 to 18 years were included in the study based on complete information on overweight and obesity, psychological distress assessment, and physical exercise variables. The Kessler Psychological Distress Scale was used to measure their psychological distress, with scores above 25 indicating high psychological distress. The BMI group of the adolescents was evaluated according to the Chinese standard "WS/T 586-2018 Screening for Overweight and Obesity in School-age Children and Adolescents", including underweight, normal weight, overweight, and obesity. The individual's BMI Z-score (BMIZ) was evaluated using the WHO standard and divided into ten groups based on the population percentile distribution. The survey collected the subjects' average daily physical exercise time and divided them into two groups: less than 1 hour and greater than or equal to 1 hour. Logistic regression analysis was used to analyze the relationship between overweight and obesity and high psychological distress among children and adolescents and the differences in association between different physical exercise groups. Results: The detection rates of overweight and obesity among Han Chinese children and adolescents aged 13 to 18 years in 2019 were 14.5%, and 7.6%, respectively. The rate of high psychological distress was 37.6%, and the rate of average daily physical exercise time exceeding 1 hour was 17.1%. Using the population with a BMIZ P 10 below as a reference, the association strength between high psychological distress and the population gradually increased, with an OR (95% CI ) value of 1.08 (1.02-1.14), 1.09 (1.02-1.14), 1.10 (1.03-1.16), and 1.16 (1.09-1.23) for BMIZ in the P 60 -, P 70 -, P 80 Chinese children and adolescents face the problem of obesity and high psychological distress, with a positive correlation between these two problems. Physical activity may moderate the association between obesity and psychological distress in children and adolescents. Adequate physical exercise may offset the potential high psychological distress caused by obesity in children and adolescents. Thus, strengthening physical exercise among children and adolescents reduces the risks of both obesity and psychological health problems effectively.P 90 groups. Compared to normal weight, both overweight and obesity were positively associated with high psychological distress in children and adolescents, with obesity showing a more significant correlation, while underweight was negatively associated with high psychological distress. The detection rates of high psychological distress in normal weight, underweight, overweight, and obese groups were 37.6%, 37.0%, 38.2%, and 38.7%, respectively, with an OR (95% CI ) value of 0.93 (0.88-0.98) for the underweight group and 1.05 (1.01-1.10) and 1.13 (1.07-1.19) for the overweight and obese groups, respectively. The positive correlation between BMIZ, overweight, and obesity with high psychological distress was significant only in adolescents who exercised less than 1 hour per day on average. Conclusions: Chinese children and adolescents face the problem of obesity and high psychological distress, with a positive correlation between these two problems. Physical activity may moderate the association between obesity and psychological distress in children and adolescents. Adequate physical exercise may offset the potential high psychological distress caused by obesity in children and adolescents. Thus, strengthening physical exercise among children and adolescents reduces the risks of both obesity and psychological health problems effectively.

Objective: To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents., Methods: Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years., Results: The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group ( OR =1.417, 95% CI : 1.19-1.69), and lower in the catch-up growth group( OR =0.66, 95% CI : 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group ( OR =1.25, 95% CI : 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group ( OR =0.79, 95% CI : 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population., Conclusion: There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.

Objective: To investigate the status of depression and social anxiety in children and adolescents, and to analyze the association between body fat distribution and depression, social anxiety in children and adolescents., Methods: A total of 1 412 children aged 7 to 18 years in Beijing were included by stratified cluster random sampling method. Body fat distribution, including total body fat percentage (total BF%), Android BF%, Gynoid BF% and Android-to-Gynoid fat ratio (AOI), were obtained by dual-energy X-ray absorption method. Depression and social anxiety were evaluated by Children Depression Inventory and Social Anxiety Scale for Children. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non-linear correlation between body fat distribution and depression and social anxiety., Results: 13.1% and 31.1% of the children and adolescents had depressive symptoms and social anxiety symptoms respectively, and the detection rate of depression and social anxiety in the boys and young groups was significantly lower than those in the girls and old groups. There was no significant linear correlation between total BF%, Android BF%, Gynoid BF%, AOI and depression and social anxiety in the children and adolescents. However, total BF% and Gynoid BF% had significant nonlinear correlation with depression, showing an inverted U-shaped curve relationship with the tangent points of 26.8% and 30.9%, respectively. In terms of the nonlinear association of total BF%, Android BF%, Gynoid BF% and AOI with depression and social anxiety, the change trends of the boys and girls, low age group and high age group were consistent. The overall anxiety risk HR of body fat distribution in the boys was significantly higher than that in the girls, and the risk HR of depression and social anxiety were significantly higher in the high age group than those in the low age group., Conclusion: There was no significant linear correlation between body fat distribution and depression and social anxiety in children and adolescents. Total BF% and depression showed an inverted U-shaped curve, mainly manifested in Gynoid BF%, and this trend was consistent in different genders and different age groups. Maintaining children and adolescents' body fat distribution at an appropriate level is the future direction of the prevention and control of depression and social anxiety in children and adolescents.

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs . 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 ( n = 153) or 96 weeks ( n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients. In recent studies, we and others have demonstrated that it is the serum HBV RNA that reflects the cccDNA activity in infected hepatocytes, particularly among the patients on NAs. Here we suggest that instead of measuring serum HBV DNA only, simultaneous measurement of both viral DNA and RNA would improve the accuracy to reflect the cccDNA activity; therefore, the virological response should be redefined as consistent loss (less than the lower limit of detection) of both serum HBV DNA and RNA, which indicates the safety of drug discontinuation. Accumulating evidence has suggested that for the CHB patients with lower serum HBsAg, switch-to or add-on pegylated interferon (Peg-IFN) treatment would result in loss of serum HBsAg in a relatively large proportion of CHB patients. Since serum HBV RNA is an ideal biomarker to reflect the intrahepatic cccDNA activity, for the patients with a serum HBsAg level lower than 1 500 IU/ml after long-term NAs treatment, the serum HBV RNA should be measured. If serum HBV RNA is detected, peg-IFN should be added on; if serum HBV RNA is not detected, NAs treatment should be switched to peg-IFN treatment. We believe the therapy based on serum HBV RNA would make the functional cure of CHB (serum HBsAg loss or even conversion to anti-HBs) more efficient.

Objective: To compare the clinical value in predicting the prognosis of chronic severe hepatitis between the Child-Turcotte-Pugh (CTP) score and the model for end-stage liver disease (MELD) score., Methods: Fifty-five cases with chronic severe hepatitis were scored by CTP and MELD score systems based on their biochemical and coagulation parameters, and related signs within 24 hours after their admission. The termination date of observation was the 90th day after their admission. The actual survival time were recorded. The comparison scores of CTP/MELD were conducted respectively and compared between the survival group and death group, among different clinical stages of chronic severe hepatitis. The correlation of CTP/MELD score with the clinical stages was analyzed respectively. The survival time, mortality and survival rate were compared respectively among the groups classified by CTP/MELD score according to Kaplan-Meier (K-M) survival curve., Results: The CTP score and the MELD score in death group were higher than those in survival group (both P<0.01). The CTP and MELD scores in the advanced stage group were also higher than those in the early and middle stage (both P<0.01). The correlation of the MELD score with the stage was higher (r(s) =0.689,P<0.01) than that of the CTP score (r(s)=0.428, P<0.01). The survival time of patients with CTP<12 scores, was longer than with CTP>or=12 scores, and their survival rate was also higher(both P<0.01). When the MELD score lowered, survival time was longer, and survival rate was higher. The survival time, mortality and survival rate showed significant difference among the groups classified by MELD score (or=40 points, all P<0.01)., Conclusion: The parameters employed in MELD score system are more, Objective: and easy to achieve, the score range for patients classification is wider and more practical, and the correlation with the clinical stage is higher than CTP score system, suggesting the MELD score system is better in predicting the prognosis of patients with chronic severe hepatitis than the CTP score system.