Application value of liver/spleen CT value， controlled attenuation parameter， and magnetic resonance imaging-proton density fat fraction in chronic hepatitis B patients with hepatic steatosis / 临床肝胆病杂志

ObjectiveTo investigate the application value of liver/spleen CT value （CTL/S）， controlled attenuation parameter （CAP）， and magnetic resonance imaging-proton density fat fraction （MRI-PDFF） in chronic hepatitis B （CHB） patients with hepatic steatosis. MethodsA retrospective analysis was performed for the clinical data of 213 CHB patients who underwent liver CT， CAP， and MRI-PDFF examinations in Affiliated Hospital of Yan’an University from October 2018 to December 2022. According to MRI-PDFF， the 213 patients were divided into CHB group with 111 patients （MRI-PDFF<5%） and CHB+hepatic steatosis group with 102 patients （MRI-PDFF≥5%）， among whom there were 69 patients with mild hepatic steatosis and 33 patients with moderate to severe hepatic steatosis. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Bland-Altman plot was used to evaluate the consistency in MRI-PDFF measurement between two physicians. The Spearman’s correlation coefficient was used to analyze the correlation between CTL/S and MRI-PDFF and between CAP and MRI-PDFF. The receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to investigate the value of CTL/S and CAP in the diagnosis of different degrees of hepatic steatosis， and the DeLong test was used to compare the AUCs of the two radiological examinations. ResultsMRI-PDFF had relatively high repeatability and stability in CHB patients. There is a significant negative correlation between CTL/S and MRI-PDFF （r=-0.800， P<0.001） and a significant positive correlation between CAP and MRI-PDFF （r=0.692， P<0.001）. Both CTL/S and CAP had a relatively high accuracy in the diagnosis of hepatic steatosis in CHB patients， with an AUC of 0.951 and 0.902， respectively， and CTL/S had a better accuracy than CAP （P<0.05）. In the diagnosis of mild and moderate-to-severe hepatic steatosis， CTL/S had an AUC of 0.921 and 0.895， respectively， and CAP had an AUC of 0.859 and 0.825， respectively， suggesting that CTL/S had a slightly higher diagnostic efficiency than CAP. ConclusionMRI-PDFF has high repeatability and stability in CHB patients， and CTL/S and CAP have a high diagnostic value for different degrees of hepatic steatosis in CHB patients.

Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b / 临床肝胆病杂志

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

Correlation between serum HBV RNA and duration of treatment with nucleos（t）ide analogues in patients with chronic hepatitis B / 临床肝胆病杂志

‍ ObjectiveTo investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B （CHB） and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos（t）ide analogues （NAs）. MethodsA total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July， 2022， were enrolled as subjects. Related clinical data were collected， and according to the duration of antiviral therapy， they were divided into untreated group with 73 patients， treatment duration ≤1 year group with 91 patients， and treatment duration >1 year group with 136 patients. Serum HBV RNA load， HBV DNA load， and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups， further pairwise comparison using Bonferroni method； the chi-square test was used for comparison of categorical data； a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. ResultsThe positive rate of HBeAg was 18.3%， and among the patients with negative HBV DNA， the patients with positive HBV RNA accounted for 44.1% （86/195）. There was a significant difference in the distribution of the serum levels of HBV RNA， HBV DNA， and HBsAg between the positive HBeAg group and the negative HBeAg group （Z=10.740， 6.300， and 7.280， all P<0.05）. There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA， HBV DNA， and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group （P<0.05）. The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA， HBV DNA， and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg （r=-0.247 and -0.138， both P<0.05） and a strong negative correlation with the level of HBV DNA （r=-0.771， P<0.001）. There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg （r=0.360 and 0.442， both P<0.001）. Further stratified analysis showed that in the untreated group， there was a strong positive correlation between HBV RNA and HBV DNA （r=0.752， P<0.001） and a moderate positive correlation between HBV RNA and HBsAg （r=0.559， P<0.001）； in the treatment duration ≤1 year group， there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg （r=0.396 and r=0.388， both P<0.001）； in the treatment duration >1 year group， there was a low degree of positive correlation between HBV RNA and HBsAg （r=0.352， P<0.001）. ConclusionSerum HBV RNA is negatively correlated with the duration of treatment with NAs， and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore， it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent， with a relatively high accuracy in reflecting the level of viral replication in untreated patients.

Analysis of advanced fibrosis in metabolic dysfunction-associated fatty liver disease patients with chronic hepatitis B / 中华内科杂志

Objective:To investigate the clinical and pathological characteristics of chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as associations with advanced fibrosis.Methods:CHB patients who underwent liver biopsy at Tianjin Second People′s Hospital from June 2016 to September 2019 were included in the study. The patients were divided into two groups based on whether they had concomitant MAFLD; a CHB group and a MAFLD-CHB group. t-tests and Chi-square tests were used to compare pathological characteristics and basic features in the two groups. Logistic regression analysis was used to analyze factors associated with advanced fibrosis. Results:The CHB group included 110 patients, and the MAFLD-CHB group included 272 patients. There were significant differences in smoking, alcohol consumption, hypertension incidence, body metabolic index, alanine aminotransferase, gamma-glutamyl transferase (GGT), high-density lipoprotein, low-density lipoprotein, fasting plasma glucose, and platelets (PLT) between the two groups (all P<0.05). The MAFLD-CHB group had a higher incidence of advanced fibrosis than the CHB group ( P<0.05). In logistic regression analysis MAFLD [odds ratio ( OR)=2.204, 95% confidence interval ( CI) 1.018-4.774, P=0.045], GGT ( OR=1.008, 95% CI 1.002-1.013, P=0.005), and PLT ( OR=0.995, 95% CI 0.991-0.999, P=0.019) were associated with advanced fibrosis (all P<0.05). In the MAFLD-CHB group type 2 diabetes ( OR=3.281, 95% CI 1.375-7.832, P=0.007), GGT ( OR=1.011, 95% CI 1.003-1.018, P=0.005), and PLT ( OR=0.993, 95% CI 0.988-0.998, P=0.004) were associated with advanced fibrosis ( P<0.05). Conclusion:Patients with MAFLD-CHB are more likely to develop advanced fibrosis than patients with CHB alone. In the MAFLD-CHB group type 2 diabetes mellitus was associated with advanced fibrosis. It is important to strictly control relevant risk factors in MAFLD-CHB patients, especially in patients with type 2 diabetes.

Progress towards elimination of hepatitis B / 临床肝胆病杂志

This paper summarizes the latest progress in the elimination of hepatitis B worldwide and in China. Although the global burden of hepatitis B is decreasing， there is a large difference in the progress towards elimination across different countries， and among the 20 countries with the heaviest disease burden， Bangladesh， India， Indonesia， Japan， and Russia have achieved substantial progress. China continues to maintain a high HBV vaccination coverage for neonates， with an inoculation rate of 95.6% for timely birth dose and 99.6% for 3 doses. From 2016 to 2022， the diagnosis rate of patients with chronic hepatitis B in China have increased from 19% to 24%， and treatment rate have increased from 11% to 15%； however， there is still a big gap compared with the WHO targets by 2030. Further efforts are needed to eliminate viral hepatitis by 2030 globally and in China.

Focus on the timing and strategies of antiviral therapy for special populations with chronic hepatitis B / 临床肝胆病杂志

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.

Low-level viremia in chronic hepatitis B patients treated with first-line treatment with nucleos（t）ide analogues and its treatment strategies / 临床肝胆病杂志

Highly effective oral antiviral therapy with low drug resistance can strongly inhibit HBV replication； however， some patients may still have low-level viremia （LLV） after receiving entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide， or tenofovir amibufenamide for 48 weeks or more. Multiple studies in China and globally show that LLV after antiviral therapy is closely associated with the progression of chronic hepatitis B liver fibrosis， the risk of decompensated liver cirrhosis and hepatocellular carcinoma， and the reduction in long-term survival rate. Therefore， this article reviews the development， risk factors， and clinical harm of LLV after first-line treatment with nucleos（t）ide analogues， as well as different treatment regimens， in order to provide a reference for the treatment of LLV in chronic hepatitis B patients in the future.

Expert consensus on integrated traditional Chinese and Western medicine diagnosis and treatment of chronic hepatitis B / 临床肝胆病杂志

Chronic hepatitis B （CHB） is still a major public health issue in China， and without effective control， it can further progress to liver cirrhosis and liver cancer， bringing huge social and economic burdens. At present， antiviral therapy is the main treatment method for CHB， and integrated traditional Chinese and Western medicine therapy is the characteristic treatment method for CHB in China and can improve clinical efficacy by complementing each other’s advantages. In order to promote the concept integrated traditional Chinese and Western medicine collaborative diagnosis and treatment， facilitate the development of integrated traditional Chinese and Western medicine diagnosis and treatment techniques for CHB， and establish standardized disease diagnosis and treatment regimens， Expert Committee on Hepatology in Doctor Society of Integrative Medicine， Chinese Medical Doctor Association， established a consensus expert group to discuss and formulate Expert consensus on integrated traditional Chinese and Western medicine diagnosis and treatment of chronic hepatitis B， which elaborated on the concept of integrated traditional Chinese and Western medicine collaborative diagnosis and treatment from the four aspects of CHB epidemiology， pathogenesis and etiology， integrated traditional Chinese and Western medicine diagnosis and syndrome differentiation， and integrated traditional Chinese and Western medicine therapy and proposed related recommendations， in order to improve the prognosis and quality of life of CHB patients.

Key recommendations in guidelines for the prevention， diagnosis， care and treatment for people with chronic hepatitis B infection released by the World Health Organization in 2024 / 临床肝胆病杂志

In March 2024， the World Health Organization released the latest version of guidelines for the prevention， diagnosis， care and treatment for people with chronic hepatitis B infection. The guidelines were updated in several aspects， including expanding and simplifying the indications for chronic hepatitis B treatment， adding alternative antiviral treatment regimens， broadening the indications for antiviral therapy to prevent mother-to-child transmission， improving the diagnosis of hepatitis B virus， and adding hepatitis D virus （HDV） testing. This article summarizes and gives an excerpt of the recommendations in the guidelines.

Hepatitis B vaccine： From prevention to treatment / 临床肝胆病杂志

Hepatitis B vaccination is the most economical and effective way to prevent HBV infection. The advances in molecular biology and genetic engineering have continuously improved the manufacturing process of vaccines， and hepatitis B vaccine has gradually developed from the initial plasma-derived vaccine to the currently used recombinant vaccine. Preventive hepatitis B vaccine has been clinically tested in patients with HBsAg seroclearance to increase the level of anti-HBs， with certain safety and efficacy. As one of the multiple targets for new drugs in the treatment of chronic hepatitis B， a therapeutic hepatitis B vaccine based on HBsAg is already in the stages of research and development and clinical trial.

Role of HBeAg-induced immune activition and immunosuppression in chronic hepatitis B / 临床肝胆病杂志

Chronic hepatitis B induced by HBV infection is a significant risk factor leading to liver cirrhosis and liver cancer. Half a century ago， HBeAg was first discovered in the serum of HBV infected individuals， and although HBeAg does not participate in HBV infection or replication in hepatocytes， studies have shown that it can interfere with the innate and adaptive immune responses of the host and play an important role in immune activation and immunosuppression during chronic HBV infection. HBV has no cytotoxicity to the infected hepatocytes， and the antiviral action and inflammatory response mediated by immune response determine whether HBV is cleared or induces liver inflammation-related diseases. Therefore， this article reviews the formation of HBeAg and its immune activation and immunosuppression mechanisms in chronic HBV infection， with a focus on the different immune effects caused by HBeAg on innate immune and adaptive immune cells， and this article also elaborates on the dual role of HBeAg in inducing immune responses and explores the conversion role of HBeAg in different stages of chronic HBV infection.

Correlation of serum angiopoietin-1， angiopoietin-2， and angiopoietin-1/angiopoietin-2 ratio with HBV DNA and alanine aminotransferase in patients with chronic hepatitis B or liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the correlation of serum angiopoietin-1 （Ang-1）， angiopoietin-2 （Ang-2）， and Ang-1/Ang-2 ratio with HBA DNA and alanine aminotransferase （ALT） in patients with chronic hepatitis B （CHB） or liver cirrhosis. MethodsClinical data and serum specimens were collected from 99 patients with CHB and 59 patients with liver cirrhosis who were admitted to Beijing YouAn Hospital， Capital Medical University， from March 2018 to October 2019， and 46 individuals who underwent physical examination were enrolled as control group. PCR was used to measure serum HBV DNA level， and ELISA was used to measure the serum levels of Ang-1 and Ang-2. The serum levels of Ang-1 and Ang-2 and Ang-1/Ang-2 ratio were compared between groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Bonferroni method was used for further comparison between two groups； the Spearman correlation analysis was used to investigate the correlation of Ang-1， Ang-2， and Ang-1/Ang-2 ratio with HBV DNA and ALT. ResultsCompared with the control group， the CHB group and the liver cirrhosis group had a significant reduction in the level of Ang-1 （479.0 pg/mL and 208.4 pg/mL vs 671.0 pg/mL， both P<0.05）， and compared with the CHB group， the liver cirrhosis group had a significant reduction in the level of Ang-1 （P<0.001）. Compared with the control group， the CHB group and the liver cirrhosis group had a significant increase in the level of Ang-2 （286.1 pg/mL and 438.4 pg/mL vs 198.0 pg/mL， both P<0.001）， and compared with the CHB group， the liver cirrhosis group had a significant increase in the level of Ang-2 （P<0.001）. Compared with the control group， the CHB group and the liver cirrhosis group had a significant reduction in Ang-1/Ang-2 ratio （1.6 and 0.5 vs 3.4， both P<0.001）， and compared with the CHB group， the liver cirrhosis group had a significant reduction in Ang-1/Ang-2 ratio （P<0.001）. The Spearman correlation analysis showed that in the CHB group， Ang-1 was negatively correlated with HBV DNA and ALT （r=-0.400 and -0.394， both P˂0.001）， Ang-2 was positively correlated with HBV DNA and ALT （r=0.365 and 0.351， both P<0.001）， and Ang-1/Ang-2 ratio was negatively correlated with HBV DNA and ALT （r=-0.463 and -0.473， both P<0.001）； in the liver cirrhosis group， Ang-1， Ang-2， and Ang-1/Ang-2 ratio had no correlation with HBV DNA or ALT （all P>0.05）. ConclusionThere are significant changes in the serum levels of Ang-1 and Ang-2 and Ang-1/Ang-2 ratio in patients with CHB or liver cirrhosis， and Ang-1， Ang-2， and Ang-1/Ang-2 ratio reflects the degree of liver injury in patients with CHB to a certain extent.

Incidence rate of low-level viremia and related influencing factors in treatment-experienced chronic hepatitis B patients： A Meta-analysis / 临床肝胆病杂志

ObjectiveTo systematically evaluate the incidence rate of low-level viremia （LLV） in chronic hepatitis B （CHB） patients and related influencing factors， and to provide evidence-based medicine evidence for effective intervention and prevention of LLV in clinical practice. MethodsThis study was conducted according to the PRISMA guideline， with a PROSPERO registration number of CRD42023455304. CNKI， Wanfang Data， VIP， SinoMed， PubMed， Embase， Web of Science， and the Cochrane library were searched for observational studies on LLV and related influencing factors in CHB patients published up to July 21， 2023. Stata 16.0 software was used to perform the meta-analysis. ResultsA total of 12 articles were included， with a total sample size of 3408 cases， among whom there were 1181 patients with LLV. The meta-analysis showed that the incidence rate of LLV was 32.8% （95% confidence interval ［CI］： 27.6%‍ ‍—‍ ‍38.3%） in treatment-experienced CHB patients. High HBsAg quantification （odds ratio ［OR］=2.107， 95%CI： 1.782‍ ‍—‍ ‍2.491， P<0.001）， positive HBeAg （OR=3.258， 95%CI： 2.629‍ ‍—‍ ‍4.038， P<0.001）， high HBV DNA level at baseline （OR=1.286， 95%CI： 1.157‍ ‍—‍ ‍1.430， P<0.001）， and history of entecavir treatment （OR=3.089， 95%CI： 1.880‍ ‍—‍ ‍5.074， P<0.001） were risk factors for LLV； duration of antiviral therapy ≥3 years （OR=0.175， 95%CI： 0.093‍ ‍—‍ ‍0.331， P<0.001） and high alanine aminotransferase level at baseline （OR=0.985， 95%CI： 0.978‍ ‍—‍ ‍0.992， P<0.001） were protective factors against LLV. The sensitivity analysis showed no significant change in effective value， suggesting that the results of the meta-analysis were relatively stable. The funnel plot of the studies included was basically symmetrical， and the results of the Egger’s test and the Begg’s test suggested that there was no obvious publication bias in the articles included. ConclusionClinicians should guide decision making based on the influencing factors for LLV and related clinical evidence， so as to reduce long-term clinical risks and avoid adverse outcomes.

Virological features of chronic hepatitis B patients with metabolic associated fatty liver disease： A stratified analysis / 临床肝胆病杂志

ObjectiveTo investigate the virological features of patients with chronic hepatitis B （CHB） and metabolic associated fatty liver disease （MAFLD） through a stratified analysis. MethodsA retrospective analysis was performed for 131 patients with CHB and MAFLD and 168 patients with CHB alone who underwent percutaneous liver biopsy and did not receive antiviral therapy or withdrew from drugs for more than 6 months in Beijing YouAn Hospital， Capital Medical University， from January 1， 2013 to December 31， 2019. The two groups were compared in terms of general data， biochemical parameters， and virological parameters. The patients in the two groups were stratified according to liver inflammation grade （G） and liver fibrosis stage （S）， and the patients with CHB and MAFLD were further analyzed based on the degree of hepatic steatosis and NAFLD activity score （NAS）. Virological features （the serum levels of HBV DNA and HBV HBsAg） were compared between groups. The Wilcoxon test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the CHB group， the CHB+MAFLD group had a significantly higher proportion of male patients， a significantly higher proportion of patients with hypertension or type 2 diabetes mellitus， and significantly higher levels of the blood biochemical parameters of triglyceride， low-density lipoprotein cholesterol， apolipoprotein B， alanine aminotransferase， gamma-glutamyl transpeptidase， uric acid， and fasting blood glucose （all P<0.05）， as well as significantly lower levels of high-density lipoprotein cholesterol， apolipoprotein A1， and HBV DNA （all P<0.05）. The stratified analysis based on liver fibrosis stage showed that for both the patients with CHB alone and those with CHB and MAFLD， the significant fibrosis （S2‍ ‍—‍ ‍4） group had a significantly lower level of HBV DNA than the non-significant fibrosis （S0‍ ‍—‍ ‍1） group （P<0.05）， and for the patients with CHB alone， the significant fibrosis （S2‍ ‍—‍ ‍4） group had a significantly lower level of HBsAg than the non-significant fibrosis （S0‍ ‍—‍ ‍1） group （P<0.05）. The stratified analysis based on inflammation grade showed that for the patients with CHB and MAFLD， the high inflammation grade （G3） group had a significantly higher level of HBV DNA than the low inflammation grade （G1‍ ‍—‍ ‍2） group （P<0.05）， and in the low inflammation grade （G1‍ ‍—‍ ‍2） group， the patients with CHB and MAFLD had a significantly lower level of HBsAg than the patients with CHB alone （P<0.05）. The stratified analysis based on the degree of hepatic steatosis showed that the level of HBV DNA gradually decreased with the increase in the degree of steatosis， and the severe steatosis group had a significantly lower level of HBV DNA than the mild group （P<0.05）， while there was no significant difference in HBsAg level between the groups with different degrees of hepatic steatosis （P>0.05）. The stratified analysis based on NAS score showed that the NAS≥4 group had significantly higher levels of HBV DNA and HBsAg than the NAS<4 group （both P<0.05）. ConclusionPatients with CHB and MAFLD have significant abnormalities in metabolic markers and aminotransferases， while virological indicators show different features in stratified analyses based on various indicators.

Chronic hepatitis B virus infection and metabolic associated fatty liver disease： The known and unknown aspects / 临床肝胆病杂志

Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.

Significance of high-sensitivity polymerase chain reaction in detecting hepatitis B virus in chronic hepatitis B patients with a very low viral load / 临床肝胆病杂志

ObjectiveTo investigate the significance of high-sensitive polymerase chain reaction （PCR） in detecting hepatitis B virus （HBV） among the population with a very low viral load （HBV DNA 10‍ — ‍99 IU/mL）. MethodsThis study was conducted among the chronic hepatitis B （CHB） patients who were treated with nucleos（t）ide analogues for ≥48 weeks in The Fifth Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2022 and had an HBV DNA load below the lower limit of ordinary-sensitivity detection （100 IU/mL）. Then high-sensitivity HBV DNA detection was performed for all patients， and according to these results， the patients were divided into very low viral load group （VLVL group with an HBV DNA load of 10‍ — ‍99 IU/mL） and complete virologic response group （CVR group with an HBV DNA load of <10 IU/mL or without HBV DNA detected）. The two groups were compared in terms of general characteristics， serum virological indicators， biochemical parameters， and noninvasive fibrosis markers； the value of related serum virological indicators in predicting the results of high-sensitivity HBV DNA above the lower limit of detection were assessed； the influencing factors for failure to achieve CVR were analyzed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The receiver operating characteristic （ROC） curve was used to investigate the value of related serum virological indicators in predicting the results of high-sensitivity HBV DNA above the lower limit of detection， and a binary logistic regression analysis was used to investigate the influencing factors for failure to achieve CVR. ResultsA total of 106 CHB patients were enrolled， with 24 in the VLVL group and 82 in the CVR group. Compared with the CVR group， the VLVL group had a significantly younger age （P=0.004） and significantly higher quantitative hepatitis B surface antigen （qHBsAg） level （P=0.002）， HBeAg positive rate （P=0.002）， pgRNA positive rate （P=0.010）， and alanine aminotransferase level （P=0.017）. The qHBsAg level had an area under the ROC curve of 0.717 （P=0.002） in predicting the results of high-sensitivity HBV DNA above the lower limit of detection （>10 IU/mL）， with an optimal cut-off value of 1 214.5 IU/mL， a sensitivity of 95.5%， and a specificity of 53.9%. Positive HBeAg （odds ratio ［OR］=3.654， 95% confidence interval ［CI］： 1.162‍ —‍ ‍11.489， P=0.027） and qHBsAg （OR=2.985， 95%CI： 1.058‍ — ‍8.422， P=0.039） were independent influencing factors for failure to achieve CVR. ConclusionSome CHB patients have an HBV DNA load of <100 IU/mL by ordinary-sensitivity detection， but with the presence of VLVL determined by high-sensitivity PCR. The VLVL group had significantly higher level of inflammatory damage and positive rates of pgRNA and HBeAg. Positive HBeAg and high qHBsAg level are independent influencing factors for failure to achieve CVR. Clinicians should not ignore the presence of VLVL in CHB patients， and high-sensitivity HBV DNA detection should be performed in a timely manner.

Efficacy of ursodeoxycholic acid in the prevention and treatment of COVID-19 in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the potential effect of ursodeoxycholic acid （UDCA） in the prevention and treatment of COVID-19 in patients with chronic hepatitis B. MethodsClinical data were collected from 324 patients with chronic hepatitis B who were treated in Beijing Ditan Hospital， Capital Medical University， from January to December 2022， and according to whether UDCA was administered， they were divided into UDCA group and control group. The propensity score matching （PSM） method was used to balance the confounding factors such as age， sex， and chronic complications， and the two groups were compared in terms of SARS-CoV-2 infection rate， symptoms， and recovery time after COVID-19. The two groups were also compared in terms of related laboratory markers （white blood cell count ［WBC］， hemoglobin ［Hb］， platelet count ［PLT］， alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， albumin ［Alb］， alkaline phosphatase ［ALP］， total bilirubin ［TBil］， triglyceride ［TG］， and total cholesterol ［TC］）， vaccination， and the incidence rate of liver disease symptoms after COVID-19. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups； the chi-square test and the continuously corrected chi-square test were used for comparison of categorical data between two groups. The binary Logistic regression model was used for univariate and multivariate analyses to investigate the influencing factors for COVID-19 after matching. ResultsThere were 87 patients in the UDCA group and 237 patients in the control group， and after PSM， there were 78 patients in the UDCA group and 137 patients in the control group， with good balance between the two groups. There was a significant difference in SARS-CoV-2 infection rate between the UDCA group and the control group ［82.1% （64/78） vs 95.6% （131/137）， χ2=10.847， P=0.001］. After COVID-19， compared with the control group， the UDCA group had a significantly lower proportion of the patients with chill （10.9% vs 38.9%， χ2=16.124， P<0.001） and cough （56.3% vs 74.8%， χ2=6.889， P=0.009）. There was a significant difference between the UDCA group and the control group in the proportion of the patients with a recovery time of ≤7 days after COVID-19 （79.7% vs 61.1%， χ2=6.760， P=0.009）. Both univariate and multivariate logistic regression analyses showed that UDCA was an independent influencing factor for COVID-19 （odds ratio=0.21 and 0.17， both P<0.05）. ConclusionUDCA is an protective factor against COVID-19 in patients with chronic hepatitis B and can alleviate related symptoms to some extent and shorten the recovery time， and therefore， it has an important value in the prevention and treatment of COVID-19.

Diagnostic and prognostic values of the ratio of red blood cell distribution width to platelet count for hepatitis B and liver cirrhosis / 中国基层医药

Objective:To analyze the diagnostic and prognostic values of the red blood cell distribution width-to-platelet count ratio (RPR) for hepatitis B and liver cirrhosis.Methods:The clinical data of 80 patients with hepatitis B and liver cirrhosis who were diagnosed and treated in Yiwu Central Hospital from June 2020 to August 2021 were retrospectively analyzed. These patients were included in the hepatitis B and liver cirrhosis group. They were subdivided into survival ( n = 69) and death ( n = 11) groups according to their prognosis outcomes. Eighty patients with chronic hepatitis B were included in the chronic hepatitis B group. Eighty healthy controls who concurrently underwent physical examination were included in the control group. The diagnostic and prognostic values of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) for hepatitis B and liver cirrhosis were analyzed. Results:Red blood cell distribution width, alanine transaminase, and aspartate transaminase in the hepatitis B and liver cirrhosis group and chronic hepatitis B group were significantly higher compared with the control group (all P < 0.05). Platelet count in the hepatitis B and liver cirrhosis group and chronic hepatitis B group was significantly lower than that in the control group (both P < 0.05). Red blood cell distribution width in the hepatitis B and liver cirrhosis group was significantly higher than that in the chronic hepatitis B group [(18.25 ± 3.28)% vs. (14.67 ± 2.15)%, t = 8.16, P < 0.05]. Platelet count, alanine transaminase, and aspartate transaminase levels in the hepatitis B and liver cirrhosis group were (78.47 ± 11.43) × 10 9/L, (49.48 ± 6.85) U/L, (45.86 ± 6.28) U/L, respectively, which were significantly lower than (133.36 ± 18.42) × 10 9/L, (128.36 ± 15.40) U/L, (98.67 ± 14.41) U/L in the chronic hepatitis B group ( t = -22.65, -41.86, -30.05, all P < 0.05). PRP, APRI, and FIB-4 in the hepatitis B and liver cirrhosis group were (0.23 ± 0.05), (1.85 ± 0.44), (4.25 ± 0.81) respectively, which were significantly higher than (0.11 ± 0.02), (1.46 ± 0.33), (3.38 ± 0.63) in the chronic hepatitis B group ( t = 19.93, 6.34, 7.58, all P < 0.001). The RPR, APRI, and FIB-4 in the death group were (0.25 ± 0.08), (1.97 ± 0.48), (4.52 ± 1.31), respectively, which were significantly higher than (0.18 ± 0.05), (1.68 ± 0.40), (3.69 ± 1.21) in the survival group ( t = 3.94, 2.17, 2.09, all P < 0.05). The receiver operating characteristic curve revealed that PRP has an extremely high value in diagnosing hepatitis B and liver cirrhosis and predicting the death of patients with hepatitis B and liver cirrhosis. Conclusion:RPR has an extremely high value in diagnosing hepatitis B and liver cirrhosis and predicting the prognosis of this disease.

Relationship between peripheral blood lipid level and hepatitis B-related liver cancer / 中国基层医药

Objective:To investigate the relationship between peripheral blood lipid levels and hepatitis B-related liver cancer, and to provide a theoretical basis for the early prevention and treatment of liver cancer.Methods:A total of 188 patients with hepatitis B-related liver cancer who received treatment in The First Hospital of Shanxi Medical University from June 2018 to June 2021 met the inclusion and exclusion criteria and had complete data, were included in this study. They were divided into three groups: chronic hepatitis B group ( n = 72), hepatitis B cirrhosis group ( n = 62), and hepatitis B-related liver cancer group ( n = 54) according to different stages of the disease. All patients' medical records were obtained from the medical data room. Fasting venous blood was collected in all patients on the second day after admission to detect peripheral blood lipid, liver function, and other relevant indicators. General data and biochemical indicators were collected. The Kruskal-Wallis test was performed to compare the measurement data among groups. The chi-squared test was performed to compare the count data among groups. Spearman's correlation (bivariate) was performed. Binary logistic regression was performed to analyze the influential factors of liver cancer. Results:There were significant differences in the levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) among the three groups ( F = 32.14, 27.59, 10.88, 34.09, all P < 0.05). TC and LDL-C levels in the hepatitis B-related liver cancer group were significantly higher than those in the hepatitis B cirrhosis group ( F = -32.31, -50.19, both P < 0.05). There were no significant differences in TG and HDL-C levels between hepatitis B-related liver cancer and hepatitis B cirrhosis groups ( F = -10.69, 4.46, both P > 0.05). TC, TG, HDL-C and LDL-C levels in the hepatitis B cirrhosis group were significantly lower than those in the chronic hepatitis B group ( F = 53.30, 46.98, 24.61, 48.57, all P < 0.05). LDL-C level was positively correlated with the occurrence of liver cancer ( r = 0.20, P < 0.05). HDL-C level was negatively correlated with the occurrence of liver cancer ( r = -0.15, P < 0.05). LDL-C was an independent risk factor for liver cancer ( OR = 3.35, P < 0.05), and HDL-C was a protective factor for liver cancer ( OR = 0.12, P < 0.05). Conclusion:Compared with patients with chronic hepatitis B and hepatitis B cirrhosis, patients with hepatitis B-related liver cancer had abnormal peripheral blood lipid levels, which may be related to the abnormal lipid metabolism of tumor cells. Moreover, peripheral blood lipid levels may affect the occurrence and development of tumor cells.

Efficacy of peginterferon alfa-2a combined with entecavir in sequential treatment of chronic hepatitis B / 中国基层医药

Objective:To investigate the efficacy of peginterferon alfa-2a (Peg-IFNα-2a) combined with entecavir in sequential treatment of chronic hepatitis B.Methods:A total of 106 patients with chronic hepatitis B who received treatment in Affiliated Hangzhou Xixi Hospital of Zhejiang University School of Medicine from January 2020 to February 2022 were included in this study. They were divided into a control group (entecavir treatment, n = 53) and a study group (sequential therapy with Peg-IFNα-2a followed by entecavir, n = 53). Liver function indicators, liver fibrosis indicators, clinical treatment efficacy, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:After treatment, total bilirubin, alanine aminotransferase and aspartate transaminase in the control and study groups were (94.79 ± 8.71) μmol/L and (67.67 ± 9.19) μmol/L, (256.93 ± 44.07) U/L and (186.56 ± 48.37) U/L, (256.47 ± 43.73) U/L and (200.69 ± 41.34) U/L, and they were (140.05 ± 26.15) μmol/L and (141.32 ± 25.35) μmol/L, (433.66 ± 77.16) U/L and (429.77 ± 73.73) U/L, (352.34 ± 65.19) U/L and (354.05 ± 66.13) U/L before the treatment. After treatment, these indexes in each group were decreased compared with before treatment ( t = 19.19, -12.13, -28.85, -20.96, -19.27, -12.03, all P < 0.05). After treatment, these indexes in the study group were significantly lower than those in the control group ( t = -6.49, -7.30, -6.74, all P < 0.001). After treatment, the levels of hyaluronic acid, laminin, type III procollagen peptide, and type IV collagen in the control and study groups were (124.91 ± 22.99) μg/L and (101.29 ± 22.67) μg/L, (132.71 ± 25.37) μg/L and (110.56 ± 25.49) μg/L, (116.93 ± 20.29) μg/L and (93.14 ± 20.39) μg/L, (63.14 ± 12.19) μg/L and (50.81 ± 11.63) μg/L, and they were (175.73 ± 48.56) μg/L and (177.61 ± 48.51) μg/L, (163.43 ± 41.52) μg/L and (165.57 ± 41.59) μg/L, (139.71 ± 31.75) μg/L and (141.72 ± 31.78) μg/L, (106.97 ± 32.24) μg/L and (104.02 ± 34.12) μg/L before treatment. After treatment, the levels of these indexes in each group were significantly decreased compared with before treatment ( t = -13.04, -8.68, -10.43, -5.82, -13.35, -6.26, -13.02, -10.72, all P < 0.05). After treatment, the levels of these indexes in the study group were significantly lower than those in the control group ( t = -5.32, -4.48, -6.02, -5.32, all P < 0.001). The total response rate in the study group was 88.68% (47/53), which was significantly higher than 62.26% (33/53) in the control group ( χ2 = 9.98, P < 0.05). The HBsAg conversion rate in the study group was 33.96% (18/53), which was significantly higher than 1.32% (6/53) in the control group ( χ2 = 7.75, P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the study and control groups [26.42% (14/53) vs. 30.19% (16/53), χ2 = 0.81, P > 0.05]. Conclusion:Sequential therapy with Peg-IFNα-2a followed by entecavir can effectively improve liver function,reduce liver fibrosis , improve clinical treatment efficacy, and will not increase adverse reactions.