Functional cure of chronic hepatitis B （CHB） is defined as HBsAg<0.05 IU/mL and serum HBV DNA<10 IU/mL for at least 24 weeks after discontinuation of antiviral therapy. This requires suppression of HBV replication and reduction of viral antigen production， as well as restoration of immune response to HBV infection. About 30% — 50% of highly selected CHB patients treated with nucleos（t）ide analogues can achieve functional cure after add-on therapy or monotherapy with pegylated interferon-α or a finite course of treatment with nucleos（t）ide analogues among patients with HBsAg<100 IU/mL. At present， clinical trials are being conducted for more than 40 types of novel anti-HBV drugs and immunomodulators. The combination of drugs that inhibit viral replication， reduce antigen burden， and restore immune response to HBV infection may be an ideal strategy to achieve the functional cure of CHB. However， further studies are needed to determine the optimal drug combination， the timing and sequence of medication， and the duration of treatment.

Existing nucleos（t）ide analogues and pegylated interferon exhibit limited efficacy in the functional cure of hepatitis B. Recently， small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， have brought unprecedented breakthroughs in the functional cure of hepatitis B with their brand-new mechanisms of action and remarkable efficacy in early clinical studies. Small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， can reduce the level of HBsAg and strive to achieve HBsAg seroclearance. The reduction in HBsAg may restore the hepatitis B-specific immune function of the body to some extent and may further transform the simple clearance of HBsAg into hard endpoints with clinical value， such as reducing hepatitis B-related liver events. By meticulously analyzing the dynamic trajectory of HBsAg alterations within the context of new drug applications and further optimizing combined treatment strategies and regimens， it is expected to transform the functional cure of hepatitis B into the ultimate goal of improving survival rates and quality of life.

Functional cure is currently the ideal treatment endpoint for chronic hepatitis B （CHB） in China and globally. HBsAg seroclearance and HBV DNA that cannot be detected in peripheral blood for more than 24 weeks marks the regression of hepatitis B virus （HBV） infection. However， there is still a lack of systematic description of the characteristics of intrahepatic HBV markers after HBsAg seroclearance. This article elaborates on the issues including the latest definition of functional cure， the characteristics of intrahepatic virological markers after HBsAg seroclearance， the significance of ultrasensitive serum HBsAg detection， and antiviral therapy for CHB patients with a low level of HBsAg， so as to improve the understanding of functional cure among clinicians.

Functional cure is currently recommended by guidelines as the ideal treatment goal for the prevention and treatment of chronic hepatitis B （CHB） in China and globally， and it is defined as sustained and undetectable serum HBsAg and HBV DNA， HBeAg clearance， and presence or absence of HBsAg seroconversion， accompanied by resolution of liver inflammation， histopathological improvements， and a significant reduction in the incidence rate of end-stage liver disease. HBV can integrate into the host genome and contribute to the continuous production of HBsAg， which can occur in the early stage of chronic HBV infection. In addition to the covalently closed circular DNA that is hard to be eliminated in liver tissue， HBsAg derived from HBV integration independent of viral replication may be the most important factor for the difficulty in achieving functional cure after antiviral therapy in patients with hepatitis B. This article reviews the research advances in HBV integration in recent years and discusses its impact on functional cure.

Up to half of patients with hepatocellular carcinoma （HCC） in China are diagnosed at an advanced stage and often with a dismal prognosis. More effective treatment strategies are mandatory. In recent years， the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has shown a promising treatment effect in advanced HCC with prolonged survival of patients， which also offered an opportunity for sequential curative surgery. Sequential curative hepatectomy or liver transplantation following conversion therapy brings survival benefits to patients. Aiming to improve the long-term survival of overall population with liver cancer and contribute to the goal of a 15% increase in the 5-year survival of overall cancer patients outlined in the “Healthy China 2030” blueprints， the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association， Chinese Society of Liver Cancer， and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts. These discussions focus on the latest progress since the release of Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma （2021 edition） and have reached new consensus on the modifications and supplements to some key points. This consensus aims to further guide clinical practice， standardize medical protocol， and usher the new development in liver surgery.

Recently， Asian Pacific Association for the Study of the Liver published the recommendations for the diagnosis and management of non-cirrhotic portal fibrosis （NCPF）/idiopathic portal hypertension （IPH）. The guidelines mainly elaborate on the definition， diagnosis， histological features， natural history， and management of NCPF/IPH， in order to strengthen the understanding of NCPF/IPH-related issues and establish a global consensus. This article makes an excerpt of the key statements in the guidelines.

ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

ObjectiveTo investigate the expression level of HBV cccDNA in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） and its correlation with HBV markers and liver histopathological changes. MethodsA total of 30 patients in the convalescence stage of HBV-ACL who were hospitalized in The Ninth Hospital of Nanchang from January 2015 to October 2023 were enrolled as liver failure group， and 9 patients with chronic hepatitis B （CHB）， matched for sex and age， were enrolled as control group. The content of HBV cccDNA in liver tissue was measured， and its correlation with clinical data and laboratory markers was analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and a one-way analysis of variance or the Kruskal-Wallis H test was used for comparison between multiple groups； the Fisher’s exact test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed. ResultsThe liver failure group had a significantly lower content of HBV cccDNA in liver tissue than the control group （-0.92±0.70 log₁₀ copies/cell vs -0.13±0.91 log₁₀ copies/cell， t=2.761， P=0.009）. In the liver failure group， there was no significant difference in the content of HBV cccDNA in liver tissue between the HBeAg-positive patients and the HBeAg-negative patients （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different grades （G0-G2， G3， and G4） of liver inflammatory activity （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different stages （S0-S2， S3， and S4） of liver fibrosis （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with negative HBV DNA and those with positive HBV DNA （P>0.05）. For the liver failure group， the content of HBV cccDNA in liver tissue was positively correlated with the content of HBV DNA in liver tissue （r=0.426， P=0.043） and was not significantly correlated with the content of HBV DNA in serum （P>0.05）. ConclusionThere is a significant reduction in the content of HBV cccDNA in liver tissue in the convalescence stage of HBV-ACLF. HBV cccDNA exists continuously and stably in liver tissue and can better reflect the persistent infection and replication of HBV than HBV DNA in serum and liver tissue.

ObjectiveTo investigate the difference in the risk of cardiovascular diseases between patients with different subtypes of non-alcoholic fatty liver disease （NAFLD） from the perspective of metabolism， since cardiovascular events induced by metabolic disorders are the leading cause of death in NAFLD. MethodsThe cluster sampling method was used to conduct a multicenter cross-sectional study among three representative hospitals in Pudong New Area of Shanghai， China. A total of 37 122 sets of physical examination data from July 2022 to June 2023 were collected and stratified according to body mass index （BMI）. The chi-square test was used for comparison of continuous data between groups， and a multivariable Logistic regression analysis was used to investigate the association between NAFLD subtypes and cardiometabolic risk factors. ResultsA total of 9 372 cases of NAFLD were detected， with a detection rate of 25.25%， and more than 97% of these patients were diagnosed with metabolic associated fatty liver disease （MAFLD）. The subgroup analysis showed that the detection rates of lean， overweight， and obese NAFLD were 7.72%， 33.99%， and 63.56%， respectively. Compared with the patients with lean or overweight NAFLD， the patients with obese NAFLD showed a significantly higher proportion of patients with abnormalities in blood pressure， blood glucose， triglyceride （TG）， high-density lipoprotein （HDL） or uric acid （all P<0.001）. Among related risk factors， lean NAFLD was associated with the increase in total cholesterol （TC）（P<0.05）， while overweight NAFLD and obese NAFLD were not associated with TC abnormalities （P>0.05）； obese NAFLD was not associated with TG abnormalities， while lean NAFLD and overweight NAFLD were associated with TG abnormalities （both P<0.05）； all types of NAFLD were associated with the abnormalities of waist-hip ratio， blood pressure， blood glucose， low-density lipoprotein， HDL， and uric acid （all P<0.05）. ConclusionThe detection rates of different subtypes of NAFLD in Shanghai Pudong are close to those reported in China and globally， and the epidemiologic data of NAFLD can be used analogously for MAFLD. There are certain differences in the distribution and association of cardiometabolic risk factors between different subtypes of NAFLD， and targeted interventions should be formulated based on the metabolic characteristics of each type of NAFLD.