2024 No. 7

Treatment of metastatic liver cancer： Current status and future perspectives

Xiangyu WANG, Jinhong CHEN

2024, 40(7): 1289-1294. DOI: 10.12449/JCH240701

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The liver is a common metastatic site of malignant tumors， and liver metastasis is also the leading cause of death due to metastatic tumors. Metastatic liver cancer has high heterogeneity， and there has been slow progress in the treatment of metastatic liver cancer for a long time. In recent years， the development of surgical techniques， systemic therapy， and the multidisciplinary team （MDT） diagnostic and therapeutic mode has led to revolutionary changes in the clinical management of metastatic liver cancer. The article reviews the recent progress in the treatment of metastatic liver cancer from the three aspects of surgical treatment， systemic therapy， and locoregional therapy. Combined therapy based on chemotherapy， targeted therapy， and immunotherapy remains the basic multimodality therapy for metastatic liver cancer. In addition， the development of locoregional therapy has brought new treatment options for patients with metastatic liver cancer. Standardized diagnosis and treatment based on high-level evidence-based evidence and related guidelines and individualized precise treatment under the guidance of MDT will be the future directions for the clinical management of metastatic liver cancer.

Treatment strategy of non-radical surgical resection for colorectal cancer liver metastases

Rui ZHANG, Jinhong CHEN

2024, 40(7): 1295-1300. DOI: 10.12449/JCH240702

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Effective treatment of colorectal cancer liver metastases is crucial for improving the survival rate and quality of life of patients with colorectal cancer. With the application of systemic chemotherapy， there have been increases in the conversion rate and surgical resection rate of patients with colorectal cancer liver metastases. Non-radical resection is one of the surgical strategies in tumor surgery. This article reviews the treatment of patients with initially unresectable colorectal cancer liver metastases， including extrahepatic metastasis， R1 resection of liver metastases， staged surgery for liver metastases， and debulking surgery， as well as the application of non-radical resection in the treatment of colorectal cancer liver metastases.

Surgical intervention strategies for liver metastasis of neuroendocrine tumors

Junqing WANG, Yongjun CHEN

2024, 40(7): 1301-1306. DOI: 10.12449/JCH240703

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Neuroendocrine tumors are a group of rare tumor diseases that can occur in various visceral organs of the human body and exhibit significant tumor heterogeneity， and they often lead to secondary tumors mostly involving the liver and carcinoid syndrome. Liver metastasis is an important cause of treatment failure in patients with neuroendocrine tumor， and timely and reasonable surgical interventions that can effectively control disease progression to achieve the disease-free state or the goal of radical treatment and prolong the overall survival of patients has been a focus of research by clinicians and researchers in recent years. With reference to actual clinical work and working experience， this article reviews and discusses the surgical treatment strategies for liver metastasis of neuroendocrine tumors based on related strategies in China and globally and the latest diagnosis and treatment guidelines in China.

Research advances in the treatment of cervical cancer with liver metastasis

Shangdan XIE, Qunchao HU, Haiyan ZHU

2024, 40(7): 1307-1311. DOI: 10.12449/JCH240704

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Though liver metastasis of cervical cancer has a relatively low incidence rate， it is often accompanied by metastasis in other sites and thus has a poor prognosis. For the patients with liver metastasis of cervical cancer， it is necessary to formulate individualized treatment regimens based on various factors such as general status， lesion distribution， initial treatment modality， and life expectancy， so as to prolong the overall survival of patients and improve their quality of life. With reference to related studies in China and globally， this article reviews the clinical features， treatment， and prognosis of cervical cancer with liver metastasis.

Chinese guideline for diagnosis and treatment of autoimmune pancreatitis （Shanghai， 2023）

National Clinical Research Center for Digestive Diseases （Shanghai）； National Key Laboratory of Immunity and Inflammation；Professional Committee of Pancreatic Disease， Chinese Medical Doctor Association； Pancreas Study Group， Society of Gastroenterology，Chinese Medical Association； Editorial Board of Chinese Journal of Pancreatology

2024, 40(7): 1312-1320. DOI: 10.12449/JCH240705

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Autoimmune pancreatitis （AIP） is an immune⁃mediated， special type of chronic pancreatitis， which can involve multiple organs. The clinical manifestation of AIP is complex and varied， making the diagnosis and treatment challenging. With reference to the latest guidelines and studies from both domestic and international sources， this guideline comprises 20 recommendations regarding the diagnosis， treatment， follow⁃up， and prognosis of AIP. The aim of this guideline is to promote the care capability and improve the outcome of patients with AIP in China.

An excerpt of the American College of Gastroenterology clinical guideline on alcohol-associated liver disease in 2024

Furong SUN, Bingyuan WANG

2024, 40(7): 1321-1323. DOI: 10.12449/JCH240706

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The American College of Gastroenterology published the clinical guideline on alcohol-associated liver disease （ALD） in January 2024 in American Journal of Gastroenterology. This guideline elaborates on the epidemiology and disease burden of ALD and alcohol use disorder， the risk factors for ALD， the diagnosis and treatment of alcohol use disorder， the disease spectrum of ALD， the management of ALD， and public policy and prevention. This article gives an excerpt of the recommendations and key points/statements in this guideline.

Interpretation of guidelines for the diagnosis and treatment of primary liver cancer （2024 edition）

Zhao LI, Jiye ZHU

2024, 40(7): 1324-1327. DOI: 10.12449/JCH240707

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In June 2017， National Health Commission of the People’s Republic of China released Guidelines for the diagnosis and treatment of primary liver cancer （2017 edition）， which provided important recommendations for the diagnosis， staging， and treatment of liver cancer. Since then， high-level evidence in line with the principles of evidence-based medicine has been continuously obtained from the research on primary liver cancer in China and globally. Therefore， National Health Commission released Guidelines for the diagnosis and treatment of primary liver cancer （2024 edition）. This article gives an interpretation of the updated key points in the guidelines， in order to better guide clinical practice.

Establishment of a noninvasive predictive model for antiviral therapy in patients with chronic hepatitis B virus infection and an age of ≤30 years

Changxiang LAI, Qingrong TANG, Xiulian ZHANG, Qiyuan TANG, Zhiyu LI, Xuan ZHOU, Wenjie XIAN, Ruikun CHEN, Xiaojuan WU, Fang WANG

2024, 40(7): 1328-1333. DOI: 10.12449/JCH240708

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Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus （HBV） infection and an age of ≤30 years by establishing a noninvasive model， and to investigate the diagnostic value of this model. Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People’s Hospital from January 2017 to January 2023 and met the inclusion criteria， and according to the results of liver biopsy， they were divided into treatment group with 41 patients （with indications for antiviral therapy） and observation group with 134 patients （without indications for antiviral therapy）. The two groups were analyzed in terms of the indicators including clinical data， imaging examinations， and serum biochemical parameters. The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy， and different models for predicting the need for antiviral therapy were constructed based on related parameters. The receiver operating characteristic （ROC） curve was used to compare the diagnostic value of different models. The independent-samples t test was used for comparison of normally distributed continuous variables between groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Results There were significant differences between the treatment group and the observation group in alanine aminotransferase， ferritin， total cholesterol （CHOL）， triglyceride， platelet count， liver stiffness measured by sound touch elastography （STE）， and procollagen III N-terminal propeptide （PIIIP）（all P<0.05）. The multivariate Logistic regression analysis showed that CHOL （odds ratio ［OR］=0.4， 95% confidence interval ［CI］： 0.2‍ ‍—‍ ‍1.0）， STE （OR=1.5， 95%CI： 1.0‍ ‍—‍ ‍2.1）， and PIIIP （OR=1.1， 95%CI： 1.0‍ ‍—‍ ‍1.1） were independent predictive factors for the indications for antiviral therapy. Model 1 （STE+PIIIP+CHOL）， model 2 （STE+PIIIP）， model 3 （STE+CHOL）， model 4 （PIIIP+CHOL） had an area under the ROC curve of 0.908， 0.848， 0.725， and 0.725， respectively， while STE， PIIIP， and CHOL used alone had an AUC of 0.836， 0.725， and 0.634， respectively， suggesting that model 1 had the largest AUC， with a specificity of 77.34% and a sensitivity of 96.36%， and had a significant difference compared with STE， PIIIP， CHOL， and the models 2， 3， and 4 （Z=0.21， 3.08， 3.06， 3.23， 0.89， and 0.88， all P<0.05）. Conclusion The noninvasive model established based on CHOL， STE， and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of ≤30 years.

Incidence rate of low-level viremia and related influencing factors in treatment-experienced chronic hepatitis B patients： A Meta-analysis

Lu XIE, Yanan LIU, Guangwei LIU, Pengyu LI, Xinning HU, Qiujia KANG, Huijun GUO

2024, 40(7): 1334-1342. DOI: 10.12449/JCH240709

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Objective To 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. Methods This 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. Results A 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. Conclusion Clinicians 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

Lingna LYU, Qi LI, Wenxia MA, Huiguo DING, Hui LIU

2024, 40(7): 1343-1348. DOI: 10.12449/JCH240710

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Objective To investigate the virological features of patients with chronic hepatitis B （CHB） and metabolic associated fatty liver disease （MAFLD） through a stratified analysis. Methods A 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. Results Compared 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）. Conclusion Patients 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.

Expression of serum 25-hydroxyvitamin D and its clinical significance in patients with nonalcoholic fatty liver disease and obesity

Linlin WU, Fan ZHANG

2024, 40(7): 1349-1353. DOI: 10.12449/JCH240711

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Objective To investigate the serum level of 25-hydroxyvitamin D in patients with nonalcoholic fatty liver disease （NAFLD） and obesity， as well as the correlation of 25-hydroxyvitamin D with liver function， blood lipids， and inflammatory indicators. Methods A total of 90 patients with NAFLD who attended Shanxi Bethune Hospital from January 2022 to March 2023 were enrolled， and according to the body mass index （BMI）， they were divided into NAFLD+obesity group with 60 patients （BMI≥28 kg/m²） and NAFLD group with 30 patients （BMI<28 kg/m²）； 30 individuals who underwent physical examination during the same period of time were enrolled as control group. Related indications were measured for all three groups， including serum 25-hydroxyvitamin D， liver function parameters （alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， alkaline phosphatase ［ALP］， gamma-glutamyl transpeptidase ［GGT］， total bilirubin ［TBil］， and direct bilirubin ［DBil］）， blood lipid parameters （high-density lipoprotein ［HDL］， low-density lipoprotein ［LDL］， total cholesterol ［TC］， and triglyceride ［TG］）， inflammatory indicators （high-sensitivity C-reactive protein ［H-CRP］ and Golgi protein 73 ［GP-73］）， cytokines （interleukin-2 ［IL-2］， interleukin-4 ［IL-4］， interleukin-6 ［IL-6］， interleukin-10 ［IL-10］， interleukin-17 ［IL-17］， interleukin-1β ［IL-1β］， tumor necrosis factor-α ［TNF-α］， and interferon gamma ［IFN-γ］）， and liver/spleen volume ratio. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test or the Tamhane’s T2 test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. A Pearson or Spearman correlation analysis was performed. Results Compared with the control group， the NAFLD+obesity group had significant reductions in 25-hydroxyvitamin D， HDL， cytokines （IL-2， IL-4， IL-10， and IFN-γ）， and liver/spleen volume ratio （all P<0.05）， as well as significant increases in liver function parameters （ALT， AST， ALP， GGT， TBil， and DBil）， blood lipid parameters （LDL， TC， and TG）， inflammatory indicators （H-CRP and GP-73）， and cytokines （IL-1β， IL-17， and TNF-α）（all P<0.05）. There were significant differences between the NAFLD+obesity group and the NAFLD group in all the above indicators except liver/spleen volume ratio and H-CRP （all P<0.05）. The correlation analysis showed that 25-hydroxyvitamin D level was negatively correlated with ALT （r=-0.324， P=0.012）， AST （r=-0.421， P=0.001）， ALP （r=-0.435， P=0.001）， GGT （r=-0.343， P=0.007）， TBil （r=-0.532， P<0.001）， DBil （r=-0.521， P<0.001）， LDL （r=-0.405， P=0.001）， TC （r=-0.466， P<0.001）， TG （r=-0.551， P<0.001）， H-CRP （r=-0.434， P=0.014）， GP-73 （r=-0.421， P=0.001）， IL-1β （r=-0.433， P=0.001）， IL-17 （r=-0.465， P<0.001）， and TNF-α （r=-0.533， P<0.001）， and it was positively correlated with HDL （r=0.632， P<0.001）， IL-2 （r=0.546， P<0.001）， IL-4 （r=0.533， P<0.001）， IL-10 （r=0.456， P<0.001）， and liver/spleen volume ratio （r=0.543， P<0.001）. Conclusion Serum 25-hydroxyvitamin D is significantly correlated with liver function parameters， blood lipid parameters， and inflammatory indicators in patients with NAFLD and obesity， and it may alleviate the symptoms of patients with NAFLD and obesity by reducing inflammatory response， which provides new intervention strategies for the treatment of NAFLD.

Association between sleep disorders and different stages of nonalcoholic fatty liver disease

Jingjie ZHAO, Xinyu ZHAO, Chaoru HAN, Kaihui XIAO, Zhengzhao LU, Linyan QIN, Dong XU, Hong YOU

2024, 40(7): 1354-1359. DOI: 10.12449/JCH240712

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Objective To investigate the association of sleep disorders with the development and progression of nonalcoholic fatty liver disease （NAFLD）. Methods A total of 1 868 participants from the health examination cohort and fatty liver cohort of Beijing Friendship Hospital from June 2022 to June 2023 were enrolled as subjects. Related data were collected from all subjects， including age， sex， education level， chronic medical history， and biochemical parameters， and all subjects completed Pittsburgh Sleep Quality Index （PSQI） scale independently. According to the diagnostic criteria， the subjects were divided into non-NAFLD group with 1 122 subjects and NAFLD group with 746 subjects， and according to the stage of progression， the patients in the NAFLD group were further divided into simple fatty liver group （SFL group with 624 subjects） and nonalcoholic steatohepatitis （NASH） group with 122 subjects. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between three groups. The chi-square test was used for comparison of categorical data between the three groups. The binary Logistic regression analysis was used to investigate the association between sleep factors and NAFLD， and the multinomial Logistic regression analysis was used to investigate the association between sleep factors and the different stages of NAFLD； two multivariate models were constructed for adjustment of potential confounding factors， i.e.， an age-sex adjustment model and a multivariate adjustment model， and the multivariate adjustment model adjusted the factors of age， sex， education level， smoking， diabetes， hypertension， body mass index （BMI）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C）. Results There were significant differences in age， sex， BMI， education level， smoking， diabetes， hypertension， alanine aminotransferase， TG， and HDL-C between the non-NAFLD， SFL， and NASH groups （all P<0.05）. There were also significant differences between the three groups in the total score of PSQI scale and the proportion of subjects with a score of 0‍ ‍—‍ ‍3 points for the 7 sleep components （all P<0.05）. The multivariate adjustment model showed no significant association between sleep disorders and SFL， while long sleep latency （odds ratio ［OR］=4.04， 95% confidence interval ［CI］： 2.33‍ ‍—‍ ‍7.03， P<0.001）， short sleep duration （OR=3.53， 95%CI： 1.83‍ ‍—‍ ‍6.82， P<0.001）， and severe sleep disorders （OR=2.96， 95%CI： 1.48‍ ‍—‍ ‍5.93， P=0.002） were closely associated with the risk of NASH. Conclusion Overall sleep condition and its components of sleep disorders are not significantly associated with the simple fatty liver； however， long sleep latency， short sleep duration， and severe sleep disorders can increase the risk of NASH， which should be taken seriously in clinical practice.

Association between Helicobacter pylori and nonalcoholic fatty liver disease： A Meta-analysis

Yuzhen YU, Liewang QIU, Ping HE

2024, 40(7): 1360-1369. DOI: 10.12449/JCH240713

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Objective To investigate the association between Helicobacter pylori infection and nonalcoholic fatty liver disease （NAFLD）. Methods This study was conducted acoording to the PRISMA guideline， with a PROSPERO registration number of CRD42023408932. Databases including PubMed， the Cochrane Library， Web of Science， Embase， CBM， Wanfang Data， CNKI， and VIP were searched for related articles published up to June 2023. This study was conducted for the case-control studies， cross-sectional studies， and cohort studies that included clear detection criteria for HP and evaluation criteria for NAFLD and performed the multivariate analysis to investigate the association between HP infection and NAFLD. Odds ratio （OR） and its 95% confidence interval （CI） were selected as the effect measures， and STATA 15.0 software was used to perform the Meta-analysis. Results A total of 33 primary studies were included， with 236 514 subjects in total. The Meta-analysis showed that HP was associated with the high prevalence rate of NAFLD （OR=1.25， 95%CI： 1.16‍ ‍—‍ ‍1.35， P<0.05， I²=93.7%）. Subgroup analysis was conducted in terms of sample size， the diagnostic method for HP， the quality of primary study， the health status of subjects， and the type of primary study， but no clear source of heterogeneity was found. The Meta-regression analysis was conducted with the covariates of sample size， the diagnostic method for HP， the quality of primary study， the health status of subjects， and the type of primary study， and the results showed that the health status of subjects and the type of primary study might be the sources of heterogeneity. Sensitivity analysis showed that the overall results were stable， and funnel plots and the Egger test showed no significant publication bias. Conclusion HP is associated with the high prevalence rate of NAFLD in the general population， and large-scale prospective cohort studies are still needed to specifically and comprehensively evaluate the association between HP and NAFLD.

Effect of ursodeoxycholic acid on symptoms after severe acute respiratory syndrome coronavirus 2 infection in patients with primary biliary cholangitis and their family members

Gui JIA, Chunmei YANG, Xiufang WANG, Juan DENG, Ruiqing SUN, Linhua ZHENG, Yulong SHANG, Ying HAN

2024, 40(7): 1370-1374. DOI: 10.12449/JCH240714

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Objective To investigate the effect of ursodeoxycholic acid （UDCA） on the symptoms after severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） infection in patients with primary biliary cholangitis （PBC） and their family member. Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22， 2023 and 128 family members， including demographic information， comorbidities， UDCA administration， SARS-CoV-2 infection， vaccination， symptoms， therapeutic medication， and the changes in liver disease-related symptoms. 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. Results The median age was 51 years in the PBC patients and 49 years in the family members， with no significant difference between the two groups （P>0.05）. Compared with the family member group， the PBC group had significantly lower body mass index （22.2±2.4 kg/m² vs 23.3±2.9 kg/m²， P<0.001） and proportion of male individuals （10% vs 55%， P<0.001）. All PBC patients received UDCA at a dose of 13‍ ‍—‍ ‍15 mg/kg， and SARS-CoV-2 infection rate was 100% in both groups. The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients （91% vs 57%， P<0.001）. Compared with the family members， the PBC patients had significantly milder symptoms of sneezing， nasal obstruction， chest pain， and abnormal taste （P<0.05）. Compared with the family members， the PBC patients had significantly lower rates of use of compound cold medicine （11% vs 20%， P<0.05） and Lianhua Qingwen capsules （12% vs 21%， P<0.05）. For the PBC patients after SARS-CoV-2 infection， the liver disease-related symptoms such as fatigue， abdominal distension， dry mouth and dry eyes， pruritus， and yellow skin were aggravated by 37%， 2%， 27%， 10%， and 3%， respectively. Conclusion Compared with the immediate family members of PBC patients who do not take UDCA， the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate， but UDCA may have a certain effect on alleviating infection-related symptoms in such patients. PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection， and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.

Influencing factors for rebleeding and 5-year survival rate after treatment in patients with liver cirrhosis and spontaneous splenorenal shunt

Chengzhao WENG, Wei JIANG, Shiyao CHEN, Linlin ZHENG

2024, 40(7): 1375-1381. DOI: 10.12449/JCH240715

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Objective To investigate the influencing factors for rebleeding and 5-year survival rate after treatment in patients with liver cirrhosis and spontaneous splenorenal shunt （SSRS）， and to provide a basis for clinical prognostic assessment. Methods A total of 95 patients with liver cirrhosis and SSRS who were admitted to Zhongshan Hospital and Xiamen Branch of Fudan University from June 2014 to June 2018 were enrolled， and all patients were followed up for at least 5 years. According to the presence or absence of gastrointestinal bleeding during follow-up， the patients were divided into rebleeding group with 27 patients and non-rebleeding group with 68 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Univariate and multivariate Cox regression analyses were used to investigate the influencing factors for the prognosis of patients with SSRS， and the Kaplan-Meier method was used to describe survival outcomes. A Pearson or Spearman correlation analysis was performed. Results Compared with the non-rebleeding group， the rebleeding group had significantly higher splenorenal shunt diameter ［4.60（3.20 ‍—‍ 5.90） mm vs 3.45（2.10 ‍—‍ 5.45） mm， Z=1.973， P=0.048］ and hepatic venous pressure gradient（18.57±6.60 mmHg vs 15.06±5.82 mmHg， t=2.280， P=0.026） and a significantly lower portal vein diameter（14.04±2.90 mm vs 15.45±2.90 mm， t=2.138， P=0.035）. The correlation analysis showed that splenorenal shunt diameter was negatively correlated with portal vein diameter（r_s =-0.211， P=0.040）. Adverse events within 5 years after treatment included rebleeding（27.4%）， portal vein thrombosis（11.6%）， infection（4.2%）， cerebral hemorrhage（1.1%）， and cerebral infarction（1.1%）. Splenorenal shunt diameter（risk ratio ［RR］=1.173， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.374， P=0.048） and superior mesenteric vein diameter（RR=0.844， 95%CI： 0.746 ‍—‍ 0.956， P=0.007） were independent influencing factors for gastrointestinal rebleeding within 5 years after treatment. Bilirubin（RR=1.028， 95%CI： 1.010 ‍—‍ 1.046， P=0.002） and blood urea nitrogen（RR=1.347， 95%CI： 1.116 ‍—‍ 1.625， P=0.002） were independent risk factors for 5-year survival rate after treatment. Conclusion Splenorenal shunt diameter is closely associated with the prognosis of cirrhotic patients， and it is recommended to enhance imaging follow-up of splenorenal shunt diameter for cirrhotic patients with SSRS.

Effect of miRNA-933 on the apoptosis and proliferation of LX-2 cells and its molecular mechanism

Long HAI, Lina MA, Xia LUO, Xiangchun DING

2024, 40(7): 1382-1389. DOI: 10.12449/JCH240716

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Objective To investigate the regulatory effect of miRNA-933 on the apoptosis and proliferation of human hepatic stellate cell line LX-2 and its mechanism. Methods Firstly， with human liver tissue for research， gene microarray technology was used to detect the differentially expressed genes in liver tissue between liver cirrhosis/chronic hepatitis B tissue and normal liver tissue， among which the significantly differentially expressed miRNAs were identified， and thus miRNA-933 was determined as the research object. Then， with the human hepatic stellate cell line LX-2 for research， miRNA-933 mimic and inhibitor （miRNA-933 siRNA） were used to construct the LX-2 models of overexpression and knockdown， and the cells transfected with mimic-NC （overexpression） or siRNA-NC （knockdown） were established as the negative control group. Quantitative real-time PCR and Western blot were used to measure the expression levels of miRNA-933 and activation biomarkers； techniques such as cell proliferation assay and flow cytometry were used to investigate the effect and mechanism of miRNA-933 on cell apoptosis， proliferation， and activation. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and Bonferroni correction was also performed. Results A total of 18 significantly differentially expressed miRNAs were obtained based on the results of gene microarray， among which miRNA-933 was significantly downregulated （P<0.05）. After LX-2 cells were transfected with miRNA-933 mimic or siRNA， compared with the negative control group， miRNA-933 siRNA significantly downregulated the expression of miRNA-933 （P=0.000 7）， while miRNA-933 mimic significantly upregulated the expression of miRNA-933 （P=0.000 3）. Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly upregulated the expression of collagen I and α-SMA （P<0.001）， while miRNA-933 mimic significantly inhibited the expression of collagen I and α-SMA （P<0.05）. Flow cytometry showed that compared with the negative control group， miRNA-933 siRNA significantly downregulated the apoptosis rate of LX-2 cells （P=0.031 9）， and miRNA-933 mimic significantly upregulated the apoptosis rate of LX-2 cells （P=0.005 5）. Western blot showed that compared with the negative control group， miRNA-933 siRNA could inhibit the expression of Caspase-3 （P=0.006 7） and poly（ADP-ribose） polymerase-1 （PARP-1）（P=0.003 0） and upregulate the expression of B-cell lymphoma-2 （Bcl-2） in LX-2 cells （P=0.002 0）， while miRNA-933 mimic could significantly upregulate the expression of Caspase-3 （P=0.011 8） and PARP-1 （P=0.049 5） and downregulated the expression of Bcl-2 （P=0.002 1）. Cell proliferation assay showed that compared with the negative control group， miRNA-933 siRNA could promote the proliferation of LX-2 cells （P=0.011 5）， while on the contrary， miRNA-933 mimic could inhibit the proliferation of LX-2 cells （P=0.001 2）. Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly inhibited the expression of Kruppel-like factor 6 （KLF6） and downregulated the expression of activating transcription factor 4 （ATF4）， activating transcription factor 3 （ATF3）， and C/EBP homologous protein （CHOP）， while miRNA-933 mimic promoted the expression of the above proteins （all P<0.05）. Conclusion This study shows that miRNA-933 may promote cell apoptosis and inhibit cell activation and proliferation by promoting the activation of the KLF6/ATF4/ATF3/CHOP/Bcl-2 signal axis in LX-2 cells.

Expression and clinical significance of cell cycle protein-dependent kinase 1 and aurora kinase A in the serum of patients with hepatitis B virus-related hepatocellular carcinoma

Yanfang HE, Jiaojiao XIE, Lanlan ZHENG, Cai GUO, Yanhua MA

2024, 40(7): 1390-1396. DOI: 10.12449/JCH240717

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Objective To investigate the value of serum cell cycle protein-dependent kinase 1 （CDK1） and aurora kinase A （AURKA） in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma （HBV-HCC）. Methods A total of 50 HBV-HCC patients， 50 patients with hepatitis B virus-related liver cirrhosis （HBV-LC）， and 50 chronic hepatitis B （CHB） patients who were hospitalized in Department of Gastroenterology， Gansu Provincial Hospital， from June 2022 to December 2023 were enrolled， and 50 healthy individuals， matched for age and sex， who received physical examination at Physical Examination Center during the same period of time were enrolled as control group. Related data were recorded for all patients， including age， sex， complications， and the results of routine blood test， liver function， and coagulation for the first time after admission. ELISA was used to measure the serum levels of CDK1 and AURKA. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between CDK1 and AURKA， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the value of CDK1 and AURKA in the diagnosis of HBV-HCC. Results There were significant differences in liver function parameters between the HBV-HCC patients and the control group （all P<0.05）； there were significant differences between the CHB group and the HBV-HCC group in albumin， Glb， direct bilirubin， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， and alkaline phosphatase （all P<0.05）； there were significant differences between the HBV-LC group and the HBV-HCC group in Glb， AST， and GGT （all P<0.05）. The HBV-HCC group had significantly higher serum levels of CDK1 and AURKA than the HBV-LC group， the CHB group， and the control group （all P<0.05）. There was a significant positive correlation between CDK1 and AURKA in the overall study population and the HBV-HCC patients （r=0.526 6 and 0.815 2， P<0.001）. With the control group as reference， CDK1 had an AUC of 0.832 3 in the diagnosis of HBV-HCC， with a sensitivity of 92.86% and a specificity of 75%， and AURKA had an AUC of 0.886 6 in the diagnosis of HCC， with a sensitivity of 95.80% and a specificity of 74%. With the CHB group as reference， CDK1 had an AUC of 0.833 3 in the diagnosis of HBV-HCC， with a sensitivity of 93.75% and a specificity of 75%， and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC， with a sensitivity of 95.83% and a specificity of 91.67%. With the HBV-LC group as reference， CDK1 had an AUC of 0.608 5 in the diagnosis of HBV-HCC， with a sensitivity of 66.67% and a specificity of 54.17%， and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC， with a sensitivity of 95.83% and a specificity of 47.92%. Conclusion The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease， and significant increases in serum CDK1 and AURKA have a certain value in the diagnosis of HBV-HCC.

Efficacy and safety of three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma： A Meta-analysis

Kaifu LI, Yongcheng TANG, Hao TANG, Xi ZHANG, Benjian GAO, De LUO, Song SU, Bo LI, Xiaoli YANG

2024, 40(7): 1397-1403. DOI: 10.12449/JCH240718

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Objective To systematically evaluate the efficacy and safety of three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma. Methods This study was conducted according to PRISMA guidelines， with a PROSPERO registration number of CRD42023488398. PubMed， Embase， Web of Science， the Cochrane Library， CNKI， Wanfang Data， VIP， and CBM were searched for Chinese and English articles on three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma published up to March 2023. After quality assessment and data extraction of the studies included， RevMan 5.4 software was used to perform the meta-analysis. Results A total of 11 studies were included， with 972 patients in total， among whom 447 underwent ablation assisted by three-dimensional visualization technology （3D group） and 525 underwent ablation assisted by traditional two-dimensional imaging technology （2D group）. The meta-analysis showed that compared with the 2D group， the 3D group had significantly higher success rate of first-time ablation treatment （odds ratio ［OR］=5.43， 95% confidence interval ［CI］： 2.64‍ ‍—‍ ‍11.18， P<0.001）， technical efficiency （OR=6.15， 95%CI： 3.23‍ ‍—‍ ‍11.70， P<0.001）， and complete ablation rate （OR=2.50， 95%CI： 1.08‍ ‍—‍ ‍5.78， P=0.03）， as well as significantly lower incidence rate of major complications （OR=0.45， 95%CI： 0.24‍ ‍—‍ ‍0.87， P=0.02）， local recurrence rate （OR=0.35， 95%CI： 0.17‍ ‍—‍ ‍0.72， P=0.004）， and local tumor progression rate （OR=0.29， 95%CI： 0.16‍ ‍—‍ ‍0.50， P<0.001）， while there was no significant difference in the incidence rate of mild complications between the two groups （P>0.05）. Conclusion Three-dimensional visualization technology is safe and feasible in assisting ablation therapy for hepatocellular carcinoma and can improve ablation rate and reduce the incidence rate of serious complications， local recurrence rate， and local tumor progression rate， thereby showing an important application value in clinical practice.

Value of contrast-enhanced ultrasound combined with shear wave elastography in the diagnosis of benign and malignant liver tumors： A Meta-analysis

Jun SONG, Lujia NI, Hanyu ZHANG, Xingzhao LI

2024, 40(7): 1404-1410. DOI: 10.12449/JCH240719

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Objective To investigate the value of contrast-enhanced ultrasound （CEUS） combined with shear wave elastography （SWE） in the diagnosis of liver tumors. Methods This study was conducted according to the PRISMA guideline， with a PROSPERO registration number of CRD42023491288. PubMed， Embase， the Cochrane Library， CNKI， VIP， and Wanfang Data were searched for articles on CEUS combined with SWE in the diagnosis of liver tumors published from January 2000 to October 2023， and a total of 12 articles were included， with 1 328 patients in total. The QUADAS-2 tool was used to assess the quality of the articles included. Stata 15.0 software was used to calculate pooled sensitivity， specificity， positive likelihood ratio， negative likelihood ratio， diagnostic odds ratio， and heterogeneity. The summary receiver operating characteristic （SROC） curve was plotted， and the area under the SROC curve （AUC） was calculated. Results There were 1 457 lesions for the patients included， among whom there were 764 malignant lesions and 693 benign lesions， with a positive rate of 52.44% and a negative rate of 47.56%. Calculations obtained a pooled sensitivity of 0.94 （95% confidence interval ［CI］： 0.91‍ ‍—‍ ‍0.96）， a specificity of 0.92 （95%CI： 0.87‍ ‍—‍ ‍0.95）， a positive likelihood ratio of 12.00 （95%CI： 7.40‍ ‍—‍ ‍19.40）， a negative likelihood ratio of 0.06 （95%CI： 0.04‍ — ‍0.10）， and a diagnostic odds ratio of 191 （95%CI： 87‍ ‍—‍ ‍417）. The tests for heterogeneity showed Q=54.78， df=11.00， P<0.001， and I²=79.92% （95%CI： 69.18%‍ ‍—‍ ‍90.66%）， with an AUC of 0.98. Conclusion CEUS combined with SWE has a relatively high diagnostic value for benign and malignant liver tumors and thus holds promise for clinical application.

Performance of a nomogram model established based on clinical indices and magnetic resonance imaging signs in the diagnosis of traditional Chinese medicine syndrome types of primary liver cancer

Ying WANG, Xirong ZHANG

2024, 40(7): 1411-1419. DOI: 10.12449/JCH240720

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Objective To investigate the performance of a nomogram model established based on clinical indices and magnetic resonance imaging （MRI） signs in determining the traditional Chinese medicine （TCM） syndrome types of primary liver cancer. Methods A retrospective analysis was performed for the clinical data of 138 patients with primary liver cancer who were hospitalized in The Affiliated Hospital of Shaanxi University of Chinese Medicine from September 2018 to July 2023， and the patients were divided into excess syndrome group with 84 patients and deficiency syndrome group with 54 patients. All patients underwent Gd-EOB-DTPA contrast-enhanced MRI scan before treatment. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square or the Fisher’s exact test was used for comparison of categorical data between groups. A Logistic regression analysis was used to investigate the independent predictive factors for the TCM syndrome type of primary liver cancer， and a nomogram model was established. The patients were randomly divided into training group with 110 patients and validation group with 28 patients at a ratio of 8∶2， and the calibration curve， the receiver operating characteristic （ROC） curve， and the decision curve were used to evaluate the clinical performance of this model. Results There were significant differences between the excess syndrome group and the deficiency syndrome group in neutrophils， lymphocyte count （LYM）， platelet count， albumin （Alb）， neutrophil-lymphocyte ratio （NLR）， prothrombin time （PT）， alpha-fetoprotein （AFP）， direct bilirubin （DBil）， indirect bilirubin， total bilirubin， presence or absence of portal vein invasion， number of tumors， hepatobiliary tumor signal， and apparent diffusion coefficient （ADC）（all P<0.05）. The Logistic regression analysis showed that AFP （odds ratio ［OR］=0.003， 95% confidence interval ［CI］： 0.000‍ ‍—‍ ‍0.052， P<0.001）， PT （OR=0.032， 95%CI： 0.004‍ ‍—‍ ‍0.286， P=0.002）， LYM （OR=0.032， 95%CI： 0.004‍ ‍—‍ ‍0.286， P=0.002）， Alb （OR=0.009， 95%CI： 0.001‍ ‍—‍ ‍0.163， P=0.001）， NLR （OR=0.040， 95%CI： 0.003‍ ‍—‍ ‍0.457， P=0.010）， DBil （OR=0.014， 95%CI： 0.001‍ ‍—‍ ‍0.198， P=0.002）， portal vein cancer thrombus （OR=0.005， 95%CI： 0.000‍ ‍—‍ ‍0.115， P=0.001）， number of tumors （OR=12.740， 95%CI： 1.212‍ ‍—‍ ‍133.937， P=0.034）， and ADC （OR=19.269， 95%CI： 3.163‍ ‍—‍ ‍117.387， P=0.001） were independent predictive factors for TCM syndrome types of primary liver cancer. In the training group， the model had an area under the ROC curve （AUC） of 0.962， a sensitivity of 84.1%， a specificity of 92.4%， and an accuracy of 89.1%， and in the validation group， the model had an AUC of 0.848， a sensitivity of 63.6%， a specificity of 100.0%， and an accuracy of 85.7%. The calibration curve showed that the nomogram model had good consistency between predicted syndrome types and actual syndrome types in the training group and the validation group， and the decision curve showed that the nomogram model had good net benefits within a relatively wide range of threshold probability. Conclusion The nomogram model based on clinical indices and MRI signs has good clinical efficacy and value in judging the TCM syndrome type of primary liver cancer.

Role and prognostic value of matrix metalloproteinase-7 in the migration and immune cell infiltration of hepatocellular carcinoma

Shuyan LIU, Qichang YANG, Yi SHEN, Hong ZHOU, Jinfeng QIAN

2024, 40(7): 1420-1427. DOI: 10.12449/JCH240721

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Objective To investigate the role and prognostic value of matrix metalloproteinase-7 （MMP7） in the migration and immune cell infiltration of hepatocellular carcinoma. Methods MMP7_siRNA for downregulating the target gene MMP7 and pMMP7 for upregulating MMP7 were constructed and were used to transfect hepatocellular carcinoma cell line （MHCC97H）. RT-qPCR and Western Blot were used to measure the mRNA and protein expression levels of the target gene in cells. Scanning electron microscopy and Transwell assay were used to observe the changes in cell pseudopodia and migration ability， and bioinformatics methods were used to investigate the correlation of MMP7 with immune cells and immune infiltration score in TCGA and TIMER databases in patients with hepatocellular carcinoma， as well as the association between MMP7 and the prognosis of patients with hepatocellular carcinoma. The Spearman method was used for correlation analysis. Sanger Box online tool was used to assess the value of MMP7 in the overall survival curve and disease-specific survival of hepatocellular carcinoma. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of prognosis between different samples. Results After MHCC97H cells were transfected with MMP7_siRNA or pMMP7， there was a significant reduction or increase in the expression of the target gene MMP7； after downregulation of MMP7， there were significant reductions in the number and length of the pseudopodia， while after MMP7 overexpression， there were significant increases in the number and length of filopodia with radial arrangement. The Transwell chamber assay showed that MMP7_siRNA2 significantly reduced the migration ability of cells （P<0.05）， and there was a significant increase in migration ability after pMMP7 transfection. The expression of MMP7 was significantly correlated with B lymphocytes （r=0.37， P<0.05）， CD4⁺ T lymphocytes （r=0.40， P<0.05）， neutrophils （r=0.49， P<0.05）， macrophages （r=0.49， P<0.05）， and dendritic cells （r=0.47， P<0.05）. In the TCGA database， the patients with hepatocellular carcinoma were divided into MMP7 high expression group with 267 patients and MMP7 low expression group with 146 patients based on overall survival， and the results showed that the MMP7 high expression group had a significantly shorter overall survival time than the MMP7 low expression group （P<0.05）； based on the disease-specific survival time， the patients were divided into MMP7 high expression group with 257 patients and MMP7 low expression group with 145 patients， and the analysis showed that the MMP7 high expression group also had a significantly shorter disease-specific survival time than the MMP7 low expression group （P<0.05）. Conclusion MMP7 promotes the migration of hepatocellular carcinoma cells and plays a major role in immune cell infiltration， and the expression of MMP7 is also significantly associated with the prognosis of hepatocellular carcinoma.

Expression of Midkine in cholangiocarcinoma and its value in predicting prognosis based on bioinformatics analysis

Yueyue GU, Shumin YU, Xiujuan CHANG, Xudong GAO, Jiagan HUANG, Xiaodong JIA, Zhen ZENG

2024, 40(7): 1428-1437. DOI: 10.12449/JCH240722

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Objective To investigate the expression of Midkine （MDK） in cholangiocarcinoma （CCA） and its value in predicting the prognosis of CCA， as well as the potential mechanism of the effect of MDK on the progression of CCA. Methods The data of CCA samples were obtained from TCGA database to analyze the difference in the expression of MDK between cancer tissue and paracancerous tissue and its association with clinical features， and the data collected from GEO database and 11 CCA patients who underwent surgical resection in The Fifth Medical Center of Chinese PLA General Hospital from June 2018 to September 2021 were used for validation. STRING and Cytoscape were used to construct a protein-protein interaction network， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were used to investigate the biological functions and tumor-related pathways involving MDK-related genes. In addition， TIMER and TISIDB databases were used to analyze the correlation between MDK expression and immune cell infiltration in CCA tissue. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. The Spearman correlation analysis was used to investigate the correlation between two variables. Results The expression level of MDK in cancer tissue and paracancerous tissue of CCA patients was compared based on TCGA database， and the results of the non-paired and paired analyses showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in paracancerous tissue （P<0.001）. Transcriptome sequencing was performed for the tumor tissue and its corresponding paracancerous tissue from 11 CCA patients， and the results showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in corresponding paracancerous tissue （P<0.01）. High expression of MDK was associated with lymph node metastasis （P=0.045） and vascular invasion （P=0.044）. Survival analysis showed that compared with the CCA patients with low MDK expression， the CCA patients with high MDK expression had significantly shorter overall survival time （χ²=5.30， P=0.028） and disease-specific survival time （χ²=6.25， P=0.019）. The GO and KEGG enrichment analyses showed that the 30 MDK-related genes were closely associated with ubiquitin-mediated proteolysis and affected the prognosis of CCA patients. The TIMER analysis showed that the expression level of MDK was positively correlated with the infiltration of B cells （r=0.356， P=0.035 6） and dendritic cells （r=0.409， P=0.014 7） in tumor microenvironment of CCA； the TISIDB analysis showed that the expression level of MDK was positively correlated with CXCL16 （r=0.465， P=0.004 67） and was negatively correlated with CXCL12 （r=-0.389， P=0.019 7） and CXCR5 （r=-0.393， P=0.018 5）， and it was also negatively correlated with the immune checkpoint regulators VTCN1 （r=-0.393， P=0.018 3）， LTA （r=-0.380， P=0.022 7）， and PVR （r=-0.350， P=0.037 3）. Conclusion High expression of MDK is associated with poor prognosis in CCA patients， and MDK has the potential of being used as a molecular marker for predicting the prognosis of CCA. MDK may promote the development and progression of CCA by regulating ubiquitin-mediated proteolysis and the infiltration of B cells and dendritic cells.

Influencing factors for chronic pancreatitis complicated by pancreatogenic portal hypertension and establishment of a predictive model

Jiani YANG, Zhini MA, Yingxia HU, Zongshuai LI, Yan LIU, Hairong ZHANG, Yinglei MIAO

2024, 40(7): 1438-1445. DOI: 10.12449/JCH240723

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Objective To investigate the influencing factors for chronic pancreatitis （CP） complicated by pancreatogenic portal hypertension （PPH）， and to establish a predictive model. Methods A retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University， Chuxiong Yi Autonomous Prefecture People’s Hospital， Wenshan People’s Hospital， and Puer People’s Hospital from January 2017 to December 2022， and these patients were enrolled as PPH group. The incidence density sampling method was used to select 198 CP patients from databases as control group. 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 Least Absolute Shrinkage and Selection Operator （LASSO） regression model was used to identify the potential predictive factors for CP complicated by PPH， and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors， which were used to establish a nomogram prediction model. The receiver operating characteristic （ROC） curve， the calibration curve， and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model， and the clinical decision curve was used to assess the clinical practicability of the model. Results There were significant differences between the two groups in sex， history of recurrent acute pancreatitis attacks， acute exacerbation of CP， bile duct stones， peripancreatic fluid accumulation， pseudocysts， pulmonary infection， elevated C-reactive protein （CRP）， elevated procalcitonin， fibrinogen （FIB）， neutrophil-lymphocyte ratio （NLR）， gamma-glutamyl transpeptidase， total bilirubin， direct bilirubin， low-density lipoprotein （LDL）， serum amylase， D-dimer， and serum albumin （all P<0.05）. The predictive variables obtained by the LASSO regression analysis included sex， recurrent acute pancreatitis attacks， bile duct stones， peripancreatic fluid accumulation， pulmonary infection， pseudocysts， CRP， NLR， FIB， and LDL. The multivariate Logistic regression analysis showed that sex （odds ratio ［OR］=2.716， P<0.05）， recurrent acute pancreatitis attacks （OR=2.138， P<0.05）， peripancreatic fluid accumulation （OR=2.297， P<0.05）， pseudocysts （OR=2.805， P<0.05）， and FIB （OR=1.313， P<0.05） were independent risk factors for CP complicated by PPH. The above factors were fitted into the model， and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787 （95% confidence interval： 0.730 — 0.844）， and the calibration curve was close to the reference curve. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting （χ²=7.469， P=0.487）. The clinical decision curve analysis showed that the prediction model had good clinical practicability. Conclusion Male sex， recurrent acute pancreatitis attacks， peripancreatic fluid accumulation， pseudocysts， and FIB are independent risk factors for CP complicated by PPH， and the nomogram model established has good discriminatory ability， calibration， and clinical practicability.

Clinical cure of acute hepatitis B virus infection-related liver failure with HBsAg seroconversion： A case report

Xufeng QUAN, Shue XIONG, Wenqing ZHOU, Ruxia ZHOU, Jia LIU, Xin ZHENG

2024, 40(7): 1446-1449. DOI: 10.12449/JCH240724

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About 1% of the patients with acute hepatitis B can progress to acute liver failure， and 75% of the patients with hepatitis B virus （HBV）-related acute liver failure need to undergo liver transplantation or face death. This article reports a patient with HBV infection-related acute liver failure who achieved clinical cure and HBsAg seroconversion after antiviral therapy and symptomatic/supportive treatment， and dynamic monitoring was performed for immunological markers in peripheral blood.

Role of lipophagy in the prevention and treatment of nonalcoholic fatty liver disease

Zhili XIAO, Chenxia LU, Danni ZHOU, Zhuangzhuang CHEN, Mingzhong XIAO, Xiaodong LI

2024, 40(7): 1450-1458. DOI: 10.12449/JCH240725

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Nowadays， the prevalence of nonalcoholic fatty liver disease （NAFLD） is constantly rising in China and globally， and its incidence rate is increasing year by year， which has seriously affected human life and health. Lipophagy is molecular chaperone-mediated autophagy and has the functions of promoting lipolysis， maintaining the lipid homeostasis of hepatocytes， and alleviating hepatocyte fatty degeneration. Lipophagy has three main processes of lipid droplet catabolism， lipid droplet autophagy， and fatty acid β-oxidation， which are regulated by key genes， receptors， and enzymes. Currently， important advances have been achieved for the intervention methods of traditional Chinese medicine， Western medicine， diet， and exercise in the research on lipophagy， which provides new perspectives for the prevention and treatment strategies for NAFLD.

Mechanism of action of sterol regulatory element-binding proteins in nonalcoholic fatty liver disease and related therapeutic targets

Anqi LI, Peiran ZHAO, Yuqiang ZHAO, Rui WANG, Jing YANG

2024, 40(7): 1459-1465. DOI: 10.12449/JCH240726

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Nonalcoholic fatty liver disease （NAFLD） has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma. However， the pathogenesis of NAFLD remains unclear， and there is still a lack of specific treatment measures. Sterol regulatory element-binding proteins （SREBP） are an important nuclear transcription factor， which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol， fatty acids， and triglycerides， and therefore， SREBP are a target for the treatment of metabolic diseases. This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD. It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage. Therefore， excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD. In conclusion， SREBP is a promising therapeutic target for NAFLD； the molecular mechanism of SREBP in lipid metabolism is regulated by many factors， and these factors are being deeply explored and analyzed， which has an important clinical significance for the treatment of NAFLD.

Mechanism of action of follicular helper T cells in autoimmune hepatitis

Longlong LUO, Lifei WANG, Guojing XING, Ying ZHENG, Lixia LU, Chuyi LI, Bin LI, Jun MA, Xiaohui YU, Jiucong ZHANG

2024, 40(7): 1466-1469. DOI: 10.12449/JCH240727

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Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system， and with the prolongation of disease course， it may gradually progress to liver cirrhosis and even hepatocellular carcinoma. Although great achievements have been made in the understanding and treatment of AIH， its etiology and pathogenesis still remain unclear. T cells play a crucial role in the development and progression of AIH， and by focusing on follicular helper T cells， this article elaborates on the research advances in follicular helper T cells in AIH， in order to provide new ideas and strategies for the clinical treatment of AIH.

Advances in the diagnosis and treatment of intrahepatic cholangiocarcinoma

Di HU, Jintao HUANG, Binyan ZHONG, Jian SHEN, Xiaoli ZHU

2024, 40(7): 1470-1476. DOI: 10.12449/JCH240728

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Intrahepatic cholangiocarcinoma （ICC） is a relatively rare type of primary liver cancer， and its incidence rate has gradually increased in recent years. Due to its insidious onset and atypical clinical symptoms， most patients are already in the advanced stage of the disease at the time of confirmed diagnosis， and therefore， timely diagnosis and treatment are of great importance. Radical surgical resection is the standard treatment regimen for early-stage ICC patients， while systemic chemotherapy is the basic treatment for patients with advanced ICC and is often combined with interventional treatment， targeted therapy， and immunotherapy. This article reviews the advances in the diagnosis and treatment of ICC.

Research advances in the mechanism of action of traditional Chinese medicine in inhibiting angiogenesis in hepatocellular carcinoma

Xiangxiang LI, Zhen WANG, Xing YANG, Suling LI

2024, 40(7): 1477-1485. DOI: 10.12449/JCH240729

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Angiogenesis is a key process in the development and progression of hepatocellular carcinoma （HCC） and can provide essential material conditions for the proliferation， invasion， and metastasis of HCC cells. Inhibition of angiogenesis has become a research hotspot in the field of HCC therapy. Traditional Chinese medicine has become a potential drug for HCC therapy due to its characteristics of multiple targets and pathways， enhancing efficacy and reducing toxicity， improving tumor prognosis， and prolonging survival time. Modern studies have confirmed that traditional Chinese medicine can inhibit tumor angiogenesis by inhibiting the expression of angiogenic factors， upregulating the levels of anti-angiogenic factors， inhibiting endothelial cell proliferation， reducing the microvascular density of HCC tissue， and regulating related signaling pathways， and therefore， traditional Chinese medicine has unique advantages in the treatment of HCC. By summarizing related articles in China and globally in recent years， this article analyzes the mechanism of action of traditional Chinese medicine on inhibiting HCC angiogenesis， in order to provide certain theoretical basis and reference for the optimization of HCC treatment strategies in clinical practice.

Research advances in liver cancer organoids

Li ZHAO, Ziqi GUO, Yong YANG, Hongxin YANG

2024, 40(7): 1486-1492. DOI: 10.12449/JCH240730

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Organoids are a novel disease model that is self-assembled from stem cells or malignant tumors and is used in clinical research. They are similar to tissues and organs in the body and have partially functional 3D cell structures. There are two types of traditional models for liver cancer research， i.e.， in vivo models （animal models of liver cancer established by induction） and in vitro cell experiments using corresponding cell lines. Organoids have the advantages of the two types of traditional models and show unique advantages in tumor research. Traditional models cannot fully reflect the microenvironment of cells， which often leads to the inconsistency with clinical research findings， and the emergence of new research models provides a new direction for the research on liver cancer. This article reviews the research advances in liver cancer organoids， in order to provide a new perspective for future research on liver cancer.

Mechanism of action and potential therapeutic targets of ferroptosis suppressor protein 1 in liver diseases

Sisi WANG, Yaru WANG, Rui LIU, Jie QIN

2024, 40(7): 1493-1497. DOI: 10.12449/JCH240731

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Ferroptosis suppressor protein 1 （FSP1） is another major ferroptosis regulator besides glutathione peroxidase 4， which can scavenge intracellular reactive oxygen species and lipid peroxides and inhibit ferroptosis. In view of the key role of the liver in iron and lipid metabolism and its susceptibility to oxidative damage， more and more evidence has shown that FSP1 plays an important role in liver diseases such as metabolic associated fatty liver disease， hepatocellular carcinoma， acute liver failure， and alcoholic liver disease， and the related targets of FSP1 are expected to become a potential treatment option. This article comprehensively reviews FSP1， with a focus on the role of FSP1 in the pathophysiology of several common liver diseases and the potential of FSP1 as a target of liver diseases， in order to provide new ideas for the treatment of liver diseases.

Metal ion metabolism： New ideas for the traditional Chinese medicine prevention and treatment of chronic liver disease

Xinhua GUO, Jiahui WANG, Xuelin DUAN, Yue PENG, Tiejian ZHAO, Yang ZHENG, Bin ZHAO

2024, 40(7): 1498-1504. DOI: 10.12449/JCH240732

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Chronic liver disease （CLD） tends to have a high incidence rate and impose a serious burden on society and families. Studies have shown that metal ion metabolism is closely associated with CLD， and some Chinese herbal medicines can play a role in the prevention and treatment of CLD by regulating metal ion metabolism. At present， the synthetic drugs currently used for the treatment of CLD fail to achieve a satisfactory effect， and therefore， a variety of Chinese herbal medicines are being used as supplementary and alternative therapies for CLD. This article introduces the role of metal ion metabolism in CLD and the regulatory effect of Chinese herbal medicines and their active components on CLD， and the analysis shows that metal ion metabolism is expected to provide new ideas for the research on CLD and a theoretical basis for the clinical treatment of CLD. For the role of metal ion metabolism in the treatment of CLD， more prospective clinical study data are needed in the future to provide effective and safe treatment regimens for patients with CLD.

Gut｜High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy

2024, 40(7): 1320-1320. DOI: 10.12449/JCH2407.gwqkjpwzjj1

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Hepatology｜Hepatocyte-derived MASP1-enriched small extracellular vesicles activate HSCs to promote liver fibrosis

2024, 40(7): 1333-1333. DOI: 10.12449/JCH2407.gwqkjpwzjj2

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Hepatology｜Limited disassembly of cytoplasmic hepatitis B virus nucleocapsids restricts viral infection in murine hepatic cells

2024, 40(7): 1419-1419. DOI: 10.12449/JCH2407.gwqkjpwzjj3

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Current reviewers

2024, 40(7): 1389-1389. DOI: 10.12449/JCH2407.zhixie

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