2024 No. 8

Research advances and challenges in herb-induced liver injury

Chenghai LIU

2024, 40(8): 1505-1511. DOI: 10.12449/JCH240801

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Herb-induced liver injury （HILI） shows a high incidence rate and has great impacts on the clinical medication safety of traditional Chinese medicine and the healthy development of the industry. In recent years， the research on HILI has attracted wide attention and made remarkable progress， and related clinical diagnosis and treatment guidelines have been formulated and updated by the academic organizations in China and globally. This article compares the recent guidelines on HILI formulated by different organizations and elaborates on the main achievements in terms of mechanism of toxicity， clinical diagnosis and disease assessment， risk factors， and clinical prevention and treatment， and it also proposes the unmet needs， the research difficulties that need to be taken seriously， and possible prevention and treatment strategies.

The material basis and toxic mechanism of herb-induced liver injury

Xueying LIU, Huihui SHI, Haowen WANG, Tao YANG

2024, 40(8): 1512-1518. DOI: 10.12449/JCH240802

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Herb-induced liver injury （HILI） tends to have complex toxic material basis and toxic mechanism， which greatly affects the safety of traditional Chinese medicine. This article summarizes the main toxic components of Chinese herbal medicine causing liver injury and their mechanism of action. The toxic components of Chinese herbal medicine causing liver injury can be classified into two categories of drug-derived and non-drug-derived toxic components. Drug-derived toxic components mainly include alkaloids， terpenoids， anthraquinones， and phenylpropanoids， and their mechanism of action involves oxidative stress， apoptosis and necrosis， CYP450 enzymes， and genotoxicity. Non-drug-derived toxic components mainly include pesticide residues， sulfur dioxide residues， heavy metals， fungi， and plant growth regulators， and their mechanisms involve oxidative stress， apoptosis， metabolic disorders， and CYP450 enzymes. On this basis， this article further proposes the unsolved problems and research difficulties， in order to promote the basic research on the hepatotoxicity of traditional Chinese medicine.

Influence of combined drug administration on herb-induced liver injury

Hui ZHENG, Rong SUN

2024, 40(8): 1519-1524. DOI: 10.12449/JCH240803

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With the wide application of traditional Chinese medicine （TCM） globally and combined drug use in clinical practice， there have been significant increases in herb-induced liver injury （HILI） events and drug safety events， bringing great challenges to the research and development of new TCM drugs and the development of the TCM industry. At present， there are still shortcomings in systematically summarizing the effect of combined drug use on HILI and analyzing its clinical features， pathogenesis and interaction mechanism， especially the research on pharmacodynamics and pharmacotoxicology processes after the combination of TCM and Western drugs. It is urgently needed to further construct an integrated research system， especially in the aspects of target molecules， intercellular communication， tissue crosstalk， and invivo toxicity assessment. Based on the basic research combining clinical and fundamental studies， it is necessary to put forward HILI prevention and control strategies in accordance with TCM theory and application rules， which will provide fundamental support and reliable evidence for improving the level of combined use of TCM and Western drugs in the context of diseases and syndromes.

Phenotypic characteristics and toxicological mechanisms of herb-induced liver injury

Tingting HE, Zhaofang BAI, Jiabo WANG, Xiaohe XIAO

2024, 40(8): 1525-1532. DOI: 10.12449/JCH240804

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In order to deal with the problem of the safety of Chinese herbal medicine in a scientific way and further meet the growing health needs of people， it is particularly important to deepen the research on herb-induced liver injury. This article elaborates on the phenotypic characteristics and toxicological mechanisms of herb-induced liver injury and emphasizes that it should not only rely on the previous knowledge of the toxicity of Chinese herbal medicine， but also understand the new types of idiosyncratic toxicity， indirect toxicity， and mixed toxicity， which provide a new perspective for understanding the toxicological mechanisms of herb-induced liver injury and are of great importance to investigate the phenotype and toxicological mechanism of herb-induced liver injury.

Diagnosis of herb-induced liver injury： Challenges in practice

Yinuo DONG, Yang ZHI, Jieting TANG, Yimin MAO

2024, 40(8): 1533-1537. DOI: 10.12449/JCH240805

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With the increasingly wide application of herbal medicines and dietary supplements worldwide， herb-induced liver injury （HILI） has become an important etiology of drug-induced liver injury. Due to the diverse manifestations of HILI， the difficulty in medical history collection， and the lack of specific biomarkers， how to identify suspected patients and make a correct diagnosis has become a major challenge in practice. Causality assessment is commonly used in the diagnosis of HILI， but there is still a lack of prospective cohort studies with a large sample size. In addition， further studies are needed to search for the specific biomarkers for the diagnosis of HILI. The diagnosis and differential diagnosis of HILI are challenging， and currently there is still no universally accepted uniform and standard method for the diagnosis of all-cause HILI.

Management and treatment of herb-induced liver injury

Xin SUN, Qiong LUO, Tao YANG, Chenghai. LIU

2024, 40(8): 1538-1542. DOI: 10.12449/JCH240806

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Due to the diverse application forms of Chinese herbal medicine products， the wide range of users， and the complex conditions of medication in China， adverse events including herb-induced liver injury （HILI） occur frequently in recent years. In order to further understand HILI and standardize its risk management and prevention and treatment measures， this article discusses the risk management， clinical evaluation， prevention， and treatment of HILI based on related clinical research advances and experience in recent years. In the multiple links of traditional Chinese medicine including production and clinical application after marketing， the establishment of a comprehensive control system is of great importance for the prevention and treatment of HILI and other adverse events， involving product quality control， patient safety education， rational drug use by clinicians， regular monitoring， and graded and classified treatment， which provides a reference for the rational and safe clinical use of Chinese herbal medicine in the future.

Expert recommendations on screening， testing and management for hepatitis B virus infection in adults

Society of Prevention and Control of Infectious Diseases of Chinese Preventive Medicine Association, Working Committee of Promoting the Elimination of Viral Hepatitis of Chinese Preventive Medicine Association

2024, 40(8): 1543-1550. DOI: 10.12449/JCH240807

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The prevalence of hepatitis B represents a significant public health concern with a heavy disease burden. In China， there is still a big gap between the current diagnosis and treatment rates of hepatitis B and the goal of eliminating viral hepatitis as a public health threat by 2030 set by the World Health Organization （WHO）. In order to achieve the WHO goal and the goal of 2030 Healthy China Outline， the Chinese Preventive Medicine Association organized domestic experts in the fields of clinical medicine， public health and clinical laboratory medicine to develop theExpert Recommendations on Screening， Testing and Management for Hepatitis B Virus Infection in Adultsafter several rounds of discussion based on comprehensive review of relevant domestic and international guidelines and literatures， the purpose is to facilitate universal screening of hepatitis B virus （HBV） infection in adults and provide practical guidance on disease assessment， treatment and long-term follow-up management of people infected with HBV and vaccination for people susceptible to HBV infection， thus promoting the elimination of the threat of hepatitis B.

Expert recommendations on hepatitis B vaccination in adults

Working Committee of Promoting the Elimination of Viral Hepatitis of Chinese Preventive Medicine Association, Society of Prevention and Control of Infectious Diseases of Chinese Preventive Medicine Association

2024, 40(8): 1551-1556. DOI: 10.12449/JCH240808

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In order to achieve the target of eliminating viral hepatitis as a public health threat by 2030 and to prioritize the role of hepatitis B vaccination in reducing new hepatitis B virus infections， the Chinese Preventive Medicine Association commissioned experts to develop the Expert Recommendations on Hepatitis B Vaccination in Adults to scientifically guide adult hepatitis B vaccination， build the herd immunity in population， and reduce the hepatitis B virus infection rate and incidence of hepatitis B.

Chinese practice guideline for the prevention and treatment of mother-to-child transmission of hepatitis B virus （version 2024）

Infectious Diseases Physicians Branch， Chinese Medical Doctor Association, Chinese Society of Infectious Diseases， Chinese Medical Association

2024, 40(8): 1557-1566. DOI: 10.12449/JCH240809

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The 2019 Chinese practice guideline for the prevention and treatment of mother-to-child transmission of hepatitis B virus developed by Chinese Society of Infectious Diseases， Chinese Medical Association， has shown a good guiding effect in standardizing the process for blocking the mother-to-child transmission of hepatitis B virus in China. Clinical practice guidelines and consensus statements require timely updates based on new research evidence， in order to better guide clinical practice and research. Chinese Physician Association for Infectious Diseases， Chinese Medical Doctor Association， and Chinese Society of Infectious Diseases， Chinese Medical Association， cooperated with multidisciplinary experts and performed updates and supplementations to the above guideline， in order to provide guidance and a reference for clinical physicians and medical staff engaged in maternal and child health care.

An excerpt of EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease in 2024

Wenjing NI, Nan GENG, Xue BAI, Jie LI

2024, 40(8): 1567-1574. DOI: 10.12449/JCH240810

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In June 2024， the European Association for the Study of the Liver， the European Association for the Study of Diabetes， and the European Association for the Study of Obesity jointly released the latest edition of clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease （MASLD）， which comprehensively elaborates on the definition， prevalence rate， natural disease history， screening， diagnosis， and treatment of MASLD and proposes 33 statements and 72 recommendations. This article gives an excerpt of the key points in this document.

An excerpt of Asian Pacific Association for the Study of the Liver clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure in 2024

Jiaxuan HU, Tao HAN

2024, 40(8): 1575-1578. DOI: 10.12449/JCH240811

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Acute-on-chronic liver failure （ACLF） is a syndrome characterized by the rapid progression of organ failure and has a high short-term mortality rate. Kidney is one of the most frequently affected extrahepatic organs in ACLF patients. Recently Asian Pacific Association for the Study of the Liver （APASL） published APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure， which proposed related consensus statements and recommendations for the early diagnosis， pathophysiology， prevention， and management of acute kidney injury in patients with ACLF， and it also highlighted the need for more high-quality studies in the future.

Risk factors for the development of advanced liver fibrosis in nonalcoholic fatty liver disease and establishment of a nomogram model

Jinqiu YANG, Wenxia ZHAO, Cheng ZHOU, Tong LIU

2024, 40(8): 1579-1584. DOI: 10.12449/JCH240812

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Objective To investigate the risk factors for the development of advanced liver fibrosis by analyzing the clinical features of patients with in nonalcoholic fatty liver disease （NAFLD） and advanced liver fibrosis， and to establish a nomogram model for predicting the risk of advanced liver fibrosis. Methods A retrospective analysis was performed for the clinical data of 406 NAFLD patients who attended The First Affiliated Hospital of Henan University of Chinese Medicine from January 2022 to October 2023， and according to whether liver stiffness measurement （LSM） measured by FibroScan was ≥11.0 kPa， the patients were divided into advanced liver fibrosis group with 65 patients and non-advanced liver fibrosis group with 341 patients. Related data were collected， including general information， laboratory markers， and medical history. 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 was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to identify independent risk factors， and a nomogram model was established based on these factors. The receiver operating characteristic （ROC） curve was used to evaluate the discriminatory ability of the nomogram model， and the calibration curve was used to evaluate its effectiveness. Results The univariate analysis showed that there were significant differences between the advanced liver fibrosis group and the non-advanced liver fibrosis group in age， controlled attenuation parameter （CAP）， total bilirubin， direct bilirubin （DBil）， indirect bilirubin， globin， alanine aminotransferase， aspartate aminotransferase， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， glucose， body mass index （BMI）， and history of diabetes （all P<0.05）. The multivariate Logistic regression analysis showed that CAP （odds ratio ［OR］=1.015， 95% confidence interval ［CI］： 1.006‍ ‍—‍ ‍1.024， P=0.010）， DBil （OR=1.345， 95%CI： 1.139‍ ‍—‍ ‍1.590， P=0.001）， ALP （OR=1.019， 95%CI： 1.008‍ ‍—‍ ‍1.029， P=0.001）， GGT （OR=1.004， 95%CI： 1.000‍ ‍—‍ ‍1.008， P=0.035） and BMI （OR=1.240， 95%CI： 1.137‍ ‍—‍ ‍1.353， P=0.001） were independent risk factors for the development of advanced liver fibrosis in NAFLD. A nomogram model was established based on the results of the multivariate Logistic regression analysis. The ROC curve analysis showed that this nomogram model had an area under the ROC curve of 0.841 （95%CI： 0.791‍ ‍—‍ ‍0.891） in predicting the development of advanced liver fibrosis in the NAFLD population， and the calibration curve showed a good degree of fitting between the observed and predicted values for the development of advanced liver fibrosis. Conclusion Elevated levels of CAP， BMI， DBil， ALP， and GGT are independent risk factors for advanced liver fibrosis in NAFLD. The nomogram model established based on these factors has good predictive performance and a certain value in predicting advanced liver fibrosis.

Association between nonalcoholic fatty liver disease and osteoporosis in elderly patients

Qian XUE, Chunling JIA, Jingtong WANG

2024, 40(8): 1585-1590. DOI: 10.12449/JCH240813

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Objective To investigate the association between nonalcoholic fatty liver disease （NAFLD） and osteoporosis in elderly patients. Methods A total of 824 patients， aged ≥60 years， who were hospitalized in Department of Gerontology， Peking University People’s Hospital， from June 2016 to April 2023 were enrolled， with 398 patients in the osteoporosis group and 426 in the non-osteoporosis group. Related data were collected from all subjects， including general information， blood biochemical parameters， liver ultrasound， and bone mineral density measured by dual-energy X-ray examination. 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 was used for comparison of categorical variables； a binary Logistic regression analysis was used to investigate the independent risk factors for osteoporosis. Results Compared with the non-osteoporosis group， the osteoporosis group had a significantly higher age， a significantly higher proportion of female patients or patients with diabetes， and a significantly lower body mass index （all P<0.05）. The osteoporosis group had a significantly higher proportion of patients with NAFLD than the non-osteoporosis group （36.2% vs 24.6%， χ²=12.878， P<0.001）. Compared with the non-osteoporosis group， the osteoporosis group had significantly lower levels of hemoglobin， uric acid， and albumin and significantly higher levels of total cholesterol， low-density lipoprotein cholesterol （LDL-C）， bone-specific alkaline phosphatase， and tartrate-resistant acid phosphatase （all P<0.05）. The binary Logistic regression analysis showed that old age （odd ratio ［OR］=1.040， 95% confidence interval ［CI］： 1.015‍ ‍—‍ ‍1.066， P=0.002）， female sex （OR=4.089， 95%CI： 2.607‍ ‍—‍ ‍6.411， P<0.001）， NAFLD （OR=1.697， 95%CI： 1.076‍ ‍—‍ ‍2.678， P=0.023）， diabetes （OR=1.509， 95%CI： 1.008‍ ‍—‍ ‍2.260， P=0.046）， and LDL-C （OR=1.431， 95%CI： 1.010‍ ‍—‍ ‍2.029， P=0.044） were independent risk factors for osteoporosis in elderly patients. Considering the impact of diabetes on the research findings， a subgroup analysis was performed for the patients without diabetes， and the results showed that NAFLD （OR=1.573， 95%CI： 1.015‍ ‍—‍ ‍2.439， P=0.043） was an independent risk factor for osteoporosis in the elderly patients without diabetes. Conclusion NAFLD， old age， and female sex are independent risk factors for osteoporosis in elderly patients.

Association of metabolic associated fatty liver disease with carotid atherosclerotic plaque and stenosis

Yingdie ZHU, Zhijiao ZHANG, Guilin ZHANG, Yunkun GAO, Mengyao ZHENG, Hua HUANG, Gongfang ZHAO

2024, 40(8): 1591-1597. DOI: 10.12449/JCH240814

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Objective To investigate the association between metabolic associated fatty liver disease （MAFLD） and carotid atherosclerotic plaque. Methods A total of 1 107 patients who were hospitalized in The Second Affiliated Hospital of Kunming Medical University from July， 2014 to December， 2022 were enrolled， and all patients underwent abdominal ultrasound and CT angiography of the head and neck arteries. Baseline data and clinical diagnosis were collected， and the patients were divided into MAFLD group with 499 patients and non-MAFLD group with 608 patients based on medical history， clinical tests， and imaging findings. According to the CT value， carotid plaques were classified into calcified plaques， non-calcified plaques， and mixed plaques. According to the NASCET criteria， carotid stenosis was categorized as normal vessel， slight stenosis， mild stenosis， moderate stenosis， and severe stenosis/occlusion. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for carotid atherosclerosis. Results Compared with the non-MAFLD group， the MAFLD group had a significantly higher proportion of patients with calcified plaques （74.3% vs 63.3%， P<0.05）， non-calcified plaques （27.1% vs 17.1%， P<0.05）， or mixed plaques （27.3% vs 20.7%， P<0.05）， as well as a significantly higher proportion of patients with mild stenosis （50.9% vs 44.9%， P<0.05）， moderate stenosis （14.6% vs 8.4%， P<0.05）， or severe stenosis/occlusion （6.6% vs 3.5%， P<0.05）. The univariate logistic regression analysis showed that MAFLD was a risk factor for calcified carotid plaques， non-calcified plaques， and mixed plaques， and it was also a risk factor for mild stenosis， moderate stenosis， and severe stenosis/occlusion of the carotid artery （all P<0.05）. After adjustment for confounding factors， the multivariate Logistic regression analysis showed that MAFLD was an independent risk factor for calcified plaque， non-calcified plaque， mixed plaque， and moderate stenosis of the carotid arteries （all P<0.05）. Conclusion MAFLD is an independent risk factor for moderate stenosis， calcified plaques， non-calcified plaques， and mixed plaques of the carotid arteries.

Primary biliary cholangitis with metabolic associated fatty liver disease： Clinical features and risk factors

Linna YUAN, Yihui CHEN, Hengbin NA, Jie LU, Ye LIU, Wu LI

2024, 40(8): 1598-1604. DOI: 10.12449/JCH240815

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Objective To investigate the clinical features and risk factors of primary biliary cholangitis （PBC） comorbid with metabolic associated fatty liver disease （MAFLD） and the interaction between the two diseases. Methods A total of 187 patients who were diagnosed with PBC， MAFLD， or PBC with MAFLD in The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2022 were enrolled and divided into PBC group with 70 patients， PBC+MAFLD group with 38 patients， and MAFLD group with 79 patients. Related data were collected， including general information， clinical symptoms， serological parameters， transient elastography （FibroScan）， and non-invasive fibrosis markers， which were compared between the three groups. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups， the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the binary Logistic regression analysis was used for multivariate analysis. Results There were significant differences between the three groups in sex， age， height， weight， body mass index （BMI）， and history of autoimmune diseases （P<0.05）. In the PBC+MAFLD group， female patients accounted for 89.5%， with a mean age of 57.26±12.72 years and a BMI of 23.35±3.70 kg/m²， and in the PBC group， the detection rate of autoimmune diseases was 25.7% （18 patients）. There were significant differences between the three groups in the incidence rates of weakness， poor appetite， pruritus， jaundice， varices， ascites， and splenomegaly （all P<0.05）. The PBC+MAFLD group had the common symptoms of weakness in 18 patients （47.4%）， poor appetite in 15 patients （39.5%）， abdominal pain in 14 patients （36.8%）， and abdominal distension in 16 patients （42.1%）； the MAFLD group had the common symptoms of abdominal pain in 34 patients （43%） and abdominal distension in 32 patients （40.5%）； the PBC group had the common symptoms of weakness in 37 patients （52.9%）， poor appetite in 25 patients （35.7%）， jaundice in 25 patients （35.7%）， abdominal pain in 18 patients （25.7%）， abdominal distension in 25 patients （35.7%）， varices in 19 patients （27.9%）， ascites in 23 patients （32.9%）， and splenomegaly in 44 patients （62.9%）. The PBC+MAFLD group had a controlled attenuation parameter （CAP）， which was higher than that of the PBC group， and the PBC group had significantly higher levels of liver stiffness measurement， aspartate aminotransferase-to-platelet ratio index （APRI）， and fibrosis-4 （FIB-4） than the MAFLD group （all P<0.05）. The factors without multicollinearity were included in the regression analysis， and with the PBC group as the reference group， FIB-4 （odds ratio ［OR］=0.218， 95% confidence interval ［CI］： 0.069 ‍—‍ 0.633， P<0.05） and history of autoimmune diseases （OR=0.229， 95%CI： 0.067‍ — ‍0.810， P<0.05） were influencing factors for the onset of PBC with MAFLD； with the MAFLD group as the reference group， ALT （OR=0.157， 95%CI： 0.025‍ —‍ ‍1.000， P<0.05） and TBil （OR=0.995， 95%CI： 0.990‍‍ — ‍0.999， P<0.05） were influencing factors for the onset of PBC with MAFLD. Conclusion PBC with MAFLD lacks specific clinical manifestations， and PBC patients tend to have more severe clinical manifestations and a higher incidence rate of liver function decompensation. PBC comorbid with MAFLD may not aggravate the disease progression of PBC.

Establishment and evaluation of a nomogram prediction model for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with liver cirrhosis and esophagogastric variceal bleeding

Xinyi LI, Jiaojiao LI, Wei SUN

2024, 40(8): 1605-1611. DOI: 10.12449/JCH240816

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Objective To establish a nomogram prediction model for the development of overt hepatic encephalopathy （OHE） in patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt （TIPS） after esophagogastric variceal bleeding， and to evaluate the predictive ability of the model. Methods This study was conducted among 113 patients with esophagogastric variceal bleeding due to liver cirrhosis who were admitted to The First Affiliated Hospital of Soochow University from January 2020 to December 2022 and underwent TIPS after failed medical or endoscopic therapy. All patients were followed up for 6 months after surgery， and according to the presence or absence of OHE after TIPS， they were divided into OHE group with 32 patients and non-OHE group with 81 patients. Related data were collected from all patients， including clinical data， routine blood test results， serum biochemistry， and coagulation test results. 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 independent risk factors for the onset of OHE after TIPS， and then a nomogram prediction model was established. The index of concordance （C-index） was calculated and the calibration curve was plotted to evaluate the predictive ability of the model， and the clinical decision curve was plotted to analyze the net clinical benefit of the model. The receiver operating characteristic （ROC） curve was used to validate the predictive ability of the model. Results There were significant differences between the OHE group and the non-OHE group in age， diabetes， Child-Pugh class， ascites， main portal vein diameter before surgery， gamma-glutamyl transpeptidase （GGT） level， prothrombin time， and Freiburg index of post-TIPS survival （FIPS） score （all P<0.05）. The multivariate Logistic regression analysis showed that Child-Pugh class （odds ratio ［OR］=17.498， 95% confidence interval ［CI］： 2.561‍ ‍—‍ ‍119.548， P=0.004）， main portal vein diameter before surgery （OR=1.361， 95%CI： 1.057‍ ‍—‍ ‍1.752， P=0.017）， GGT （OR=1.032， 95%CI： 1.013‍ ‍—‍ ‍1.052， P=0.001）， and FIPS score （OR=2.838， 95%CI： 1.277‍ ‍—‍ ‍6.311， P=0.010） were independent influencing factors for the development of OHE after TIPS. The nomogram model established based on the above four indicators had a C-index of 0.875， good fitting of the calibration curve， and an area under the ROC curve of 0.875 （95%CI： 0.799 ‍—‍ 0.929， P<0.001）， and the decision curve analysis showed that the 0.3 ‍—‍ 0.9 threshold probability model had a good net benefit. Conclusion Child-Pugh class， main portal vein diameter before surgery， GGT， and FIPS score have a certain value in predicting the development of OHE after TIPS in patients with esophagogastric variceal bleeding due to liver cirrhosis， and the nomogram model established based on these indicators can be used to individually predict the onset of OHE after TIPS in patients with esophagogastric variceal bleeding due to liver cirrhosis.

Effect of Yiguan Decoction on the efficacy of M1 bone marrow-derived macrophages in treatment of liver cirrhosis rats and its mechanism

Mengyao ZONG, Xun JIAN, Danyang WANG, Yannan XU, Xinrui ZHENG, Feifei XING, Gaofeng CHEN, Jiamei CHEN, Ping LIU, Yongping MU

2024, 40(8): 1612-1619. DOI: 10.12449/JCH240817

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Objective To investigate the effect and mechanism of Yiguan Decoction （YGJD） on the efficacy of M1 bone marrow-derived macrophages （M1-BMDMs） in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl₄. Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide. A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats. The rats for modeling were given subcutaneous injection of 50% CCl₄ twice a week. Since week 7， the rats for modeling were randomly divided into model group （M group）， YGJD group， M1-BMDM group， M1-BMDM+YGJD group， and sorafenib （SORA） group， and they were given subcutaneous injection of 30% CCl₄ to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF. CCR2 inhibitors were added to the drinking water， and each group was given the corresponding intervention. Related samples were collected at week 9. The rats were observed in terms of serum liver function parameters， liver pathology， hydroxyproline （Hyp） content in liver tissue， hepatic stellate cell activation， hepatic fibrosis and inflammation factors， and the expression levels of molecules associated with the Wnt signaling pathway. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. Results Compared with the M group， the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase， aspartate aminotransferase， and total bilirubin （TBil）（all P<0.05） and a significant increase in the content of albumin （Alb）（P<0.05）， and compared with the M1-BMDM group， the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil （P<0.05） and a significant increase in the serum level of Alb （P<0.05）. Compared with the M1-BMDM group， the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α （P<0.05）. Compared with the M1-BMDM group， the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area （P<0.05）. As for the non-canonical Wnt signaling pathway molecules， compared with the M1-BMDM group， the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a （P<0.05） and mRNA expression level of Fzd2 （P<0.05）， as well as significant reductions in the mRNA expression levels of Wnt4， Wnt5b， and Fzd3 （P<0.05）， while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin， LRP5， LRP6， Fzd5， and TCF. Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl₄， possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway， which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Efficacy and safety of tyrosine kinase inhibitor combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma

Hong NIE, Binyan ZHONG, Jian SHEN, Xiaoli ZHU

2024, 40(8): 1620-1626. DOI: 10.12449/JCH240818

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Objective To investigate the efficacy and safety of tyrosine kinase inhibitor （TKI） combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma （HCC）. Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology， The First Affiliated Hospital of Soochow University， from January 2018 to December 2022， and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to second-line TKI with or without immune checkpoint inhibitor. The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group， and the 31 patients receiving second-line TKI alone were enrolled as single treatment group. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response， and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS） for the two groups， and the two groups were compared in terms of objective response rate （ORR） and disease control rate （DCR）. The chi-square test was used for comparison of baseline data and follow-up results between groups. Results The median follow-up time was 16.5 （3.2‍ — ‍53.4） months for the 63 patients. The combination group had an mOS of 24.3 （95% confidence interval ［CI］： 20.0‍ — ‍28.6） months and an mPFS of 9.8 （95%CI： 7.5‍ — ‍12.1） months， while the single treatment group had an mOS of 15.8 （95%CI： 11.4‍ — ‍20.1） months and an mPFS of 4.1 （95%CI： 3.2‍ — ‍4.9） months， and there were significant differences in mOS and mPFS between the two groups （P=0.029 and 0.038）. The combination group had an ORR of 47% and a DCR of 84%， while the single treatment group had an ORR of 19% and a DCR of 65%； there was a significant difference in ORR between the two groups （P=0.021）， but with no significant difference in DCR between the two groups （P=0.070）. As for adverse events， 4 patients （12.5%） in the combination group and 3 （10.0%） in the single treatment group experienced grade Ⅲ‍ — ‍Ⅳ serious adverse events， with no fatal drug reactions in either group， and there was no significant difference in the incidence rate of adverse events between the two groups （P=0.783）. Conclusion Compared with TKI alone， TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC， without increasing serious adverse reactions.

Liver disease phenotypes and clinical features of patients with different genotypes of Wilson’s disease

Yuanzhi HUANG, Fuchuan WANG, Yi DONG, Zhiqiang XU, Yinjie GAO, Jianguo YAN, Lili CAO, Danni FENG, Min ZHANG

2024, 40(8): 1627-1632. DOI: 10.12449/JCH240819

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Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson’s disease （WD）. Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023， and clinical manifestations， laboratory examination， pathological examination， imaging examination， and ATP7B genetic testing results were collected. According to ATP7B gene mutation， the patients were divided into groups as follows： R778L mutation group and non-R778L mutation group； P992L mutation group and non-P992L mutation group； truncation mutation group and non-truncation mutation group. Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation （R778L mutation）， c.2975C>T/p.P992L mutation （P992L mutation）， and truncation mutation of the ATP7B gene. The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Results The 163 patients with WD had varying severities of liver disease phenotypes， among whom 121 （74.23%） were diagnosed with chronic liver disease， 36 （22.09%） were diagnosed with decompensated cirrhosis， and 6 （3.68%） were diagnosed with fulminant WD， and in addition， there were 5 patients （2 with chronic liver disease and 3 with decompensated cirrhosis） with neurological abnormalities. For the 163 patients with WD， R778L mutation （with an allele frequency of 28.2%） was the most common mutation in the ATP7B gene， followed by P992L mutation （with an allele frequency of 12.6%）， and truncation mutation showed an allele frequency of 11.0%. There was no significant difference in the distribution of the three mutations across different liver disease phenotypes （P>0.05）. The R778L mutation group had a significantly lower level of ceruloplasmin （CP） than the non-R778L mutation group ［0.04 （0.02‍ ‍—‍ ‍0.08） g/L vs 0.08 （0.03‍ ‍—‍ ‍0.13） g/L， Z=-2.889， P=0.004］. Compared with the non-P992L mutation group， the P992L mutation group had significantly higher levels of alanine aminotransferase ［135.0 （80.5‍ ‍—‍ ‍237.0） U/L vs 80.5 （36.0‍ ‍—‍ ‍173.3） U/L， Z=2.684， P=0.007］ and aspartate aminotransferase ［121.4 （77.0‍ ‍—‍ ‍195.0） U/L vs 84.0 （39.0‍ ‍—‍ ‍123.3） U/L， Z=3.388， P<0.001］. Compared with the non-truncation mutation group， the truncation mutation group had significantly lower levels of CP ［0.03 （0.02‍ ‍—‍ ‍0.08） g/L vs 0.06 （0.03‍ ‍—‍ ‍0.11） g/L， Z=-3.136， P=0.002］ and serum copper ［3.20 （2.15‍ ‍—‍ ‍5.00） mg/L vs 4.20 （2.60‍ ‍—‍ ‍7.50） mg/L， Z=-2.296， P=0.025］. Conclusion R778L mutation， P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients； however， R778L mutation is associated with a lower level of CP， P992L mutation is associated with higher levels of ALT and AST， and truncation mutation is associated with lower levels of CP and serum copper.

Value of intestinal fatty acid binding protein in predicting the development and progression of acute-on-chronic liver failure

Caijun HAN, Meihua PIAO, Yuan HUANG, Zhengxie WU, Xing JIN, Guangyi LI

2024, 40(8): 1633-1638. DOI: 10.12449/JCH240820

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Objective To investigate the value of intestinal fatty acid binding protein （I-FABP） in predicting the development and progression of acute-on-chronic liver failure （ACLF）. Methods A retrospective analysis was performed for the clinical data of 168 patients with decompensated liver cirrhosis who were admitted to The Affiliated Hospital of Yanbian University from September 2020 to March 2023. The conditions of the patients with ACLF on admission were observed， and the patients were followed up for 6 months to identify new-onset ACLF cases. ELISA was used to measure the serum level of I-FABP on admission. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H rank sum test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups； the Jonckheere-Terpstra test was used for trend analysis. The Spearman correlation analysis was used to investigate the correlation between two variables， and the multivariate Cox regression analysis was used to investigate the influencing factors for new-onset ACLF during follow-up. The Kaplan-Meier curve was used to analyze the onset of ACLF in different groups， and the log-rank test was used for the analysis of such differences. The receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the performance of I-FABP in predicting the development and progression of ACLF. Results Among the 168 patients enrolled in this study， there were 43 patients with ACLF and 125 patients without ACLF， among whom 19 developed ACLF during follow-up. The patients with ACLF on admission had a significantly higher level of I-FABP than those without ACLF （Z=4.359， P<0.001）. The patients with new-onset ACLF had a significantly higher level of I-FABP than those without new-onset ACLF （Z=3.414， P<0.001）. The level of I-FABP increased with the increase in ACLF severity grade （H=17.385， P<0.001，P_trend<0.001）. The multivariate Cox regression analysis showed that I-FABP was independently associated with new-onset ACLF during follow-up （hazard ratio=2.138， 95% confidence interval ［CI］： 1.297 — 3.525， P=0.003）， and the tertile of I-FABP showed a good discriminatory ability （χ²=12.16， P<0.001）. The ROC curve showed that I-FABP had a good performance in predicting the development and progression of ACLF， with an area under the ROC curve of 0.854 （95%CI： 0.791 — 0.903） and 0.747 （95%CI： 0.661 — 0.820）， respectively， and an optimal cut-off value of 2.07 μg/L and 1.86 μg/L， respectively. Conclusion I-FABP can be used as a biomarker to predict the development and progression of ACLF， and it may help to identify high-risk patients and improve clinical management.

Value of urinary liver fatty acid-binding protein in predicting the short-term prognosis of patients with acute-on-chronic liver failure

Hualan WU, Changze HONG, Xiuhua JIANG, Jinjun CHEN

2024, 40(8): 1639-1645. DOI: 10.12449/JCH240821

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Objective To investigate the value of liver fatty acid-binding protein （L-FABP） in predicting the severity and short-term prognosis of patients with acute-on-chronic liver failure （ACLF）. Methods A total of 149 patients with ACLF were selected from a prospective multicenter cohort assessing the platelet function of ACLF patients， and according to the 28-day prognosis after admission， they were divided into survival group with 97 patients and death group with 52 patients. The patients were analyzed in terms of sex， age， etiology， and blood routine， biochemical parameters， and organ failure status within 24 hours after admission， and the level of L-FABP in urine and blood was measured. 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 was used for comparison of categorical data between two groups. The Spearman test was used to evaluate the correlation between urinary L-FABP and indicators for liver failure. The receiver operating characteristic （ROC） curve was plotted to assess the value of CLIF-OFs， MELD score， and urinary L-FABP in predicting the short-term prognosis of ACLF patients； the Kaplan-Meier analysis was used to evaluate short-term mortality in the high urinary L-FABP group and the low urinary L-FABP group； the Cox proportional hazards model was used to investigate the association of each factor with the short-term prognosis of ACLF. Results There were significant differences between the two groups in white blood cell count， serum total bilirubin （TBil）， international normalized ratio， CLIF-OFs， MELD score， urinary L-FABP level， and the proportion of patients with cerebral failure， liver failure， coagulation failure， renal failure， or respiratory failure （all P<0.05）. The Spearman correlation analysis showed that urinary L-FABP was significantly positively correlated with serum TBil （r=0.225， P=0.006）. Urinary L-FABP level had an area under the ROC curve of 0.804 （95% confidence interval ［CI］： 0.729 ‍—‍ 0.865， P<0.001） and a cut-off value of 4.779 µg/dL， with a sensitivity of 73.08%， a specificity of 73.91%， and a Youden index of 0.469 9. The Kaplan-Meier survival analysis showed that compared with the low urinary L-FABP group （urinary L-FABP≤4.779 µg/dL）， the high urinary L-FABP group （urinary L-FABP>4.779 µg/dL） had a significantly lower 28-day survival rate （P<0.001）. The Cox proportional hazards model analysis showed that serum TBil （hazard ratio ［HR］=1.003， 95%CI： 1.001‍‍ —‍ ‍1.004， P<0.05）， CLIF-OFs （HR=2.283， 95%CI： 1.814 — 2.873， P<0.05）， and high urinary L-FABP level （HR=4.568， 95%CI： 2.424 — 8.608， P<0.05） were independent risk factors for the short-term prognosis of ACLF. Conclusion High urinary L-FABP level can be used as a clinical indicator for predicting the short-term prognosis of ACLF， and further studies with larger sample sizes are needed to evaluate its predictive value.

Therapeutic effect of mesenchymal stem cells on acute-on-chronic liver failure： A Meta-analysis

Hang DING, Xiaofen LI, Yan XIONG, Yanyan LI, Xiuji CHEN, Xiaolin WANG

2024, 40(8): 1646-1652. DOI: 10.12449/JCH240822

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Objective To systematically evaluate the efficacy and safety of mesenchymal stem cells （MSC） in the treatment of acute-on-chronic liver failure （ACLF）. Methods This study was conducted according to PRISMA guidelines， with the PROSPERO registration number of CRD42024517851. PubMed， Embase， Wanfang Data， VIP， CNKI， CBM， and the Cochrane Library were searched for randomized controlled trials （RCT） and cohort studies on MSC in the treatment of ACLF published up to November 1， 2023， and the articles were screened according to inclusion and exclusion criteria. After data extraction and quality assessment， RevMan 5.3 software was used to perform the Meta-analysis. Results A total of 11 articles involving 803 subjects were included in this meta-analysis. The results showed that for the patients with ACLF， MSC could improve 8-week survival rate （odds ratio ［OR］=2.71， 95% confidence interval ［CI］： 1.58‍ ‍—‍ ‍4.67， P=0.000 3）， 12-week survival rate （OR=2.24， 95%CI： 1.36‍ ‍—‍ ‍3.69， P=0.001）， 24-week survival rate （OR=2.09， 95%CI： 1.37‍ ‍—‍ ‍3.17， P=0.000 6）， and 48-week survival rate （OR=2.09， 95%CI： 1.29‍ ‍—‍ ‍3.40， P=0.003） and reduce 12-week Model for End-Stage Liver Disease （MELD） score （mean difference ［MD］=-3.27， 95%CI： -6.07 to -0.48， P=0.02） and 24-week MELD score （MD=-2.24， 95%CI： -3.16 to -1.33， P<0.000 01）； it could also reduce the level of total bilirubin after 4 weeks of treatment （MD=-36.86， 95%CI： -48.72 to -25.01， P<0.000 01） and increase 4-week albumin level （MD=2.11， 95%CI： 0.62‍ ‍—‍ ‍3.61， P=0.006） and 24-week albumin level （MD=3.54， 95%CI： 2.06‍ ‍—‍ ‍5.02， P<0.000 01）. Adverse events were evaluated in 6 studies， with no serious adverse events. Conclusion MSC have a good safety in treatment and can improve the survival rate of patients and enhance liver function to some extent， and therefore， it holds promise for clinical application.

Association between preoperative N-terminal pro-brain natriuretic peptide and acute kidney injury after liver transplantation

Naifan PAN, Xuesong SONG

2024, 40(8): 1653-1660. DOI: 10.12449/JCH240823

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Objective To investigate the association between preoperative N-terminal pro-brain natriuretic peptide （NT-proBNP） and acute kidney injury （AKI） after liver transplantation （LT）， to clarify the influencing factors for AKI after liver transplantation， and to provide diagnostic reference indicators for the early prevention of AKI after LT. Methods A retrospective analysis was performed for the medical records of the adult patients who underwent LT in The First Hospital of Jilin University from September 13， 2020 to June 30， 2022， and according to the presence or absence of AKI after LT， the patients were divided into AKI group and non-AKI group. The propensity score matching （PSM） method was used to match the basic information of the two groups at a ratio of 1∶4. 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 independent risk factors for AKI after LT. Results A total of 144 patients were included in this study， among whom 22 （15.3%） developed AKI after surgery and 122 （84.7%） did not develop postoperative AKI. A total of 93 patients were included after PSM， with 19 patients in the AKI group and 74 patients in the non-AKI group. The multivariate Logistic regression analysis showed that preoperative NT-proBNP （odds ratio ［OR］=7.692， 95% confidence interval ［CI］： 1.473‍ ‍—‍ ‍40.159， P=0.016）， preoperative fibrinogen level （OR=5.520， 95%CI： 1.160‍ ‍—‍ ‍26.267， P=0.032）， time of operation （OR=15.802， 95%CI： 2.418‍ ‍—‍ ‍103.268， P=0.004）， and intraoperative blood loss （OR=13.246， 95%CI： 2.291‍ ‍—‍ ‍76.594， P=0.004） were independent risk factors for AKI after LT. Conclusion Preoperative NT-proBNP level may be used as a predictive factor for AKI after LT and can provide a certain reference for establishing a risk predictive model for AKI after LT.

Value of triglyceride glucose-body mass index in evaluating the severity of hyperlipidemic acute pancreatitis

Pingping LUO, Qun LIU, Liwen HUANG

2024, 40(8): 1661-1665. DOI: 10.12449/JCH240824

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Objective To investigate the value of triglyceride glucose-body mass index （TyG-BMI） index in predicting the severity of hyperlipidemic acute pancreatitis （HLAP）. Methods A retrospective analysis was performed for the clinical data of 185 patients with HLAP who were admitted to Tianyou Hospital Affiliated to Wuhan University of Science and Technology from January 2021 to December 2023， and according to the revised Atlanta classification criteria for acute pancreatitis， they were divided into mild group with 95 patients and moderate or severe group with 90 patients. Clinical features were compared between the two groups to analyze the correlation between TyG-BMI and the severity of HLAP， and the efficacy of TyG-BMI in predicting the severity of HLAP was analyzed. 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 was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for the severity of HLAP. A Spearman correlation analysis was used to investigate the correlation between TyG-BMI and the severity of HLAP， and the receiver operating characteristic （ROC） curve was used to analyze the efficacy of TyG-BMI in predicting the severity of HLAP. Results There were significant differences between the mild group and the moderate or severe group in creatinine， blood glucose （GLU）， triglyceride， TyG-BMI， and Bedside Index for Severity in Acute Pancreatitis （BISAP） score （Z=-2.059，-7.217，-7.799，-9.566 and-11.386，all P<0.05）. The multivariate Logistic regression analysis showed that BISAP score （odds ratio ［OR］=4.221， 95% confidence interval ［CI］： 1.421‍ ‍—‍ ‍12.538， P=0.001）， TyG-BMI （OR=1.262， 95%CI： 1.140‍ ‍—‍ ‍1.396， P=0.010）， and GLU （OR=1.316， 95%CI： 1.040‍ ‍—‍ ‍1.666， P=0.022） were independent risk factors for the severity of HLAP and were positively correlated with the severity of HLAP （r=0.839， 0.705， and 0.532， all P<0.05）. In the comparison of the efficacy of these indicators in predicting the severity of HLAP， TyG-BMI had a slightly lower efficacy than BISAP score （Z=-4.368， P<0.001） and a significantly better efficacy than GLU （Z=2.155， P<0.001）， with an area under the ROC curve of 0.891， a sensitivity of 91.10%， and a specificity of 96.80%. Conclusion TyG-BMI index has a certain value in predicting the severity of HLAP and can be used in clinical comprehensive assessment of HLAP.

Primary biliary cholangitis-autoimmune hepatitis overlap syndrome comorbid with pulmonary cryptococcosis： A case report

Mingming ZHANG, Huan LIU, Dongmei ZHANG, Dongbo WU, Hong TANG

2024, 40(8): 1666-1669. DOI: 10.12449/JCH240825

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Patients with overlap syndrome （OS） of autoimmune liver disease may present with more than one biochemical， immunological， histological or cholangiography features of autoimmune liver disease （AILD） and often require a combination of immunosuppressants for treatment. Pulmonary cryptococcosis is a type of invasive pneumomycosis caused by Cryptococcus neoformans or Cryptococcus gattii and has a relatively high incidence rate in immunocompromised patients. This case report presents a patient with OS who was found to have pulmonary cryptococcosis during immunosuppressive therapy and developed abnormal liver function during antifungal treatment. Based on the liver function of the patient， the feasibility of adjusting antifungal agents was assessed， and active treatment strategies for novel cryptococcal infection were developed under the close monitoring of liver function， which helped to avoid the progression of infection. It is suggested that before the initiation of immunosuppressive therapy， systemic foci of infection should be comprehensively evaluated， and suspicious foci of infection should be monitored continuously.

The role of circadian clock-controlled mitochondrial dynamics in nonalcoholic fatty liver disease

Ce ZHANG, Jiarui MIAO, Xu FAN

2024, 40(8): 1670-1676. DOI: 10.12449/JCH240826

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Nonalcoholic fatty liver disease （NAFLD） is a disease closely associated with metabolic abnormalities and is currently one of the most common chronic liver diseases. Mitochondria are highly dynamic organelles involved in a variety of metabolic and bioenergetic pathways in the liver， and they respond to environmental changes in a highly dynamic manner through mitochondrial dynamics. The circadian clock is able to modulate mitochondrial dynamics， making it exhibit rhythmic changes. In case of circadian rhythm disorders， mitochondrial dynamics loses rhythmicity， and mitochondria are unable to respond to changing energy demands in different environments， leading to the development and progression of NAFLD. This article summarizes the important role of circadian clock-controlled mitochondrial dynamics in the etiology of NAFLD.

The role of necroptosis in liver fibrosis

Xuan WU, Hui LI, Haijian DONG, Xikun YANG, Kaixin WANG

2024, 40(8): 1677-1681. DOI: 10.12449/JCH240827

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As a crucial link in the progression of various chronic liver diseases to liver cirrhosis， liver fibrosis affects the prognosis and outcome of chronic liver diseases. Necrotosis is a novel pattern of programmed cell death （PCD）， and studies have shown that it plays an important role in the pathophysiology of various diseases and is considered a potential target for improving liver fibrosis. Necroptosis of various types of intrahepatic cells （including hepatocytes， hepatic stellate cells， liver macrophages， and hepatic sinusoidal endothelial cells） can promote or inhibit liver fibrosis. This article elaborates on the above mechanisms and discusses the therapeutic strategies for targeting liver fibrosis mediated by necroptosis.

Advances in the application of direct-acting antivirals in patients with hepatitis C cirrhosis

Xiping RAN, Dachuan CAI

2024, 40(8): 1682-1687. DOI: 10.12449/JCH240828

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Chronic hepatitis C virus （HCV） infection can lead to liver cirrhosis， and complications after liver cirrhosis， including hepatocellular carcinoma （HCC）， are the leading causes of death in patients with chronic liver diseases. Antiviral therapy can help to realize sustained virologic response， improve hepatitis and liver fibrosis， and delay disease progression. The safety and efficacy of direct-acting antivirals （DAAs） have been confirmed in patients with HCV-related liver cirrhosis， and whether DAAs can improve the complications and prognosis of patients with liver cirrhosis has gradually become a research hotspot. Related data are mainly reported by foreign scholars， and since DAAs have not been marketed in China for a long time， there is still a lack of mid- and long-term data. This article reviews the latest studies on the application of DAAs in patients with HCV-related liver cirrhosis and the impact of DAAs on clinical prognosis.

Association of lipid metabolism reprogramming with the development and progression of primary liver cancer

Feiyan LI, Minggang WANG, Dewen MAO, Riyun ZHANG, Na WANG, Yinbing LUO, Xiaoping LIU, Yupei LIN

2024, 40(8): 1688-1692. DOI: 10.12449/JCH240829

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Lipid metabolism， as the basis of life maintenance， is a prerequisite for cell survival， and lipid homeostasis can rapidly respond to metabolic changes in a coordinated manner. In cancers， there is an increase in lipid metabolism in cancer cells to meet the requirements for plasma membrane synthesis and energy production. Abnormal lipid metabolism plays an important role in the progression of primary liver cancer. This article reviews the association between abnormal lipid metabolism and primary liver cancer， in order to find targets for the prevention and treatment of primary liver cancer.

Role of ferroptosis in hepatic ischemia-reperfusion injury

Jiaxin LIANG, Baolin XU, Yu CHENG, Yong WEI

2024, 40(8): 1693-1698. DOI: 10.12449/JCH240830

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Ferroptosis is a new type of regulatory cell death and is mainly caused by changes in intracellular iron homeostasis due to various inducers， which promotes the occurrence of iron ion-dependent lipid peroxidation， thereby leading to the accumulation of toxic lipid peroxides and finally resulting in cell death. Hepatic ischemia-reperfusion injury is a common and serious complication after liver surgery， with the main mechanisms of anaerobic respiration， mitochondrial injury， oxidative stress response， inflammatory response， calcium overload， and microcirculation dysfunction. This article introduces the concepts and mechanisms of ferroptosis and hepatic ischemia-reperfusion injury and summarizes some related treatment strategies， so as to provide a reference for exploring new treatment methods for hepatic ischemia-reperfusion injury.

Role of biliary microbiota in the development and progression of common biliary tract diseases

Li HUO, Zhihui CHANG

2024, 40(8): 1699-1703. DOI: 10.12449/JCH240831

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The composition of biliary microbiota is closely associated with the development and progression of biliary diseases， and imbalance of biliary microbiota may lead to a series of biliary tract diseases such as gallstones， biliary tract infections， autoimmune cholangitis， and cholangiocarcinoma. This article reviews the articles on the association between biliary microbiota and biliary tract diseases and summarizes the influence of biliary microbiota on various biliary tract diseases and the role of specific bacterial flora in biliary tract diseases， in order to guide further clinical research and provide new ideas for the prevention， diagnosis， and treatment of biliary tract diseases.

Molecular mechanism of traditional Chinese medicine active components in regulating glucose metabolism against cholangiocarcinoma

Fangyan ZHAO, Shan LI, Xiangqi WANG, Yi YIN

2024, 40(8): 1704-1708. DOI: 10.12449/JCH240832

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Cholangiocarcinoma is a highly heterogeneous tumor with an insidious onset， severe conditions， a high degree of malignancy， and an extremely poor prognosis. Glucose is a major energy source for the proliferation and metastasis of cholangiocarcinoma， and the glucose metabolism pathway of cholangiocarcinoma cells will be re-edited in the process of rapid proliferation to produce a large amount of energy for their own needs. Traditional Chinese medicine has unique advantages in the treatment of cholangiocarcinoma， and studies have shown that the active components of traditional Chinese medicine can inhibit the development and progression of cholangiocarcinoma by regulating glucose metabolism. This article reviews the characteristics of glucose metabolism in cholangiocarcinoma and the role of the active components of traditional Chinese medicine in regulating glucose metabolism against cholangiocarcinoma， in order to provide new ideas for the treatment of cholangiocarcinoma.

Research advances in hereditary pancreatitis in children

Xiaozheng YU, Jie WU

2024, 40(8): 1709-1714. DOI: 10.12449/JCH240833

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Hereditary pancreatitis （HP） is one of the major causes of pancreatitis in children and has a high risk of carcinogenesis after they become adults. This article reviews the recent research advances in HP， including historical development， epidemiology， pathogenic mechanism， and related pathogenic genes， clinical features， and diagnosis and treatment， in order to provide new reference information for delaying the progression of HP in children and conducting related basic research.

Pathogenesis of pancreatogenic diabetes

Chenxiao WANG, Xiao WANG, Xiwang WANG, Jingjing JIN, Ying WANG, Jiangkai LIU, Shuxun YAN

2024, 40(8): 1715-1720. DOI: 10.12449/JCH240834

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Pancreatogenic diabetes is a type of diabetes secondary to pancreatic exocrine disease， and it was officially named by American Diabetes Association in 2014. Chronic pancreatitis and pancreatic cancer are the most common causes of pancreatogenic diabetes. The pathogenesis of this disease remains unclear， and there is still a lack of systematic treatment regimens， which leads to the extremely high misdiagnosis rate of pancreatogenic diabetes in China and globally. In addition， studies have shown that compared with patients with type 2 diabetes， patients with pancreatogenic diabetes tend to have higher risks of death and readmission， which brings great challenges to the health and clinical treatment of patients. Therefore， the comprehensive understanding and early accurate identification and diagnosis of pancreatogenic diabetes are of great significance in reducing the disability and mortality rates of this disease. This article elaborates on the possible pathogenesis of pancreatogenic diabetes.

Journal of Hepatology｜Endothelial POFUT1 controls injury-induced liver fibrosis by repressing fibrinogen synthesis

2024, 40(8): 1537-1537. DOI: 10.12449/JCH2408.gwqkjpwzjj1

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Nutrition Journal｜Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial

2024, 40(8): 1626-1626. DOI: 10.12449/JCH2408.gwqkjpwzjj2

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Journal of the American Medical Association｜Aspirin for metabolic dysfunction-associated steatotic liver disease without cirrhosis: A randomized clinical trial

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