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Epidemiology of liver diseases:global disease burden and forecasted research trends

Science China Life Sciences 2024年

作者： Jia Xiao Fei Wang Yuan Yuan Jinhang Gao Lu Xiao Chao Yan Feifei Guo Jiajun Zhong Zhaodi Che Wei Li Tian Lan Frank Tacke Vijay H.Shah Cui Li Hua Wang Erdan Dong Division of gastroenterology and hepatology Mayo Clinic Department of Health Sciences National Natural Science Foundation of China Department of Oncology The First Affiliated Hospital Institute for Liver Diseases of Anhui Medical University Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University Research center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital(Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of gastroenterology Qingdao Central Hospital University of Health and Rehabilitation Sciences Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai Hospital Affiliated with Jinan University Division of gastroenterology Seventh Affiliated Hospital of Sun Yat-sen University School of Biological Sciences Jinan University Aier Institute of Ophthalmology Central South University Lab of gastroenterology and hepatology West China Hospital Sichuan University clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan University Faculty of Pharmaceutical Sciences Toho University Department of hepatology and gastroenterology Charité-Universit?tsmedizin Berlin Campus Virchow-Klinikum and Campus Charité Mitte

We assessed the global incidence, mortality, and disability-adjusted life years(DALYs) associated with various liver diseases, including alcohol-related liver disease(ALD), hepatitis B/C virus infections(HBV or HCV), liver cancer, metabolic dysfunction-associated steatotic liver disease(MASLD), and other chronic liver diseases, from the 2019 Global Burden of Disease study. Additionally, we analyzed the global trends in hepatology research and drug development. From 2000 to 2019, prevalence rates increased for ALD, MASLD and other liver diseases, while they decreased for HBV, HCV, and liver cancer. Countries with a high socio-demographic index(SDI) exhibited the lowest mortality rates and DALYs. The burden of liver diseases varied due to factors like sex and region. In nine representative countries, MASLD,along with hepatobiliary cancer, showed highest increase in funding in hepatology research. Globally, the major research categories in hepatology papers from 2000 to 2019 were cancer, pathobiology, and MASLD. The United States(U.S.) was at the forefront of hepatology research, with China gradually increasing its influence over time. Hepatologists worldwide are increasingly focusing on studying the communication between the liver and other organs, while underestimating the research on ALD. Cancer, HCV, and MASLD were the primary diseases targeted for therapeutic development in clinical trials. However, the proportion of new drugs approved for the treatment of liver diseases was relatively low among all newly approved drugs in the U.S., China, Japan, and the European Union. Notably, there were no approved drug for the treatment of ALD in the world.

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Immunology demystified: A guide for transplant hepatologists

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World Journal of Transplantation 2024年第1期14卷 48-61页

作者： Iva Kosuta Tomislav Kelava Ana Ostojic Vibor Sesa Anna Mrzljak Hrvoje Lalic Department of Intensive Care Medicine University Hospital Centre ZagrebZagreb 10000Croatia Department of Physiology School of MedicineUniveristy of ZagrebZagreb 10000Croatia Laboratory for Molecular Immunology Croatian Institute for Brain ResearchZagreb 10000Croatia Department of gastroenterology and hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Physiology University of Zagreb School of MedicineZagreb 10000Croatia Laboratory for Cell Biology Croatian Institute for Brain ResearchUniversity of Zagreb School of MedicineZagreb 10000Croatia Department of Laboratory Immunology Clinical Department of Laboratory DiagnosticsUniversity Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation has become standard practice for treating end-stage liver *** success of the procedure relies on effective immunosuppressive medications to control the host's immune *** the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune *** ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic ***,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased *** that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive *** knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

关键词： Liver transplantation Allograft rejection Operational immune tolerance Immune reaction Immunosuppression

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羧基酯脂肪酶通过与脂肪酸合成酶结合预防代谢功能障碍相关性脂肪性肝炎（英文）

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Engineering 2024年第10期 204-215页

作者：宋阳钟巍刘焯晞张雅婷官华宇谢茗旭夏芷君首第文周永健许鸿志于君张翔 Department of Medicine and Therapeutics Institute of Digestive Disease State Key Laboratory of Digestive Disease Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Shenzhen Research Institute The Chinese Unviersity of Hong Kong Department of gastroenterology & Institute for Microbial Ecology & Xiamen Key Laboratory of Intestinal Microbiome and Human Health & clinical Research center for Gut Microbiota and Digestive Diseases of Fujian Province Zhongshan Hospital of Xiamen University School of Medicine Xiamen University Division of gastroenterology and hepatology Renji Hospital School of Medicine Shanghai Jiaotong University Department of gastroenterology and hepatology Guangzhou Digestive Disease Center Guangzhou First People's Hospital

Carboxyl ester lipase(CEL), a pivotal enzyme involved in lipid metabolism, is recurrently mutated in obese mice. Here, we aimed to elucidate the functional significance, molecular mechanism, and therapeutic potential of CEL in metabolic dysfunction-associated steatohepatitis(MASH). Hepatocyte-specific carboxyl ester lipase gene(Cel) knockout(CelΔHEP) and wildtype(WT) littermates were fed with cholinedeficient high-fat diet(CD-HFD) for 16 weeks, or methionine-and choline-deficient diet(MCD) for three weeks to induce MASH. Liquid chromatography–mass spectrometry and co-immunoprecipitation were employed to identify the downstream targets of CEL. CD-HFD/MCD-fed WT mice received intravenous injections of CEL-adeno-associated viral, serotype 8(AAV8) to induce specific overexpression of CEL in the liver. We observed a decrease in CEL protein levels in MASH induced by CD-HFD or MCD in mice. CelΔHEPmice fed with CD-HFD or MCD exhibited pronounced hepatic steatosis, inflammation, lipid peroxidation, and liver injury compared to WT littermates, accompanied by increased hepatic nuclear factor kappa-light-chain-enhancer of activated B cell(NF-κB) activation. Consistently, Cel knockdown in mouse primary hepatocytes and AML12 cells aggravated lipid accumulation and inflammation,whereas CEL overexpression exerted the opposite effect. Mechanistically, CEL directly bound to fatty acid synthase(FASN), resulting in reduced FASN SUMOylation, which in turn promoted FASN degradation through the proteasome pathway. Furthermore, inhibition of FASN ameliorated hepatocyte lipid accumulation and inflammation induced by Cel knockdown in vivo and in vitro. Hepatocyte-specific CEL overexpression using AAV8-Cel significantly mitigated steatohepatitis in mice fed with CD-HFD or MCD. CEL protects against steatohepatitis development by directly interacting with FASN and suppressing its expression for de novo lipogenesis. CEL overexpression confers a therapeutic benefit in steatohepatitis.

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A study of pulmonary embolism after abdominal surgery in patients undergoing prophylaxis

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World Journal of gastroenterology 2009年第3期15卷 344-348页

作者： Mirko D Kerkez Dorde M ulafi Dragana D Mija Vitomir I Rankovi Nebja S Leki Dejan Z Stefanovi Clinic of Surgery Institute of Digestive Diseases Clinical Center of SerbiaMedical Faculty11000 BelgradeRepublic of Serbia Clinic of gastroenterology and hepatology Institute of Digestive DiseasesClinical Center of SerbiaMedical Faculty11000 BelgradeRepublic of Serbia

AIM： To determine risk factors for pulmonary embolism and estimate effects and benefits of prophylaxis. METHODS： We included 78 patients who died subsequently to a pulmonary embolism after major abdominal surgery from 1985 to 2003. A first, retrospective analysis involved 41 patients who underwent elective surgery between 1985 and 1990 without receiving any prophylaxis. In the prospectively evaluated subgroup, 37 patients undergoing major surgery between 1991 and 2003 were enrolled： all of them had received a prophylaxis consisting in lowmolecular weight heparin, given subcutaneously at a dose of 2850 IU AXa/0.3 mL （body weight 〈 50 kg） or 5700 IU AXa/0.6 mL （body weight ≥ 50 kg）. RESULTS： A higher incidence of thromboembolism （43.9% and 46.34% in the two groups, respectively） was found in older patients （〉 60 years）. The incidence of pulmonary embolism after major abdominal surgery in patients who had received the prophylaxis was significantly lower compared to the subjects with the same condition who had not received any prophylaxis （P 〈 0.001, OR = 2.825; 95% CI, 1.811-4.408）. Furthermore, the incidence of pulmonary embolism after colorectal cancer surgery was significantly higher compared to incidence of pulmonary embolism after other abdominal surgical procedures. Finally, the incidence of pulmonary embolism after colorectal cancer surgery among the patients who had received the prophylaxis （11/4316, 0.26%） was significantly lower compared to subjects undergoing a surgical procedure for the same indication but without prophylaxis （10/1562, 0.64%）（P 〈 0.05, OR = 2.522; 95% Ct, 1.069-5.949）. CONCLUSION： Prophylaxis with low molecular weight heparin is highly recommended during the preoperative period in patients with diagnosis of colorectal cancer due to high risk of pulmonary embolism after elective surgery.

关键词： Pulmonary embolism Surgery Colorectal cancer Risk factor Prevention

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The gut microbiome modulate response to immunotherapy in cancer

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Science China Life Sciences 2024年

作者： Shan-Shan Jiang Zi-Ran Kang Ying-Xuan Chen Jing-Yuan Fang Division of gastroenterology and hepatology Shanghai Institute of Digestive Disease NHC Key Laboratory of Digestive Diseases State Key Laboratory for Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University

Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of *** investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.

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Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1

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Journal of clinical and Translational hepatology 2024年第3期12卷 227-235页

作者： Ning Zhang Pengyao Yang Yanmeng Li Qin Ouyang Fei Hou Guixin Zhu Bei Zhang Jian Huang Jidong Jia Anjian Xu Experimental and Translational Research center Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of gastroenterology Beijing Shunyi HospitalBeijingChina Department of Critical Liver Diseases Beijing Friendship HospitalCapital Medical UniversityBeijingChina MOE Key Laboratory of Protein Science School of Life SciencesTsinghua UniversityBeijingChina Liver Research center Beijing Friendship HospitalCapital Medical UniversityBeijingChina

Background and Aims:Liver iron overload can induce hepatic expression of bone morphogenic protein(BMP)6 and activate the BMP/SMAD ***,serum iron overload can also activate SMAD but does not induce BMP6 ***,the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain *** study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD ***:A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin(Holo-Tf).A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 *** blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of ***:Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to *** E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression;specifically,SMURF1 expression dramatically decreased when the serum iron concentration was ***,the expression of SMURF1 substrates,which are important molecules involved in the transduction of BMP/SMAD signaling,was significantly ***,in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron ***:SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.

关键词： BMP/SMAD pathway Hepcidin Holo-transferrin Ubiquitin-proteasome degradation Hemochromatosis

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A toolbox for genetic manipulation in intestinal Clostridium symbiosum

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Synthetic and Systems Biotechnology 2024年第1期9卷 43-54页

作者： Pengjie Yang Jinzhong Tian Lu Zhang Hui Zhang Gaohua Yang Yimeng Ren Jingyuan Fang Yang Gu Weihong Jiang CAS-Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai200032China University of Chinese Academy of Sciences Beijing100049China Xianghu Laboratory Hangzhou311231China NHC Key Laboratory of Digestive Diseases Division of Gastroenterology and HepatologyShanghai Institute of Digestive DiseaseRenji HospitalSchool of MedicineShanghai Jiao Tong University145 Middle Shandong RoadShanghai200001China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518120China The Wallenberg Laboratory Department of Molecular and Clinical MedicineSahlgrenska AcademyUniversity of GothenburgBruna Straket 16Gothenburg41345Sweden

Gut microbes are closely related with human health,but remain much to *** symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal ***,the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth ***,we obtained the complete genome sequence of *** ATCC 14940,a representative strain of *** this basis,we further developed a series of genetic manipulation methods for this ***,following the identification of a functional replicon pBP1 in *** ATCC 14940,a highly efficient conjugative DNA transfer method was established,enabling the rapid introduction of exogenous plasmids into ***,we constructed a dual-plasmid CRISPR/Cas12a system for genome editing in this bacterium,reaching over 60% repression for most of the chosen genes as well as efficient deletion(>90%)of three target ***,this toolbox was used for the identification of crucial functional genes,involving growth,synthesis of important metabolites,and virulence of *** ATCC *** work has effectively established and optimized genome editing methods in intestinal ***,thereby providing strong support for further basic and application research in this bacterium.

关键词： Gut Clostridium symbiosum Toolbox Gene overexpression Gene deletion Gene regulation

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Interplay between chronic hepatitis B and atherosclerosis:Innovative perspectives and theories

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World Journal of gastroenterology 2022年第4期28卷 497-499页

作者： Ivan Ranković Vladimir Milivojević Aleksandra PavlovićMarković Mihailo Bezmarević Clinic for gastroenterology and hepatology University Clinical Center of SerbiaBelgrade 11000Serbia Clinic for gastroenterology and hepatology University Clinical Center of SerbiaSchool of MedicineUniversity of BelgradeBelgrade 11000Serbia Department of Hepatobiliary and Pancreatic Surgery Clinic for General SurgeryMilitary Medical AcademyUniversity of DefenseBelgrade 11000Serbia

Elaboration of carotid atherosclerosis in the setting of hepatitis B virus(HBV)infection should emphasize the significance of extrahepatic manifestations of the infection *** processes comprise the pathoevolution of HBV infection,rendering it a multi-systemic disease in its *** work not only exemplified atherosclerosis as an often-underestimated contributor to the severity of HBV infection but has also highlighted the bidirectional relationship between the ***,it is suggested that HBV-induced inflammation is one of the root causes of atherosclerosis,which in turn has a consequent effect on the severity of the chronic infection disease state,creating a vicious ***,we coupled prior data with the current concepts of HBV infection to postulate intriguing perspectives and theories.

关键词： Hepatitis B virus infection Carotid atherosclerosis Hepatitis B e antigen Arterial inflammation Perspectives and trends

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Drain amylase value as an early predictor of pancreatic fistula after cephalic duodenopancreatectomy

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World Journal of gastroenterology 2014年第26期20卷 8691-8699页

作者： Vladimir D Dugalic Djordje M Knezevic Vladan N Obradovic Miroslava G Gojnic-Dugalic Slavko V Matic Aleksandra R Pavlovic-Markovic Predrag D Dugalic Srbislav M Knezevic Department of Hepatobiliary and Pancreatic Surgery First Surgical University HospitalClinical Center of SerbiaSchool of MedicineUniversity of Belgrade St. Joseph’s Hospital Health center Clinic for Gynecology and Obstetrics Clinical Center of SerbiaSchool of MedicineUniversity of Belgrade Clinic for gastroenterology and hepatology Clinical Center of SerbiaSchool of MedicineUniversity of Belgrade Clinic for gastroenterology and hepatology University Hospital Zemun

AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period.

关键词： Cephalic duodenopancreatectomy Periampullary tumors Pancreatic fistula Drain fluid amylase level Prediction

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Sepsis during short bowel syndrome hospitalizations:Identifying trends,disparities,and clinical outcomes in the United States

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World Journal of Gastrointestinal Pathophysiology 2024年第1期15卷 26-36页

作者： Dushyant Singh Dahiya Jennifer Wachala Shantanu Solanki Dhanshree Solanki Asim Kichloo Samantha Holcomb Uvesh Mansuri Khwaja Saad Haq Hassam Ali Manesh Kumar Gangwani Yash R Shah Teresa Varghese Hafiz Muzaffar Akbar Khan Simon Peter Horslen Thomas D Schiano Syed-Mohammed Jafri Division of gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States Department of Internal Medicine Samaritan Medical CenterWatertownNY 13601United States Division of gastroenterology hepatology&Nutrition The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Medicine Institute for Foreign Medical Graduate EducationHoustonTX 77030United States Department of Internal Medicine MedStar Harbor HospitalBaltimoreMD 21225United States Department of Internal Medicine WellStar Spalding Regional HospitalGriffinGA 30224United States Division of gastroenterology Hepatology and NutritionEast Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of gastroenterology and hepatology University of Arkansas for Medical SciencesLittle RockAR 72205United States Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States Division of gastroenterology and hepatology SUNY Upstate Medical UniversitySyracuseNY 13210United States Department of Pediatrics School of Medicine and UPMC Children’s Hospital of PittsburghUniversity of PittsburghPittsburghPA 15219United States Division of Liver Diseases Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Division of gastroenterology and hepatology Henry Ford HospitalDetroitMI 48202United States

BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with *** is a significant paucity of data on adult SBS hospitalizations in the United States and across the *** To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United *** The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between *** study cohort was further divided based on the presence or absence of *** were identified,and hospitalization characteristics and clinical outcomes were *** of mortality for SBS hospitalizations complicated with sepsis were *** Of 247097 SBS hospitalizations,21.7%were complicated by *** SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS *** Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

关键词： Short bowel syndrome Sepsis Outcomes Mortality Trends

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