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Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China Organ Transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China institute of Organ Donation and Transplantation of Qingdao University Qingdao 266000China Department of gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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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TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway

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Current Medical Science 2024年第3期44卷 519-528页

作者： Jia SONG Dong-lei SUN Chen-yang LI Yu-xin LUO Qian LIU Yue YAO Hong ZHANG Ting-ting YANG Mei SONG Xin-li BAI Xiao-lan ZHANG Department of gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesShijiazhuang050000China Department of Pediatrics The Second Hospital of Hebei Medical UniversityShijiazhuang050000China

Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis *** study aimed to explore the effects of TL1A on human colonic *** A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal *** human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)*** proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western *** metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT *** growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT *** proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 ***1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co *** of CCD-18Co cells with TL1A increased the expression of TGF-β1 and *** TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

关键词： tumor necrosis factor ligand-related molecule-1A fibrosis inflammatory bowel disease myofibroblasts transforming growth factor-β1

FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 1605-1623页

作者： Zhifeng Huang Tongtong Pan Liang Xu Lu Shi Xiong Ma Liya Zhou Luyao Wang Jiaojiao Wang Guoqing Zhu Dazhi Chen Lingtao Song Xiaomin Pan Xiaodong Wang Xiaokun Li Yongde Luo Yongping Chen hepatology Diagnosis and Treatment Center Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseasesthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China School of Laboratory Medicine and Life Sciences Wenzhou Medical University&Key Laboratory of Laboratory MedicineMinistry of EducationWenzhou Medical UniversityWenzhou 325035China Division of gastroenterology and hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Hangzhou Medical College Hangzhou 311300China

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

关键词： Fibroblast growthfactor 4 Fibroblast growth factor receptor 4 Immune liver injury Ca^(2+)/Calmodulin dependent protein

Peptidome data-driven comprehensive individualized monitoring of membranous nephropathy with machine learning

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Chinese Chemical Letters 2024年第5期35卷 402-406页

作者： Zixing Xu Ruiying Chen Chuanming Hao Qionghong Xie Chunhui Deng Nianrong Sun Department of gastroenterology and hepatology Zhongshan Hospitaland Department of ChemistryFudan UniversityShanghai 200433China Division of Nephrology Huashan HospitalFudan UniversityShanghai 200040China School of Chemistry and Chemical Engineering Nanchang UniversityNanchang 330031China

As the most common pathological type of nephrotic syndrome,membranous nephropathy(MN)presents diversity in progression trends,facing severe *** precise discrimination of MN from healthy people,other types of nephrotic syndrome or those with therapeutic remission has always been huge challenge in clinics,not to mention comprehensive individualized monitoring relied on minimally invasive molecular detection ***,we construct a functionalized pore architecture to couple with machine learning to aid all-round peptidome enrichment and data profiling from hundreds of human serum samples,and finally establish a set of defined peptide panel consisting of 12 specific feature *** addition to the realization of above-mentioned precise discrimination with more than 97%of sensitivity,88%of accuracy and f1 score,the simultaneously comprehensive individualized monitoring for MN can also be achieved,including conventionally screening diagnosis,congeneric distinction and prognostic *** work greatly advances the development of peptidome data-driven individualized monitoring means for complex diseases and undoubtedly inspire more devotion into molecular detection field.

关键词： Membranous nephropathy Serum peptidome Machine learning Disease diagnosis

Gastroesophageal reflux following peroral endoscopic myotomy for achalasia:Bumps in the road to success

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World Journal of gastroenterology 2024年第29期30卷 3461-3464页

作者： David Itskoviz Stephen David Howard Malnick Kaplan Medical Center Institute of Gastroenterology and HepatologyHebrew University Medical School of JerusalemRehovot 76100Israel Kaplan Medical Center Department of Internal Medicine CHebrew University Medical School of JerusalemRehovot 76100Israel

Achalasia can significantly impair the quality of *** clinical presentation typically includes dysphagia to both solids and liquids,chest pain,and *** can be delayed in patients with atypical presentations,and they might receive a wrong diagnosis,such as gastroesophageal reflux disease(GERD),owing to overlapping symptoms of both *** the cause of achalasia is poorly understood,its impact on the motility of the esophagus and gastroesophageal junction is well *** treatment modalities have been utilized,with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon ***,peroral endoscopic myotomy(POEM)has gained popularity as an effective treatment for achalasia,despite a relatively high incidence of GERD occurring after treatment compared to other *** magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related *** longterm sequelae of post-POEM GERD are yet to be determined,but it appears to have a benign course and is usually manageable with clinically available *** risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

关键词： Achalasia Per-oral endoscopic myotomy Gastroesophageal reflux Pneumatic dilatation Heller myotomy Proton pump inhibitor Acidic fermentation

Metabolic disease and the liver: A review

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World Journal of hepatology 2024年第1期16卷 33-40页

作者： Márcia Vargas Sheila de Castro Cardoso Toniasso Patricia G Riedel Camila Pereira Baldin Francielle Lopes dos Reis Robson Martins Pereira Maria Carlota Borba Brum Dvora Joveleviths Mario Reis Alvares-da-Silva Program of Graduate Science in gastroenterology and hepatology Federal University of Rio Grande do SulPorto Alegre 90040-060Rio Grande do SulBrazil School of Medicine Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Program of Graduate Science in gastroenterology and hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90410000Brazil Medicine Faculty Federal University of Rio Grande do Sul Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Division of gastroenterology and hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90035007Brazil

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin *** presence of metabolic comorbidities coexisting with liver disease varies substantially among *** is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with *** steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of *** diagnosis is based on the presence of steatosis,noninvasive scores and altered liver *** scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely ***,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical ***,there is no definite pharmacological treatment for the *** public health policies to treat patients with risk factors for MASLD prevention is essential.

关键词： Nonalcoholic fatty liver disease Primary care Metabolic risk Liver Metabolism

Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 550-556页

作者： Xu Zhang Fei Tang Yan-Ying Gao De-Zhao Song Jing Liang Department of gastroenterology and hepatology The Third Central Hospital of TianjinTianjin 300170China Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Artificial Cell Engineering Technology Research CenterTianjin Institute of Hepatobiliary DiseaseTianjin 300170China Department of Interventional Radiology The Third Central Hospital of TianjinTianjin 300170China

BACKGROUND Light chain(AL)amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells,which leads to progressive dysfunction of the affected *** two most commonly affected organs are the heart and kidneys,and liver is rarely the dominant affected organ with only 3.9%of cases,making them prone to misdia-gnosis and missed *** SUMMARY A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked ***,based on enhanced computed tomography scan and angiography,Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was ***,addi-tional diagnostic procedures,including liver biopsy and bone marrow-exami-nation,revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular *** disease course was progre-ssive and fatal,and the patient eventually died 5 mo after initial presentation of *** AL amyloidosis with isolated liver involvement is very rare,and can be easily misdiagnosed as a vascular disease.

关键词： Jaundice Hepatomegaly Liver amyloidosis Kappa light chain Pseudo-Budd-Chiari syndrome Case report

Diagnostic delay in inflammatory bowel diseases in a German population

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World Journal of gastroenterology 2024年第29期30卷 3465-3478页

作者： Elisabeth Blüthner Annalena Dehe Carsten Büning Britta Siegmund Matthias Prager Jochen Maul Alexander Krannich Jan Preiß Bertram Wiedenmann Florian Rieder Raneem Khedraki Frank Tacke Andreas Sturm Anja Schirbel Department of hepatology and gastroenterology Campus Virchow-Klinikum and Campus CharitéMitteCharité-Universitätsmedizin BerlinBerlin 10117Germany Department of gastroenterology Vivantes Klinikum im FriedrichshainBerlin 10249Germany Department of Internal Medicine Krankenhaus WaldfriedeBerlin 14163Germany Department of gastroenterology Infectious Diseases and RheumatologyCharité-Universitätsmedizin BerlinBerlin 12203Germany Praxis für Gastroenterologie Berlin Zehlendorf Berlin 14195Germany Gastroenterologie am Bayrischen Platz Berlin 10825Germany Clinical Trial Office Charité-Universitätsmedizin BerlinBerlin 10117Germany Department of gastroenterology Diabetology and HepatologyVivantes Klinikum NeuköllnBerlin 10117Germany Department of gastroenterology Hepatology and NutritionDigestive Diseases and Surgery InstituteThe Cleveland Clinic FoundationClevelandOH 44195United States Department of Internal Medicine DRK Kliniken Berlin WestendBerlin 14050Germany Gastroenterologie im Havelland Straße der EinheitFalkensee 14612Germany

BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients *** To identify risk factors leading to prolonged diagnostic time in a German IBD *** Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD *** diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time *** The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD *** UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic *** We demonstrated that CD patients compared to UC are at risk of long diagnostic *** efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

关键词： Diagnostic time Diagnostic delay Crohn’s disease Ulcerative colitis Germany