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Effect of viral hepatitis on type 2 diabetes:A Mendelian randomization study

World Journal of Diabetes 2024年第2期15卷 220-231页

作者： Yun-Feng Yu Gang Hu Ke-Ke Tong Xin-Yu Yang Jing-Yi Wu Rong Yu The First Hospital of Hunan University of Chinese Medicine Changsha 410007Hunan ProvinceChina The Hospital of Hunan University of Traditional Chinese Medicine Changde 415213Hunan ProvinceChina College of Chinese Medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina The Third Hospital of Zhejiang Chinese Medical University Hangzhou 310005Zhejiang ProvinceChina

BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.

关键词： viral hepatitis Chronic hepatitis B Chronic hepatitis C Type 2 diabetes Mendelian randomization

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viral hepatitis:Innovations and expectations

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World Journal of Gastroenterology 2022年第5期28卷 517-531页

作者： Simona Leoni Alberto Casabianca Benedetta Biagioni Ilaria Serio Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIRCCS Azienda Ospedaliero-Universitaria di BolognaBologna 40138Italy

viral hepatitis is a significant health problem worldwide,associated with morbidity and mortality.hepatitis B,C,D,and occasionally E viruses(HBV,HCV,HDV,and HEV)can evolve in chronic infections,whereas hepatitis A virus(HAV)frequently produces acute self-limiting hepatitis.In the last years,different studies have been performed to introduce new antiviral therapies.The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications.This review analyzes currently available therapies,in particular for viruses associated with chronic liver disease.The focus is especially on HBV and HCV therapies,investigating new drugs already introduced in clinical practice and clinical trials.We also describe new entry inhibitors,developed for the treatment of chronic HDV and HBV and currently available treatments for HEV.The last drugs introduced have shown important efficacy in HCV,with achievable target HCV elimination by 2030.Concurrently,renewed interest in curative HBV therapies has been registered;current nucleotide/nucleoside analogs positively impact liver-related complications,ensuring high safety and tolerability.Novel approaches to HBV cure are based on new antivirals,targeting different steps of the HBV life cycle and immune modulators.The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents,as bulevirtide,the first drug conditionally approved in Europe for HDV associated compensated liver disease.Further studies are required to identify a new therapeutic approach in hepatitis E,especially in immunosuppressed patients.

关键词： viral hepatitis Chronic liver disease Treatments Antiviral Immunotherapy Vaccination

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viral hepatitis:Past,present,and future

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World Journal of Gastroenterology 2022年第14期28卷 1405-1429页

作者： Matthew August Odenwald Sonali Paul Department of Medicine Section of GastroenterologyHepatologyand NutritionCenter for Liver DiseasesUniversity of ChicagoChicagoIL 60637United States

Each hepatitis virus—hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the natural clinical and immunologic history of acute and chronic infections has been generated.Basic discoveries about host immunologic responses to acute and chronic viral infections,combined with virologic data,has led to vaccines to prevent hepatitis A,B,and E and highly efficacious antivirals for hepatitis B and C.These therapeutic breakthroughs are transforming the fields of hepatology,transplant medicine in general,and public and global health.Most notably,there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade.While attainable,there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local,national,and international scales.Herein,we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.

关键词： viral hepatitis hepatitis A hepatitis B hepatitis C hepatitis D hepatitis E hepatitis G

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viral hepatitis: A global burden needs future directions for the management

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World Journal of Gastroenterology 2022年第16期28卷 1718-1721页

作者： Henu Kumar Verma Kiran Prasad Pramod Kumar Bhaskar Lvks Department of Immunopathology Institute of Lungs Biology and DiseaseComprehensive Pneumology CenterHelmholtz ZentrumMunich 80331BayrenGermany Department of Zoology Guru Ghasidas VishwavidyalayaBilaspur 495001ChhattisgarhIndia Department of Drug Delivery Institute of Lung Biology and DiseaseHelmholtz Research CenterMunich 80331BayrenGermany

viral hepatitis is an acute or chronic liver disease due to the infection from hepatitis A,B,C,D and E viruses.It can cause severe liver damage such as cirrhosis,liver failure and liver cancer.To avoid such fatal complications,hepatitis patients must be diagnosed,pathologized and treated as soon as possible.Furthermore,these hepatitis viruses infect through different routes,resulting in distinct disease pathologies,severity and even the need for specific treatment strategies to combat the infection.

关键词： viral hepatitis Vaccination Chronic Acute viral therapy

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Eliminating viral hepatitis in children after liver transplants:How to reach the goal by 2030

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World Journal of Gastroenterology 2022年第3期28卷 290-309页

作者： Palittiya Sintusek Kessarin Thanapirom Piyawat Komolmit Yong Poovorawan The Thai Pediatric Gastroenterology Hepatology and Immunology(TPGHAI)Research UnitChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology Department of PediatricsFaculty of MedicineKing Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology Department of MedicineLiver Fibrosis and Cirrhosis Research UnitFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10330Thailand Center of Excellence in Liver Diseases King Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand Center of Excellence in Clinical Virology Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand

viral hepatitis infections are a great burden in children who have received liver transplant.Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term.Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection,rendering the condition difficult to manage.Prevention strategies using vaccinations are agreeable to patients,safe,cost-effective and practical.Hence,strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant.Although a vaccine has been developed to prevent hepatitis C and E viruses,its use is not licensed worldwide.Consequently,eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy.Good hygiene and sanitation are also important to prevent hepatitis A and E infections.Donor blood products and liver grafts should be screened for hepatitis B,C and E in children who are undergoing liver transplantation.Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E.Moreover,novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.

关键词： viral hepatitis Children Adolescent Liver transplantation Infection Elimination

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High prevalence of chronic viral hepatitis B and C in Minnesota Somalis contributes to rising hepatocellular carcinoma incidence

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World Journal of Gastroenterology 2022年第35期28卷 5217-5229页

作者： Essa A Mohamed Nasra H Giama Abubaker O Abdalla Hassan M Shaleh Abdul M Oseini Hamdi A Ali Fowsiyo Ahmed Wesam Taha Hager Ahmed Mohammed Jessica Cvinar Ibrahim A Waaeys Hawa Ali Loretta K Allotey Abdiwahab O Ali Safra A Mohamed William S Harmsen Eimad M Ahmmad Numra A Bajwa Mohamud D Afgarshe Abdirashid M Shire Joyce E Balls-Berry Lewis R Roberts Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55905United States Center for Clinical and Translational Science Mayo ClinicRochesterMN 55905United States School of Nursing University of MinnesotaMinneapolisMN 55455United States Division of Digestive Diseases Emory School of MedicineAtlantaGA 30322United States Department of Laboratory Medicine and Pathology Mayo ClinicRochesterMN 55905United States Department of Internal Medicine NewYork-Presbyterian QueensFlushingNY 11355United States Department of Pediatrics University of Nevada Las VegasLas VegasNV 89154United States Department of Quantitative Health Sciences Mayo ClinicRochesterMN 55905United States Department of Medicine Gargar Urgent Care and ClinicMinneapolisMN 55406United States Office of the Director Shire ScientificMinneapolisMN 55405United States Department of Neurology Washington University School of Medicine in St LouisSt LouisMO 63130United States Knight Alzheimer Disease Research Center Washington University School of MedicineSt LouisMO 63130United States

BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.

关键词： viral hepatitis Liver disease Community engagement African Immigrant health

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viral hepatitis update: Progress and perspectives

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World Journal of Gastroenterology 2021年第26期27卷 4018-4044页

作者： María B Pisano Cecilia G Giadans Diego M Flichman Viviana E Ré María V Preciado Pamela Valva Virology Institute CONICETSchool of Medical SciencesNational University of CórdobaCordoba X5016Argentina Multidisciplinary Institute for Investigation in Pediatric Pathologies(IMIPP)CONICET-GCBA Laboratory of Molecular BiologyPathology DivisionRicardo Gutiérrez Children’s HospitalCABA C1425Buenos AiresArgentina Institute of Biomedical Investigations in Retrovirus and AIDS(INBIRS) School of MedicineUniversity of Buenos AiresCONICETCABA C1121ABGBuenos AiresArgentina

viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.

关键词： viral hepatitis hepatitis A virus hepatitis B virus hepatitis C virus hepatitis D virus hepatitis E virus

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viral hepatitis:Milestones,unresolved issues,and future goals

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World Journal of Gastroenterology 2021年第28期27卷 4603-4638页

作者： Pietro Torre Andrea Aglitti Mario Masarone Marcello Persico Internal Medicine and Hepatology Unit Department of MedicineSurgery and Dentistry“Scuola Medica Salernitana”University of SalernoSalerno 84081Italy

In this review the current overall knowledge on hepatitis A,B,C,D,and E will be discussed.These diseases are all characterized by liver inflammation but have significant differences in distribution,transmission routes,and outcomes.hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood,and in addition to acute infection,they can cause chronic hepatitis,which in turn can evolve into cirrhosis.It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide.hepatitis D virus,which is also transmitted by blood,only affects hepatitis B virus infected people,and this dual infection results in worse liver-related outcomes.hepatitis A and E spread via the fecal-oral route,which corresponds mainly to the ingestion of food or water contaminated with infected stools.However,in developed countries hepatitis E is predominantly a zoonosis.Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis,a serious,rarely fatal illness is also possible,and in immunosuppressed patients,such as organ transplant recipients,hepatitis E virus infection can become chronic.The description of goals achieved,unresolved issues,and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.

关键词： viral hepatitis hepatitis A hepatitis B hepatitis C hepatitis D hepatitis E

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viral hepatitis:A narrative review of hepatitis A–E

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World Journal of Meta-Analysis 2022年第3期10卷 99-121页

作者： Zunirah Ahmed Akshay Shetty David W Victor Sudha Kodali Division of Gastroenterology and Hepatology Underwood Center for Digestive DisordersHouston Methodist HospitalHoustonTX 77030United States Department of Gastroenterology and Hepatology University of CaliforniaLos AngelesCA 90095United States Department of Hepatology J C Walter Jr Transplant CenterSherrie and Alan Conover Center for Liver Disease and TransplantationWeill Cornell Medical CollegeHoustonTX 77030United States

viral hepatitis continues to be a major health concern leading to hepatic decompensation ranging from acute hepatitis to cirrhosis and hepatocellular carcinoma.The hepatic and extrahepatic manifestations are not only debilitating but also associated with a significant economic burden.Over the last two decades,the field of virology has made significant breakthroughs leading to a better understanding of the pathophysiology of viral hepatitis,which in turn has led to new therapeutic options.The advent of direct-acting antiviral agents changed the landscape of hepatitis C virus(HCV)therapy,and new drugs are in the pipeline for chronic hepatitis B virus(HBV)treatment.There has also been a significant emphasis on screening and surveillance programs,widespread availability of vaccines,and linkage of care.Despite these efforts,significant gaps persist in care,and there is a pressing need for increased collaboration and teamwork across the globe to achieve a reduction of disease burden and elimination of HBV and HCV.

关键词： viral hepatitis Recent advances Novel therapies Barriers to cure Future direction

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Type 1 interferon-induced IL-7 maintains CD8＋ T-cell responses and homeostasis by suppressing PD-1 expression in viral hepatitis

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Cellular & Molecular Immunology 2015年第2期12卷 213-221页

作者： Lifei Hou Zuliang Jie Yuejin Liang Mayura Desai Lynn Soong Jiaren Sun Department of Microbiology and Immunology Institute for Human Infections and Immunity University of Texas Medical Branch Galveston TX USA and Department of Pathology Institute for Human Infections and Immunity University of Texas Medical Branch Galveston TX USA These authors contributed equally to this work

Type 1 interferon （IFN-I） promotes antigen-presenting cell maturation and was recently shown to induce hepatic IL-7 production during infection. Herein, we further explored the underlying mechanisms used by I FN-I to orchestrate antiviral immune responses in the liver. Acute viral hepatitis was induced by i.v. injection of adenovirus （Ad） in IFN-a receptor knockout （IFNAR-/-） and control mice. To disrupt signaling, monoclonal antibodies （mAbs） against IL-7 receptor alpha （IL-7Re） or PD-L1 were i.p. injected. We found that CD8＋ T cells in IFNAR-/- mice were less effective than those in control mice. The reduced T-cell function was accompanied by increased levels of PD-1 expression, apoptosis and decreased IFN-7 production. The lack of IFN-I signaling also impaired the expression of accessory molecules in both intrahepatic dendritic cell （DCs） and hepatocytes. PD-L1 was comparably and highly expressed on hepatocytes in both IFNAR-/- and control mice. Injection of PD-Ll-specific mAb in IFNAR-/- mice reversed the compromised immune responses in the liver. Further investigation showed that hepatic IL-7 elevation was less pronounced in IFNAR-/- mice compared to the controls. A treatment with recombinant IL-7 suppressed PD-1 expression on CD8＋ T cells in vitro. Accordingly, blocking IL-7R signaling in vivo resulted in increased PD-1 expression on CD8＋ T cells in Ad-infected mice. Collectively, the results suggest that IFN-I-induced hepatic IL-7 production maintains antiviral CD8＋ T-cell responses and homeostasis by suppressing PD-1 expression in acute viral hepatitis.

关键词： CD8＋ T cell interleukin-7 PD-1 type 1 interferon viral hepatitis

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