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Hepatoma Research 2022年第1期8卷 445-457页

作者： Qian Wan Chimaobi Anugwom Hailemichael desalegn jose d.debes department of Medicine Division of Infectious Disease and International Medicine&Division of GastroenterologyHepatology and NutritionUniversity of MinnesotaMinneapolisMN 55455USA Health Partners digestive Care Saint PaulMN 55130USA Millennium Hospital Addis Ababa 1000Ethiopia Arusha Lutheran Medical Centre ArushaTanzania

Human immunodeficiency virus(HIV)and hepatitis-B virus(HBV)infections are weighty public health challenges,especially in the African *** direct carcinogenic effect of HBV means that it remains a potent cause of early-onset hepatocellular carcinoma(HCC)in Sub-Saharan Africa(SSA),where it causes significant morbidity and *** presence of HIV infection in HBV-infected patients poses a complicating factor,as coinfection has been shown to hasten the progression of liver disease to cirrhosis and HCC,and often resulting in early-age hepatocarcinogenesis with consequent late diagnosis and lower *** this review,we discuss this unique conundrum,the epidemiology of HIV-HBV coinfection in SSA,its effect on liver disease and development of HCC,as well as practices and barriers to HCC surveillance in this distinct *** propose a way forward to curb this considerable health burden focusing on reduction of disease stigma,the need for easy-to-measure biomarkers,and implementation of large prospective studies in this population.

关键词： HBV HIV coinfection hepatocellular carcinoma surveillance Sub-Saharan Africa

Mechanisms of Accelerated Liver Fibrosis Progression during HIV Infection

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Journal of Clinical and Translational Hepatology 2016年第4期4卷 328-335页

作者： jose d.debes Paul R.Bohjanen Andre Boonstra department of Medicine Division of Infectious Disease and International Medicine University of MinnesotaMinneapolis MN USA department of Gastroenterology and Hepatology Erasmus MC Rotterdam The Netherlands

With the introduction of antiretroviral therapy (ART),a dramatic reduction in HIV-related morbidity and mortality has been ***,it is now becoming increasingly clear that liver-related complications,particularly rapid fibrosis development from ART as well as from the chronic HIV infection itself,are of serious concern to HIV *** pathophysiology of liver fibrosis in patients with HIV is a multifactorial process whereby persistent viral replication,and bacterial translocation lead to chronic immune activation and inflammation,which ART is unable to fully suppress,promoting production of fibrinogenic mediators and *** addition,mitochondrial toxicity,triggered by both ART and HIV,contributes to intrahepatic damage,which is even more severe in patients co-infected with viral *** recent years,new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV has been obtained,and these are detailed and discussed in this review.

关键词： HIV Liver fibrosis Mitochondrial toxicity Bacterial translocation

Understanding immune perspectives and options for the use of checkpoint immunotherapy in HCC post liver transplant

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Hepatoma Research 2022年第1期8卷 65-77页

作者： Chimaobi M.Anugwom Thomas M.Leventhal jose d.debes HealthPartners digestive Care Saint PaulMinnesotaMN 55130USA department of Medicine Division of GastroenterologyHepatology and Nutrition and Division of Infectious Disease and International MedicineUniversity of MinnesotaMinneapolisMN 55455USA department of Gastroenterology and Hepatology Erasmus Medical CenterPostbus 2040The Netherlands

Treatment modalities for hepatocellular carcinoma(HCC)vary from surgical techniques and interventional radiologic strategies to systemic *** the latter,the use of immune checkpoint inhibitors(ICIs)has gained popularity due to successful trials showing increased *** patients who have undergone liver transplantation,recurrence of HCC poses a significant *** is indeed considerable debate on the efficacy and safety of ICI use in liver transplant recipients due to competing immune interests in maintaining a healthy graft and combating the *** reports and case series have highlighted a role for the type of immune therapy,timing of therapy,tissue expression of Pd-1 and modulation of immunosuppression,in the understanding of the efficacy and risks of ICIs for HCC in liver *** this article,we appraise the available literature on the usage of ICIs for HCC in liver transplant recipients and provide perspectives on immune concerns as well as potential recommendations to consider during the management of such complex cases.

关键词： Hepatocellular carcinoma liver transplant checkpoint inhibitors

Unveiling the brain’s symphony:exploring the necessity and sufficiency of neural networks in behavior control

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Neural Regeneration Research 2025年第1期20卷 186-187页

作者： Fernando jose Bustos Instituto de Ciencias Biomedicas Facultad de Medicina y Facultad de Ciencias de la VidaUniversidad Andres BelloSantiagoChile Millennium Nucleus of Neuroepigenetics and Plasticity(EpiNeuro) SantiagoChile

Since the pioneering work by Broca and Wernicke in the 19th century,who examined individuals with brain lesions to associate them with specific behaviors,it was evident that behaviors are complex and cannot be fully attributable to specific brain areas ***,they involve connectivity among brain areas,whether close or *** that time,this approach was considered the optimal way to dissect brain circuitry and *** pioneering efforts opened the field to explore the necessity or sufficiency of brain areas in controlling behavior and hence dissecting brain ***,the connectivity of the brain and the mechanisms through which various brain regions regulate specific behaviors,either individually or collaboratively,remain largely *** animal models,researchers have endeavored to unravel the necessity or sufficiency of specific brain areas in influencing behavior;however,no clear associations have been firmly established.

关键词： behavior connectivity neural

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

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World Journal of Gastroenterology 2024年第19期30卷 2488-2495页

作者： Angelo Zambam de Mattos Isadora Zanotelli Bombassaro Arndt Vogel jose d.debes department of Internal Medicine Universidade Federal de Ciências da Saúde de Porto AlegreRSPorto Alegre 90020090Brazil Graduate Program in Medicine:Hepatology Federal University of Health Sciences of Porto AlegreRSPorto Alegre 90050-170Brazil division of Gastroenterology Hepatology University of TorontoHannover M5R 0A3Canada department of Medicine University of MinnesotaMinneapolisMN 55455United States

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated *** particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver *** makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the *** underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining ***,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

关键词： Hepatocellular carcinoma Etiology Epidemiology Surveillance Therapy

Immune aspects of hepatocellular carcinoma:From immune markers for early detection to immunotherapy

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 1132-1143页

作者： Ângelo Z Mattos jose d.debes Andre Boonstra Arndt Vogel Angelo A Mattos Graduate Program in Medicine:Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Brazil Gastroenterology and Hepatology Unit Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Brazil department of Medicine Division of Gastroenterology and Infectious DiseasesUniversity of MinnesotaMinneapolisMN 55812United States department of Gastroenterology and Hepatology Erasmus Medical CenterRotterdam NL-3015The Netherlands department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolHannover 30625Germany

Hepatocellular carcinoma(HCC)is one of the most prevalent cancers and one of the main causes of cancer-related deaths *** HCCs develop in an inflammatory microenvironment,and mounting evidence emphasizes the importance of immune aspects in *** normal physiology,both innate and adaptive immune responses are responsible for eliminating malignantly transformed cells,thus preventing the development of liver ***,in the setting of impaired natural killer cells and exhaustion of T cells,HCC can *** immunogenic features of HCC have relevant clinical *** is a large number of immune markers currently being studied for the early detection of liver cancer,which would be critical in order to improve surveillance ***,novel immunotherapies have recently been proven to be effective,and the combination of atezolizumab and bevacizumab is currently the most effective treatment for advanced *** is expected that in the near future different subgroups of patients will benefit from specific *** better we understand the immune aspects of HCC,the greater the benefit to patients through surveillance aiming for early detection of liver cancer,which allows for curative treatments,and,in cases of advanced disease,through the selection of the best possible therapy for each individual.

关键词： Hepatocellular carcinoma Immunology Hepatocarcinogenesis Surveillance Biomarker Immunotherapy

Non-alcoholic fatty liver disease-related hepatocellular carcinoma:Is there a role for immunotherapy?

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World Journal of Gastroenterology 2022年第28期28卷 3595-3607页

作者： Ângelo Z Mattos jose d.debes Arndt Vogel Marco Arrese Xavier Revelo Tales Henrique S Pase Muriel Manica Angelo A Mattos Graduate Program in Medicine:Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Brazil Gastroenterology and Hepatology Unit Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90050-170Brazil department of Medicine University of MinnesotaMinneapolisMN 55455United States department of Gastroenterology and Hepatology Erasmus Medical CenterRotterdam 999025Netherlands department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolHannover 30625Germany department of Gastroenterology School of Medicine and Center for Aging and RegenerationFaculty of Biological SciencesPontificia Universidad Católica de ChileSantiago 3580000Chile department of Integrative Biology and Physiology University of MinnesotaMinneapolisMN 55455United States Internal Medicine Unit Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Brazil

Hepatocellular carcinoma(HCC)is among the most common cancers and it is a major cause of cancer-related ***-alcoholic fatty liver disease(NAFLd)affects approximately one fourth of individuals worldwide and it is becoming one of the most important causes of *** pathogenic mechanisms leading to NAFLd-related HCC are complex and not completely ***,metabolic,fibrogenic,oncogenic,inflammatory and immunological pathways seem to be ***-line therapy of advanced HCC has recently undergone major changes,since the combination of atezolizumab and bevacizumab was proven to increase survival when compared to *** immune-oncology drugs are also demonstrating promising results in patients with advanced HCC when compared to traditional systemic ***,initial studies raised concerns that the advantages of immunotherapy might depend on the underlying liver disease,which seems to be particularly important in NAFLd-related HCC,as these tumors might not benefit from *** article will review the mechanisms of NAFLd-related hepatocarcinogenesis,with an emphasis on its immune aspects,the efficacy of traditional systemic therapy for advanced NAFLd-related HCC,and the most recent data on the role of immunotherapy for this specific group of patients,showing that the management of this condition should be individualized and that a general recommendation cannot be made at this time.

关键词： Non-alcoholic fatty liver disease Hepatocellular carcinoma Hepatocarcinogenesis Immunology Immunotherapy Tyrosine kinase inhibitors

Current impact of viral hepatitis on liver cancer development: The challenge remains

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World Journal of Gastroenterology 2021年第24期27卷 3556-3567页

作者： Ângelo Zambam de Mattos jose d.debes Andre Boonstra Ju-dong Yang domingo C Balderramo Giovana d P Sartori Angelo Alves de Mattos department of Gastroenterology and Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90020-090Brazil Gastroenterology and Hepatology Unit Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90050-170Brazil department of Medicine Division of Gastroenterology and Infectious DiseasesUniversity of MinnesotaMinneapolisMN 55455United States department of Gastroenterology and Hepatology Erasmus Medical CenterRotterdam NL-3015Netherlands division of digestive and Liver diseases Department of MedicineCedars-Sinai Medical CenterLos AngelesCA 90048United States department of Gastroenterology Hospital Privado Universitario de CórdobaCórdoba 5016Argentina department of Medicine Instituto Universitario de Ciencias Biomédicas de CórdobaCórdoba 5016Argentina department of Internal Medicine Hospital Nossa Senhora da ConceiçãoPorto Alegre 91350-200Brazil

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma(HCC)worldwide,and this association is likely to remain during the next ***,viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life *** order to reduce such a burden,some major challenges must be *** vaccination against hepatitis B virus,especially in the neonatal period,is probably the most relevant primary preventive measure against the development of ***,considering the large adult population already infected with hepatitis B and C viruses,it is also imperative to identify these individuals to ensure their access to *** hepatitis B and C currently have highly effective therapies,which are able to diminish the risk of development of liver ***,it is essential for individuals at high-risk of HCC to be included in surveillance programs,so that tumors are detected at an early *** with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance *** hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis,other high-risk groups of patients with hepatitis B are also candidates for *** effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

关键词： Hepatitis B virus Hepatitis C virus Hepatocellular carcinoma Epidemiology Vaccination Surveillance

Hepatocellular carcinoma in nonalcoholic fatty liver disease:A growing challenge

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World Journal of Hepatology 2021年第9期13卷 1107-1121页

作者： Angelo Z Mattos jose d.debes Renu dhanasekaran Jihane N Benhammou Marco Arrese Andre Luiz V Patricio Amanda C Zilio Angelo A Mattos Graduate Program in Medicine:Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90020-090Rio Grande do SulBrazil Gastroenterology and Hepatology Unit Irmandade Santa Casa de Misericordia de Porto AlegrePorto Alegre 90020-090Rio Grande do SulBrazil department of Medicine Division of Infectious Diseases and of GastroenterologyUniversity of MinnesotaMinneapolisMN 55455United States department of Gastroenterology and Hepatology Erasmus Medical CenterRotterdam 3015 CNSouth HollandNetherlands division of Gastroenterology and Hepatology Stanford UniversityStanfordCA 94305United States The Vatche and Tamar Manoukian division of digestive diseases University of CaliforniaLos AngelesCA 90095United States department of Gastroenterology Pontificia Universidad Catolica de ChileSantiago 3580000Chile

Nonalcoholic fatty liver disease(NAFLd)is the most common cause of liver disease worldwide,and its prevalence increases *** it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis,it is not surprising that the incidence of NAFLd-related hepatocellular carcinoma would also *** of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver,and they help explain why liver cancer develops even in patients without *** and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this ***,it is consensual that patients with NAFLd-related cirrhosis should be surveilled with ultrasonography every 6 mo(with or without alpha-fetoprotein),but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver ***,the performance of the methods of surveillance are lower in NAFLd than they are in other liver ***,it is not clear which subgroups of patients without cirrhosis should undergo *** the mechanisms of hepatocarcinogenesis in NAFLd could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these *** improving surveillance,tumors could be detected in earlier stages,amenable to curative treatments.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Hepatocellular carcinoma Hepatocarcinogenesis Surveillance

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado jose M.Santiago Samuel E.Ocasio Rivera dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge d.Miranda department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma