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Higher cardiovascular risk scores and liver fibrosis risk estimated by biomarkers in patients with metabolic-dysfunction-associated fatty Liver disease

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World Journal of Hepatology 2022年第8期14卷 1633-1642页

作者： Giovanni Alejandro Salgado Alvarez Samanta Mayanin Pinto Galvez Uriel Garcia Mora Ana Delfina Cano Contreras Cristina Durán Rosas Bryan Adrián Priego-Parra Arturo Triana Romero Mercedes Amieva Balmori Federico Roesch Dietlen Sophia Eugenia Martinez Vazquez Ines Osvely Mendez Guerrero Luis Alberto Chi-Cervera Raúl Bernal Reyes Leonardo Alberto Martinez Roriguez Maria Eugenia Icaza Chavez Jose Maria Remes Troche Instituto de Investigaciones Médico-biologicas Universidad VeracruzanaVeracruz 91700VeracruzMexico Department of Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMéxico 14080MéxicoMexico Clínica de Especialidades Gastrointestinales y Hepáticas Hospital Star MedicaMerida 97133YucatanMexico Department of Gastroenterologia Sociedad Española de BeneficenciaPachuca 42000HidalgoMexico Department of Gastroenterologia Clínica de Rehabilitación Metabólica Digestiva y HepáticaMexico 14080MexicoMexico Department of Gastroenterologia Hospital Star Médica de MéridaMerida 97133YucatanMexico

BACKGROUND The definition of metabolic-dysfunction-associated fatty Liver disease(MAFLD)allows identification of metabolically complicated patients.Fibrosis risk scores are related to cardiovascular risk(CVR)scores and could be useful for the identification of patients at risk of systemic complications.AIM To evaluate the relationship between MAFLD and CVR using the Framingham risk score in a group of Mexican patients.METHODS Cross-sectional,observational and descriptive study carried out in a cohort of 585 volunteers in the state of Veracruz with MAFLD criteria.The risk of liver fibrosis was calculated with aspartate aminotransferase-to-platelet ratio index,nonalcoholic fatty Liver disease score and fibrosis-4,as well as with transient hepatic elastography with Fibroscan~?.The CVR was determined by the Framingham system.RESULTS One hundred and twenty-five participants(21.4%)with MAFLD criteria were evaluated,average age 54.4 years,63.2%were women,body mass index 32.3 kg/m~2.The Framingham CVR was high in 43 patients(33.9%).Transient elastography was performed in 55.2%of volunteers;39.1%with high CVR and predominance in advanced fibrosis(F3–F4).The logistic regression analysis showed that liver fibrosis,diabetes and hypertension independently increased CVR.CONCLUSION One of every three patients with MAFLD had a high CVR,and in those with high fibrosis risk,the CVR risk was even greater.

关键词： Fatty liver Cardiovascular risk Hepatic steatosis Fibrosis Liver disease

COVID-19 and Liver disease: Are we missing something?

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World Journal of Hepatology 2022年第2期14卷 479-481页

作者： Tarana Gupta Department of Medicine Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical SciencesRohtak 124001HaryanaIndia

Since the coronavirus disease 2019(COVID-19)has hit the world as a pandemic,researchers all over the world have worked on its diagnostics,prognosticating factors,etc.The present study showed liver enzymes,especially aspartate aminotransferase(AST)levels,to be high in non-survivors with raised AST/alanine aminotransferase ratio.Considering the non-specific nature of AST with its presence in organs other than liver such as muscle,heart,kidney and brain makes it difficult to interpret.Even pre-existing metabolic syndrome and non-alcoholic fatty Liver disease are confounding factors for deranged liver functions detected during COVID-19 disease.Therefore,the results of the study should be taken with caution.

关键词： COVID-19 Liver disease Transaminases Non-alcoholic fatty Liver disease Hepatocytes Cholangiocytes

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with Liver disease receiving broad-spectrum antibiotic therapy

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World Journal of Hepatology 2023年第11期15卷 1226-1236页

作者： Jessica A Ward Jason Yerke Mollie Lumpkin Aanchal Kapoor Christina C Lindenmeyer Stephanie Bass Department of Pharmacy Cleveland ClinicClevelandOH 44195United States Department of Critical Care Medicine Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Hepatologyand NutritionCleveland ClinicClevelandOH 44195United States

BACKGROUND Rifaximin is frequently administered to critically ill patients with Liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy.Due to overlapping spectrums of activity,combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary.A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with Liver disease.It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.AIM To determine the clinical,safety,and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.METHODS This was a single-center,quasi-experimental,pre-post study based on a pilot pharmacist-driven protocol.Patients in the protocol group were prospectively identified via the medical intensive care unit(ICU)(MICU)protocol to have rifaximin withheld during broad-spectrum antibiotic treatment.These were compared to a historical cohort who received combination therapy with broadspectrum antibiotics and rifaximin.All data were collected retrospectively.The primary outcome was days alive and free of delirium and coma(DAFD)to 14 d.Safety outcomes included MICU length of stay,48-h change in vasopressor dose,and ICU mortality.Secondary outcomes characterized rifaximin cost savings and protocol adherence.Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.RESULTS Each group included 32 patients.The median number of delirium-and coma-free days was similar in the control and protocol groups[3 interquartile range(IQR 0,8)vs 2(IQR 0,9.5),P=0.93].In multivariable analysis,group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d.The protocol resulted in a reduced median duration of rifaximin

关键词： Rifaximin Hepatic encephalopathy Critical illness Antibiotics Liver disease Cirrhosis

Interrelationship between physical activity and depression in nonalcoholic fatty Liver disease

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World Journal of Hepatology 2022年第3期14卷 612-622页

作者： Ali A Weinstein Leyla De Avila Saisruthi Kannan James M Paik Pegah Golabi Lynn H Gerber Zobair M Younossi Betty and Guy Beatty Center for Integrated Research Inova Health SystemFalls ChurchVA 22042United States Global and Community Health George Mason UniversityFairfaxVA 22030United States Center for Liver disease Department of MedicineInova Fairfax Medical CampusFalls ChurchVA 22042United States Inova Medicine Inova Health SystemFalls ChurchVA 22042United States

BACKGROUND Nonalcoholic fatty Liver disease(NAFLD)is associated with a sedentary lifestyle and depressive symptoms.It is also well established that physical inactivity and depressive symptoms are related.However,an investigation of the interaction between all of these factors in NAFLD has not been previously conducted.AIM To investigate the interrelationship between physical inactivity and depressive symptoms in individuals with NAFLD.METHODS Data from the Rancho Bernardo Study of Healthy Aging were utilized.589 individuals were included in the analyses(43.1%male;95.8%non-Hispanic white;aged 60.0±7.0 years).NAFLD was defined by using the hepatic steatosis index,depression using the Beck Depression Inventory,and physical activity by selfreport of number of times per week of strenuous activity.Multivariable generalized linear regression models with Gamma distribution were performed to investigate the proposed relationship.RESULTS About 40%of the sample had evidence of NAFLD,9.3%had evidence of depression,and 29%were physically inactive.Individuals with NAFLD and depression were more likely to be physically inactive(60.7%)compared to individuals with neither NAFLD nor depression(22.9%),individuals with depression without NAFLD(37.0%),and individuals with NAFLD without depression(33.3%).After accounting for various comorbidities(i.e.,age,sex,diabetes,hypertension,obesity),individuals with NAFLD and higher levels of physical activity were at a decreased odds of having depressive symptoms[16.1%reduction(95%confidence interval:-25.6 to-5.4%),P=0.004],which was not observed in those without NAFLD.CONCLUSION Individuals with NAFLD have high levels of physical inactivity,particularly those with depressive symptoms.Because this group is at high risk for poor outcomes,practitioners should screen for the coexistence of depressive symptoms and NAFLD.This group should receive appropriate interventions aimed at increasing both participation and levels of intensity of physical activity.

关键词： Liver disease Outcomes research Psychiatric disorders Exercise

Living with Liver disease in the era of COVID-19-the impact of the epidemic and the threat to high-risk populations

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World Journal of Clinical Cases 2022年第36期10卷 13167-13178页

作者： Pranav Barve Prithi Choday Anphong Nguyen Tri Ly Isha Samreen Sukhwinder Jhooty Chukwuemeka A Umeh Sumanta Chaudhuri Department of Internal Medicine Hemet Global Medical CenterMenifeeCA 92585United States Department of Internal Medicine Hemet Global Medical CenterHemetCA 92543United States College of Medicine American University of AntiguaManipal Education America’sNew YorkNY 10005United States

The cardinal symptoms of severe acute respiratory syndrome coronavirus 2 infection as the pandemic began in 2020 were cough,fever,and dyspnea,thus characterizing the virus as a predominantly pulmonary disease.While it is apparent that many patients presenting acutely to the hospital with coronavirus disease 2019(COVID-19)infection have complaints of respiratory symptoms,other vital organs and systems are also being affected.In fact,almost half of COVID-19 hospitalized patients were found to have evidence of some degree of liver injury.Incidence and severity of liver injury in patients with underlying Liver disease were even greater.According to the Centers of disease Control and Prevention,from August 1,2020 to May 31,2022 there have been a total of 4745738 COVID-19 hospital admissions.Considering the gravity of the COVID-19 pandemic and the incidence of liver injury in COVID-19 patients,it is imperative that we as clinicians understand the effects of the virus on the liver and conversely,the effect of underlying hepatobiliary conditions on the severity of the viral course itself.In this article,we review the spectrum of novel studies regarding COVID-19 induced liver injury,compiling data on the effects of the virus in various age and high-risk groups,especially those with preexisting Liver disease,in order to obtain a comprehensive understanding of this disease process.We also provide an update of the impact of the new Omicron variant and the changing nature of COVID-19 pathogenesis.

关键词： liver injury Hepatobiliary injury COVID-19 SARS-CoV-2 High-risk populations Liver disease

COVID-19 emergency: Changes in quality of life perception in patients with chronic Liver disease-An Italian single-centre study

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World Journal of Hepatology 2022年第1期14卷 274-286页

作者： Alessandra Zannella Silvia Fanella Massimo Marignani Paola Begini Department of Gastroenterology Sant’Andrea HospitalRome 00189Italy

BACKGROUND In December 2019,the coronavirus disease-2019(COVID-19)emerged and rapidly spread worldwide,becoming a global health threat and having a tremendous impact on the quality of life(QOL)of individuals.AIM To evaluate the awareness of patients with chronic Liver disease(CLD)regarding the COVID-19 emergency and how it impacted on their QOL.METHODS Patients with an established diagnosis of CLD(cirrhosis,autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing cholangitis)who had been evaluated at our Outpatient Liver disease Clinic during the 6-mo period preceding the start of Italian lockdown(March 8,2020)were enrolled.Participants were asked to complete a two-part questionnaire,administered by telephone according to governmental restrictions:The first section assessed patients’basic knowledge regarding COVID-19,and the second evaluated the impact of the COVID-19 emergency on their QOL.We used the Italian version of the CLD questionnaire(CLDQ-I).With the aim of evaluating possible changes in the QOL items addressed,the questionnaire was administered to patients at the time of telephone contact with the specific request to recall their QOL perceptions during two different time points.In detail,patients were asked to recall these perceptions first during time 0(t0),a period comprising the 2 wk preceding the date of ministerial lockdown decree(from February 23 to March 7,2020);then,in the course of the same phone call,they were asked to recall the same items as experienced throughout time 1(t1),the second predetermined time frame encompassing the 2 wk(from April 6 to April 19)preceding our telephone contact and questionnaire administration.All data are expressed as number(%),and continuous variables are reported as the median(interquartile range).The data were compared using the Wilcoxon paired non-parametric test.RESULTS A total of 111 patients were enrolled,of whom 81 completed the questionnaire.Forty-nine had liver cirrhosis,and all of them had compensated disease;32 patients had autoimmune li

关键词： COVID-19 Liver disease Quality of life liver cirrhosis Chronic Liver disease questionnaire

Anti-inflammatory pathways and alcoholic Liver disease: Role of an adiponectin/interleukin-10/heme oxygenase-1 pathway

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World Journal of Gastroenterology 2010年第11期16卷 1330-1336页

作者： Palash Mandal Michele T Pritchard Laura E Nagy Department of Pathobiology and Gastroenterology Cleveland ClinicLerner Research Institute/NE-40

The development of alcoholic Liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. Enhanced inflammation in the liver during ethanol exposure is an important contributor to injury. Kupffer cells, the resident macrophages in liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharide via Toll-like receptor 4. This sensitization enhances production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species, that contribute to hepatocyte dysfunction, necrosis, apoptosis, and fibrosis. Impaired resolution of the inflammatory process probably also contributes to ALD. The resolution of inflammation is an active, highly coordinated response that can potentially be manipulated via therapeutic interventions to treat chronic inflammatory diseases. Recent studies have identif ied an adiponectin/interleukin-10/heme oxygenase-1 (HO-1) pathway that is profoundly effective in dampening the enhanced activation of innate immune responses in primary cultures of Kupffer cells, as well as in an in vivo mouse model of chronic ethanol feeding. Importantly, induction of HO-1 also reduces ethanol-induced hepatocellular apoptosis in this in vivo model. Based on these data, we hypothesize that the development of therapeutic agents to regulate HO-1 and its downstream targets could be useful in enhancing the resolution of inflammation during ALD and preventing progression of early stages of liver injury.

关键词： Liver disease Alcohol Macrophages Hemeoxygenase-1 Inflammation

Rodent models and metabolomics in non-alcoholic fatty Liver disease: What can we learn?

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World Journal of Hepatology 2022年第2期14卷 304-318页

作者： Maria Martin-Grau Vannina G Marrachelli Daniel Monleon Department of Pathology University of ValenciaValencia 46010Spain Department of Physiology University of ValenciaValencia 46010Spain Health Research Institute INCLIVA Valencia 46010Spain CIBER de Fragilidad y Envejecimiento Saludable(CIBERfes) Madrid 28029Spain

Non-alcoholic fatty Liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to fibrosis.Several molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate proposal.Previous studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary widely.The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge.Among certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible method.Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease.Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding.In this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.

关键词： Non-alcoholic fatty Liver disease Liver disease Rodent models Metabolic profiling Metabolomics Biomarkers

Epstein-Barr virus:Silent companion or causative agent of chronic Liver disease?

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World Journal of Gastroenterology 2010年第33期16卷 4130-4134页

作者： Mihaela Petrova Victor Kamburov Clinic of Gastroenterology Ministry of Interior Gastroenterology Division First Multiprofile Hospital for Active Treatment

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic Liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.

关键词： Epstein-Barr virus Chronic hepatitis Liver disease Chronic active Epstein-Barr virus Post-transplant lymphoproliferative disorder Infectious mononucleosis