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World Journal of Gastroenterology 2021年第26期27卷 4004-4017页

作者： Fátima Higuera-de la Tijera Alfredo Servín-Caamaño Luis Servín-Abad department of Gastroenterology and Hepatology Hospital General de MéxicoMexico City 06726Mexico department of Internal Medicine Hospital General de MéxicoMexico City 06726Mexico department of Gastroenterology Saint Cloud HospitalSaint CloudMN 56303United States

Chronic viral hepatitis is a significant health problem throughout the world,which already represents high annual mortality.By 2040,chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria,vitellogenesis-inhibiting hormone,and tuberculosis altogether.In this review,we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups,the goals set by the World Health Organization for the year 2030,and the key points to achieve them,such as timely access to antiviral treatment of direct-acting antiviral,which represents the key to achieving hepatitis C virus elimination.Likewise,we review the strategies to prevent transmission and achieve control of hepatitis B virus.finally,we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.

关键词： Hepatitis C Hepatitis B Vaccination Elimination program Telemedicine Direct antiviral agents

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19

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Liver Research 2021年第1期5卷 21-27页

作者： Fátima Higuera-de la Tijera Alfredo Servín-Caamaño Daniel Reyes-Herrera Argelia flores-López Enrique J.A.Robiou-Vivero felipe Martínez-Rivera Victor Galindo-Hernández Oscar Chapa-Azuela Alfonso Chávez-Morales Victor H.Rosales-Salyano Multidisciplinary Team for the Attention and Care of Patients with COVID-19 Hospital General de México Dr.Eduardo LiceagaMexico CityMexico Gastroenterology and Hepatology department Hospital General de México Dr.Eduardo LiceagaMexico CityMexico Internal Medicine department Hospital General de México Dr.Eduardo LiceagaMexico CityMexico Hepatobiliary and Pancreatology Clinic Surgery DepartmentHospital General de México Dr.Eduardo LiceagaMexico CityMexico Intensive Care Unit Hospital General de México Dr.Eduardo LiceagaMexico CityMexico

Background and aim Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for the current pandemic,can have multi-organ impact.Recent studies show that liver injury could be a manifestation of the disease,and that liver disease could also be related to a worse prognosis.Our aim was to compare the characteristics of patients with severe coronavirus disease 2019(COVID-19)due to SARS-CoV-2 who required intubation versus stable hospitalized patients to identify the early biochemical predictive factors of a severe course of COVID-19 and subsequent requirement for intubation,specifically in Mexican.Methods This was an observational case-control study nested in a cohort study.Complete medical records of patients admitted for confirmed COVID-19 at a tertiary level center in Mexico City were reviewed.Clinical and biochemical data were collected,and the characteristics of patients who required invasive mechanical ventilation(IMV)(cases)were compared with stable hospitalized patients without ventilation(controls).Results We evaluated 166 patients with COVID-19 due to SARS-CoV-2 infection;114(68.7%)were men,the mean age was 50.6±13.3 years,and 27(16.3%)required IMV.The comparative analysis between cases and controls showed(respectively)significantly lower blood oxygen saturation(SpO_(2))(73.5±12.0%vs.83.0±6.8%,Planine aminotransferase(ALT)(128(14–1123)IU/L vs.33(8–453)IU/L,P=0.003),aspartate aminotransferase(AST)(214(17–1247)vs.44(12–498)IU/L,P=0.001),lactic dehydrogenase(LDH)(764.6±401.9 IU/L vs.461.0±185.6 IU/L,P=0.001),and D-dimer(3463(524–34,227)ng/mL vs.829(152–41,923)ng/mL,P=0.003)concentrations.Patients in the cases group were older(58.6±12.7 years vs.49.1±12.8 years,P=0.001).Multivariate analysis showed that important factors at admission predicting the requirement for IMV during hospitalization for COVID-19 were AST≥250 IU/L(odds ratio(OR)=64.8,95%confidence interval(CI)7.5–560.3,Pfi

关键词： Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirus disease 2019(COVID-19) Liver enzymes D-dimer Disease severity Invasive mechanical ventilation(IMV) Multi-organ failure

Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

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World Journal of Gastroenterology 2015年第16期21卷 4975-4985页

作者： Fátima Higuera-de la Tijera Alfredo I Servín-Caamano Aurora E Serralde-Zúniga Javier Cruz-Herrera Eduardo Pérez-Torres Juan M Abdo-francis francisco Salas-Gordillo JoséL Pérez-Hernández Liver Clinic Gastroenterology DepartmentHospital General de MéxicoDr.Eduardo LiceagaMexico City 06720Mexico Internal Medicine department Hospital General de MéxicoDr.Eduardo LiceagaMexico City 06720Mexico fundación Mexicana para la Salud A.C Mexico City 06720Mexico

AIM:To evaluate the impact of metadoxine(MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis(AH).METHODS:This study was an open-label clinical trial,performed at the"Hospital General de México,Dr.Eduardo Liceaga".We randomized 135 patients who met the criteria for severe AH into the following groups:35 patients received prednisone(PDN)40 mg/d,35patients received PDN+MTD 500 mg three times daily,33 patients received pentoxifylline(PTX)400 mg three times daily,and 32 patients received PTX+MTD 500 mg three times daily.The duration of the treatment for all of the groups was 30 d.RESULTS:In the groups treated with the MTD,thesurvival rate was higher at 3 mo(PTX+MTD 59.4%vs PTX 33.3%,P=0.04;PDN+MTD 68.6%vs PDN20%,P=0.0001)and at 6 mo(PTX+MTD 50%vs PTX18.2%,P=0.01;PDN+MTD 48.6%vs PDN 20%,P=0.003)than in the groups not treated with MTD.A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo.The patients receiving MTD maintained greater abstinence than those who did not receive it(74.5%vs 59.4%,P=0.02).CONCLUSION:MTD improves the 3-and 6-mo survival rates in patients with severe AH.Alcohol abstinence is a key factor for survival in these patients.The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.

关键词： Alcoholic hepatitis Metadoxine Survival Alcohol abstinence

Malnutrition negatively impacts the quality of life of patients with cirrhosis: An observational study

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World Journal of Hepatology 2017年第5期9卷 263-269页

作者： Gabriela Rojas-Loureiro Alfredo Servín-Caamano Elizabeth Pérez-Reyes Luis Servín-Abad fátima higuerade la tijera Liver Clinic Gastroenterology DepartmentHospital General de México“Dr.Eduardo Liceaga” Internal Medicine department Hospital General de México“Dr.Eduardo Liceaga” Gastroenterologist at lakeland Regional Medical Center

AIM To verify how malnutrition is related to health-related quality of life(HRQL) impairment in patients with cirrhosis.METHODS Data was retrospectively abstracted from medical records and obtained by direct interview. We included patients with cirrhosis from any etiology, evaluated at the Liver Clinic from Gastroenterology department in a tertiary healthcare center, from June 2014 to June 2016. Child-Pugh score, data about complications, and demographic, clinical and anthropometric characteristics of patients were obtained. Nutritional status was evaluated by the Subjective Global Assessment(SGA). HRQL was evaluated through the Chronic Liver Disease Questionnaire. Patients were requested to assess their global HRQL with the following code: 0 = impairment of HRQL, when it was compared with other healthy subjects; 1 = good HRQL, if it was similar to the quality of life of other healthy subjects. To compare the primary outcome between malnourished and well-nourished groups, the χ~2 test, fisher's exact test or Student's t-test were used, based on the variable type. Associations between predictor variables and deterioration of HRQL were determined by calculating the hazard ratio and 95% confidence interval using Cox proportional hazards regression. RESULTS A total of 127 patients with cirrhosis were included, and the mean age was 54.1 ± 12.3 years-old. According to Child-Pugh scoring, 25(19.7%) were classified as A(compensated), 76(59.8%) as B, and 26(20.5%) as C(B/C = decompensated). According to SGA, 58(45.7%) patients were classified as well-nourished. Sixty-nine patients identified HRQL as good, and 76 patients(59.8%) perceived impairment of their HRQL. Multivariate analysis to determine associations between predictor variables and self-perception of an impairment of HRQL found strong association with malnutrition(P f body pain, dyspnea on exertion with daily activities, decreased appetite, generalized weakness, troub

关键词：营养不良主观全球评价生活的健康相关的质量肝硬化长期的肝疾病问询表

Pathophysiological mechanisms involved in non-alcoholic steatohepatitis and novel potential therapeutic targets

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World Journal of Hepatology 2015年第10期7卷 1297-1301页

作者： fatima higuera-de la tijera Alfredo I Servin-Caamano Liver Clinic Gastroenterology DepartmentMexico’s General Hospital "Dr. Eduardo Liceaga" Diabetes Obesity and Metabolic Syndrome ClinicInternal Medicine DepartmentMexico’s General Hospital "Dr. Eduardo Liceaga"

Non-alcoholic fatty liver disease(NAfLD) is a major health care problem and represents the hepatic expression of the metabolic syndrome. NAfLD is classified as nonalcoholic fatty liver(NAfL) or simple steatosis,and non-alcoholic steatohepatitis(NASH). NASH is characterized by the presence of steatosis and inflammation with or without fibrosis. The physiopathology of NAfL and NASH and their progression to cirrhosis involve several parallel and interrelated mechanisms,such as,insulin resistance(IR),lipotoxicity,inflammation,oxidative stress,and recently the gut-liver axis interaction has been described. Incretin-based therapies could play a role in the treatment of NAfLD. Glucagon-like peptide-1(GLP-1) is an intestinal mucosa-derived hormone which is secreted into the bloodstream in response to nutrient ingestion; it favors glucose-stimulated insulin secretion,inhibition of postprandial glucagon secretion and delayed gastric emptying. It also promotes weight loss and is involved in lipid metabolism. Once secreted,GLP-1 is quickly degraded by dipeptidyl peptidase-4(DPP-4). Therefore,DPP-4 inhibitors are able to extend the activity of GLP-1. Currently,GLP-1 agonists and DPP-4 inhibitors represent attractive options for the treatment of NAfLD and NASH. The modulation of lipid and glucose metabolism through nuclear receptors,such as the farsenoid X receptor,also constitutes an attractive therapeutic target. Obeticholic acid is a potent activator of the farnesoid X nuclear receptor and reduces liver fat content and fibrosis in animal models. Ursodeoxycholic acid(UDCA) is a hydrophilic bile acid with immunomodulatory,antiinflammatory,antiapoptotic,antioxidant and antifibrotic properties. UDCA can improve IR and modulate lipid metabolism through its interaction with nuclear receptors such as,TGR5,farnesoid X receptor-a,or the small heterodimeric partner. finally,pharmacologic modulation of the gut microbiota could have a role in the therapy of NAfLD and NASH. Probiotics prevent bacterial translocation and epithelial invas

关键词： Insulin resistance Lipotoxicity Non-alcoholic steatohepatitis Physiopathology Therapeutic targets

Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions

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World Journal of Clinical Cases 2018年第15期6卷 922-930页

作者： Nahum Méndez-Sánchez felipe Zamarripa-Dorsey Arturo Panduro Emma Purón-González Edgar Ulises Coronado-Alejandro Carlos Alejandro Cortez-Hernández fátima higuera de la tijera José Luis Pérez-Hernández Eira Cerda-Reyes Heriberto Rodríguez-Hernández Vania César Cruz-Ramón Oscar Lenin Ramírez-Pérez Nancy Edith Aguilar-Olivos Olga fabiola Rodríguez-Martínez Samantha Cabrera-Palma Guillermo Cabrera-álvarez Liver Research Unit Medica Sur Clinic and Foundation department of Gastroenterology Hospital "Juárez" of México department of Molecular Biology in Me-dicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" department of Internal Medicine "Christus Muguerza "Super Specialty" Hospital" Monterrey department of Gas-troenterology "University Hospital "Jose Eleuterio González" Monterrey department of Gastroenterology "General Hospital of Mexico "Dr.Eduardo Liceaga" department of Gastroenterology "Central Military Hospital" faculty of Medicine and Nutrition Juárez University of the State of Durango Liver Clinic Regional General Hospital IMSS 1

AIM To investigate the main current etiologies of cirrhosis in Mexico.METHODS We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period(January 2012-december 2017). RESULTS A total of 1210 patients were included. The mean age was 62.5 years(SD = 12.1), and the percentages of men and women were similar(52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus(HCV)(36.2%), alcoholic liver disease(ALD)(31.2%), and nonalcoholic steatohepatitis(23.2%), and the least frequent were hepatitis B virus(1.1%), autoimmune disorders(7.3%), and other conditions(1.0%).CONCLUSION HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease(NAfLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAfLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.

关键词： Alcoholic liver disease Hepatitis C virus Nonalcoholic steatohepatitis Liver cirrhosis

Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients

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World Journal of Hepatology 2021年第2期13卷 218-232页

作者： Moises Martinez-Castillo Abigail Hernandez-Barragan Ivonne flores-Vasconcelos Marina Galicia-Moreno Dorothy Rosique-Oramas Jose Luis Perez-Hernandez fatima higuera-de la tijera Eduardo E Montalvo-Jave Aldo Torre-delgadillo Paula Cordero-Perez Linda Muñoz-Espinosa David Kershenobich Gabriela Gutierrez-Reyes Liver Pancreas and Motility LaboratoryUnit of Experimental MedicineSchool of MedicineGeneral Hospital of MexicoUniversidad Nacional Autonoma de MexicoMexico City 06726Mexico department of Molecular Biology and Genomics Institute of Molecular Biology in Medicine and Gene TherapyHealth Science University CenterUniversity of GuadalajaraGuadalajara 06726Mexico department of Gastroenterology General Hospital of Mexico“Dr.Eduardo Liceaga”Mexico City 06726Mexico department of General Surgery General Hospital of Mexico“Dr.Eduardo Liceaga”School of MedicineUniversidad Nacional Autonoma de MexicoMexico City 06726Mexico Hepatology and Liver Transplant National Institute of Medical Sciences and Nutrition“Salvador Zubirán”Mexico City 06726Mexico University Hospital“Dr.JoséEleuterio González ”Autonomous University of Nuevo LeonMonterrey 06726Mexico

BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver.However,there are few studies on the regulation of liver MMPs in fibrosis progression in humans.AIM To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C(CHC).METHODS A prospective,cross-sectional,multicenter study was conducted.CHC patients were categorized in fibrosis grades through fibroTest®and/or fibroScan®.Serum MMP-2,-7,and-9 were determined by western blot and multiplex suspension array assays.Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests.The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated.Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test,whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays.RESULTS Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects.MMP-7 distinguished early and advanced stages,with a correlation of 0.32(Pder the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in f4(area under the receiver operating characteristic,0.705;95%confidence interval:0.605-0.805;Plagenolytic activity was detected at f0 and f1,whereas gelatinase activity was not detected at any fibrosis stage.Tissue inhibitor of metalloproteinase-1 determination showed upregulation in f0 and f1 but downregulation in f2(Pf inactive MMPs were present in the serum of CHC patients,reflecting the impossibility to restrain liver fibrosis progression.MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.

关键词： Extracellular matrix Matrix metalloproteinases Liver fibrosis Chronic hepatitis C fibrogenesis fibrolysis

Mean platelet volume as a novel predictor of systematic inflammatory response in cirrhotic patients with culturenegative neutrocytic ascites

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World Journal of Hepatology 2015年第7期7卷 1001-1006页

作者： Marisol Galvez-Martinez Alfredo I Servin-Caamano Eduardo Perez-Torres francisco Salas-Gordillo Xaira Rivera-Gutierrez fatima higuera-de la tijera Gastroenterology department Hospital General de México "Dr. Eduardo Liceaga" Internal Medicine department Hospital General de México "Dr. Eduardo Liceaga" faculty of Medicine "Universidad Veracruzana"

AIM: To identify a mean platelet volume(MPV) cutoff value which should be able to predict the presence of bacterial infection.METHODS: An observational, analytic, retrospective study. We evaluated medical records of cirrhotic patients who were hospitalized from January 2012 to January 2014 at the Gastroenterology department of "Hospital General de México Dr. Eduardo Liceaga", we included 51 cirrhotic patients with ascites fluid infection(AfI), and 50 non-infected cirrhotic patients as control group. Receiver operator characteristic curves were used to identify the best cutoff value of several parameters from hematic cytometry, including MPV, to predict the presence of ascites fluid infection.RESULTS: Of the 51 cases with AfI, 48 patients(94.1%) had culture-negative neutrocytic ascites(CNNA), 2(3.9%) had bacterial ascites, and one(2%)had spontaneous bacterial peritonitis. Infected patients had greater count of leucocytes and polymorphonuclear cells, greater levels of MPV and cardiac frequency(P fected patients(P = 0.009). Leucocytes, polymorphonuclear count, MPV and cardiac frequency resulted to be good or very good predictive variables of presence of AfI in cirrhotic patients(area under the receiving operating characteristic > 0.80). A cutoff MPV value of 8.3 fl was the best to discriminate between cirrhotic patients with AfI and those without infection. CONCLUSION: Our results support that MPV can be an useful predictor of systemic inflammatory response syndrome in cirrhotic patients with AfI, particularly CNNA.

关键词： Mean platelet volume Cirrhosis Ascites fluid infection Culture negative neutrocytic ascites Systemic inflammatory response