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World Journal of Gastroenterology 2016年第22期22卷 5285-5292页

作者： javier ampuero K Rajender Reddy Manuel Romero-Gomez Inter-Centre Unit of Digestive Diseases and CIBERehd Virgen Macarena Virgen del Rocio University Hospitals University of Sevilla 41018 Sevilla Spain Instituto de Biomedicina de Sevilla 41018 Sevilla Spain Division of Gastroenterology and Hepatology Department of Medicine University of Pennsylvania Philadelphia PA 19107 United States

AIM: To address the therapeutic efficacy of various treatment regimens in genotype 3 selecting randomized clinical trials and prospective National Cohort ***:(1) PEG-INF-based therapy including sofosbuvir(SOF) + RBV for 12 wk vs SOF + RBV 24 wk;(2) SOF + RBV therapy 12 wk/16 wk vs 24 wk; and(3) the role of RBV in SOF + daclatasvir(DCV) and SOF + ledipasvir(LDV) combinations. This metaanalysis provides robust information with the intention of addressing treatment strategy for hepatitis C virus genotype ***: A combination treatment including SOF + RBV + PEG-IFN for 12 wk notes better SVR than with only SOF + RBV for 12 wk, although its association with more frequent adverse effects may be a limiting factor. Longer duration therapy with SOF + RBV(24 wk) has achieved higher SVR rates than shorter durations(12 or 16 wk). SOF + LDV are not an ideal treatment for genotype 3. CONCLUSION: Lastly, SOF + DCV combination is probably the best oral therapy option and the addition of RBV does not appear to be needed to increase SVR rates substantially.

关键词： Hepatitis C Genotype 3 Sofosbuvir Daclatasvir Ledipasvir

Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

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World Journal of Gastroenterology 2013年第42期19卷 7327-7340页

作者： María Rojas-Feria Manuel Castro Emilio Suárez javier ampuero Manuel Romero-Gómez Unit for Medical and Surgical Management of Digestive Diseases and CIBERehd Valme University HospitalUniversity of SevilleE-41014 SevillaSpain

Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic *** and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal *** sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in *** 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these *** common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver *** B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with *** prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral *** negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load *** the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history *** of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is *** in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically *** hepatotoxicity has been describ

关键词： Inflammatory bowel disease Hepatobiliary disorders Extraintestinal manifestations Primary sclerosing cholangitis Drug-induced liver injury Hepatotoxicity Hepatitis B Hepatitis C

Glutaminolysis-ammonia-urea Cycle Axis,Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 356-362页

作者： Ángela Rojas María Rosario García-Lozano Antonio Gil-Gómez Manuel Romero-Gómez javier ampuero Department of Unit of Digestive Diseases Virgen del Rocío University HospitalSevilleSpain SeLiver group at the Insti-tute of Biomedicine of Seville(IBIS) Virgen del Rocío University Hospital/CSIC/University of SevilleSevilleSpain Center for the Study of Liver and Gastrointestinal Diseases(CIBERehd) Carlos III National Institute of HealthMadridSpain De-partment of Organic and Medicinal Chemistry Faculty of PharmacyUniversity of SevilleE-41071SevilleSpain

The prevalence of non-alcoholic fatty liver disease(NAFLD)is increasing worldwide,reflecting the current epidemics of obesity,insulin resistance,type 2 diabetes mellitus,and metabolic *** is characterized by the accumulation of fat in the liver,and is known to be a cause of *** many pathways have been proposed,the cause of NAFLD-linked fibrosis progression is still unclear,which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular *** is associated with activation of hepatic stellate cells(HSC)and accumulation of excess extracellular matrix proteins,and inhibiting the activation of HSCs would be expected to slow the progression of *** molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC *** mechanisms are plausible antifibrotic targets in NASH,as the activation of HSCs the proliferation of myofibroblasts depend on those *** review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression,and shows how the axis could be a novel therapeutic target.

关键词： Non-alcoholic fatty liver disease Cirrhosis Fibrosis Glutaminoly-sis Ammonia Urea

Prevention of hepatocellular carcinoma by correction of metabolic abnormalities: Role of statins and metformin

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World Journal of Hepatology 2015年第8期7卷 1105-1111页

作者： javier ampuero Manuel Romero-Gomez Unit for the Clinical Management of Digestive Diseases Valme University Hospital

Hepatocellular carcinoma is the third leading cause of cancer-related deaths in the world. It is associated with an important mortality rate and the incidence is increasing. Patients showing metabolic syndrome seem to have higher incidence and mortality rates from hepatocellular carcinoma than healthy subjects, especially those with type 2 diabetes mellitus and obesity. Thus, metformin and statins, both to treat features of metabolic syndrome, have been proposed to decrease the risk of hepatocellular carcinoma. Otherwise, liver cancer is the result of a complex process which impairs several signaling cascades, such as RAS/RAF/mitogen-activated protein kinase kinase(MEK)/extracellularsignal-regulated kinase(ERK), phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/AKT/mammalian target of rapamycin(m TOR) and Wnt/β-catenin signaling. Metformin(through 5′-adenosine monophosphateactivated protein kinase pathway activation) and statins(through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/m TOR and Wnt/β-catenin signaling cascades. On the other hand, metformin and statins have been found to reduce the risk of hepatocellular carcinoma up to 50% and 60%, respectively. Furthermore, both drugs have shown a dose-dependent protective effect. However, information about chemopreventive role of metformin and statins is mainly obtained of observational studies,which could not take into account some bias. In conclusion, given the rising of incidence of hepatocellular carcinoma and the important morbidity and mortality rates associated with this cancer, looking for chemopreventive strategies is an essential task. Randomized controlled trials are needed to determine the definite role of metformin and statins on the prevention of hepatocellular carcinoma.

关键词： Hepatocellular carcinoma Metformin Metabolic syndrome Mammalian target of rapamycin Statin

Wilson's disease:Revisiting an old friend

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World Journal of Hepatology 2021年第6期13卷 634-649页

作者： Ana Lucena-Valera Domingo Perez-Palacios Rocio Muñoz-Hernandez Manuel Romero-Gómez javier ampuero Department of Gastroenterology Hospital Universitario Virgen del RocioSevilla 41013Spain SeLiver Group Instituto de Biomedicina de Sevilla(IBiS)Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaEspaña Department of Unit of Digestive Diseases Hospital Universitario Virgen del RocioSevilla 41014Spain

Wilson's disease(WD)is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs,such as the central nervous *** is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B *** protein facilitates the incorporation of copper into *** than 800 mutations associated with WD have been *** onset of the disease frequently includes manifestations related to the liver(as chronic liver disease or acute liver failure)and neurological symptoms,although it can sometimes be *** it being more frequent in young people,WD has been described in all life *** to its fatal prognosis,WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric *** diagnosis is established with a combination of clinical signs and tests,including the measurement of ceruloplasmin,urinary copper excretion,copper quantification in liver biopsy,or genetic *** pharmacological therapies include chelating drugs,such as D-penicillamine or trientine,and zinc salts,which are able to change the natural history of the disease,increasing the survival of these *** some cases of end-stage liver disease or acute liver failure,liver transplantation must be an option to increase *** this narrative review,we offer an overview of WD,focusing on the importance of clinical suspicion,the correct diagnosis,and treatment.

关键词： Wilson´s disease Copper ATP7B Ceruloplasmin Chelator Liver disease

Assessing cardiovascular risk in hepatitis C: An unmet need

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World Journal of Hepatology 2015年第19期7卷 2214-2219页

作者： javier ampuero Manuel Romero-Gómez Intercentre Unit of Digestive Diseases Virgen Macarena - Virgen del Rocio University Hospitals

Chronic hepatitis C virus(HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases(CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct rolein altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease. HCV core protein plays an essential role in promoting insulin resistance and oxidative stress. On the other hand, atherosclerosis is a common disease in which the artery wall thickens due to accumulation of fatty deposits. The main step in the formation of atherosclerotic plaques is the oxidation of low density lipoprotein particles, together with the increased production of proinflammatory markers [tumor necrosis factor-α, interleukin(IL)-6, IL-18 or C-reactive protein]. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus. Consequently, the number of studies evaluating this association is growing. Data derived from these studies have demonstrated the strong link between HCV infection and the atherogenic process, showing a higher risk of coronary heart disease, carotid atherosclerosis, peripheral artery disease and, ultimately, CVD-related mortality.

关键词： Hepatitis C Atherosclerosis Coronary artery diseas

Cardiovascular assessment in liver transplant for nonalcoholic steatohepatitis patients:What we do,what we should do

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World Journal of Hepatology 2017年第15期9卷 697-703页

作者： Yolanda Sanchez-Torrijos javier ampuero Manuel Romero-Gómez Unidad Intercentros de Aparato Digestivo Hospitales Universitarios Virgen del Rocio-Virgen Macarena Instituto de Biomedicina de Sevilla Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd)

Non-alcoholic fatty liver disease(NAFLD) is increasing considerably due to the current lifestyle,which means that it is becoming one of the main indications for liver *** the other hand,there is a strong association between NAFLD and cardiovascular *** has been evidenced in many studies revealing a higher presence of carotid plaques or carotid intima-media thickness,leading to cardiovascular events and,ultimately,*** to the liver transplant guidelines,screening for heart disease in transplant candidates should be performed by electrocardiogram and transthoracic echocardiography while a stress echocardiogram should be reserved for those with more than two cardiovascular risk factors or greater than 50 years ***,there are no specific recommendations in NAFLD patients requiring a liver transplantation,despite its well-known cardiovascular risk *** studies have shown that these patients probably require a more exhaustive assessment and a global approach including other specialists such as cardiologists or ***,the incidence of cardiovascular disease is also increased in NAFLD patients in the post-transplantation period in comparison with other etiologies,because of the pre-existent risk factors together with the immunosuppressive ***,an early intervention on the lifestyle and the individualized selection of the immunosuppressive regimen could lead to a modification of the cardiovascular risk factors in NAFLD patients requiring a liver transplantation.

关键词： Cardiovascular risk Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Pre-transplant assessment Liver transplantation

Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis

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World Journal of Gastroenterology 2016年第45期22卷 10064-10070页

作者： Astrid Ruiz-Margáin Ricardo Ulises Macías-Rodríguez javier ampuero Francisco javier Cubero Luis Chi-Cervera Silvia L Ríos-Torres Andrés Duarte-Rojo Ángeles Espinosa-Cuevas Manuel Romero-Gómez Aldo Torre Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán14080 México City México Department of Internal Medicine Ⅲ University Hospital RWTH Aachen52074 Aachen Germany Unit for the Clinical Management of Digestive Diseases Virgen del Rocio-Virgen Macarena University Hospital41009 Sevilla Spain Department of Immunology Complutense University School of Medicine28040 Madrid Spain University of Arkansas for Medical Sciences Little Rock AR 72205 United States Department of Nephrology and Mineral Merabolism Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán México City 14080 México

AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic *** This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. MannWhitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic *** Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy(18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. KaplanMeier curves showed a higher proportion of HE in the group with low phase angle(39%) compared to the normal phase angle group(13%)(P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80(1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.

关键词： Malnutrition Hepatic encephalopathy Phase angle Cachexia Prognosis

Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid-and long-term prediction of hepatocellular carcinoma among cirrhotic patients

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World Journal of Gastroenterology 2021年第48期27卷 8343-8356页

作者： Antonio Gil-Gómez Ángela Rojas Chang-Hai Liu Rocio Gallego-Duran Rocio Muñoz-Hernandez Giorgio Fassina Patrizia Pontisso javier ampuero Manuel Romero-Gómez SeLiver Group Institute of Biomedicine of SevilleSeville 41013Spain CIBERehd Instituto de Salud Carlos IIIMadrid 28029Spain Mucosal Immunity Lab IRCCS Humanitas Research HospitalMilan 20089Italy Center of Infectious Diseases West China Hospital of Sichuan UniversityChengdu 610017Sichuan ProvinceChina State Key Laboratory of Biotherapy and Center of Infectious Diseases West China HospitalChengdu 610017Sichuan ProvinceChina Life Biotechnology Padua UniversityVenice 30175Italy Department of Clinical and Experimental Medicine University of PadovaPadova 35123Italy UCM Digestive Diseases Virgen del Rocío University HospitalSeville 41014Spain

BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine *** To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of *** Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver *** estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at *** were followed-up for 60 mo,being censored at the time of the appearance of *** There were 10.8%and 23.1%of HCC development at two-and five-years *** with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear *** multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year *** We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,esp

关键词： Squamous cell carcinoma antigen Hepatocellular carcinoma prediction Precision medicine Stratification of cirrhotic patient

Impact of COVID-19 on liver disease: From the experimental to the clinic perspective

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World Journal of Virology 2021年第6期10卷 301-311页

作者： Sheila Gato Ana Lucena-Valera Rocío Muñoz-Hernández JoséManuel Sousa Manuel Romero-Gómez javier ampuero SeLiver Group Instituto de Biomedicina de SevillaSevilla 41013Spain Digestive Department Hospital Universitario Virgen del RocioSevilla 41013Spain University of Seville Sevilla 41013Spain

Coronavirus disease 2019(COVID-19)has caused a global pandemic unprecedented in over a *** severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a predominantly respiratory infection,various degrees of liver function abnormalities have been ***-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies,but it can critically compromise survival and trigger hepatic *** collapse of the healthcare services has negatively impacted the diagnosis,monitoring,and treatment of liver diseases in non-COVID-19 *** this review,we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.

关键词： SARS-CoV-2 COVID 19 Liver disease Transaminases