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Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis:Differences and similarities

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World Journal of Gastroenterology 2009年第4期15卷 462-466页

作者： Marcello Persico Mario Masarone Vincenzo La Mura Eliana Persico Francesco Moschella Monica Svelto Savino Bruno Roberto Torella Internal Medicine and hepatology unit Second University of Naples Internal Medicine and hepatology unit Fatebenefratelli Hospital

AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively evaluated 852 consec- utive patients （726 CHC and 126 CriB） who had under- gone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome （MS）, body mass index （BMI）, and apparent disease duration （ADD）. RESULTS： Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biop- sies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis （〉 30%） and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis 〉 30% in CHC, whereas only age and BMI were related to steatosis in CriB. CONCLUSION： These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.

关键词： Insulin resistance Diabetes Metabolicsyndrome Hepatitis C virus Hepatitis B virus

Costimulatory molecule programmed death-1 in the cytotoxic response during chronic hepatitis C

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World Journal of Gastroenterology 2009年第41期15卷 5129-5140页

作者： Juan Ramón Larrubia Selma Benito-Martínez Joaquín Miquel Miryam Calvino Eduardo Sanz-de-Villalobos Trinidad Parra-Cid Translational hepatology unit Guadalajara University Hospital University of Alcalá

Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 （PD-1）. This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^＋ T cells are exhausted with impairment of several effector mechanisms, such as： type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand （PD-L1）. After this blockade, HCV-specific CD8^＋ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^＋ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.

关键词： Chronic hepatitis Exhaustion Hepatitis C virus core Hepatitis C virus Programmed death-1 Programmed death-1 ligand

Exhaled breath analysis in hepatology: State-of-the-art and perspectives

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World Journal of Gastroenterology 2019年第30期25卷 4043-4050页

作者： Antonio De Vincentis Umberto Vespasiani-Gentilucci Anna Sabatini Raffaele Antonelli-Incalzi Antonio Picardi unit of Clinical Medicine and hepatology Unit of GeriatricsDepartment of MedicineCampus Bio-Medico University HospitalRome 00128Italy unit of Electronics for sensor systems Department of EngineeringUniversity Campus Bio-Medico of RomeRome 00128Italy

Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of *** the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical *** VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing *** results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver ***,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained *** the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.

关键词： Exhaled breath analysis Electronic nose Gas chromatography Breath print Liver cirrhosis Nonalcoholic fatty liver disease Hepatic encephalopathy

Chronic liver failure-consortium acute-on-chronic liver failure and acute decompensation scores predict mortality in Brazilian cirrhotic patients

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World Journal of Gastroenterology 2017年第28期23卷 5237-5245页

作者： Rafael Veiga Picon Franciele Sabadin Bertol Cristiane Valle Tovo Angelo Zambam de Mattos Gastroenterology and hepatology unit Nossa Senhora da Conceicao Hospital Gastro-enterology and hepatology unit Federal University of Health Sciences of Porto Alegre Gastroenterology and hepatology unit Pontifical Catholic University of Rio Grande do Sul

To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian *** is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium (CLIF-C) acute decompensation score (CLIF-C AD) and CLIF-C acute-on-chronic liver failure score (CLIF-C ACLF), regarding 28-d and 90-d mortality, as well as to compare them to other prognostic models, such as Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na), Child-Pugh (CP) score, and the CLIF-C Organ Failure score (CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic (ROC) curves, area under the curves (AUC) and 95%*** hundred and thirteen cirrhotic patients were included. At admission, 18 patients had acute-on-chronic liver failure (ACLF) and 95 individuals had acute decompensation (AD) without ACLF, of which 24 eventually developed ACLF during the course of hospitalization (AD evolving to ACLF group). The AD group had significantly lower 28-d (9.0%) and 90-d (18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group (both P < 0.001). On the other hand, 28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group (P = 0.542 and P = 0.708, respectively). Among patients with ACLF, at 28 d from the diagnosis, CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line, with an AUC (95%CI) of 0.71 (95%CI: 0.54-0.88, P = 0.021). Among patients with AD, all prognostic scores performed significantly better than the reference line regarding 28-d mortality, presenting with similar AUCs: CLIF-C AD score 0.75 (95%CI: 0.63-0.88), CP score 0.72 (95%CI: 0.59-0.85), MELD score 0.75 (95%CI: 0.61-0.90),

关键词： Cirrhosis Acute-on-chronic liver failure Mortality Prediction Prognosis Acute decompensation of cirrhosis

Occult hepatitis B virus infection:A complex entity with relevant clinical implications

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World Journal of Gastroenterology 2011年第12期17卷 1529-1530页

作者： Juan-Ramon Larrubia Translational hepatology unit Guadalajara University Hospital University of Alcalá

Occult hepatitis B virus(HBV) infection is a world-wide entity,following the geographical distribution of detectable hepatitis *** entity is defined as the persistence of viral genomes in the liver tissue and in some instances also in the serum,associated to negative HBV surface antigen *** molecular basis of the occult infection is related to the life cycle of HBV,which produces a covalently closed circular DNA that persists in the cell nuclei as an episome,and serves as a template for gene *** mechanism responsible for the HBsAg negative status in occult HBV carriers is a strong suppression of viral replication,probably due to the host’s immune response,co-infection with other infectious agents and epigenetic *** is emerging evidence of the potential clinical relevance of occult HBV infection,since this could be involved in occult HBV transmission through orthotopic liver transplant and blood transfusion,reactivation of HBV infection during immunosuppression,impairing chronic liver disease outcome and acting as a risk factor for hepatocellular *** it is important to bear in mind this entity in cryptogenetic liver diseases,hepatitis C virus/ HIV infected patients and immunosupressed *** is also necessary to increase our knowledge in this fascinating field to define better strategies to diagnose and treat this infection.

关键词： Hepatitis B virus Occult infection Persistent infection

Serious drug-induced liver disease secondary to ezetimibe

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World Journal of Gastroenterology 2008年第32期14卷 5098-5099页

作者： José Castellote Javier Ariza Rosa Rota Anna Girbau Xavier Xiol hepatology and Liver Transplant unit IdibellHospital Universitario de Bellvitge

Ezetimibe is the f irst member of a new family of lipid- lowering drugs that inhibits uptake of dietary and bili- ary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years. Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce seri- ous toxic hepatitis and prompt withdrawal is mandatory in case of a signif icant abnormality in liver testing after beginning or during treatment with ezetimibe.

关键词： Ezetimibe Hepatitis Drug-induced liverdisease

Is transient elastography a useful tool for screening liver disease?

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World Journal of Gastroenterology 2009年第12期15卷 1409-1414页

作者： Paolo Del Poggio Silvia Colombo hepatology unit Treviglio HospitalTreviglio(Bg)24047Italy

Transient elastography(TE)is a new non invasive tool for measuring liver stiffness,which is correlated to the histologic stage of liver *** studies in chronic liver disease(CLD)have determined a good accuracy of TE in predicting significant fibrosis and an optimal accuracy in predicting *** liver stiffness ranges between 3.3-7.8 KPa and using a cut off of 7.1 KPa,significant fibrosis and cirrhosis can be excluded with a very high negative predictive value(NPV).Positive predictive value(PPV)for the diagnosis of cirrhosis is lower using just a single scan but increases to 90% if high stiffness values are confirmed by a second independent *** the presence of fatty liver and metabolic syndrome slightly increases the readings and may reduce the accuracy of the *** is uncertain if this increase is related to the presence of steatofibrosis or ifit is caused by steatosis *** can be used in screening patients attending the liver clinics to identify those with signifi cant fi brosis or cirrhosis and may be particularly useful in discriminating HBV inactive carriers from chronic hepatitis B ***,however,is not reliable in predicting the presence of esophageal varices in *** potential indication for TE is the systematic screening of populations at high risk for CLD,such as intravenous drug users and alcoholics,but further studies are needed to determine its diagnostic accuracy in these settings.

关键词： Transient elastography Screening Liverdisease Hepatitis B Hepatitis C Non alcoholic steatohepatitis Cirrhosis

Gender disparities and woman-specific trends in Barrett’s esophagus in the united States:An 11-year nationwide populationbased study

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World Journal of Methodology 2025年第1期15卷 60-71页

作者： Karina Fatakhova Faisal Inayat Hassam Ali Pratik Patel Attiq Ur Rehman Arslan Afzal Muhammad Sarfraz Shiza Sarfraz Gul Nawaz Ahtshamullah Chaudhry Rubaid Dhillon Arthur Dilibe Benjamin Glazebnik Lindsey Jones Emily Glazer Division of Gastroenterology and hepatology Mather Hospital and Zucker School of Medicine at Hofstra UniversityPort JeffersonNY 11777United States Department of Internal Medicine Allama Iqbal Medical CollegeLahorePunjab 54550Pakistan Division of Gastroenterology and hepatology East Carolina University Brody School of MedicineGreenvilleNC 27834United States Division of Gastroenterology and hepatology Geisinger Wyoming Valley Medical CenterWilkes-BarrePA 18711United States Department of Internal Medicine East Carolina University Brody School of MedicineGreenvilleNC 27834United States Department of Internal Medicine St.Dominic's HospitalJacksonMS 39216United States Department of Gastroenterology Hepatologyand NutritionCleveland Clinic FoundationClevelandOH 44195United States Department of Internal Medicine Mather Hospital and Hofstra University ZuckerSchool of MedicinePort JeffersonNY 11777United States

BACKGROUND Barrett's esophagus(BE)is a known premalignant precursor to esophageal adenocarcinoma(EAC).The prevalence rates continue to rise in the united States,but many patients who are at risk of EAC are not *** practice guidelines include male gender as a predisposing factor for BE and *** population-based clinical evidence regarding female gender remains *** To study comparative trends of gender disparities in patients with BE in the united *** A nationwide retrospective study was conducted using the 2009-2019 National Inpatient Sample(NIS)*** with a primary or secondary diagnosis code of BE were *** major outcome of interest was determining the gender disparities in patients with *** analysis for respective outcomes for females was also reported to ascertain any time-based *** We identified 1204190 patients with BE for the study *** the included patients,717439(59.6%)were men and 486751(40.4%)were *** mean age was higher in women than in men(67.1±0.4 vs 66.6±0.3 years,P<0.001).The rate of BE per 100000 total NIS hospitalizations for males increased from 144.6 in 2009 to 213.4 in 2019(P<0.001).The rate for females increased from 96.8 in 2009 to 148.7 in 2019(P<0.001).There was a higher frequency of obesity among women compared to men(17.4%vs 12.6%,P<0.001).Obesity prevalence among females increased from 12.3%in 2009 to 21.9%in 2019(P<0.001).A lower prevalence of smoking was noted in women than in men(20.8%vs 35.7%,P<0.001).However,trend analysis showed an increasing prevalence of smoking among women,from 12.9%in 2009 to 30.7%in 2019(P<0.001).Additionally,there was a lower prevalence of alcohol abuse,Helicobacter pylori(***),and diabetes mellitus among females than males(P<0.001).Trend analysis showed an increasing prevalence of alcohol use disorder and a decreasing prevalence of *** and diabetes mellitus among women(P<0.001).CONCLUSION The prevalence of BE among

关键词： Barrett’s esophagus Gender disparity Epidemiological trends Esophageal adenocarcinoma Screening endoscopy Female gender Risk factors

Secondary bile acids and the biliary epithelia: The good and the bad

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World Journal of Gastroenterology 2023年第2期29卷 357-366页

作者： Ilaria Lenci Martina Milana Alessandro Signorello Giuseppe Grassi Leonardo Baiocchi hepatology unit Policlinico Tor VergataRome 00133Italy

The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the *** several researches demonstrated an important role of biliary epithelia(***)in bile *** study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases,such as primary biliary cholangitis or primary sclerosing *** acids(BAs),produced by the liver,are the most represented organic molecules in *** physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling *** this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary(deriving by bacterial manipulation of primary molecules)*** class of BAs is demonstrated to have relevant biological effects,ranging from toxic to therapeutic *** this family ursodeoxycholic and lithocholic acid present the most interesting *** molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic *** findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.

关键词： Cholangiocytes Biliary secretion Cholestasis Bile acids Secondary bile acids Ursodeoxycholic acid Lithocholic acid