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BACKGROUND: Recent studies have suggested an association between H. pylori and metabolic-disfunction associated fatty liver disease (MASLD). However, epidemiologic studies have yielded inconsistent results. We aim to evaluate the association of H. pylori and G-allele PNPLA3 in MASLD diagnosis, and markers of severity. METHODS: A multi-center cross-sectional study was conducted. A total 224 functional dyspepsia (FD) patients cohort who underwent gastroscopy was selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, LSM by VCTE, gastric biopsies, H. pylori status, and rs738409 PNPLA3 were evaluated. A second retrospective cohort of 86 patients with biopsy-proven MASLD who underwent gastroscopy with gastric biopsies was analyzed. RESULTS: In the FD cohort MASLD was observed in 52%, and H. pylori-positive in 51%. H. pylori infection was associated with MASLD prevalence, but in multivariate analyses adjusted for G-allele PNPLA3, it became not significant. Then in MASLD-only dyspeptic cohort, H. pylori infection was significantly linked to elevated serum AST levels and increased liver stiffness measurements, suggesting a potential role in liver injury and fibrosis. Histopathological analysis in biopsy-proven MASLD patients further supported these findings, showing a significant association between H. pylori infection and increased NAS score, fibrosis stage, and prevalence of MASH. Notably, the combination of H. pylori infection and G-allele PNPLA3 appeared to exacerbate MASLD severity beyond individual effects. CONCLUSIONS: Our results suggest that H. pylori infection may play a role in the progression of liver injury and fibrosis in patients with MASLD, especially in those with specific genetic predispositions.
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Infecciones por Helicobacter , Helicobacter pylori , Lipasa , Proteínas de la Membrana , Humanos , Masculino , Femenino , Lipasa/genética , Proteínas de la Membrana/genética , Persona de Mediana Edad , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Adulto , Estudios Transversales , Estudios Retrospectivos , Hígado Graso/genética , Hígado Graso/complicaciones , Alelos , Polimorfismo de Nucleótido Simple , Dispepsia/microbiología , Dispepsia/genética , Dispepsia/complicaciones , Hígado/patología , Hígado/metabolismo , Aciltransferasas , Fosfolipasas A2 Calcio-IndependienteRESUMEN
INTRODUCTION AND OBJECTIVES: Recent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects. PATIENTS AND METHODS: A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated. RESULTS: A cohort comprised of 61 % women and 39 % men with a median age of 52 (40-60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2-5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38-11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88-12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22-14.49). CONCLUSIONS: In our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.
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Antígenos Bacterianos , Proteínas Bacterianas , Diagnóstico por Imagen de Elasticidad , Infecciones por Helicobacter , Helicobacter pylori , Cirrosis Hepática , Humanos , Masculino , Femenino , Persona de Mediana Edad , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Adulto , Cirrosis Hepática/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Factores de Riesgo , Gastroscopía , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Biopsia , Virulencia , Factores de Virulencia/genéticaRESUMEN
Intrahepatic cholestasis as a paraneoplastic manifestation was first described by Dr. Maurice H. Stauffer in 1961. This paraneoplastic manifestation was primarily associated with renal cell carcinoma characterized by abnormal liver enzymes without hepatic metastasis. Stauffer syndrome is classified into 2 types: classical and jaundice variants. Indeed, the jaundice variant is extremely rare and only described in 13 published cases. We report a case of intrahepatic cholestasis associated with a type 1 papillary renal cell carcinoma with complete resolution after surgical treatment.
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BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro-inflammatory cascade, nucleotide-binding oligomerization domain 1 (NOD-1), and interleukin-1 beta (IL-1ß) in HpD was not explored. AIM: To evaluate the association of NOD1-796G>A and IL-1B-511C>T gene variants and low-grade duodenal eosinophilia in HpD. METHODS: A multicenter cross-sectional study was conducted. A total of 253 patients who met Rome-IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated. RESULTS: Sixty-four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1-796G>A and IL-1B-511C>T gene variants. Low-grade duodenal eosinophilia was significantly increased in NOD1-796 GG versus single A-allele, but not in IL-1B-511 single T-allele or CC-allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low-grade duodenal eosinophilia with isolated variants NOD1-796 GG and IL-1B-511 single T-allele, but not without cagA. When we performed combined polymorphism analysis with NOD1-796 GG/IL-1B-511 single T-allele, a synergistic effect on low-grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD. CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is significantly associated with NOD1-796 GG allele specially in cagA strain and with allelic combination NOD1-796 GG/IL-1B-511 single T-allele independent of cagA strain infection in HpD patients.
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Dispepsia , Eosinofilia , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/genética , Estudios Transversales , Dispepsia/genética , Dispepsia/complicaciones , Eosinofilia/complicaciones , Gastritis/complicaciones , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Proteína Adaptadora de Señalización NOD1/genética , Polimorfismo GenéticoRESUMEN
BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder with no targeted therapy. Duodenal eosinophilia and low-grade inflammation are potential pathogenic mechanisms. However, the impact of duodenal eosinophils (D-EO) histologic evaluation in real-life clinical practice was not explored. AIM: To evaluate the clinical utility of D-EO and low-grade inflammation in FD in real-life practice. MATERIALS AND METHODS: A multicenter prospective study was conducted. A total of 636 patients who meet Rome-III criteria were selected before upper endoscopy and 516 patients were included after normal endoscopy were assessed. Clinical parameters, Helicobacter pylori ( H. pylori), and duodenal histology were evaluated. RESULTS: FD subtypes were 231 (45%) patients who had epigastric pain syndrome (EPS), 168 (33%) postprandial distress syndrome (PDS), and 117 (22%) EPS/PDS overlap. Two hundred fifty-nine (50.3%) patients were H. pylori+ . Histologic duodenal grading of chronic inflammation and intraepithelial lymphocytes showed no difference between FD subtypes. Increased in D-EO densities (>10 per high power field) was significant in PDS compared with EPS and EPS/PDS overlap subtypes. The odds ratio of PDS in subjects with duodenal eosinophilia densities was 2.28 (95% CI, 1.66-3.14; P <0.0001), adjusting for age, gender, H. pylori and nonsteroidal anti-inflammatory drug the odds ratio was 3.6 (95% CI, 2.45-5.28; P <0.0001). receiver operating characteristic curve analysis further demonstrated that low-grade duodenal eosinophilia, in particular H. pylori- , was highly accurate for PDS with the area under the curve 0.731 compared with H. pylori+ area under the curve 0.598. Furthermore, low-grade duodenal eosinophilia was significantly correlated with treatment response under 4 to 6 weeks of proton pump inhibitor therapy. CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is associated with PDS subtype non- H. pylori FD patients and could be a useful marker of treatment response.
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Dispepsia , Eosinofilia , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Dispepsia/epidemiología , Estudios Prospectivos , Eosinofilia/epidemiología , Endoscopía Gastrointestinal , Infecciones por Helicobacter/complicaciones , InflamaciónRESUMEN
BACKGROUND AND AIM: Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and H. pylori virulence genes in HpD was not explored. We aim to evaluate the association of H. pylori virulence genes and low-grade duodenal eosinophilia in HpD. METHODS: A multi-center cross-sectional study was conducted. A total of 301 patients who meet Rome-III criteria were selected before upper endoscopy, and 95 patients were included after normal endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori virulence genes (cagA, oipA, and vacA) and duodenal histology were evaluated. RESULTS: Sixty-nine (72%) patients had epigastric pain syndrome (EPS), 17 (18%) post-prandial distress syndrome (PDS) and 9 (10%) EPS/PDS overlap. FD syndromes were not associated with cagA or oipA strains. A significantly trend of vacA s1/m1 (78%) and s1/m2 (80%) positive strains in EPS was observed. Histological duodenal grading of chronic inflammation, low-grade duodenal eosinophilia and intra-epithelial lymphocytes showed no difference in oipA and vacA strains. Low-grade duodenal eosinophilia was significant in cagA positive strain, and the OR for low-grade duodenal eosinophilia with H. pylori cagA positive strain was 4.2 (95% CI, 1.78-9.93). Adjusting for age, gender, smoking, diabetes, alcohol, PPI, and NSAID, the OR was 5.44 (1.989-14.902). CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is significantly associated with cagA strain in HpD.
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Dispepsia , Eosinofilia , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Dispepsia/complicaciones , Helicobacter pylori/genética , Estudios Transversales , Genotipo , Gastritis/complicaciones , Eosinofilia/complicaciones , Infecciones por Helicobacter/complicacionesRESUMEN
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new nomenclature recently proposed by a panel of international experts so that the entity is defined based on positive criteria and linked to pathogenesis, replacing the traditional non-alcoholic fatty liver disease (NAFLD), a definition based on exclusion criteria. NAFLD/MAFLD is currently the most common form of chronic liver disease worldwide and is a growing risk factor for development of hepatocellular carcinoma (HCC). It is estimated than 25% of the global population have NAFLD and is projected to increase in the next years. Major Scientific Societies agree that surveillance for HCC should be indicated in patients with NAFLD/ MAFLD and cirrhosis but differ in non-cirrhotic patients (including those with advanced fibrosis). Several studies have shown that the annual incidence rate of HCC in NAFLD-cirrhosis is greater than 1%, thus surveillance for HCC is cost-effective. Risk factors that increase HCC incidence in these patients are male gender, older age, presence of diabetes and any degree of alcohol consumption. In non-cirrhotic patients, the incidence of HCC is much lower and variable, being a great challenge to stratify the risk of HCC in this group. Furthermore, large epidemiological studies based on the general population have shown that diabetes and obesity significantly increase risk of HCC. Some genetic variants may also play a role modifying the HCC occurrence among patients with NAFLD. The purpose of this review is to discuss the epidemiology, clinical and genetic risk factors that may influence the risk of HCC in NAFLD/MAFLD patients and propose screening strategy to translate into better patient care.
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BACKGROUND: Ursodeoxycholic acid (UDCA) is the first-line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients. AIM: To evaluate the long-term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA-refractory PBC. METHODS: Fifty-nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow-up. RESULTS: Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA-bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P < 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK-PBC prognosis models. CONCLUSIONS: Adding bezafibrate to UDCA in patients with UDCA-refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long-term cohort studies and controlled trials.
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Cirrosis Hepática Biliar , Ácido Ursodesoxicólico , Bezafibrato/uso terapéutico , Biopsia , Colagogos y Coleréticos/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Cirrosis Hepática Biliar/tratamiento farmacológico , Estudios Longitudinales , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease worldwide, with an estimated global prevalence of approximately 25%, that is much higher in patients with overweight, obesity and type 2 diabetes. NAFLD is considered as the hepatic manifestation of metabolic syndrome. It has a wide spectrum, from simple steatosis to steatohepatitis, fibrosis, cirrhosis and its complications, such as hepatocellular carcinoma. Most of the affected patients will not evolve to advanced fibrosis or cirrhosis. Despite this, it has been described that the hepatic disease is the third cause of death among patients with nonalcoholic fatty liver, after cardiovascular and malignant diseases. Among the huge number of patients affected, the main challenge is to identify those who are at risk of developing cirrhosis or its complications and to recognize the diagnostic and treatment options. In this Guideline, endorsed by the Argentine Association for the Study of Liver Diseases, the definitions, epidemiological aspects, natural history and a practical approach to possible algorithms to estimate the severity of liver disease in the individual patient are reviewed; in addition to analyzing advances in treatment and proposing recommendations for follow-up. It is important to note that no data on the incidence or prevalence of the disease have been published in the general population of Argentina, and it is encouraged to carry them out.
El hígado graso no alcohólico (HGNA) es la enfermedad hepática crónica más frecuente en todo el mundo, con una prevalencia aproximada de 25% a nivel global. Su prevalencia es mucho mayor en pacientes con sobrepeso, obesidad y diabetes tipo 2 y es considerada como la manifestación hepática del síndrome metabólico. El espectro de la enfermedad hepática es muy amplio, desde la esteatosis simple a la esteatohepatitis, fibrosis, cirrosis y sus complicaciones, como el hepatocarcinoma. La mayoría de los pacientes afectados no progresará a la fibrosis avanzada/cirrosis. A pesar de esto, se ha descripto que la hepatopatía es la tercera causa de muerte entre los pacientes con HGNA, luego de las enfermedades cardiovasculares y las malignas. Entre la enorme cantidad de afectados, lo más importante es identificar a los que están en riesgo de evolución a la cirrosis o sus complicaciones y conocer las opciones de diagnóstico y tratamiento. En esta Guía organizada por la Asociación Argentina para el Estudio de las Enfermedades del Hígado se revisan las definiciones, los aspectos epidemiológicos, la historia natural y un enfoque práctico sobre algoritmos posibles para estimar la gravedad de la hepatopatía en cada caso, además de analizar los avances en el tratamiento y recomendaciones para el seguimiento. Es importante señalar que no se han publicado datos sobre incidencia o prevalencia de la enfermedad en población general de Argentina, y se alienta a la realización de los mismos.
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Enfermedad del Hígado Graso no Alcohólico , Argentina , Diabetes Mellitus Tipo 2 , Humanos , Hígado , Cirrosis Hepática , Neoplasias Hepáticas , Factores de RiesgoRESUMEN
The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community-based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct-acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0-18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4-96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7-98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI -0.24-0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.
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Competencia Clínica , Hepatitis C/epidemiología , Atención al Paciente , Pautas de la Práctica en Medicina , Telemedicina , Adulto , Anciano , Antivirales/uso terapéutico , Argentina/epidemiología , Quimioterapia Combinada , Femenino , Geografía , Hepatitis C/diagnóstico , Hepatitis C/terapia , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Respuesta Virológica Sostenida , Telemedicina/métodosRESUMEN
GOALS: We aim to describe the efficacy, safety profile, and variables associated with survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib in South America. BACKGROUND: Sorafenib has been shown to improve survival in patients with advanced HCC. There are few data on sorafenib use for HCC in South America. STUDY: We performed a retrospective analysis of HCC cases treated with sorafenib from 8 medical centers in 5 South American countries, between January 2010 and June 2017. The primary endpoint was overall survival (OS), which was defined as time from sorafenib initiation to death or last follow-up. Risk factors for decreased OS were assessed using Cox proportional hazard regression and log-rank tests. RESULTS: Of 1336 evaluated patients, 127 were treated with sorafenib and were included in the study. The median age of individuals was 65 years (interquartile range, 55 to 71) and 70% were male individuals. Median OS in all patients was 8 months (interquartile range, 2 to 17). Variables associated with survival on multivariate analysis were platelets >/<250,000 mm (2 vs. 8 mo, P=0.01) and Barcelona Clinic Liver Cancer (BCLC) stage (A/B, 13 vs. C/D, 6 mo; P=0.04). In a subanalysis of patients with BCLC stage C, platelets >/<250,000 mm were also independently associated with survival (2 vs. 5.5 mo, P=0.03). Patients lived longer if they experienced any side effects from sorafenib use (11 vs. 2 mo, P=0.009). Patients who stopped sorafenib because of side effects had shorter survival compared with patients who were able to tolerate side effects and continue treatment (7.5 vs. 13 mo, P=0.01). CONCLUSIONS: Pretreatment elevation of platelets and advanced BCLC stage were independently associated with poor survival on sorafenib in a South American cohort.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Plaquetas/metabolismo , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Sorafenib/efectos adversos , América del Sur , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America. METHODS: We evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations. RESULTS: Sixty-eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV-related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance, and there was no difference in age of diagnosis between those diagnosed incidentally vs by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (P = .01). CONCLUSIONS: Our study represents the largest cohort to date reporting characteristics and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programmes, with associated increased mortality in those patients.
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Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Datos Preliminares , Estudios Retrospectivos , Factores de Riesgo , América del Sur/epidemiología , Resultado del TratamientoAsunto(s)
Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Demografía , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , América del Sur/epidemiología , Adulto JovenRESUMEN
There is scarce data pertaining to acute hepatitis C (aHC) infection in South America. We aimed to describe clinical characteristics and evolution of aHC in a South American cohort. A retrospective survey was conducted at 13 hepatology units. All patients ≥16 years old with aHC diagnosis were included. Demographic, clinical and outcome information were registered in a standardized ad hoc questionnaire. Sixty-four patients were included. The majority were middle-aged (median age: 46 years) and female (65.6%); most of them were symptomatic at diagnosis (79.6%). HCV-1 was the most prevalent genotype (69.2%). Five patients had liver failure: three cases of severe acute hepatitis, one case of fulminant hepatitis and one case of acute-on-chronic liver failure. Nosocomial exposure was the most prevalent risk factor. Evolution was assessed in 46 patients. In the untreated cohort, spontaneous resolution occurred in 45.8% and was associated with higher values of AST/ALT and with the absence of intermittent HCV RNA viremia (P = 0.01, 0.05, and 0.01, respectively). In the treated cohort, sustained virological response was associated with nosocomial transmission and early treatment initiation (P = 0.04 each). The prevalence of nosocomial transmission in this South-American cohort of aHC stresses the importance of following universal precautions to prevent HCV infection. J. Med. Virol. 89:276-283, 2017. © 2016 Wiley Periodicals, Inc.
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Hepatitis C/epidemiología , Hepatitis C/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Infección Hospitalaria/epidemiología , Infección Hospitalaria/patología , Infección Hospitalaria/transmisión , Transmisión de Enfermedad Infecciosa , Femenino , Hepatitis C/transmisión , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , América del Sur/epidemiología , Encuestas y Cuestionarios , Viremia , Adulto JovenRESUMEN
BACKGROUND & AIMS: Hepatocyte apoptosis, the hallmark of non-alcoholic steatohepatitis (NASH) contributes to liver injury and fibrosis. Although, both the intrinsic and extrinsic apoptotic pathways are involved in the pathogenesis of NASH, the final common step of apoptosis is executed by a family of cysteine-proteases termed caspases. Thus, our aim was to ascertain if administration of Emricasan, a pan-caspase inhibitor, ameliorates liver injury and fibrosis in a murine model of NASH. METHODS: C57/BL6J-mice were fed regular chow or high fat diet (HFD) for 20 weeks. All mice were treated with vehicle or Emricasan. RESULTS: Mice fed a HFD diet demonstrate a five-fold increase in hepatocyte apoptosis by the TUNEL assay and a 1.5-fold and 1.3-fold increase in caspase-3 and-8 activities respectively; this increase in apoptosis was substantially attenuated in mice fed a HFD treated with Emricasan (HFD-Em). Likewise, liver injury and inflammation were reduced in mice fed HFD-Em as compare to HFD by measuring serum aspartate aminotransferase and alanine aminotransferase levels, NAS histological score and IL 1-ß, TNF-α, monocyte chemoattractant protein (MCP-1) and C-X-C chemokine ligand-2 (CXCL2) quantitative reverse-transcription polymerase chain reaction (qPCR). These differences could not be attributed to differences in hepatic steatosis as liver triglycerides content were similar in both HFD groups. Hepatic fibrosis was reduced by Emricasan in HFD animals by decreasing αSMA (a marker for hepatic stellate cell activation), fibrosis score, Sirius red staining, hydroxyproline liver content and profibrogenic cytokines by qPCR. CONCLUSION: In conclusion, these data demonstrate that in a murine model of NASH, liver injury and fibrosis are suppressed by inhibiting hepatocytes apoptosis and suggests that Emricasan may be an attractive antifibrotic therapy in NASH.
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Apoptosis/efectos de los fármacos , Inhibidores de Caspasas/uso terapéutico , Hepatocitos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Ácidos Pentanoicos/uso terapéutico , Animales , Inhibidores de Caspasas/farmacología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Fibrosis , Hepatitis/prevención & control , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Ácidos Pentanoicos/farmacologíaRESUMEN
BACKGROUND & AIM: Retrospective studies show an association between proton pump inhibitor (PPI) therapy and spontaneous bacterial peritonitis (SBP). We investigate the relationship between PPI and SBP in decompensated cirrhotic patients in a large nationwide prospective study. METHODS: Seven hundred seventy patients with a diagnosis of decompensated cirrhosis were admitted consecutively in 23 hospitals in Argentina from March 2011 to April 2012; the patients were carefully investigated for PPI consumption in the previous 3 months. In total, 251 patients were excluded because of active gastrointestinal hemorrhage, antibiotic use during the preceding weeks, HIV-positive status and immunosuppressive therapy. RESULTS: Two hundred twenty-six out of 519 patients (43.5%) had received PPI therapy within the last 3 months. In 135 patients, PPIs were administered for longer than 2 weeks. A bacterial infection was shown in 255 patients (49.1%). SBP was diagnosed in 95 patients out of 394 patients with ascites (24.7%). There was no significant difference in the rate of PPI consumption between the infected and the non-infected patients (44.3% vs. 42.8%) or between the SBP patients and the patients with ascites without SBP (46% vs. 42%). In the SBP patients, the duration of PPI administration did not influence the rate of SBP occurrence. The type of bacteria and the origin of SBP infection were similar in the patients with and without PPI. CONCLUSION: In the current large, multicenter, prospective study, PPI therapy, specifically evaluated at admission of consecutive cirrhotic patients, was not associated with a higher risk of SBP.
Asunto(s)
Infecciones Bacterianas , Cirrosis Hepática , Peritonitis , Inhibidores de la Bomba de Protones , Adulto , Anciano , Argentina/epidemiología , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/etiología , Infecciones Bacterianas/terapia , Progresión de la Enfermedad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Pruebas de Función Hepática/métodos , Masculino , Persona de Mediana Edad , Peritonitis/diagnóstico , Peritonitis/epidemiología , Peritonitis/etiología , Peritonitis/terapia , Estudios Prospectivos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Medición de Riesgo , Factores de Riesgo , Estadística como AsuntoRESUMEN
La infección crónica por la hepatitis B representa una importante carga sanitariaen el mundo y en Argentina. Existen varias estrategias terapéuticas, cuyo objetivoes la reducción de la carga viral.ObjetivosEvaluar la costo-efectividad de las diferentes estrategias de tratamiento, tantoen pacientes positivos como negativos al antígeno e de hepatitis B (HBeAg).MétodosSe utilizó un modelo de decisión con los estados de salud de la hepatitis B. Secombinaron datos de eficacia, riesgos relativos y estadísticas vitales nacionalese internacionales. Se recabaron los costos de tratamientos y de eventos clínicosdesde la perspectiva del seguro social. Se efectuaron diversos análisis de sensibilidadde una vía.ResultadosEl tenofovir se asoció con menores costos y mayor eficacia. Esto se demostrótanto en pacientes positivos como negativos al HBeAg, donde se observó queel tratamiento con tenofovir permitía un ahorro, con un costo inferior a un productobruto interno per cápita por año de vida ajustado por calidad y tasa decosto-efectividad incremental dominante en ambos escenarios. Los resultadosfueron robustos, ya que los análisis de sensibilidad confirmaron los valores delescenario base (con el costo del tenofovir como la variable de mayor influencia).ConclusionesDesde la perspectiva de seguridad social, el tratamiento con tenofovir resultóser ahorrativo en términos de costos, comparado con las demás estrategias terapéuticas.Estos modelos podrían ser de utilidad para la toma de decisionespor parte de las autoridades de salud pública de la Provincia de Misiones.
Asunto(s)
Análisis Costo-Beneficio , Becas , Virus de la Hepatitis BRESUMEN
AIMS: Obesity arises on defective neuroendocrine pathways that increase energy intake and reduce mitochondrial metabolism. In the metabolic syndrome, mitochondrial dysfunction accomplishes defects in fatty acid oxidation and reciprocal increase in triglyceride content with insulin resistance and hyperglycemia. Mitochondrial inhibition is attributed to reduced biogenesis, excessive fission, and low adipokine-AMP-activated protein kinase (AMPK) level, but lateness of the respiratory chain contributes to perturbations. Considering that nitric oxide (NO) binds cytochrome oxidase and inhibits respiration, we explored NO as a direct effector of mitochondrial dysfunction in the leptin-deficient ob/ob mice. RESULTS: A remarkable three- to fourfold increase in neuronal nitric oxide synthase (nNOS) expression and activity was detected by western blot, citrulline assay, electronic and confocal microscopy, flow cytometry, and NO electrode sensor in mitochondria from ob/ob mice. High NO reduced oxygen uptake in ob/ob mitochondria by inhibition of complex IV and nitration of complex I. Low metabolic status restricted ß-oxidation in obese mitochondria and displaced acetyl-CoA to fat synthesis; instead, small interference RNA nNOS caused a phenotype change with fat reduction in ob/ob adipocytes. INNOVATION: We evidenced that leptin increases mitochondrial respiration and fat utilization by potentially inhibiting NO release. Accordingly, leptin administration to ob/ob mice prevented nNOS overexpression and mitochondrial dysfunction in vivo and rescued leptin-dependent effects by matrix NO reduction, whereas leptin-Ob-Rb disruption increased the formation of mitochondrial NO in control adipocytes. We demonstrated that in ob/ob, hypoleptinemia is associated with critically low mitochondrial p-AMPK and that, oppositely to p-Akt2, p-AMPK is a negative modulator of nNOS. CONCLUSION: Thereby, defective leptin-AMPK pathway links mitochondrial NO to obesity with complex I syndrome and dysfunctional mitochondria.
Asunto(s)
Adenilato Quinasa/metabolismo , Leptina/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Óxido Nítrico/metabolismo , Obesidad/metabolismo , Animales , Western Blotting , Ácidos Grasos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Microscopía Confocal , Microscopía Electrónica , Mitocondrias/ultraestructura , Óxido Nítrico Sintasa de Tipo I/genética , Óxido Nítrico Sintasa de Tipo I/metabolismo , ARN Interferente Pequeño , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
The publication of scientific findings is the main way to communicate advances. Our aim was to perform a bibliometric and comparative analysis of the Argentinean gastroenterological research output. We analyzed Argentinean gastroenterological publications selectively retrieved from LILACS (between years 1982-2006) and EMBASE (1996-2007) databases by means of specially constructed filter based on author address and subject headings. The global Argentinean scientific research output is far below that of developed countries and has been affected in direct manner by economic, political and social disturbances in the country. The gastroenterological research output from Argentina represent about 6% of national biomedical research. While 54% belongs to gastroenterology and 46% to hepatology, 65% are based on clinical research and 67% were originally contributions. Only 11% have been published in high impact factor journals. The comparative analysis within countries with health indicators similarities has shown a low biomedical and gastroenterology research output, however, the rate of acceptance at the 18 top gastroenterological journals is acceptable (15%). The contributions of registered specialists were lower for gastroenterologists compared with those from hepatologists (8.7% and 16.4% respectively). The research projects at public hospital funded by the pharmaceutical industry overcome those funded independently. Indeed, it seems that the independent research is being progressively replaced by that supported by the industry due to economic benefits for researchers even when there is a very low participation rate in publications (3%) by Argentinean researchers. We conclude that the Argentinean biomedical and gastroenterological research output is scanty compared with developed countries and countries with comparable health indicators. Our analysis suggests that efforts must be taken to attain objectives directed to develop and improve the Argentinean biomedical and gastroenterological scientific work and publication.