Inmunopatogénesis de la hepatitis C.

El conocimiento de la patogénesis de la infección crónica por el virus de la hepatitis C (VHC) es crucial tanto para la determinación de una terapia antiviral exitosa como para encontrar una vacuna. En este trabajo se explica como inmediatamente después de la infección por el VHC, este se replica eficientemente, induciendo la producción de interferones tipo I, sin embargo, el rápido incremento en la replicación viral no es reconocido en forma adecuada por la respuesta inmune adaptativa y después de un intervalo corto, la carga viral se incrementa y persiste en la mayoría de los individuos infectados. Se considera que este fenómeno tiene una naturaleza inmunológica, que involucra tanto a linfocitos T citotóxicos, como a un mecanismo indirecto que implica la síntesis de citocinas que son inducidas por el VHC. Se considera que si ocurre una respuesta insuficiente o inadecuada de células T (CD4+ y CD8+) específicas del virus, el ARN-VHC persiste en células T hepáticas, situación que se observa aún en aquellos individuos que alcanzan una respuesta terapéutica con una inhibición viral considerada como sostenida. El VHC ha desarrollado varias estrategias para escapar a la erradicación mediada por las células T, que incluye interferir con la vía de presentación de las moléculas del Complejo Mayor de Histocompatibilidad (MHC) Clase I del huésped o teniendo un “escondite” en células a las que les falta la expresión de las MHC clase I. Finalmente, se describe y reconoce la importancia que tienen varias citocinas en la respuesta inmune por el huésped posterior a la exposición al VHC

Evaluation of IL-12 and CXCL-10 in patients with hepatitis C, non-alcoholic fatty liver disease and liver damage for alcohol consumption

Introduction and Objectives: To Compare serum levels of IL-12 and CXCL-10 in different etiologies of liver disease. Materials and methods: A cross-sectional and multicenter study was carried out, including subjects with alcoholism according to criteria WHO, without (OH) and with liver injury (cirrhosis, CiOH) and (Alcoholic Hepatitis, HA); non-alcoholic fatty liver (NAFLD) and chronic Hepatitis C (CHC), diagnosed by clinical, biochemical data. They were compared with subjects control (CT). For determination of IL-12 and CXCL-10 with Multiplex®-MERCK©. Statistical analysis by SPSS V.22 using U de Mann Whitney, p<0.05; values expressed as mean ± standard error. Results: Included 20 subjects with NAFLD, 78 CHC, 14 HA, 20 CiOH, 15 OH y 60 CT. IL-12 was found elevated in OH, HA, CHC vs. CT in OH vs. HCc y HGNA (p≤0.05). CXCL-10 was found elevated in CiOH, HA and CHC vs. CT(p≤0.050). Discussion: The IL-12 showed elevated levels in subjects with alcohol consumption and CHC vs. CT that activates other cell types involved in inflammation. CXCL-10 is induced by IFN-γ, was found elevated in CiOH, HA and CHC, exerting their biological effects through CXCR3, including activation of peripheral immune cells and apoptosis. The ratio of IL-12/CXCL-10 in OH increased 4.6 times, ratifying the participation in chronic and continual inflammatory response by alcohol consumption. Conclusions: IL-12 and CXCL-10 have an important role in alcohol-induced liver disease, confirming their contribution to inflammation, being evident CXCL-10 in advanced stages of the disease, by stimulating and favoring the migration of immune cells to the damage sites. Funding: This work was partially financed by CONACyT SALUD-2016-272579 and PAPIIT- UNAM TA200515. Declaration of interest: The authors declare no potential conflicts of interest

Consenso Mexicano de Hepatitis Alcohólica

La hepatitis alcohólica es una condición frecuente en la población mexicana, se caracteriza por insuficiencia hepática aguda sobre crónica, importante reacción inflamatoria sistémica y fallo multiorgánico, que en la variante grave de la enfermedad implica una elevada mortalidad. Por lo anterior, la Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Hepatología conjuntaron un equipo multidisciplinario de profesionales de la salud para elaborar el primer consenso mexicano de hepatitis alcohólica. El consenso fue elaborado con la metodología Delphi, emitiendo 37 recomendaciones. La enfermedad hepática relacionada con el consumo de alcohol comprende un amplio espectro, que incluye esteatosis, esteatohepatitis, fibrosis en diferentes grados, cirrosis y sus complicaciones. La hepatitis alcohólica grave se define por una función modificada de Maddrey ≥ 32 o por un puntaje de MELD (Model for End- Stage Liver Disease) igual o mayor a 21. Actualmente no existe un biomarcador específico para el diagnóstico. La presencia de leucocitosis con neutrofilia, hiperbilirrubinemia (> 3 mg/dL),AST > 50 U/L ( 1.5-2 pueden orientar al diagnóstico. La piedraangular del tratamiento es la abstiencia junto con el soporte nutricional. Los esteroides estanindicados en la forma grave, en donde han resultado efectivos para reducir la mortalidad a28 días. El trasplante hepático es en la actualidad la única opción con que se cuenta parasalvar la vida de pacientes que no responden a los esteroides. Ciertos fármacos, como la N-acetilcisteína, el factor estimulante de colonias de granulocitos y la metadoxina, pueden seruna terapia adyuvante que puede mejorar la supervivencia de los pacientes

The Mexican consensus on alcoholic hepatitis

Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resultingin 37 recommendations. Alcohol-related liver disease covers a broad spectrum of patholo-gies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and itscomplications. Severe alcoholic hepatitis is defined by a modified Maddrey’s discriminant func-tion score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21.There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyper-bilirubinemia (>3 mg/dl), AST > 50 U/l ( 1.5-2 can guide thediagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone oftreatment. Steroids are indicated for severe disease and have been effective in reducing the28-day mortality rate. At present, liver transplantation is the only life-saving option for patientsthat are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colonystimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patientsurvival

Consenso Mexicano para el Tratamiento de la Hepatitis C

El objetivo del Consenso Mexicano para el Tratamiento de la Hepatitis C fue el de desarrollar un documento como guía en la práctica clínica con aplicabilidad en México. Se tomó en cuenta la opinión de expertos en el tema con especialidad en: gastroenterología, infectología y hepatología. Se realizó una revisión de la bibliografía en MEDLINE, EMBASE y CENTRAL mediante palabras claves referentes al tratamiento de la hepatitis C. Posteriormente se evaluó la calidad de la evidencia mediante el sistema GRADE y se redactaron enunciados, los cuales fueron sometidos a voto mediante un sistema modificado Delphi, y posteriormente se realizó revisión y corrección de los enunciados por un panel de 34 votantes. Finalmente se clasificó el nivel de acuerdo para cada oración. Esta guía busca dar recomendaciones con énfasis en los nuevos antivirales de acción directa y de esta manera facilitar su uso en la práctica clínica. Cada caso debe ser individualizado según sus comorbilidades y el manejo de estos pacientes siempre debe ser multidisciplinario. Abstract The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary

Los criterios de elegibilidad actuales del Seguro Popular para recibir tratamiento para el virus de la hepatitis C

Pocas cosas han avanza­do tanto como el tratamiento contra el virus de la hepatitis C (VHC). Se tienen antivirales de acción direc­ta (AAD) con los que se obtienen respuestas virales sostenidas (RVS) mayores a 90%, pero el costo de estos medicamentos es prohibitivo para los sistemas de salud

Acciones prioritarias para un programa nacional de detección, tratamiento y seguimiento de pacientes con hepatitis C

En el escenario de la salud mexicana, la epidemia por virus de la hepatitis C se encuentra presente junto con sus co­morbilidades y mortalidad prematura. Actuar de manera inmediata permitirá una contención de la misma en el corto plazo dada la existencia de herramientas de prevención, diagnóstico y terapias farmacológicas altamente eficaces. La Coalición para el estudio de la hepatitis C en México ha desarrollado una postura donde aprovecha esas medidas de contención y presenta el desarrollo de un programa nacional para la detección, tratamiento oportuno y seguimiento de pacientes con hepatitis C

Risk factors associated with prolonged hospital length-of-stay: 18-year retrospective study of hospitalizations in a tertiary healthcare center in Mexico.

BACKGROUND:Hospital length-of-Stay has been traditionally used as a surrogate to evaluate healthcare efficiency, as well as hospital resource utilization. Prolonged Length-of-stay (PLOS) is associated with increased mortality and other poor outcomes. Additionally, these patients represent a significant economic problem on public health systems and their families. We sought to describe and compare characteristics of patients with Normal hospital Length-of-Stay (NLOS) and PLOS to identify sociodemographic and disease-specific factors associated with PLOS in a tertiary care institution that attends adults with complicated diseases from all over Mexico. MATERIALS AND METHODS:We conducted a retrospective analysis of hospital discharges from January 2000-December 2017 using institutional databases of medical records. We compared NLOS and PLOS using descriptive and inferential statistics. PLOS were defined as those above the 95th percentile of length of hospitalization. RESULTS:We analyzed 85,904 hospitalizations (1,069,875 bed-days), of which 4,427 (5.1%) were PLOS (247,428 bed-days, 23.1% of total bed-days). Hematological neoplasms were the most common discharge diagnosis and surgery of the small bowel was the most common type of surgery. Younger age, male gender, a lower physician-to-patient ratio, emergency and weekend admissions, surgery, the number of comorbidities, residence outside Mexico City and lower socioeconomic status were associated with PLOS. Bone marrow transplant (OR 18.39 [95% CI 12.50-27.05, p<0.001), complex infectious diseases such as systemic mycoses and parasitoses (OR 4.65 [95% CI 3.40-6.63, p<0.001), and complex abdominal diseases such as intestinal fistula (OR 2.57 [95% CI 1.98-3.32) had the greatest risk for PLOS. Risk of mortality in patients with PLOS increased more than threefold (3.7% vs 13.3%, p<0.001). CONCLUSIONS:We report some key sociodemographic and disease-specific differences in patients with PLOS. These could serve to develop a specific model of directed hospital healthcare for patients identified as in risk of PLOS

Territorial Strategy of Medical Units for Addressing the First Wave of the COVID-19 Pandemic in the Metropolitan Area of Mexico City: Analysis of Mobility, Accessibility and Marginalization

Background. The COVID-19 pandemic has caused an exponential increase in the demand for medical care worldwide. In Mexico, the COVID Medical Units (CMUs) conversion strategy was implemented. Objective. To evaluate the CMU coverage strategy in the Mexico City Metropolitan Area (MCMA) by territory. Materials. The CMU directory was used, as were COVID-19 infection and mobility statistics and Mexican 2020 census information at the urban geographic area scale. The degree of urban marginalization by geographic area was also considered. Method. Using descriptive statistics and the calculation of a CMU accessibility index, population aggregates were counted based on coverage radii. In addition, two regression models are proposed to explain (1) the territorial and temporal trend of COVID-19 infections in the MCMA and (2) the mobility of the COVID-infected population visiting medical units. Results. The findings of the evaluation of the CMU strategy were (1) in the MCMA, COVID-19 followed a pattern of contagion from the urban center to the periphery; (2) given the growth in the number of cases and the overload of medical units, the population traveled greater distances to seek medical care; (3) after the CMU strategy was evaluated at the territory level, it was found that 9 out of 10 inhabitants had a CMU located approximately 7 km away; and (4) at the metropolitan level, the lowest level of accessibility to the CMU was recorded for the population with the highest levels of marginalization, i.e., those residing in the urban periphery