Challenges and Strategies for Access to Treatment of Hepatitis C in Latin America

With the advent of all oral direct-acting antiviral drugs (DAAs) with a low incidence of side effects and very high success rates, we are entering an exciting new era in the treatment of hepatitis C virus (HCV), and now the major goal is the elimination of this viral infection. However, at least in Latin America, there are multiple barriers that must be attended

Variation in _PNPLA3_ is associated with outcomes in alcoholic liver disease

Two recent genome-wide association studies have described associations of SNP variants in _PNPLA3_ with nonalcoholic fatty liver and plasma liver enzyme levels in population based cohorts. We investigated the contributions of these variants to clinical outcomes in Mestizo subjects with a history of excessive alcohol consumption. We show that non-synonymous variant rs738409[G] (I148M) in _PNPLA3_ is strongly associated with alcoholic liver disease and progression to alcoholic cirrhosis (unadjusted OR = 2.25, P = 1.7x10^-10^; ancestry-adjusted OR = 1.79, P = 1.9x10^-5^)

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

Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers

Background: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity. Aim: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern. Methods: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p\u3c0.05. Results: The Binge drinking group showed increased γGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: Early Activation represented by CD69 and TLR4 expression in the CD8 population; Effector Activation by CD69 expression in CD8 CD127(+)CD137(+) and CD8 CD25(+) CD137(+); and Trafficking by CXCR4 expression on total CD8 and CD8 GB(+)CXCR4(+), and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor. Conclusions: Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest recent activation, decreased sensitivity to LPS and lower migration capacity in response to chemokines SDF-1 and MCP-1. These results indicate that a binge-drinking pattern of alcohol consumption may induce an altered immune profile that could be related with liver damage and the increased susceptibility to infection reported to this behavior

The quest for universal health coverage: achieving social protection for all in Mexico

Mexico is reaching universal health coverage in 2012. A national health insurance programme called Seguro Popular, introduced in 2003, is providing access to a package of comprehensive health services with financial protection for more than 50 million Mexicans previously excluded from insurance. Universal coverage in Mexico is synonymous with social protection of health. This report analyses the road to universal coverage along three dimensions of protection: against health risks, for patients through quality assurance of health care, and against the financial consequences of disease and injury. We present a conceptual discussion of the transition from labour-based social security to social protection of health, which implies access to effective health care as a universal right based on citizenship, the ethical basis of the Mexican reform. We discuss the conditions that prompted the reform, as well as its design and inception, and we describe the 9-year, evidence-driven implementation process, including updates and improvements to the original programme. The core of the report concentrates on the effects and impacts of the reform, based on analysis of all published and publically available scientific literature and new data. Evidence indicates that Seguro Popular is improving access to health services and reducing the prevalence of catastrophic and impoverishing health expenditures, especially for the poor. Recent studies also show improvement in effective coverage. This research then addresses persistent challenges, including the need to translate financial resources into more effective, equitable and responsive health services. A next generation of reforms will be required and these include systemic measures to complete the reorganisation of the health system by functions. The paper concludes with a discussion of the implications of the Mexican quest to achieve universal health coverage and its relevance for other low-income and middle-income countries

Noninvasive Biomarkers for the Diagnosis of Liver Fibrosis and Cirrhosis

The clinical importance of monitoring liver fibrosis lies in the morbidity and mortality of the chronic liver diseases in relation to the stage and progression of fibrosis. Whether the fibrosis stabilizes or regresses depends on the specific treatment. Liver biopsy, the current standard for the diagnosis, has implicit limitations due to sampling heterogeneity. There are noninvasive imaging methods, such as transient elastography that measures the stiffness of the liver, but it has some limitations (feasibility and unreliability), particularly in obese patients. FibroTest is the most widely used noninvasive serological method worldwide which is efficacious in the extreme stages of fibrosis, but these methods cannot discern intermediate stages. Liver fibrosis is a dynamic response that involves multiple cellular and molecular events with an excessive deposit of extracellular matrix. Even though there is much information on the pathophysiology of fibrosis, that knowledge is still incomplete, greatly hindering the development of both an accurate treatment and a noninvasive diagnostic method with adequate sensitivity for all the stages of fibrosis. It is known that IGFBP participates in liver homeostasis, and thus these proteins can be used as serum biomarkers during the progression of liver fibrosis in chronic hepatitis C

Cellular Senescence in Livers from Children with End Stage Liver Disease

Senescent cells occur in adults with cirrhotic livers independent of the etiology. Aim: Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease. staining occurred in the areas of ductular transformation and in the interlobular bile ducts.Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression

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