Advances in the Elimination of Viral Hepatitis in Mexico: A Local Perspective on the Global Initiative.

Viral hepatitis (A-E) presents a major global health challenge. In 2015, the World Health Organization (WHO) launched an initiative to eliminate viral hepatitis, with the aim of reducing new infections by 90% and deaths by 65% by 2030. Mexico is one of 38 focus countries identified by the WHO, collectively accounting for 80% of global infections and deaths. While hepatitis B and C are commonly diagnosed in Mexico, routine diagnosis for hepatitis D and E is lacking, with no specific epidemiological data available. In 2020, Mexico implemented the National Hepatitis C Elimination Program, focusing on preventing new infections, reducing complications like cirrhosis and hepatocellular carcinoma, ensuring access to treatment, and improving patient care. However, this program has not been extended to hepatitis B and E. Addressing the challenges of viral hepatitis control in Mexico requires increased resource allocation, expanded diagnosis, vaccination for hepatitis A and B, and treatment coverage for hepatitis B and C, along with multisectoral engagement. This work provides an overview of Mexico's response to the global initiative, highlighting its progress, challenges, and areas of opportunity.

Age and Comorbidities as Risk Factors for Severe COVID-19 in Mexico, before, during and after Massive Vaccination.

During 2020-2023, Mexico had a large COVID-19 emergency with >331,000 adult deaths and one of the highest excess mortalities worldwide. Age at COVID-19 death has been lower in Mexico than in high-income countries, presumably because of the young demographics and high prevalence of chronic metabolic diseases in young and middle-aged adults. SARS-CoV-2 vaccination covered 85% of adults with at least one dose and 50% with booster(s) up to April 2022. No new vaccination efforts or updated boosters were introduced until October 2023; thus, we explored the public health impact of massive SARS-CoV-2 vaccination against ancestral strains and asked whether their real-world protection has persisted through time. We compared three periods with respect to vaccine roll-outs: before, during and after vaccine introduction in a national retrospective cohort of >7.5 million COVID-19 cases. The main findings were that after vaccination, COVID-19 mortality decreased, age at COVID-19 death increased by 5-10 years, both in populations with and without comorbidities; obesity stopped being a significant risk factor for COVID-19 death and protection against severe disease persisted for a year after boosters, including at ages 60-79 and 80+. Middle-aged adults had the highest protection from vaccines/hybrid immunity and they more than halved their proportions in COVID-19 deaths.

Donated Blood Screening for HIV, HCV and HBV by ID-NAT and the Residual Risk of Iatrogenic Transmission in a Tertiary Care Hospital Blood Bank in Puebla, Mexico.

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) can be transmitted by blood transfusion. Most transmission occurs during the acute viremic phase (AVP), before antibody development. To reduce transmission risk, individual donor nucleic acid testing (ID-NAT) is used. In Puebla, Mexico, serological tests and ID-NAT have been applied to screen blood donors and detect individuals in AVP. In the present study, 106,125 blood donors' data in two periods (2012-2015 and 2017-2019) were analyzed. The residual risk (RR) values were calculated considering ID-NAT results. The RR for HIV was 14 in 1 million donations or 1 in 71,428, the RR for HVC was 6.8 in 1 million donations or 1 in 147,058 and, for HBV, it was 156 in 1 million donations, or 1 in 6410. Previously, it was predicted that the transmission RR of these viruses would be reduced in Mexico through better screening with NAT. The use of ID-NAT has, indeed, increased the safety of blood reserves for HIV and HCV. However, more research is needed to determine why the residual risk of HBV did not decrease as much over the study period. ID-NAT is an important complementary tool for blood donor screening that should be implemented.

[Epidemiological Panorama of Cervical Dysplasia in a First-Level Care Unit]. / Panorama epidemiológico de las displasias cervicales en una unidad de primer nivel de atención.

Background: Cervical cancer (CaCU) is the second cancer-related cause of death for women in Mexico. Early diagnosis and monitoring of patients by cervical cytology and colposcopy are currently the preferred screening methods for identification and prevention of this disease. Objective: To describe the epidemiological panorama of cervical dysplasia diagnosed in a first-level care hospital. Methods: The study was observational, retrospective, unicentric, homodemic, transversal. Records from 6,207 women who attended the General Subzone Hospital with Familiar Medicine #8 (HGSZ/UMF 8), in Tlaxcala, Mexico were analyzed. First-time cervical cytologies were analyzed from 2019 to 2021. Results: Cervical dysplasia was found in 2.6% of the patients being the most frequent type of dysplasia NIC 1. Most of the clinical characteristics of patients with dysplasia were in agreement with those of the Mexican population. Important differences were found (comorbilities, mass index, number of sexual partners, births, positivity to changes related to HPV and vaccination) between two population sets defined by age (younger and older than 40 years). Conclusions: The only factor where a tendency to be associated to type 2 and 3 dysplasia in the population younger than 40 years was the sexually active onset of life younger than 18 years, so this possible association should be evaluated in a bigger population. Our data suggests that risks factors should be evaluated separately for these age groups due to important differences regarding their clinic and epidemiological characteristics as well as changes in risk factor exposure.

Introducción: en México, el cáncer cervicouterino (CaCU) es la segunda causa de mortalidad por cáncer en mujeres. El diagnóstico temprano y monitoreo mediante la citología cervicovaginal y la colposcopía son actualmente los métodos de tamizaje de elección para identificar y prevenir esta enfermedad. Objetivo: describir el panorama epidemiológico de displasias cervicales en un hospital de primer nivel de atención. Métodos: estudio observacional, retrospectivo, unicéntrico, homodémico, transversal. Se analizaron los expedientes de 6207 mujeres atendidas en el HGSZ/UMF No. 8, en Tlaxcala, con citologías vaginales de primera vez, durante 2019-2021. Resultados: se encontró displasia en el 2.6% de las pacientes. El tipo de displasia más frecuente fue NIC 1. Las características clínicas de las pacientes con displasia corresponden a las reportadas en población mexicana, pero se encontraron diferencias importantes (comorbilidades, IMC, NPS, gestas, positividad para cambios asociados al VPH y vacunación) entre dos tipos de población etaria (menores y mayores de 40 años). Conclusiones: el único factor donde hubo una tendencia de asociación al desarrollo de displasia tipo 2 y 3 en la población de más de 40 años fue el inicio de la vida sexual activa antes de los 18 años, por lo que se recomienda buscar una asociación en una población de mayor tamaño y evaluar factores de riesgo en los grupos etarios de manera separada por sus diferencias clínicas, epidemiológicas y factores de riesgo a los que están expuestas.

The effectiveness of a "EspaiJove.net"- a school-based intervention programme in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population: a cluster randomised controlled trial.

BACKGROUND: The aim of this study is to evaluate the short- and long-term effects of the universal mental health literacy intervention "EspaiJove.net" in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population. We also examine whether these effects depend on the intervention intensity.  METHODS: A clustered school-based randomised controlled trial (cRCT) design. SUBJECTS: 1,298 secondary pupils aged 13 and 14 were recruited from 18 schools in Barcelona (Spain) between September 2016 and January 2018. INTERVENTION: Three programmes were assessed: 1) Sensitivity Programme (SP; 1 h); 2) Mental Health Literacy (MHL; 6 h); 3) MHL plus a first-person Stigma Reduction Programme (MHL + SR; 7 h); 4) Control group (CG): waiting list. OUTCOME MEASURES: 1) MHL: EspaiJove.net EMHL Test (First part and Second Part); 2) Stigma: RIBS and CAMI; 3) Help-seeking and use of treatment: GHSQ. ANALYSIS: The data was collected at baseline, post-intervention and 6 and 12 months later. An intention-to-treat analysis and imputation method was used to analyse the missing data. Intervention effects were analysed using multilevel modelling. RESULTS: One thousand thirty-two students were included (SP = 225; MHL = 261; MHL + SR = 295 and CG = 251). The MHL and MHL + SR interventions showed short- and long-term an increase in knowledge compared to SP and CG, but no significant change post-intervention or over time (First part p = 0.52 and Second part p = 0.62) between intervention groups and CG. No significant changes were found in stigma scores post-intervention or over time (CAMI p = 0.61 and RIBS p = 0.98) or in help-seeking scores (parent p = 0.69; teacher p = 0.23 and healthcare professional p = 0.75). The MHL + SR intervention was the best valued and recommended (p < 0.005). CONCLUSIONS: The three interventions of the EspaiJove.net programme (SP, MHL and MHL + SR) seem not to be effective in terms MHL, Stigma and help-seeking behaviours. The contact with a person who has experimented mental illness first-hand did not reduce stigma attitudes. Further research should deal with the heterogeneity of MHL interventions (concept, duration and measures) and identify which components of stigma interventions are effective. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03215654 (registration date 12 July 2017).

Decrease in COVID-19 adverse outcomes in adults during the Delta and Omicron SARS-CoV-2 waves, after vaccination in Mexico.

Mexico, one of the countries severely affected by COVID-19, accumulated more than 5. 1 all-cause excess deaths/1,000 inhabitants and 2.5 COVID-19 confirmed deaths/1,000 inhabitants, in 2 years. In this scenario of high SARS-CoV-2 circulation, we analyzed the effectiveness of the country's vaccination strategy that used 7 different vaccines from around the world, and focused on vaccinating the oldest population first. We analyzed the national dataset published by Mexican health authorities, as a retrospective cohort, separating cases, hospitalizations, deaths and excess deaths by wave and age group. We explored if the vaccination strategy was effective to limit severe COVID-19 during the active outbreaks caused by Delta and Omicron variants. Vaccination of the eldest third of the population reduced COVID-19 hospitalizations, deaths and excess deaths by 46-55% in the third wave driven by Delta SARS-CoV-2. These adverse outcomes dropped 74-85% by the fourth wave driven by Omicron, when all adults had access to vaccines. Vaccine access for the pregnant resulted in 85-90% decrease in COVID-19 fatalities in pregnant individuals and 80% decrease in infants 0 years old by the Omicron wave. In contrast, in the rest of the pediatric population that did not access vaccination before the period analyzed, COVID-19 hospitalizations increased >40% during the Delta and Omicron waves. Our analysis suggests that the vaccination strategy in Mexico has been successful to limit population mortality and decrease severe COVID-19, but children in Mexico still need access to SARS-CoV-2 vaccines to limit severe COVID-19, in particular those 1-4 years old.

Long-Term Outcomes of Dose-Escalated Hypofractionated Radiotherapy in Localized Prostate Cancer.

This retrospective study aimed to provide some clinical outcomes regarding effectiveness, toxicity, and quality of life in PCa patients treated with dose-escalated moderately hypofractionated radiation therapy (HFRT). Patients received HFRT to a total dose of 66 Gy in 22 fractions (3 Gy/fraction) delivered via volume modulated arc therapy (VMAT) in 2011-2016. Treatment effectiveness was measured by the biochemical failure-free survival rate. Toxicity was assessed according to the criteria of the Radiation Therapy Oncology Group (RTOG) and quality of life according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC). In this regard, quality of life (QoL) was measured longitudinally, at a median of 2 and 5 years after RT. Enrolled patients had low-risk (40.2%), intermediate-risk (47.5%), and high-risk (12.3%) PCa. Median follow-up was 75 months. The biochemical failure-free survival rate was 94.2%. The incidence of acute grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicity was 9.84% and 28.69%, respectively. The incidence rate of late grade 2 or higher GI and GU toxicity was 1.64% and 4.10%, respectively. Expanded Prostate Cancer Index Composite (EPIC) scores showed that the majority of patients maintained their QoL. HFRT to 66 Gy with VMAT was associated with adequate biochemical control, low toxicity and good reported GU and GI quality of life.

Effectiveness, tolerability and safety of Direct Acting Antivirals in Mexican individuals with Hepatitis C virus genotype-1 and previous pegylated interferon and ribavirin therapy.

BACKGROUND: Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy. METHODS: A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment. RESULTS: SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction. CONCLUSIONS: DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals.

Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-ß, IL-28A, IL-4, IL-5, IL-13, IL-1ß, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-ß1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.

A comprehensive update of the status of hepatitis C virus (HCV) infection in Mexico-A systematic review and meta-analysis (2008-2019).

INTRODUCTION AND OBJECTIVES: HCV infection is targeted by the WHO's Global Health Sector Strategy on Viral Hepatitis to be reduced notably by 2030. However, renovated epidemiological data is needed to line up with such goals. Herein, we provide an updated review of incidence, prevalence, genotypes (GTs), and risk factors (RFs) of HCV infection in Mexico to build elimination strategies. MATERIAL AND METHODS: HCV incidence was charted using the cumulative new cases/year at week 52. Prevalence, GTs, and RFs data from low-risk (LR-G) and high-risk (HR-Gs) groups were searched in PubMed/MEDLINE/Medigraphic/Scielo databases from January 2008 to December 2019 as per PRISMA guidelines. Weighted mean prevalence (WMP) was estimated; GTs and RFs were registered. RESULTS: In this study, 25,247 new cases were reported. Ten states accumulated 76.32% of HCV incidence that peaked in men at 50-59 years and women at 60-64 years. Thirty-four studies revealed a WMP between 0.774%-2.5% in LR-Gs and 11.8%-39.6% in HR-Gs that included mainly prison inmates, drug users, and dialyzed patients. GT1 and GT2 were predominant; GT3a emerged. Subtypes 1a and 1b circulate differentially, whereas novel GT2 subtypes appeared. Unsafe blood transfusion was infrequent in younger groups, but parenteral/intravenous transmission through drug-related risk behaviors has arisen. CONCLUSIONS: HCV transmission increased notably among LR-Gs and HR-Gs in Mexico. Novel genotypes/subtypes emerged as well as risky behavioral routes of transmission. A national elimination strategy will require pro-active screening in designated risk groups, research in molecular epidemiology, medical training, robust epidemiological databases, and antiviral treatment available to all eligible HCV-infected patients.

Primary Dengue Infection in Patients Requiring Hospitalization During an Outbreak in a Low Incidence Mexican Region.

Background: Dengue manifestations can range from subclinical to fatal. The study of factors that influence dengue's clinical severity can provide information to potentially limit or predict severe cases. Secondary infection (SI) with a different dengue serotype has been recognized as an important determinant of severity. However, severe dengue (SD) manifestations, including shock, can happen during primary infection (PI) too and the mechanisms involved are less understood. To characterize the severe manifestations associated to PI, we distinguished between primary and secondary dengue cases in hospitalized patients from a region of low and recent dengue incidence in central Mexico. This region can serve as a model for dengue's behavior as it spreads to new areas worldwide. Methods: Dengue-specific immunoglobulin M (IgM) and IgG concentrations were measured in the serum of 78 hospitalized patients with dengue hemorrhagic fever, and their ratios were used to discriminate between PI and SI, as recommended by World Health Organization. Clinical and laboratory manifestations were compared between PI and SI. Results and Conclusions: PI was detected in 23% of hospitalized dengue cases, a proportion similar to that reported in high-incidence regions in Mexico. PI was more frequent in 16- to 40-year-olds, and was absent in patients older than 60 years. Only dengue with warning signs and SD were present in the studied population of hospitalized patients, and case frequency decreased with clinical severity both in PI and SI groups. No significant differences in demographics, laboratory tests, or symptoms were found between PI and SI, which illustrates that cases requiring hospitalization during outbreaks can be severe, even if they are PI. This information can help plan for sanitary contingencies in places where dengue is recently emergent and numerous PI cases are expected. The mechanisms involved in PI clinical severity need to be studied further.

[Quality of life and psychological variables affecting adherence to antiretroviral treatment in Mexican patients with HIV/AIDS]. / Calidad de vida y variables psicológicas que afectan la adherencia al tratamiento anti-retroviral en pacientes mexicanos con infección por VIH/SIDA.

BACKGROUND: Antiretroviral treatment (ART) is essential in HIV/AIDS patients. Suppressing viral load requires strict adherence to ART in addition to the patient's commitment to treatment. The failure of ART is mainly due to lack of adherence, which may in turn be due to poor quality of life and/or to psychological variables. AIM: To determine the quality of life and psychological variables and adherence to ART, in patients with HIV/AIDS. MATERIAL AND METHOD: 160 patients diagnosed with HIV/AIDS and with ART were included. The MOS SF-36 and VPAD-24 instruments, a socio-demographic survey, and clinical data were collected. Quantitative and qualitative associations were made between the variables. RESULTS: The adherence to ART was associated with avoidance of depressive behavior and with the absence of addictions. Depressive behavior associated with addictions. 87% of patients ranked in the best quality of life. Below the average of the general health score were males, with MSM sexual orientation, single, in vitality at ≥ 38 years, in corporal pain and with social function to three ART schemes. CONCLUSION: Good adherence to ART was associated with avoiding depressive behavior and with non-addictions and not associated with quality of life.

Calidad de vida y variables psicológicas que afectan la adherencia al tratamiento anti-retroviral en pacientes mexicanos con infección por VIH/SIDA / Quality of life and psychological variables affecting adherence to antiretroviral treatment in Mexican patients with HIV/AIDS

Resumen Introducción: El tratamiento anti-retroviral (TAR) es indispensable en pacientes con infección por VIH/ SIDA; suprimir la carga viral requiere de un estricto apego a éste, por compromiso del paciente. El fracaso del TAR es primordialmente por falta de adherencia, que puede ser debida a una deficiente calidad de vida y/o a variables psicológicas. Objetivo: Determinar la calidad de vida, variables psicológicas y la adherencia al TAR, en pacientes con infección por VIH/SIDA. Material y Método: Se incluyeron 160 pacientes con diagnóstico de infección por VIH/SIDA y con TAR. Se recabaron los instrumentos MOS SF-36 y VPAD-24, una encuesta demográfica, y datos clínicos. Se hicieron asociaciones cuantitativas y cualitativas entre las variables. Resultados: La adherencia al TAR estuvo asociada con evitar comportamiento depresivo y con ausencia de adicciones. El comportamiento depresivo se encontró asociado con las adicciones. Un 87% de pacientes estaba en el rango de mejor calidad de vida. Por debajo del promedio del puntaje de salud general estuvieron masculinos, con orientación sexual HSH, solteros, en la vitalidad a los ≥ 38 años, en dolor corporal y función social a tres esquemas TAR. Conclusión: La buena adherencia al TAR estuvo asociada a evitar comportamiento depresivo y a la ausencia de adicciones y no se asoció a la calidad de vida.

Background: Antiretroviral treatment (ART) is essential in HIV/AIDS patients. Suppressing viral load requires strict adherence to ART in addition to the patient's commitment to treatment. The failure of ART is mainly due to lack of adherence, which may in turn be due to poor quality of life and/or to psychological variables. Aim: To determine the quality of life and psychological variables and adherence to ART, in patients with HIV/AIDS. Material and Method: 160 patients diagnosed with HIV/AIDS and with ART were included. The MOS SF-36 and VPAD-24 instruments, a socio-demographic survey, and clinical data were collected. Quantitative and qualitative associations were made between the variables. Results: The adherence to ART was associated with avoidance of depressive behavior and with the absence of addictions. Depressive behavior associated with addictions. 87% of patients ranked in the best quality of life. Below the average of the general health score were males, with MSM sexual orientation, single, in vitality at ≥ 38 years, in corporal pain and with social function to three ART schemes. Conclusion: Good adherence to ART was associated with avoiding depressive behavior and with non-addictions and not associated with quality of life.

Effectiveness of PCR primers for the detection of occult hepatitis B virus infection in Mexican patients.

BACKGROUND: Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HVB) DNA in the liver of HBsAg negative individuals with or without detectable viral DNA in serum. OBI is a diagnostic challenge as it is characterized by a very low viral load, intermittently detectable through time. Individuals with OBI can develop chronic hepatic disease, including liver cirrhosis and hepatocellular carcinoma. The aim of this work was to produce tools to improve OBI detection of the HVB genotypes prevalent in Mexico. METHODS: We designed and tested primers to detect OBI in serum samples by nested and real-time PCR. Conserved sites in the viral genome were determined by alignment of the most frequent HBV genotypes in Mexico (H, G/H, F and D) and primers spanning the entire viral genome were designed for first round and nested PCR. Primers were tested in serum samples of 45 patients not co-infected with hepatitis C virus or with HIV, out of a group of 116 HBsAg (-)/anti-HBc (+) individuals. Primers were also tested in a control group with chronic HBV. Nested PCR products obtained from HBsAg (-)/anti-HBc (+) were sequenced and used to design primers for real-time PCR (SYBR Green). RESULTS: The most effective primer pairs to detect HBV products by nested PCR targeted ORF regions: PreS2/P, S/P, X/PreC, and C; while by real-time PCR they targeted ORF regions PreS2/P, S/P, X, and C. Out of the 45 HBsAg (-)/anti-HBc (+) patients tested, the viral genome was detected in 28 (62.2%) and 34 (75.5%), with nPCR and real-time PCR respectively. CONCLUSION: Primers designed for real-time PCR detected up to 75.5% of suspected OBI Mexican patients, with or without liver disease, which represents an improvement from previous PCR strategies.

Polymorphisms in the hepatitis C virus core and its association with development of hepatocellular carcinoma.

Little is known about the mechanisms underlying hepatocellular carcinoma (HCC). Some studies have focused on the role of HCV viral proteins in hepatocyte transformation. In this work we have compiled and analysed current articles regarding the impact of polymorphisms in the HCV core gene and protein on the development of HCC. An exhaustive search for fulltext articles until November 2016 in PubMed database was performed using the MeSH keywords: 'hepatitis C', 'polymorphisms', 'core', 'hepatocellular cancer' and 'hepatocarcinogenesis'. Nineteen full-text articles published between 2000 and 2016 were considered. Different articles associate not only the HCC development with polymorphisms at residues 70 and 91 in the core protein, but more with mortality and treatment response. Also, different polymorphisms were found in core and other viral proteins related to HCC development. Eleven articles reported that HCC development is significantly associated with Gln/His70, four associated it with Leu91 and two more associated it with both markers together. Additional studies are necessary, including those in different types of populations worldwide, to validate the possibility of the usability and influence in chronically HCV-infected patients as well as to observe their interaction with other risk factors or prognosis and genetic markers of the host.

Prevalence of Serologic Hepatitis B Markers in Blood Donors From Puebla, Mexico: The Association of Relatively High Levels of Anti-Core Antibodies With the Detection of Surface Antigen and Genomic DNA.

BACKGROUND: The hepatitis B virus (HBV) causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg) detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc) suggests either a previous or ongoing infection or occult hepatitis B infection (OBI). OBJECTIVES: The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors. Further, the study aimed to estimate the anti-HBc level at which HBV DNA is detected in putative OBI cases, as well as to search for mutations in the "a" determinant associated with the non-detection of HBsAg in serum. PATIENTS AND METHODS: We conducted a cross-sectional study from 2003-2009. The study included 120,552 blood donors from the state of Puebla, Mexico. Different commercial systems based on microparticles (enzymatic (MEIA) or chemiluminescent (CMIA)) were used to determine the HBsAg and anti-HBc levels. For the detection of HBV DNA, a nested polymerase chain reaction (nested PCR) was used and the genotypes were determined using Sanger sequencing. RESULTS: Of the 120,552 blood donors, 1437 (1.19%, 95% CI: 1.12 - 1.26) were reactive to anti-HBc, while 82 (0.066%, 95% CI: 0.053 - 0.079) were reactive to HBsAg. Some 156 plasma samples collected in 2009 from anti-HBc-positive/HBsAg-negative blood donors were submitted for HBV DNA detection in a search for probable OBI. Viral DNA was detected in 27/156 (17.3%, 95% CI: 11.5 - 23.1). Our results show an association between HBV DNA or HBsAg and anti-HBc S/CO levels ≥ 4.0. All DNA samples were identified as genotype H and some "a" determinant mutations were identified, although none corresponded to mutations previously reported to hinder the detection of HBsAg by commercial immunoassays. CONCLUSIONS: We observed that as the anti-HBc levels increase, there is a higher prevalence of the viral protein HBsAg in blood donors. Samples testing positive for HBV-DNA were seen to exhibit a ten-fold higher presence of anti-HBc S/CO ≥ 4 than those with S/CO ≥ 1 and < 4.0, which highlights the relevance of anti-HBc determination in blood donor samples.

Hepatitis B surface antibodies in medical students from a public university in Puebla, Mexico.

Although preventable with vaccination, Hepatitis B virus (HBV) infection is a major health concern, with ∼400 million people at risk of developing the chronic form of the disease worldwide. The anti-HBV vaccine consists of a recombinant HBV surface antigen (HBsAg), which induces specific anti-HBs antibodies and confers 95% protection for >20 y. The aim of the present study was to analyze the response to HBV vaccination by measuring anti-HBs antibodies in serum samples from medical students of a public university in Puebla, Mexico. HBV infection markers HBsAg and anti-HBs, were also determined. A total of 201 students were included and vaccination coverage was found at 54%. Overall seropositivity for HBsAg, anti-HBc and anti-HBs determined by ELISA was 0.5%, 1.0% and 47%, respectively. Protective levels of anti-HBs >10 mIU/mL were found in 93.2% of subjects vaccinated with 2 or 3 doses and in 40% of those vaccinated with a single dose; while only 4.8% of unvaccinated subjects were anti-HBs positive. The response to the HBV vaccine was different in each participant, despite similar vaccination scheme. A history of blood transfusion/organ transplant or more than 2 sexual partners was significantly associated with anti-HBc positivity, OR = 399 (p = 0.010) and OR = 19.9 (p = 0.044), respectively. HBV immunization coverage was low in our sample compared with reports from countries with similar HBV prevalence, but anti-HBs in vaccinated individuals were in the expected range. It is important to promote HBV vaccination and awareness among medical students, due to their exposure risk.

Hepatitis C virus infection in patients and family members attending two primary care clinics in Puebla, Mexico.

BACKGROUND: Approximately 180 million persons (~2.8%) globally are estimated to be infected by hepatitis C virus (HCV). HCV prevalence in Mexico has been estimated to be between 1.2 and 1.4%. The aim of present work was to determine the prevalence of HCV infection in patients and family members attending two primary care clinics in Puebla, Mexico. MATERIAL AND METHODS: Patients and their accompanying family members in two clinics were invited to participate in this study between May and September 2010. RESULTS: A total of 10,214 persons were included in the study; 120 (1.17%) persons were anti-HCV reactive. Of the reactive subjects, detection of viral RNA was determined in 114 subjects and 36 were positive (31%). The more frequent risk factors were having a family history of cirrhosis (33.1%) and having a blood transfusion prior to 1995 (29%). After a multiple logistic regression analysis only transfusion prior to 1995 resulted significant to HCV transmission (p = 0.004). The overall detected HCV genotypes were as follows: 1a (29%), 1b (48.5%), 2/2b (12.8%), and 3a (6.5%). CONCLUSION: The HCV prevalence in this population is in agreement with previous studies in other regions of Mexico.

Quantitative analysis of the suppressors of cytokine signaling 1 and 3 in peripheral blood leukocytes of patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by a triad of inflammation, demyelination and gliosis. Because the suppressors of cytokine signaling (Socs) regulate the immune response, we quantified SOCS1 and SOCS3 transcription in peripheral blood leukocytes of patients with MS. SOCS1 transcription decreased significantly in MS patients compared with neurologically healthy persons (0.08±0.02 vs. 1.02±0.23; p=0.0001); while SOCS3 transcription increased in MS patients compared with controls (2.76±0.66 vs. 1.03±0.27; p=0.0008). Our results showed an imbalance of SOCS1 and SOCS3 transcription in MS patients, and a moderated negative correlation between them (Spearman's r=-0.57; p=0.0003).

Promoter polymorphisms of ST3GAL4 and ST6GAL1 genes and associations with risk of premalignant and malignant lesions of the cervix.

Sialyltransferase gene expression is altered in several cancers, including examples in the cervix. Transcriptional regulation of the responsible genes depends on different promoters. We aimed to determine the association of single-nucleotide polymorphisms in the B3 promoter of the ST3GAL4 gene and the P1 promoter of the ST6GAL1 gene with cervical premalignant lesions or cervical cancer. A blood sample and/or cervical scrapes were obtained from 104 women with normal cytology, 154 with premalignant lesions and 100 with cervical cancer. We also included 119 blood samples of random donors. The polymorphisms were identified by sequencing from PCR products. For the B3 promoter, a fragment of 506 bp (from nucleotide -408 to +98) was analyzed, and for the P1 promoter a 490 bp (-326 to +164) fragment. The polymorphism analysis showed that at SNP rs10893506, genotypes CC and CT of the ST3GAL4 B3 promoter were associated with the presence of premalignant lesions (OR=2.89; 95%CI 1.72-4.85) and cervical cancer (OR=2.23; 95%CI 1.27-3.91). We detected only one allele of each polymorphism in the ST6GAL1 P1 promoter. We did not detect any genetic variability in the P1 promoter region in our study population. Our results suggest that the rs10893506 polymorphism -22C/T may increase susceptibility to premalignant and malignant lesions of the cervix.