Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability.

The immunopathogenesis and molecular mechanisms involved during a hepatitis B virus (HBV) infection have made the approaches for research complex, especially concerning the patients' responses in the course of the early acute stage. The study of molecular bases involved in the viral clearance or persistence of the infection is complicated due to the difficulty to detect patients at the most adequate points of the disease, especially in the time lapse between the onset of the infection and the viral emergence. Despite this, there is valuable data obtained from animal and in vitro models, which have helped to clarify some aspects of the early immune response against HBV infection. The diversity of the HBV (genotypes and variants) has been proven to be associated not only with the development and outcome of the disease but also with the response to treatments. That is why factors involved in the virus evolution need to be considered while studying hepatitis B infection. This review brings together some of the published data to try to explain the immunological and molecular mechanisms involved in the different stages of the infection, clinical outcomes, viral persistence, and the impact of the variants of HBV in these processes.

Toxoplasma infection in kidney donors and transplant recipients from Western Mexico: A one-year follow-up.

PURPOSE: Solid organ transplant recipients are highly susceptible to Toxoplasma gondii infection. We aimed to describe the 12-month follow-up risk of seroconversion in renal transplant recipients. METHODOLOGY: Anti-T gondii antibodies were investigated in donors and recipients of renal transplants. In donors, anti-T gondii were evaluated before transplantation. In recipients, anti-T gondii were monitored over a 12-month period to evaluate potential seroconversion or reactivation. IgG and IgM anti-T gondii antibodies were investigated through enzyme immunoassay and Western blot. Molecular diagnosis was performed on peripheral blood leukocytes using PCR to amplify fragments corresponding to the T gondii B1 gene and the repetitive 529-bp element. RESULTS: The basal frequency of seropositive IgG anti-T gondii antibodies was higher in donors than in recipients (38.4% vs 25.2%; P = .03). During the 12-month follow-up, the accumulated seroconversion to IgG and IgM antibodies was 3/99 (3.0%), and the accumulated reactivation was 11/99 (11.0%). None of the samples exhibited positivity to T gondii DNA. CONCLUSIONS: This study showed that there is an increased risk of seroconversion or reactivation in renal transplant recipients over a 12-month follow-up. Our data suggest that prophylaxis with trimethoprim and sulfamethoxazole effectively prevented toxoplasmosis, since neither T gondii DNA nor clinical toxoplasmosis was detected.

Does Toxoplasma gondii infection impact liver transplantation outcomes? A systematic review.

PURPOSE: Approximately one-third of the world's population has Toxoplasma gondii infection, and one of the main routes of transmission is organ transplantation. The aim of this study was to evaluate the impact of Toxoplasma infection on liver transplantation patients. METHODOLOGY: We searched PubMed, Lilacs, Medline, Science direct, Scielo, Ebsco, Springer, Wiley, Ovid and Google Scholar for reports published up to June 2017, and a systematic review was performed. RESULTS: Twenty cases were analysed before and after liver transplantation. Primary and reactivated infections were investigated. Before transplantation, positive IgG antibodies were the predominant serological markers in donors and recipients: 40 % (D+/R-), 20 % (D+/R+) and 20 % (D-/R+). IgM was present in only 5 % of the donors (D+/R-). In four cases, the serological markers were not specified or were negative (D?/R? or D?/R-). After transplantation, IgM anti-Toxoplasma antibodies were found in 30 % of the recipients, and in 67 % of the seronegative recipients the presence of Toxoplasma DNA or tachyzoites was reported, suggesting a primary infection. Clinical symptoms were meningitis, massive cerebral oedema, encephalitis and seizures. Treatment was administered in 70 % of the patients, and 40 % died after presenting symptoms associated with Toxoplasma infection. CONCLUSIONS: Although we review Toxoplasma infection and liver transplantation cases, problems associated with the parasite may be greater than identified. Hence, follow-up studies on Toxoplasma infection in liver transplantation patients are recommended.

The Quételet index revisited in children and adults / El índice de Quételet reevaluado en niños y adultos

BACKGROUND: The body mass index (BMI) is based on the original concept that body weight increases as a function of height squared. As an indicator of obesity the modern BMI assumption postulates that adiposity also increases as a function of height in states of positive energy balance. OBJECTIVE: To evaluate the BMI concept across different adiposity magnitudes, in both children and adults. METHODS: We studied 975 individuals who underwent anthropometric evaluation: 474 children and 501 adults. Tetrapolar bioimpedance analysis was used to assess body fat and lean mass. RESULTS: BMI significantly correlated with percentage of body fat (%BF; children: r = 0.893; adults: r = 0.878) and with total fat mass (children: r = 0.967; adults: r = 0.953). In children, body weight, fat mass, %BF and waist circumference progressively increased as a function of height squared. In adults body weight increased as a function of height squared, but %BF actually decreased with increasing height both in men (r = −0.406; p < 0.001) and women (r = −0.413; p < 0.001). Most of the BMI variance in adults was explained by a positive correlation of total lean mass with height squared (r2 = 0.709), and by a negative correlation of BMI with total fat mass (r = −0.193). CONCLUSIONS: Body weight increases as a function of height squared. However, adiposity progressively increases as a function of height only in children. BMI is not an ideal indicator of obesity in adults since it is significantly influenced by the lean mass, even in obese individuals

ANTECEDENTES: El índice de masa corporal (IMC) se basa en el concepto original de que el peso corporal aumenta en función de la talla al cuadrado. Como indicador de obesidad, el supuesto actual sobre el IMC es que la adiposidad corporal también aumenta en función de la talla en estados de balance energético positivo. OBJETIVO: Evaluar el concepto del IMC en diferentes magnitudes de adiposidad, tanto en niños como adultos. MÉTODOS: Estudiamos a 975 individuos sometidos a evaluación antropométrica: 474 niños y 501 adultos. Se usó bioimpedancia tetrapolar para evaluar la masa grasa y magra corporal. RESULTADOS: Había una correlación significativa de IMC con el porcentaje de grasa corporal (%GC; niños: r = 0,893, adultos: r = 0,878) y con la masa grasa total (niños: r = 0,967; adultos: r = 0,953). En los niños, el peso corporal, la masa grasa, el %GC y el perímetro de la cintura aumentaban progresivamente en función de la talla al cuadrado. En los adultos, el peso corporal aumentaba en función de la talla al cuadrado, pero el %GC disminuía al aumentar la talla tanto en varones (r = −0,406; p < 0,001) como en mujeres (r = −0,413; p < 0,001). La mayor parte de la varianza del IMC en adultos se explicaba por una correlación positiva de la masa magra total con la talla al cuadrado (r2 = 0,709) y por una correlación negativa del IMC con la masa grasa total (r = −0,193). CONCLUSIONES: El peso corporal aumenta progresivamente en función de la talla al cuadrado. Sin embargo, sólo en los niños la grasa corporal aumenta progresivamente en función de la talla. El IMC no es un indicador ideal de obesidad en los adultos, ya que está significativamente influido por la masa magra, aún en los obesos

The Quételet index revisited in children and adults.

BACKGROUND: The body mass index (BMI) is based on the original concept that body weight increases as a function of height squared. As an indicator of obesity the modern BMI assumption postulates that adiposity also increases as a function of height in states of positive energy balance. OBJECTIVE: To evaluate the BMI concept across different adiposity magnitudes, in both children and adults. METHODS: We studied 975 individuals who underwent anthropometric evaluation: 474 children and 501 adults. Tetrapolar bioimpedance analysis was used to assess body fat and lean mass. RESULTS: BMI significantly correlated with percentage of body fat (%BF; children: r=0.893; adults: r=0.878) and with total fat mass (children: r=0.967; adults: r=0.953). In children, body weight, fat mass, %BF and waist circumference progressively increased as a function of height squared. In adults body weight increased as a function of height squared, but %BF actually decreased with increasing height both in men (r=-0.406; p<0.001) and women (r=-0.413; p<0.001). Most of the BMI variance in adults was explained by a positive correlation of total lean mass with height squared (r(2)=0.709), and by a negative correlation of BMI with total fat mass (r=-0.193). CONCLUSIONS: Body weight increases as a function of height squared. However, adiposity progressively increases as a function of height only in children. BMI is not an ideal indicator of obesity in adults since it is significantly influenced by the lean mass, even in obese individuals.

Achievement of therapeutic targets in Mexican patients with diabetes mellitus.

BACKGROUND AND AIM: Complications of diabetes comprise the leading cause of death in Mexico. We aimed to describe the characteristics of management and achievement of therapeutic targets in Mexican patients with diabetes mellitus. METHODS: We analyzed data from 2642 Mexican patients with type 1 (T1D, n=203, 7.7%) and type 2 diabetes (T2D, n=2439, 92.3%) included in the third wave of the International Diabetes Management Practices Study. RESULTS: Of T2D patients, 63% were on oral glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22% on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on insulin were more likely to be trained on diabetes, but they were older, had worse control, longer disease duration and more chronic complications than patients on OGLD only. Glycated hemoglobin (HbA1c) <7% was achieved by 21% and 37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained the composite target of HbA1c <7%, blood pressure <130/80 mmHg and low-density lipoprotein cholesterol <100 mg/dl. T1D patients had less macrovascular but more microvascular complications, compared with T2D patients. Late complications increased with disease duration, so that about 80% of patients after 20 years of diagnosis have at least one late complication. Reaching the target HbA1c <7% was associated with a reduced number of microvascular but not with less macrovascular complications. CONCLUSION: A great proportion of these Mexican patients with diabetes did not reach therapeutic targets. Insulin was used mostly in complicated cases with advanced disease.

Hepatitis C virus infection and type 2 diabetes mellitus in Mexican patients.

OBJECTIVE: to measure the frequency of type 2 diabetes mellitus (T2DM) in patients with confirmed HCV infection. METHODS: we studied 125 adults reactive to anti-HCV antibodies (62.4 % women, mean age 46.8 years) who received confirmatory RT-PCR testing for viremia (63.2 % HCV-RNA-positive). RESULTS: twenty-two patients had T2DM (17.6 %, 95 % confidence interval: 11.8-25.3 %; mean National prevalence: 14.4 %), more frequent among patients with detectable viremia than in negative cases (23.3 % vs. 9.6 %, respectively; p = 0.04), and among those with advanced liver disease, than in compensated patients (28.9 % vs. 11.3 %, respectively; p = 0.01). Fourteen (17.7 %) patients received interferon-based treatment and 6 (42.8 %) had sustained virology response. None of the 6 responders had T2DM, but 2 of the 8 (25 %) non-responders had diabetes. T2DM patients were older than those without diabetes (57.7 vs. 44.5 years, p < 0.001), and after multivariate analysis, only age was significantly associated with diagnosis of T2DM. CONCLUSIONS: T2DM was highly prevalent among patients with chronic HCV infection. Age was the most important determining factor.

Occult hepatitis B in Mexican patients with HIV, an analysis using nested polymerase chain reaction.

Hepatitis B virus infection (HBV) with undetectable levels of HBsAg, has been named occult HBV infection and observed in immunosuppressed patients. The aim of this study was to determine the frequency of occult HBV infection in patients with HIV from the West of México, using a combination of serological markers and nPCR. Thirty eight HIV/AIDS patients, 32 men (84.2%) and 6 (5.8%) women, without liver damage related symptoms were studied. HBV coinfection was observed in 10 (26.3%) patients; while only 3 (7.9%) of them were positive to HBsAg. Thus, 7 (18.4%) occult HBV infected patients could be assessed in this population. One (10%) patient with occult HBV infection was positive to anti-HBs, in spite of the reinfection protection attributed to this serological marker. Anti-HBc was detected only in 2 (20%) patients with occult HBV infection. No significant association could be established between occult HBV infection and CD+4 cell count, biochemical, clinical parameters, AIDS stage, or any other risk factor. This study suggest that determination of HBV DNA utilizing highly sensitive techniques, as nPCR, should be performed to detect occult HBV infection, even in the absence of anti-HBc in HIV/ AIDS patients, in order to have a reliable diagnosis, prevent HBV dissemination and acute exacerbation of chronic hepatitis B or even fulminant hepatitis. To our knowledge this is the first study of occult HBV infection in Mexican patients with HIV. However, further studies are necessary in order to determine HBV genotypes and its relationship with evolution and clinical manifestation of the disease.

Albumin mRNA in peripheral white blood cells of cirrhotic patients with a superimposed alcoholic hepatitis is associated to fatal outcome.

The aim of this study was to analyze the relationship of plasma colloid osmotic pressure (COP), relative viscosity (eta) and overall outcome on the expression of albumin (ALB) mRNA in peripheral white blood cells (PWBC) of cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). ALB messanger was detected in PWBC by RT-nPCR in control individuals (C), patients with liver cirrhosis (LC) and LC+AH. A higher number of LC+AH patients were positive to ALB mRNA (67%), compared to C (30%) and LC (28%). COP was decreased in LC and LC+AH groups compared to C group. No statistically significant changes were detected in eta in the different populations studied. Most of the LC+AH patients positive to peripheral ALB expression (87%) had a fatal outcome, compared to survivors (25%). Such difference was not observed with the conventional liver function tests or Maddrey's discriminant function.