Prevalencia de los marcadores de infección de los virus de las hepatitis en pacientes portadores del VIH en el sur de España

Objectives

To determine: (a) The prevalence of active infection by the hepatitis C virus (HCV) and hepatitis B virus (HBV) in HIV-infected patients, as well as previous exposure to hepatitis A virus (HAV), HBV and HCV. (b) The proportion of patients who have been vaccinated against HAV and/or HBV. (c) The HCV genotype distribution and the percentage of patients who have started treatment against HCV infection.

Methods

All HIV-infected patients who attended the Infectious Diseases Unit of a tertiary care hospital in Southern Spain between September 2008 and February 2009 were included in a prospective cross-sectional study.

Results

A total of 520 patients were included. Three hundred and fifty-eight (69%) patients had positive HCV antibody, while 71% of them showed detectable HCV-RNA. The HCV genotype distribution was: 153 (62%) genotype 1, 49 (20%) genotype 3, and 45 (18%) genotype 4. One hundred and thirteen (36.5%) subjects had received treatment against HCV. The prevalence of active HBV infection was 4.4%, while the exposure to HBV was 54.8%. Four hundred and thirty-seven (84%) patients had positive markers of infection of HAV. Of the patients eligible to be vaccinated, 25.6% and 22.3% patients were vaccinated against HAV and HBV, respectively.

Conclusions

The current prevalence of active HCV infection remains high in our area. There were no changes in the HCV genotype distribution. The number of patients with indication for HBV and HAV vaccination and receive these vaccines is low.     

Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes

Objective

To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment.

Material and methods

A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000.

Results

A total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(−). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(−) patients, those who were AgHBe(+) were younger and had greater disease activity. This difference was statistically significant. Patients in the immunotolerant phase were the least numerous (5.26%), while AgHBe(−) patients with chronic HBV infection were the most numerous (48.32%). Patients in the immunoreactive phase showed greater histological involvement (16.67% cirrhosis). A familial history of chronic HBV was found in 21.52%. The percentage of non-Spanish patients increased in the last few years and accounted for 18.78%.

Conclusion

Chronic HBV infection in our environment occurs mainly in middle-aged persons. GPT values are normal in more than 50%, most are AgHBe(−), and approximately half are inactive carriers. The incidence of chronic infection has increased in the non-Spanish population in recent years.     

Evaluación del impacto del nuevo marco legal sanitario sobre los inmigrantes en situación irregular en España: el caso de la infección por el virus de la inmunodeficiencia humana

The immigrant population in Spain, whether legal or not, has been entitled to healthcare under the same conditions as the Spanish population since the year 2000. The entry into vigour of the Royal Decree-Law 12/2012 of 20 April has significantly restricted this right, so that unauthorized or non-resident foreigners may now only receive emergency care, if they are under 18 or pregnant women. Out of an estimated 459,909 illegal immigrants in our country, 2,700 to 4,600 are probably infected with HIV; 1,800 to 3,220 know that they are infected, and 80% of the latter could receive antiretroviral treatment. The Royal Decree-Law is likely to cause many undesirable consequences in this population infected with HIV: increasing mortality, promoting the emergence of opportunistic diseases, increasing hospital admissions, increasing infections in the population (by HIV and other pathogens), or contributing to mother to child transmission of HIV. The expected increase in morbidity and mortality will be a greater cost in patient care, a cost which will be significantly higher in the more immunosuppressed patients. Therefore, the enforcement of the Royal Decree-Law will be much less cost-effective in the short term than was expected, and will negatively affect our country's public health, especially for those patients infected with HIV who will not be covered, thus increasing healthcare medium to long term costs, and moving away from the international health goals that were established.     

Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.     

Evaluación inicial del programa de prevención de la transmisión materno-infantil de la infección por el virus de la inmunodeficiencia humana en Guinea Ecuatorial

Background

The prevalence of human immunodeficiency virus (HIV)-infected pregnant women in Equatorial Guinea (EG) has been reported as 7.3%. In 2008 an updated version of the PMTCT protocol was accepted according to the current WHO guidelines. The aim of this study was to describe the characteristics and outcome of children exposed to HIV after the introduction of the protocol.

Methods

A retrospective review was conducted on the clinical characteristics of the infants born to HIV-infected mothers in the Hospital Regional de Bata and Primary Health Care Centre Maria Rafols in Bata (EG) between June 2008 and November 2011. The diagnosis of HIV infection in children was based on rapid serology tests.

Results

A total of 103 children were included, of which 47 were males. Fifty three patients (51%) completed the follow-up (51%). Fourteen children (26%) were diagnosed with HIV infection (11 presumptive diagnosis, 3 due to persistence of antibodies at 18 months). Six children (12%) died before a definitive diagnosis. Just over than half (52%) of mothers received antiretroviral therapy (ART) during pregnancy. The transmission rate in children whose mothers received ART was 16% (3/19), compared with 43% (10/23) in children whose mothers did not receive it. Only one child was infected (8%) when the mother received ART, and child received postnatal prophylaxis.

Conclusions

The PMTCT protocol compliance was still very low. Antiretroviral therapy in pregnant women decreased the rate of vertical transmission, but the rate still remains very high. Many children were lost to follow-up. Strategies to prevent loss to follow-up and methods for earlier virological diagnostic are needed.     

Impacto del tratamiento antiviral en la historia natural del virus de la hepatitis C

Chronic hepatitis C virus infection affects around 150 million persons, and 350,000 persons worldwide die of this disease each year. Although the data on its natural history are incomplete, after the acute infection, most patients develop chronic forms of hepatitis C with variable stages of fibrosis. In these patients, continual inflammatory activity can cause significant fibrosis, cirrhosis, decompensation of the liver disease, or hepatocarcinoma. In the next few years, it is expected that hepatitis C virus infection and its complications will significantly increase, as will the incidence of hepatocarcinoma in Spain. This review presents the data on the natural history of hepatitis C virus infection and discusses the potential impact of antiviral therapy on the distinct stages of the disease.     

Patrón de inicio del seguimiento clínico en los pacientes con infección por el virus de la inmunodeficiencia humana en España

Objetive

To describe linkage to care among new HIV diagnoses in Spain; and to estimate factors associated to linkage to care within three months after diagnosis.

Methods

The distribution of the time elapsing between the date of HIV diagnosis and the date of first determination of CD4 (considered to be the date of linkage to care) was calculated among new HIV diagnoses in 2010 in the seven Autonomous Regions participating, where data on date of CD4 count was available. Linkage to care was considered «correct» if done within three months after diagnosis. Factors associated to correct linkage to care were estimated using logistic regression.

Results

A total of 1769 new HIV diagnoses were included. Of them, 83.1% had evidence of linkage to care within a year, and 75.7% were linked within three months after diagnosis. Being an injectable drug user (IDU) was the only factor inversely associated with linkage to care within 3 months (OR = 0.3; 95% CI: 0.2-0.6).

Conclusion

In Spain linkage to care after HIV diagnosis is good, but there is still room for improvement, especially among IDUs.     

Experiencia en el manejo de inmunosupresores con los fármacos inhibidores de proteasa frente al virus de la hepatitis C

Introduction

Antiviral drugs for the treatment of hepatitis C virus (HCV) infections have a large number of interactions. The aim of this study was to describe the interactions of telaprevir, boceprevir and sofosbuvir with immunosuppressive drugs in liver transplant recipients.

Methods

A retrospective observational study was performed in liver transplant patients with HCV infection who started treatment with telaprevir, boceprevir or sofosbuvir. Dose, regimens and plasma levels of tacrolimus, cyclosporine and sirolimus before and after antiviral treatment initiation were collected. Average variations in dose, dosing interval and immunosuppressive plasma levels after the start of treatment were calculated.

Results

Thirty-five patients were included. In patients treated with telaprevir (n = 18), the cyclosporine dose was reduced by an average of 59.1% (SD = 14.6%), yielding an average reduction of 14.6% (18.8%) in plasma levels. The dose of tacrolimus was reduced by 34.3% (31.7%), increasing the dosing interval by a mean of 73.4 (38.2) hours. After this variation, tacrolimus levels were increased by an average of 59.7% (89.6%).In patients treated with boceprevir (n = 4), tacrolimus started with a reduction of 18.1% (9.8%) of the initial dose and an average increase in the dosing interval of 12.0 (16.9) hours, showing a mean reduction in plasma levels of 37.7% (21.8%). Sofosbuvir therapy (n = 13) showed no significant variations in immunosuppressive drug levels.

Conclusions

The interaction of telaprevir and boceprevir with immunosuppressive drugs requires a substantial dose reduction at the beginning of treatment and close monitoring of plasma levels.     

Avances en el diagnóstico molecular de la enfermedad de Wilson

Wilsońs disease is an autosomal recessive disorder characterized by toxic copper accumulation in the liver and subsequently in the brain and other organs. Clinical diagnosis is based on the detection of low serum ceruloplasmin concentrations, increased urinary copper excretion, Kayser-Fleisher rings in the cornea, and/or high copper levels in hepatic tissue. Diagnosis can be difficult when the typical symptoms of the disease are absent, a situation that can lead to a lack of prophylactic therapy in these patients. Molecular study has improved the diagnosis of this disease, even in doubtful cases. The present article outlines the various techniques applied in the molecular diagnosis of Wilson's disease and the most commonly described mutations. Currently, direct sequencing of the ATP7B gene is the most widely used method to detect mutations. Molecular study and identification of ATP7B gene mutations allow diagnosis of individuals with Wilson's disease and their relatives, as well as the possibility of genetic counselling and prenatal and preimplantation genetic diagnosis.     

La valoración de RNA del virus de la hepatitis C realizada a las 12 semanas de finalizar el tratamiento predice la respuesta virológica sostenida en enfermos con coinfección por VIH y VHC

Objective

The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients.

Patients and methods

HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml).

Results

Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%).

Conclusion

Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response.     

Nuevos agentes para el tratamiento de la hepatitis C

The current treatment of Chronic Hepatitis C (CHC) is based on the combination of peginterferon alpha 2a or 2b and ribavirin. This treatment achieves Sustained Virological Response (SVR) rates in more than 50% of the patients. The SVR rates are higher in genotype 2 and 3 patients than in genotype 1, which account for more than 50%. For this reason, the development of new drugs is needed.     

Biología molecular aplicada del virus de la hepatitis C

Since the discovery of the hepatitis C virus (HCV), a plethora of experimental models have evolved, allowing the virus's life cycle and the pathogenesis of associated liver diseases to be investigated. These models range from inoculation of cultured cells with serum from patients with hepatitis C to the use of surrogate models for the study of specific stages of the HCV life cycle: retroviral pseudoparticles for the study of HCV entry, replicons for the study of HCV replication, and the HCV cell culture model, which reproduces the entire life cycle (replication and production of infectious particles). The use of these tools has been and remains crucial to identify potential therapeutic targets in the different stages of the virus's life cycle and to screen new antiviral drugs. A clear example is the recent approval of two viral protease inhibitors (boceprevir and telaprevir) in combination with pegylated interferon and ribavirin for the treatment of chronic hepatitis C. This review analyzes the advances made in the molecular biology of HCV and highlights possible candidates as therapeutic targets for the treatment of HCV infection.     

Tratamiento antirretroviral de inicio en pacientes infectados por el virus de la inmunodeficiencia humana en España: decisiones con relación a características inmunovirológicas específicas (estudio PERFIL-es)

Introduction

The purpose of Perfil-es study was to identify the proportion of patients starting ARV treatment based on NNRTIs or PI/r, and to identify the variables involved in the therapeutic decision-making in standard clinical practice.

Methods

An observational restrospective study performed in 65 Spanish hospitals.

Results

Was a total of 1,687 starts: 53% with NNRTI-based regimen and 42% with PI/r, and of the 642 patients analyzed, 72% had a CD4 count < 350 cells/μl.

Conclusion

The initiation of ARV treatment is still late in Spain. NNRTIs are the more frequent choice, although PI/r plays an important role.     

Nuevas estrategias en la optimización posológica de lopinavir/ritonavir en pacientes infectados por el virus de la inmunodeficiencia humana

Lopinavir/ritonavir (LPV/r) has demonstrated virological and immunological efficacy in the combined antiretroviral treatment (cART), in both naïve and experienced patients. Furthermore, LPV/r showed a high barrier to the development of resistance. Although generally well tolerated, adverse gastrointestinal side effects and metabolic disorders are frequent.     

Influencia de la positividad del anti-HBc en el donante en la selección del donante pulmonar

Introduction

The risk of hepatitis B virus (HBV) transmission through donor organs with HBsAg(−) and anti-HBc(+) serology has not been extensively studied in lung transplantation. The objectives of this study are to ascertain the influence of the anti-HBc(+) on the acceptance of the lung for transplantation, to comment on the published literature and to suggest an algorithm for action.

Methods

A survey conducted in the 7 Spanish lung transplantation teams. The updated search of the literature was performed using medical databases from 1994 to February 2012.

Results

All of the teams vaccinate the lung recipients against HBV, although none quantify the anti-HBs titers. When given an anti-HBc(+) donor, 3 teams change their strategy: one does not accept the offer, one selects the receptor from among patients in emergency status and another adds pharmacological prophylaxis. Only 3 publications refer to the serologic evolution of the receptors. At the moment there have been no reported cases of hepatitis B or HBsAg positivity post-transplant, but 4 out of the 50 anti-HBc(−) receptors changed to anti-HBc(+) in the follow-up.

Conclusions

The presence of anti-HBc in the donor influences the decision to accept a lung donor, although there is little information on its repercussions. To date, there has been no reported case of transmission of HBV, but post-transplant anti-HBc seroconversions have been described, which suggests contact with viral particles. Although rare, an anti-HBc(+) donor can harbor a hidden HBV infection. The risk of infection can be reduced with adequate anti-HBs titers or with appropriate pharmacological measures.     

Recomendaciones para la evaluación médica de la capacidad laboral en el enfermo respiratorio crónico

Chronic respiratory diseases often cause impairment in the functions and/or structure of the respiratory system, and impose limitations on different activities in the lives of persons who suffer them. In younger patients with an active working life, these limitations can cause problems in carrying out their normal work. Article 41 of the Spanish Constitution states that «the public authorities shall maintain a public Social Security system for all citizens guaranteeing adequate social assistance and benefits in situations of hardship». Within this framework is the assessment of fitness for work, as a dual-nature process (medico-legal) that aims to determine whether it is appropriate or not to recognise a person's right to receive benefits which replace the income that they no longer receive as they cannot carry out their work, due to loss of health.     

Documento de consenso: Recomendaciones para el manejo de la enfermedad ósea metabólica en pacientes con virus de la inmunodeficiencia humana

Objective

To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients.

Participants

Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS).

Methods

A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content.

Conclusions

The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients.