Re-treatment with highly purified nIFNα in Mexican nonresponder patients with chronic genotype 1 hepatitis C.

BACKGROUND AND AIMS: We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. METHODS: Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. RESULTS: Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. CONCLUSIONS: nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.

Effective use of FibroTest to generate decision trees in hepatitis C.

AIM: To assess the usefulness of FibroTest to forecast scores by constructing decision trees in patients with chronic hepatitis C. METHODS: We used the C4.5 classification algorithm to construct decision trees with data from 261 patients with chronic hepatitis C without a liver biopsy. The FibroTest attributes of age, gender, bilirubin, apolipoprotein, haptoglobin, alpha2 macroglobulin, and gamma-glutamyl transpeptidase were used as predictors, and the FibroTest score as the target. For testing, a 10-fold cross validation was used. RESULTS: The overall classification error was 14.9% (accuracy 85.1%). FibroTest's cases with true scores of F0 and F4 were classified with very high accuracy (18/20 for F0, 9/9 for F0-1 and 92/96 for F4) and the largest confusion centered on F3. The algorithm produced a set of compound rules out of the ten classification trees and was used to classify the 261 patients. The rules for the classification of patients in F0 and F4 were effective in more than 75% of the cases in which they were tested. CONCLUSION: The recognition of clinical subgroups should help to enhance our ability to assess differences in fibrosis scores in clinical studies and improve our understanding of fibrosis progression.

Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Avances en inmunosupresión en trasplante hepático / Advances in immunossuppression in liver transplantation

The history of Immunosuppresslon is a long one. From the utilization of steroids and azathloptlne In the 50's to the design of humanized molecules that specifically block cell surface receptors. Liver transplantation is one of the procedures that benefit the most with the development of new immunosuppressors and is also one of the reasons to create a new branch in research and clinical practice: transplant medicine. It also set the standards for research in the "immunologic tolerance" field. The cornerstone in the post-liver transplant stage is the utilization of calcineurin inhibitors combined with new anti-metabolites and monoclonal antibodies. All these settings conforms a promising field in the research of new and better immunosuppressing agents.

Se ha recorrido mucho camino desde el diseño de la inmunosupresión en la década de los 50's. Desde la utilización de los esteroides y la azatioprina hasta el desarrollo de moléculas humanizadas, que bloquean específicamente receptores de superficie celular para inducir tolerancia del injerto, ha transcurrido medio siglo. El trasplante hepático ha sido uno de los procedimientos más beneficiados con el desarrollo de las nuevas drogas inmunosupresoras y ha dado origen a una nueva rama de la medicina: la medicina de trasplantes. También ha sentado las bases de investigación tendiente a lograr la "tolerancia inmunológica" del órgano trasplantado. La piedra angular en la inmunosupresión postrasplante hepático es la utilización de los inhibidores de calcineurina que, en combinación con nuevos antimetabolitos y anticuerpos monoclonales, dibujan un futuro promisorio en la búsqueda de mejores agentes.

[Advances in immunossuppression in liver transplantation]. / Avances en inmunosupresión en trasplante hepático.

The history of immunosuppression is a long one. From the utilization of steroids and azathioptine in the 50's to the design of humanized molecules that specifically block cell surface receptors. Liver transplantation is one of the procedures that benefit the most with the development of new immunosuppressors and is also one of the reasons to create a new branch in research and clinical practice: transplant medicine. It also set the standards for research in the "immunologic tolerance" field. The cornerstone in the post-liver transplant stage is the utilization of calcineurin inhibitors combined with new anti-metabolites and monoclonal antibodies. All these settings conforms a promising field in the research of new and better immunosuppressing agents.

Early HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin.

INTRODUCTION: Currently, interferon alfa and ribavirin are the mainstay of therapy for patients with chronic hepatitis C. Recently the pegylation of interferon has allowed a once weekly application, resulting in an increased sustained viral response rate. The analysis of serum HCV dynamics has been shown to be useful in predicting clinical effects and optimizing the treatment regimen. AIM: The aim of the present study was to assess early serum HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b plus ribavirin. METHODS: Male and female patients aged 18 to 65 years with chronic hepatitis C were eligible for the study. All patients received peginterferon alfa 2b 1.5 micrograms/kg once-weekly for 4 weeks and then peginterferon alfa 2b 0.5 microgram/kg once-weekly until the completion of the 48 week trial period, plus ribavirin orally with meals, adjusted to body weight. HCV RNA was determined at base-line, 48 hours, 4 and 12 weeks of therapy. RESULTS: Data were obtained from 20 patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin; 16 male, 4 female, with a mean age of 44.4 +/- 11.9 years, 16 patients (80%) were infected with HCV genotype 1, the remainder were infected with genotype 2. Mean baseline HCV RNA for the total group was 1,091,405 +/- 972,715 IU/mL. Mean reductions in viral load at 48 hours, 4 and 12 weeks for the 20 patients were 1.31 +/- 0.91 log, 1.99 +/- 1.27 log and 2.31 +/- 1.25 log, respectively. A > 2 log reduction in HCV RNA was noticed in 12/20 patients (60%) at 4 weeks (early viral responders), in 9 of them (45%) HCV RNA was undetectable. This response in HCV RNA persisted at 12 weeks of therapy. Early viral responders had a significant reduction in HCV RNA at 48 hours after the initial peginterferon alfa 2b injection (> 1 log reduction). Early viral response was observed in 8/16 patients with HCV genotype 1, and in all genotype 2 patients. CONCLUSION: Treatment with peginterferon alfa 2b and ribavirin produces significant changes in the early HCV viral dynamics supporting the concept that such changes may be pivotal in achieving a sustained viral response.

Health-related quality of life and depression in patients with chronic hepatitis C.

BACKGROUND: Hepatitis C is a major cause of liver disease worldwide. It has been associated with decreased health-related quality of life (HRQL) and psychiatric symptoms. Our aim was to assess HRQL, depression, and illness understanding in patients with chronic hepatitis C without previous interferon therapy. METHODS: Consecutive patients attending a referral center were enrolled. HRQL was measured using SF-36 questionnaire, depression with Zung self-rating depression scale, and illness understanding with self-applied knowledge test. RESULTS: Of 157 patients enrolled, 112 were female (71%) and 45 male (29%). Ninety-seven patients (61.8%) had cirrhosis. HRQL was significantly decreased in chronic hepatitis C patients compared to historical normal controls in all eight domains of the SF-36 (p < 0.001). In hepatitis C cirrhotic patients, HRQL was significantly lower among Child-Pugh class B and C subjects in domains reflecting physical health (p <0.05). Ninety-two patients (58.6%) had depression that resulted in lower HRQL when compared to nondepressed patients (p <0.05). One hundred fourteen patients (72.6%) had poor illness understanding of hepatitis C. These subjects had significantly lower HRQL scores in six of eight SF-36 domains when compared to patients with better understanding of the disease (p <0.05). CONCLUSIONS: Chronic hepatitis C patients attending a tertiary-referral center had significant decrease in HRQL associated with depression (58.6%) and poor illness understanding (72.6%). Educational programs and their impact on HRQL need to be addressed in detail, particularly for the pre-treatment scenario.

Nemesis del tercer sexo: visión general de SIDA en México / Nemesis of the third sex: general vision of AIDS in Mexico

El presente trabajo es una revisión bibliográfica que tiene por objeto dar a conocer los aspectos más sobresalientes y comunes de esta entidad tan erróneamente difundida. El SIDA se define como el deterioro inexorable del aparato inmunológico, sobre todo en lo que respecta a las funciones de las células timo dependientes en ausencia de un proceso patológico que los justifique. Tocante a la etiología, estáa bien establecido que se trata de un virus linfotrópico de la familia de los retrovirus (HTLV-III/LAV), que comparte tres genes con el resto de los retrovirus y tiene otros tres que le son propios. Con respecto a la epidemiología, los grupos de riesgo definidos son principalmente: homosexuales, fármacodependientes y hemofílicos. Las infecciones oportunistas y en ocaciones las lesiones dérmicas del tipo sarcoma de Kaposi son la regla, además de las lesiones características del tejido linfático. En lo referente al tratamiento: el alfa interferon y las interleukinas dan poco resultado, se espera en poco tiempo tener una "vacuna" .