The contribution of telemedicine to hepatitis C elimination in a correctional facility.

BACKGROUND: micro-elimination has been recently proposed as an efficient strategy to achieve global hepatitis C virus (HCV) elimination. The Spanish Health Ministry Strategic Plan for hepatitis C infection highlighted intervention in prisons as a priority action. However, there are important barriers associated with the specialized care provision to the penitentiary population. AIMS: to assess the contribution of telemedicine for HCV elimination in a correctional facility in Spain. METHODS: an open label program of HCV elimination via telemedicine was started on February 3rd, 2015 in a large penitentiary of 1,200 inmates, as an alternative to referring patients to specialists. An anonymous satisfaction survey was performed among a random sample of inmates and all participating doctors. RESULTS: the prevalence of HCV viremia prior to program initiation was 12.4%. One hundred and thirty-one patients received DAA HCV treatment during the period 2015-2018; 42.74% had a HCV-HIV co-infection. Overall, 97% achieved a sustained virological response (SVR). A second regime of DAA successfully rescued non-responder patients and the HCV prevalence was zero at the end of the program. Satisfaction was high or very high according to 67% of inmates and all participating doctors. CONCLUSION: telemedicine is an effective tool for HCV elimination in penitentiary correctional facilities where referral to specialists is difficult. The extensive use of this technology should be recommended in this setting in order to facilitate equitable access to specialized care.

Transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.

Our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (PBMC) that discriminate individuals with latent tuberculosis infection (LTBI) from those with pulmonary tuberculosis (PTB) in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in individuals without NIDDM. Using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with Mycobacterium tuberculosis (Mtb) or a mutant (ΔsigH) representing a non-inflammatory model. Genes expressed in blood, with inflammatory related functions were evaluated in humans by RT-qPCR. NCF1 and ORM transcripts have the better discriminatory capacity to identify PTB subjects from LTBI and non-infected controls (NICs) independently of the presence of NIDDM. The sequential evaluation of the mRNA levels of NCF1 and ORM as multiple diagnostic tests showed 95% Sensitivity (Se) and 80% Specificity (Sp). In addition, FPR2 promises to be a good biomarker for the PTB detection in subjects with NIDDM (Se=100%; Sp=90%).

Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current genotyping procedures: a population-based study in northeast Mexico.

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman's rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.

Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis from Mexico.

Tuberculosis (TB) is an infectocontagious respiratory disease caused by members of the Mycobacterium tuberculosis complex. A 7 base pair (bp) deletion in the locus polyketide synthase (pks)15/1 is described as polymorphic among members of the M. tuberculosis complex, enabling the identification of Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to characterise this locus in TB isolates from Mexico. One hundred twenty clinical isolates were recovered from the states of Veracruz and Estado de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the locus pks15/1, while genotypic characterisation was performed by spoligotyping. One hundred and fifty isolates contained the 7 bp deletion, while five had the wild type locus. Lineages X (22%), LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates were identified as Beijing and two (1%) EAI-Manila. The wild type pks15/1 locus was observed in all Asian lineage isolates tested. Our results confirm the utility of locus pks15/1 as a molecular marker for identifying Asian lineages of the M. tuberculosis complex. This marker could be of great value in the epidemiological surveillance of TB, especially in countries like Mexico, where the prevalence of such lineages is unknown.

Differences in the use of health resources by Spanish and immigrant HIV-infected patients.

BACKGROUND: HIV-immigrant use of health services and related cost has hardly been analysed. We compared resource utilisation patterns and direct health care costs between Spanish and immigrant HIV-infected patients. METHODS: All HIV-infected adult patients treated during the years 2003-2005 (372 patients) in this hospital were included. We evaluated the number of out-patient, Emergency Room (ER) and Day-care Unit visits, and number and length of admissions. Direct costs were analysed. We compared all variables between immigrant and Spanish patients. RESULTS: Immigrants represented 12% (n=43) of the cohort. There were no differences in the number of out-patient, ER, and day-care hospital visits per patient between both groups. The number of hospital admissions per patient for any cause was higher in immigrant than in Spanish patients, 1.3 (4.4) versus 0.9 (2.7), P=.034. A high proportion of visits, both for the immigrant (45.1%) and Spanish patients (43.0%), took place in services other than Infectious Diseases. Mean unitary cost per patient per admission, out-patient visits and ER visits were similar between groups. Pharmacy costs per year was higher in Spanish patients than in immigrants (7351.8 versus 7153.9 euros [year 2005], P=.012). There were no differences in the total cost per patient per year between both groups. The global distribution of cost was very similar between both groups; almost 75% of the total cost was attributed to pharmacy in both groups. CONCLUSIONS: There are no significant differences in health resource utilisation and associated costs between immigrant and Spanish HIV patients.

Evaluation of the transcriptional immune biomarkers in peripheral blood from Warao indigenous associate with the infection by Mycobacterium tuberculosis.

INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.

Concordance between IFNγ gene +874 A/T polymorphism and interferon-γ expression in a TB-endemic indigenous setting.

INTRODUCTION:: Interferon-γ (IFN-γ) plays a crucial role in resistance to mycobacterial diseases; accordingly, variants of the gene encoding this cytokine may be associated with elevated risk of contracting pulmonary tuberculosis (TB). METHODS:: Blood samples were collected from 135 Warao indigenous individuals with newly diagnosed sputum culture-positive TB. Of these, 24 were diagnosed with active tuberculosis (ATB). The study comprised 111 participants, who were grouped as follows: 1) 14 tuberculin skin test (TST)-positive Warao indigenous individuals and 4 that were QuantiFERON-TB?Gold In-Tube (QFT-IT) test-positive, collectively comprising the latent TB infection group (LTBI), n = 18), and 2) healthy controls who were QFT-IT- and TST-negative, comprising the control group (CTRL, n = 93). Detection of the IFN γ gene (IFNG) +874A/T polymorphism was performed via PCR and quantification of IFNG expression via qPCR. RESULTS:: Relative to indigenous and white Americans, ATB and CTRL groups had a higher frequency of the IFNG SNP (+874A): 23 (95.8%) and 108 (97.3%), respectively. Indigenous Warao individuals homozygous for the IFNG (+874) A allele exhibited 3.59-fold increased risk of developing TB (95% confidence interval, 2.60-4.96, p =0.0001). A decreased frequency of the AT genotype was observed in individuals with pulmonary TB (4.16%) and controls (0.90%). The frequency of the TT genotype was decreased among controls (1.80%); none of the patients with TB were found to have this genotype. The differences in IFNG expression between the groups, under unstimulated and stimulated conditions, were not statistically significant. CONCLUSIONS:: Preliminary results demonstrate concordance between IFNG +874 A/A genotype and low expression of IFNG.

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies. METHODS: Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at "Unidad de Artritis y Rheumatismo" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen. RESULTS: Significant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA- in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05). CONCLUSION: Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

Syncytial giant cell hepatitis in human immunodeficiency virus-infected patients with chronic hepatitis C: 2 cases and review of the literature.

Syncytial giant cell hepatitis (SGCH) among adult human immunodeficiency virus (HIV)-infected patients has been rarely described. Most cases have been reported in subjects coinfected with the hepatitis C virus (HCV), but its prevalence and outcome remain unknown. We performed a retrospective analysis of all cases of SGCH among 332 liver biopsies from HIV-infected patients seen at a tertiary center in Madrid, Spain, between 1984 and March 2004. Two hundred fifty specimens were obtained from HCV-coinfected patients. There were 2 cases of SGCH, leading to an observed overall prevalence of 0.6% (0.8% when considering only HCV-coinfected patients). In addition to histological changes secondary to chronic hepatitis C, the liver cords were replaced by syncytial giant cells with up to 30 nuclei. There was no histological evidence of measles (among paramyxoviruses) or herpes viruses group infections. In patient 1, there was a progressive clinical worsening after a 3-month course of prednisone, leading to liver failure and death. His postmortem liver biopsy showed more abundant giant hepatocytes accompanied with the development of a histologic pattern of severe fibrosing cholestatic hepatitis. The second patient received a prolonged course of pegylated interferon-alpha-2b and ribavirin with clearance of syncytial giant hepatocytes despite HCV-RNA persistence. SGCH is a rare histological finding among HIV-infected patients with chronic hepatitis C. Specific treatment with pegylated interferon and ribavirin can lead to histological resolution and biochemical improvement, even in the absence of HCV-RNA clearance.

Influence of liver fibrosis on highly active antiretroviral therapy-associated hepatotoxicity in patients with HIV and hepatitis C virus coinfection.

BACKGROUND: Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is a known risk factor for hepatotoxicity in patients receiving highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the role of HCV-related liver fibrosis in HAART-associated hepatotoxicity. METHODS: In a prospective study involving 107 patients who underwent liver biopsy, fibrosis was graded according 5 stages, from F0 (no fibrosis) to F4 (cirrhosis). Hepatotoxicity was defined as an increase in levels of aspartate aminotransferase and alanine aminotransferase to >5 times the upper limit of normal, or a >3.5-fold increase if baseline levels were abnormal. The incidence of hepatotoxicity was compared with liver fibrosis stage and with time and composition of HAART. RESULTS: Overall, 27 patients (25%) had hepatotoxic events (5.1 events/100 person-years of therapy). The incidence was greater for patients with stage F3 or F4 fibrosis (38%) than for those with stage F1 or F2 fibrosis (15%; 7.6 vs. 3 events/100 person-years; relative risk, 2.75; 95% confidence interval, 1.08-6.97; P=.013). Duration of HCV infection, duration of HAART, diagnosis of acquired immunodeficiency syndrome, HCV load, HCV genotype, and nadir CD4(+) cell count did not affect the risk of hepatotoxicity. Of the 86 patients who received nonnucleoside reverse-transcriptase inhibitors (NNRTIs), 11 (13%) developed liver toxicity. In these patients, fibrosis stages F1 and F2 were associated with similar rates of toxicity (3 events/100 person-years for patients who received nevirapine, 3.3 events/100 person-years for those who received efavirenz, and 3.4 events/100 person-years for those who received non-NNRTIs). There was a greater incidence among patients with F3 or F4 fibrosis who received NNRTIs (11.7 events/100 person-years for patients who received nevirapine, and 8.6 events/100 person-years for those who received efavirenz), compared with those who received non-NNRTIs (4 events/100 person-years). CONCLUSIONS: HAART-associated hepatotoxicity correlates with liver histological stage in patients coinfected with HIV and HCV. There was no difference in hepatotoxicity risk for different antiretroviral therapies in patients with mild-to-moderate fibrosis.

[Measurement of antimicrobial consumption using DDD per 100 bed-days versus DDD per 100 discharges after the implementation of an antimicrobial stewardship program]. / Evaluación del consumo de antimicrobianos mediante DDD/100 estancias versus DDD/100 altas en la implantación de un Programa de Optimización del Uso de Antimicrobianos.

INTRODUCTION: Monitoring antimicrobial consumption in hospitals is a necessary measure. The indicators commonly employed do not clearly reflect the antibiotic selection pressure. The objective of this study is to evaluate two different methods that analyze antimicrobial consumption based on DDD, per stay and per discharge, before and after the implementation an antimicrobial stewardship program. MATERIAL AND METHODS: Comparative pre-post study of antimicrobial consumption with the implementation of an antimicrobial stewardship program using DDD per 100 bed-days and DDD per 100 discharges as indicators. RESULTS: Hospital bed days remained stable and discharges increased slightly along the period of study Antibiotic consumption in DDD per 100 bed-days decreased by 2.5% versus 3.8% when expressed as DDD per 100 discharges. Antifungal consumption decreased by more than 50%. CONCLUSIONS: When average hospital stay decreases, reductions in the consumption of antimicrobials with an antimicrobial stewardship program system occur at the expense of reducing the number of patients receiving treatment, while increases occur due to longer durations of treatment.

Description of the population structure and genetic diversity of tuberculosis in Estado de México, a low prevalence setting from Mexico.

In order to identify the genetic characteristics of the strains of mycobacteria circulating in the Estado de México, one of the states with the lowest prevalence of tuberculosis in Mexico, spoligotyping and 12-loci MIRU-VNTR typing were used to genotype tuberculosis clinical isolates. The average age of the 183 patients analyzed was 50 (± 17) years, drug resistance was noted in 57 (31%) and multidrug resistance in 22 (12%) individuals. The results from the isolates recovered showed that 80% were located in four major Euro-American lineages: Haarlem (17%), LAM (15%), T (20%) and X (29%). Other lineages found in lower proportions were: EAI, S, Beijing, West African, Turkey, Vole and Bovis. Eighteen isolates were orphans. Only 57 isolates were grouped in nine clusters and the SIT119 (X1) showed the highest number of members (23). The LAM lineage showed an increased risk for development of drug resistance (RR=4, IC: 95%: 1.05-14.2, p = 0.03). Despite the important prevalence of four major lineages found and the diversity of strains circulating in the population, we found the presence of one of the largest populations of isolates clustered to the X lineage in a setting from a Latin American country.

Associated Risk Factors for Latent Tuberculosis Infection in Subjects with Diabetes.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM2) confers a higher risk for active tuberculosis (TB). However, information on associated risk factors for latent tuberculosis infection (LTBI) inpatients with DM2 is limited. We conducted a cross-sectional study to elucidate the prevalence of LTBI and its associated factors on Mexican adults with DM2 receiving medical care at the Mexican Social Security Institute (IMSS). METHODS: Six hundred patients with DM2 without a prior history of TB from outpatient diabetes clinics were enrolled in the study. The tuberculin-skin-test (TST) was performed. The presence of LTBI was defined by a TST value of ≥ 5 mm. A standardized interview and physical examination were conducted to obtain clinical, demographic, and LTBI risk factor information; all subjects were laboratory tested to determine the presence of exclusion criteria. Microscopic examination of sputum samples and chest x-rays was performed to identify potential active TB. Subjects with any finding suggesting active TB or malignancy were excluded. A logistic regression model was used to identify variables associated with LTBI. RESULTS: LTBI prevalence among patients with DM2 was 51.3%. Risk factors for LTBI were living with a relative with TB, having been in prison, having hemoglobin values >14 g/dL, and glycosylated hemoglobin (HbA1c) values of > 7%. Blood pressure, economic income, or anthropometric measurements were not associated risk factors. CONCLUSIONS: Over one half of patients with DM harbor LTBI. Exposure to certain environmental conditions and poorly controlled DM2 (HbA1c > 7.0%) were risk factors for having LTBI in persons with DM2.

CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected patients: the role of intravenous drug use.

We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of 288 patients (176 former injecting drug users) who maintained complete virus suppression for more than 24 months. Significant differences in CD4 cell counts at 6 and 24 months were detected. Multivariate analysis showed that drug use was an independent predictor of poor immunological recovery. Injection drug abuse impairs short and long-term CD4 cell recovery in HIV-positive patients initiating successful highly active antiretroviral therapy.

Pegylated interferon alpha2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.

BACKGROUND: Hepatitis C virus (HCV) and HIV coinfection constitutes an important epidemiological and clinical problem. We evaluated the safety and efficacy of Pegylated interferon alpha2b (Peg-IFN) and a fixed dose of ribavirin in the treatment of chronic hepatitis C in HIV coinfection. METHODS: Open, prospective study in HCV-HIV coinfected patients with persistently elevated alanine aminotransferase (ALT) levels and a liver biopsy showing either portal or bridging fibrosis. Therapy included Peg-IFN (50 micro g weekly) with ribavirin 800 mg for 48 weeks. The primary end point was sustained virological response (SVR). Univariate and multivariate analyses were performed to determine factors associated with response. RESULTS: By intent-to-treat analysis, 11 of 35 patients (31%) reached SVR. SVR was significantly better for genotypes 2/3 than for genotype 1 (54% versus 21%; P < 0.05). By multivariate logistic regression analysis, only a non-1 genotype was an independent factor for SVR [odds ratio (OR), 6; 95% confidence interval (CI), 1.1-31.7; P < 0.005]. A decrease of at least 1.5 log10 HCV RNA at week 12 of therapy was highly predictive of SVR (OR, 49.9; 95% CI, 4.9-508.2; P < 0.001). Most patients developed adverse events, although only six patients (17%) discontinued treatment due to toxicity. CONCLUSIONS: The combination of low doses of Peg-IFN plus a fixed dose of ribavirin resulted in a rate of SVR similar to that obtained with higher doses of the drugs in HIV-infected patients and lower than those obtained in non-HIV patients. Response at week 12 may be useful to help guide therapy in HCV-HIV co-infected patients.

Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study.

A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.

High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin.

BACKGROUND: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfected patients. OBJECTIVE: To evaluate, among 89 patients receiving highly active antiretroviral therapy (HAART) and therapy for chronic hepatitis C, clinically relevant mitochondrial toxicity in those treated with concomitant ribavirin and didanosine (n=35, 39%). METHODS: From January 2000 to July 2002 longitudinal analysis of the incidence and clinical course of didanosine-related hyperamylasaemia, pancreatitis, hyperlactataemia/lactic acidosis or neuropathy. Risk factors were evaluated using univariate and multivariate Cox's proportional hazards model. RESULTS: Among 35 patients who received concomitant didanosine (400 mg/day in 86%) and ribavirin (> or = 10 mg/kg/day in 91%), 20 (57%) developed one or more adverse events after a mean of 87 days. Most frequent laboratory abnormalities were hyperamylasaemia (18 patients, 51%) and hyperlactataemia (eight patients, 23%). Acute pancreatitis and symptomatic hyperlactataemia developed in 10 (28%) and six (17%) patients, respectively. Two patients (6%) with pancreatitis and severe lactic acidosis died; the other patients recovered uneventfully despite continuation of anti-HCV therapy in 83% after didanosine withdrawal in 40%. In the Cox's model higher baseline amylase levels (HR: 1.04, 95% CI: 1.02-1.06, P=0.001) and three nucleoside reverse transcriptase inhibitor-based HAART (HR: 5.3, 95% CI: 1.73-16.24, P=0.003) were significantly associated to toxicity. CONCLUSIONS: The coadministration of didanosine and ribavirin should be avoided in HIV/HCV-coinfected patients, due to a high rate of clinically significant toxicity, particularly in triple nucleoside-based HAART. Amylase levels should be strictly monitored, especially if elevated at baseline.

Partial splenic embolization for the treatment of hypersplenism in cirrhotic HIV/HCV patients prior to pegylated interferon and ribavirin.

Partial splenic embolization (PSE), a non-surgical treatment for hypersplenism, has also been reported to improve hepatic function. As severe thrombocytopaenia or leukopaenia contraindicate the use of combined therapy with pegylated interferons (PEG-IFNs) and ribavirin (RBV) in HCV-related cirrhosis, we evaluated, from July 2002 to October 2003, the safety and effectiveness of PSE as a procedure to allow therapy for HCV in three Child-Pugh class B cirrhotic patients with hypersplenism and HIV co-infection. HCV genotypes were 1b (n=2) and 3a (n=1). Severe thrombocytopaenia (in all) and leukopaenia (in two) precluded therapy for HCV. PSE was successfully performed in all with a mean infarcted area of 80%, leading to a significant increase in platelet and leukocyte counts that allowed therapy with weight-adjusted RBV and PEG-IFN-alpha-2b (patients 1 and 3) or 180 microg of PEG-IFN-alpha-2a (patient 2) 8 weeks after the procedure. Moderate pain, well controlled with conservative measures, followed PSE in 100% of cases, but during follow-up (mean 422 days) there were no infectious complications or liver decompensation episodes. Although preliminary, these results suggest the potential role of PSE in HIV/HCV-cirrhotic subjects with hypersplenism as a procedure to allow the use of combined PEG-IFN and RBV.

The role of liver biopsy in the management of chronic hepatitis C in patients infected with the human immunodeficiency virus.

We evaluated the role of liver biopsy in the management of chronic hepatitis C in HIV-infected persons. Patients included had abnormal alanine transaminase (ALT) levels, detectable HCV RNA, and an interpretable liver biopsy. Demographic, epidemiologic, clinical, laboratory, histological, and therapeutic data were recorded in all patients. We also registered the clinical diagnosis of cirrhosis (previous to biopsy) and whether the biopsy result deferred the decision of initiating therapy. During the 33-month duration of the study, 112 patients were included. The degree of fibrosis in liver biopsies was none or mild (F0 or F1) in 47 patients (42%) and was significant or severe in 65 (58%). Seventeen patients (15%) had histological cirrhosis. By logistic regression analysis, only portal hypertension (odds ratio [95% confidence interval], 5.3 [1.05-25.9], P = 0.04) was independently associated with significant fibrosis. Overall, cirrhosis was predicted before biopsy in 29 patients (26%) by the caregiving physician, but only 8 of these were confirmed histologically. The clinical prediction of cirrhosis before biopsy had a sensitivity of 47%, a specificity of 78%, a positive predictive value of 28%, and a negative predictive value of 89%. Histological findings changed the decision to initiate HCV therapy in 19 patients (17%) because of little or no fibrosis. Liver biopsy is a useful tool in the management of HCV-HIV-coinfected persons. In addition to allowing grading and staging of the disease far better than any other method or combination of methods, it is important for making management decisions for patients coinfected with HCV and HIV.

Evaluation of the transcriptional immune biomarkers in peripheral blood from warao indigenous associate with the infection by mycobacterium tuberculosis

Abstract INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.