Significance of Markers of Monocyte Activation (CD163 and sCD14) and Inflammation (IL-6) in Patients Admitted for Alcohol Use Disorder Treatment.

BACKGROUND: Monocyte activation and inflammation are prominent features of alcohol-related liver disease; however, they have not been thoroughly assessed in patients with alcohol use disorder (AUD) without overt liver disease. This study aimed to analyze associations among clinical and laboratory variables and markers of monocyte activation (CD163 and sCD14), and inflammation (interleukin [IL]-6) among AUD patients. METHODS: We analyzed the aforementioned associations in the highest quartile in 289 patients (77.5% male; median age, 50 years) consecutively admitted for alcohol detoxification in 2 tertiary hospitals in the Barcelona metropolitan area, Spain. RESULTS: Median alcohol intake was 142 g/d; median glucose, albumin, creatinine, and bilirubin levels (mg/dl), 92, 40, 0.78, and 0.69, respectively; median AST, 41 U/l; median hemoglobin, median corpuscular volume, and platelet count, 14.1 g/dl, 94.8 fL, and 189 × 109 /l, respectively; median cholesterol, triglyceride, fibrinogen, and ferritin levels, 187 mg/dl, 109.3 mg/dl, 341 mg/dl, and 177 ng/ml, respectively. In addition, 36.7% patients had an erythrocyte sedimentation rate >20 mm, 32.5% had a C-reactive protein (CRP) level of >5 mg/l, and 10.9% were hepatitis C virus (HCV)-positive. Median CD163, sCD14, and IL-6 levels were 759, 1.68 × 106 , and 4.37 pg/ml, respectively. On logistic regression analyses, glucose, AST, bilirubin, hemoglobin levels, and HCV infection (adjusted odds ratio [aORs]: 1.01, 1.02, 3.04, and 9.73, respectively) were associated with CD163. Glucose, AST, triglyceride, and CRP >5 mg/l (aORs: 1.02, 1.01, 1.00, and 3.49, respectively) were associated with sCD14. Alcohol consumption upon admission, MCV, total cholesterol levels, and CRP >5 mg/l (aORs: 0.99, 1.05, 0.99, and 2.56, respectively) were associated with IL-6. CONCLUSIONS: Monocyte activation and systemic inflammation are associated with higher glucose, liver enzyme, and lipid levels, HCV infections, and CRP of >5 mg/l, thus potentially identifying patients with AUD at high risk of midterm poor outcomes.

Predictive biomarkers for death and rehospitalization in comorbid frail elderly heart failure patients.

BACKGROUND: Heart failure (HF) is associated with a high rate of readmissions within 30 days post-discharge and in the following year, especially in frail elderly patients. Biomarker data are scarce in this high-risk population. This study assessed the value of early post-discharge circulating levels of ST2, NT-proBNP, CA125, and hs-TnI for predicting 30-day and 1-year outcomes in comorbid frail elderly patients with HF with mainly preserved ejection fraction (HFpEF). METHODS: Blood samples were obtained at the first visit shortly after discharge (4.9 ± 2 days). The primary endpoint was the composite of all-cause mortality or HF-related rehospitalization at 30 days and at 1 year. All-cause mortality alone at one year was also a major endpoint. HF-related rehospitalizations alone were secondary end-points. RESULTS: From February 2014 to November 2016, 522 consecutive patients attending the STOP-HF Clinic were included (57.1% women, age 82 ± 8.7 years, mean Barthel index 70 ± 25, mean Charlson comorbidity index 5.6 ± 2.2). The composite endpoint occurred in 8.6% patients at 30 days and in 38.5% at 1 year. In multivariable analysis, ST2 [hazard ratio (HR) 1.53; 95% CI 1.19-1.97; p = 0.001] was the only predictive biomarker at 30 days; at 1 year, both ST2 (HR 1.34; 95% CI 1.15-1.56; p < 0.001) and NT-proBNP (HR 1.19; 95% CI 1.02-1.40; p = 0.03) remained significant. The addition of ST2 and NT-proBNP into a clinical predictive model increased the AUC from 0.70 to 0.75 at 30 days (p = 0.02) and from 0.71 to 0.74 at 1 year (p < 0.05). For all-cause death at 1 year, ST2 (HR 1.50; 95% CI 1.26-1.80; p < 0.001), and CA125 (HR 1.41; 95% CI 1.21-1.63; p < 0.001) remained independent predictors in multivariable analysis. The addition of ST2 and CA125 into a clinical predictive model increased the AUC from 0.74 to 0.78 (p = 0.03). For HF-related hospitalizations, ST2 was the only predictive biomarker in multivariable analyses, both at 30 days and at 1 year. CONCLUSIONS: In a comorbid frail elderly population with HFpEF, ST2 outperformed NT-proBNP for predicting the risk of all-cause mortality or HF-related rehospitalization. ST2, a surrogate marker of inflammation and fibrosis, may be a better predictive marker in high-risk HFpEF.

Optimal Use of Transient Elastography and Acoustic Radiation Force Impulse to Stage Liver Fibrosis in HIV/HCV-Coinfected Patients in Clinical Practice.

OBJECTIVES: Liver fibrosis (LF) is crucial for the individualized management of patients with hepatitis C virus (HCV). We evaluated the concordance between two noninvasive methods for staging LF, transient elastography (TE) and acoustic radiation force impulse (ARFI), in patients coinfected with human immunodeficiency virus and HCV. We propose an algorithm for optimal use of both techniques in routine clinical practice. METHODS: A total of 89 human immunodeficiency virus/HCV-coinfected patients underwent TE and ARFI on the same day. The kappa index was used to assess concordance between the techniques. An algorithm combining ARFI and TE was proposed based on the independent factors associated with a kappa index greater than or equal to 0.70, obtained from a multiple regression analysis. We performed a cost-effectiveness analysis. The study was approved by our institutional review board and all patients signed the informed consent. RESULTS: Concordance between TE and ARFI for F2, F3, and F4 was 0.55, 0.59, and 0.69, respectively. Ultrasound normal spleen size (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.05-0.91) and high viral load (OR, 0.36; 95% CI, 0.17-0.77) reduced the probability of agreement between TE and ARFI, whereas ultrasound normal left liver lobe size (OR, 3.32; 95% CI, 1.21-9.10) increased this probability. The algorithm revealed that LF was adequately assessed in 74.16%, with 25.84% of patients misclassified. The incremental cost-effectiveness ratio of TE compared with ARFI to increase concordance by 1% was €8.86. CONCLUSIONS: Concordance between TE and ARFI was moderate. In the algorithm we proposed, ARFI was cost-effective as a first technique for the staging of LF in the study population.

Patients with alcohol use disorder: initial results from a prospective multicenter registry in the Spanish Network on Addiction Disorders. CohRTA Study. / Pacientes con trastorno por uso de alcohol: resultados iniciales de un registro multicéntrico en la Red de Trastornos Adictivos-RTA. Estudio CohRTA.

The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. Methods: multicentre cohort study in adults (>18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. Results: As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country.

El Programa Alcohol de la Red de Trastornos Adictivos (RTA) requiere de un estudio clínico longitudinal para dar respuesta a preguntas de investigación en el trastorno por uso de alcohol. El proyecto CohRTA es un estudio multicéntrico de investigación cooperativa que se pone en marcha para mejorar la prevención secundaria y el diagnóstico precoz de los procesos patológicos asociados al trastorno por uso de alcohol. Método: estudio observacional en cohorte multicéntrica de pacientes mayores de 18 años que solicitan tratamiento del trastorno por primera vez y autorizan su participación. La información clínica se recoge en una plataforma online diseñada para el estudio y puede ir acompañada de una muestra biológica que se deposita en un biobanco. Se recogen datos basales y prospectivos, sociodemográficos, epidemiológicos, clínicos y de tratamiento. A diciembre de 2015 son 10 los centros proveedores de pacientes y se espera reclutar más de 1.000 pacientes en los próximos años. Resultados: se dispone de 344 pacientes (77% hombres) que cumplen los criterios de inclusión en el estudio y con una edad de 50 años (RIQ: 43-55 años). La edad de inicio de consumo de alcohol fue de 15 años (RIQ: 14-18 años) y un 61% tenían antecedente familiar de trastorno por uso de alcohol. Durante los 30 días previos al inicio del tratamiento los pacientes bebían 12.5 UBE/día (RIQ: 7.1-20 UBE/día), el 72% fumaba tabaco y el 30% consumía cocaína. Conclusiones: Disponer de una cohorte abierta y multicéntrica de pacientes con trastorno por uso de alcohol será útil para analizar las consecuencias del abuso de alcohol, potenciar la investigación traslacional y añadir valor a la investigación clínica y básica del Programa Alcohol dentro de RTA/RETICS. Con una cohorte bien establecida y representativa se espera aumentar la cantidad y calidad científica en relación a las complicaciones del trastorno por uso de alcohol y sus consecuencias clínicas y sociales en España.

Long-Term Mortality of Patients with an Alcohol-Related Wernicke-Korsakoff Syndrome.

AIMS: To characterize a series of contemporary patients with alcohol-related Wernicke's encephalopathy (WE) or Korsakoff's syndrome (KS) and to update the current prognosis of disease. METHODS: Retrospective and prospective study of patients diagnosed with an alcohol-related WE or KS between 2002 and 2011 in a tertiary hospital. Socio-demographic, alcohol use characteristics, signs and symptoms, co-morbidity and blood parameters were obtained at admission. Patients were followed up until 2013 and causes of death were ascertained through the review of charts. RESULTS: Sixty-one patients were included (51 with WE and 10 with KS). Among patients with WE, 78% were men and age at diagnosis was 57 years (interquartile range (IQR): 49-66). Twenty-three percent fulfilled the classic WE triad. Regarding Caine's criteria for WE, 70.6% presented with at least two out of four signs or symptoms. Median follow-up of patients with WE syndrome was 5.3 years (IQR: 2.6-8.8), the cumulated mortality was 45% and death rate of 7.4 × 100 person-years (95% confidence interval (CI): 4.8-10.9). Overall, 50% of patients would be expected to die within 8 years of WE episode and main causes of death included serious bacterial infections (44.5%) and cancer (33.3%). CONCLUSIONS: Survival of patients with an alcohol-related Wernicke-Korsakoff syndrome is poor; pursuing treatment of alcohol use disorder and early diagnosis of thiamine deficiency is a priority for improving clinical outcomes.

Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium.

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health.

Hepatitis C associated to substance abuse: ever closer to a treatment without Interferon.

With 3-4 million of new infections occurring annually, hepatitis C virus (HCV) infection is a global Public Health problem. In fact, hepatitis C virus infection is one of the leading causes of liver disease in the world; in Western countries, two thirds of the new HCV infections are associated with injection drug use. The treatment of hepatitis C will change in the coming years with the irruption of new anti-HCV drugs, the so called Direct Antiviral Agents (DAA) that attack key proteins of the HCV life cycle. The new antiviral drugs are effective, safer and better tolerated. The 2014 WHO HCV treatment guidelines include some of them. The new DAA are used in combination and it is expected that Interferon will be not necessary in future treatment regimens against HCV infection. The irruption of new and potent antivirals mandate the review of the current standards of care in the HCV infected population. More inclusive and proactive treatment policies will be necessary in those individuals with substance use disorders.

La infección por el virus de la hepatitis C (VHC) es un problema de Salud Pública de primera magnitud; cada año ocurren entre 3 y 4 millones de nuevas infecciones y de hecho, la hepatitis crónica C es una de las principales causas de enfermedad hepática en el mundo. Usar drogas por vía parenteral está en el origen de dos de cada tres nuevas infecciones por VHC en el mundo occidental.El tratamiento de la hepatitis C va a cambiar en los próximos años. El cambio es debido a la aparición de los llamados Antivirales de Acción Directa (AAD), unos fármacos que actúan contra proteínas clave del ciclo vital del VHC y que serán más eficaces, mejor tolerados y se administrarán durante menos tiempo. En este sentido, la nueva guía de tratamiento de la OMS en 2014 ya incluye alguno de ellos en sus recomendaciones; los nuevos fármacos se utilizarán en combinación y probablemente se podrá prescindir del Interferón.Con la aparición de más y mejores antivirales contra el VHC es probable que debamos revisar el modelo asistencial vigente y orientarlo hacia uno más ágil e integrador, que trate al mayor número posible de pacientes, incluyendo a aquellos con abuso de sustancias.

Sex-specific disease outcomes of HIV-positive and HIV-negative drug users admitted to an opioid substitution therapy program in Spain: a cohort study.

BACKGROUND: Opioid substitution therapy has improved the survival of heroin users with and without HIV infection. We aimed to analyze sex differences in mortality rates and predictors of death among those admitted to a methadone treatment program (MTP). METHODS: Longitudinal study of patients enrolled in a MTP from 1992 to 2010. Socio-demographic and drug use characteristics, and markers of viral infections were assessed at entry. Vital status was ascertained by clinical charts and the mortality register. Four calendar periods were defined according to the introduction of preventive and treatment interventions in Spain. Predictors of death were analyzed by Cox regression models. RESULTS: 1,678 patients (82.8% men) were included; age at first heroin use was 18.6 years (IQR: 16-23 years), and age at first entry into a MTP was 30.7 years (IQR: 26-36 years). A total of 441 (26.3%) deaths occurred during 15,124 person-years (p-y) of follow-up (median: 9.2 years, IQR: 4-13 years). HIV infection was the main predictor of death in men (HR = 3.5, 95% CI: 2.1-5.7) and women (HR = 3.2, 95% CI: 1.2-8.7 ) and main cause of death was HIV/AIDS. Overall mortality rate was 2.9 per 100 p-y (95% CI: 2.7-3.2 per 100 p-y) and death rates decreased over time: 7.4 per 100 p-y (95% CI: 6.3-8.8 per 100 p-y) for the 1992-1996 period to 1.9 per 100 p-y (95% CI: 1.6-2.4 per 100 p-y) for the 2007-2010 period. In women, a slightly increase in mortality was observed in recent periods specifically among HIV-positive women (3.7 per 100 p-y in period 2002-2006 and 4.5 per 100 p-y in 2007-2010). CONCLUSIONS: Significant reductions in mortality of patients in MTP are observed after nineteen years of observation. However, HIV infection shows a great impact on survival, particularly among HIV-infected women.

Impact of medical comorbidity and risk of death in 680 patients with alcohol use disorders.

BACKGROUND: The association between alcohol use disorders and increased risk of mortality is well known; however, there have been few systematic evaluations of alcohol-related organ damage and its impact on survival in younger alcoholics. Therefore, we assessed medical comorbidity with a clinical index to identify subgroups of alcoholic patients at high risk of premature death. METHODS: Hospital-based cohort of alcohol-dependent patients admitted for detoxification between 1999 and 2008 in Barcelona, Spain. At admission, sociodemographic characteristics and a history of alcohol dependence and abuse of illegal drugs were obtained through clinical interviews and questionnaires. Medical comorbidity was assessed with the Cumulative Illness Rating Scale (Substance Abuse) (CIRS-SA). Dates and causes of death were obtained from clinical records and death registers. Survival was analyzed using Kaplan-Meier methods, and Cox regression models were used to analyze the risk factors for premature death. RESULTS: Median age of the patients (686 total, 79.7% men) was 43.5 years (interquartile range [IQR], 37.8 to 50.4), average alcohol consumption was 200 g/d (IQR, 120 to 280 g/d), and duration of alcohol use disorder was 18 years (IQR, 11 to 24). Medical comorbidity by CIRS-SA at admission showed that the organs/systems most affected were liver (99%), respiratory (86%), and cardiovascular (58%). After median follow-up of 3.1 years (IQR, 1.5 to 5.1), 78 (11.4%) patients died with a mortality rate of 3.28 × 100 person-years; according to Kaplan-Meier estimates, 50% (95% confidence interval [95% CI], 24 to 69%) of patients with severe medical comorbidity died in the first decade after treatment. In multivariate analysis, severe medical comorbidity (hazard ratio [HR], 5.5; 95% CI, 3.02 to 10.07) and being treated with methadone at admission (HR, 2.60; 95% CI, 1.50 to 4.51) were independent risk factors for premature death. CONCLUSIONS: Systematic assessment of alcohol-related organ damage is relevant for the identification and treatment of those at increased risk of death.

Pneumocystis jirovecii pneumonia in HIV-1-infected patients in the late-HAART era in developed countries.

BACKGROUND: In developed countries with free access to health care, primary chemoprophylaxis with co-trimoxazole, and antiretroviral treatment, Pneumocystis pneumonia (PCP) in HIV-infected subjects should be restricted to undiagnosed late presenters. METHODS: We retrospectively identified confirmed PCP hospital admissions in HIV-1 patients (period 1986-2010) and examined their characteristics and factors associated with mortality. RESULTS: Three hundred and twelve episodes (median CD4 27 cells/µl) were identified during 3 periods: pre-HAART (1986-1995), 49%; early-HAART (1996-1999), 17.3%; and late-HAART (2000-2010), 33.7%. PCP was the initial AIDS-defining diagnosis in only 86 (27.6%). Thirty-four (10.9%) patients died during their hospital stay, without a significant reduction in mortality in recent periods (p = 0.311). However, the 12-month mortality decreased through the periods (33.3% to 16.2%; p = 0.003). Drug users (p = 0.001) and those naïve to HAART (p < 0.001) decreased in the late-HAART era, while heterosexuals (p = 0.001), immigrants (p < 0.001), and HAART initiation before hospital discharge (p < 0.001) increased. A partial pressure of oxygen (PaO2) ≤ 55 (p = 0.04), intensive care admission (p < 0.001), and the absence of HAART initiation before discharge (p = 0.02) were correlated with mortality. CONCLUSIONS: The epidemiology and 12-month mortality of HIV-1-infected subjects with PCP have changed significantly in the late-HAART era, while mortality during hospital stay has remained unchanged. HIV diagnosed individuals lost to follow-up in care have emerged as the main driver of PCP in developed countries. Like HIV late presenters, they are more likely to have AIDS-defining illnesses, to be hospitalized, and to die. This finding has important implications for the design of better strategies to retain HIV-1-infected individuals in care.

[Prediction of bacteremia in patients with suspicion of infection in emergency room]. / Predicción de bacteriemia en los pacientes con sospecha de infección en urgencias.

BACKGROUND AND OBJECTIVES: To evaluate the relationship between some clinical and analytical data and the presence of bacteremia in order to establish a clinical decision rule. PATIENTS AND METHODS: All the patients with blood cultures obtained from the emergency room in a two months period were analyzed. Patients were randomly assigned to derivation or validation sets. A logistic regression of the significant values in the univariate analysis was performed and a score obtained. The prevalence of bacteraemia for every score was calculated. The diagnostic efficacy curves and the performance of the predictive model were calculated. RESULTS: 412 patients were enrolled. The blood cultures were positive in 12.8% of them. The significant values in the univariate analysis were Charlson index ≥2 and PCT > 0.4ng/ml. Four groups of increasing risk of bacteraemia were designed, from 0 to 35% in the derivation set and from 2.9% to 27.2% in the validation set. In the diagnostic efficacy curve, the AUC was 0.8 in the derivation set and 0.74 in the validation set. The model presented a negative predictive value of 95.2% in the derivation set and 95.3% in the validation set. CONCLUSIONS: A model that includes Charlson index and PCT makes possible to define a group of patients with a very low risk of bacteremia.

Cannabis use is associated with monocyte activation (sCD163) in patients admitted for alcohol use disorder treatment.

BACKGROUND: The effect of concomitant cocaine and cannabis use on monocyte activation and inflammation in patients with alcohol use disorder (AUD) is unknown. METHODS: To analyze the impact of cocaine and cannabis use on levels of markers of monocyte activation (sCD163 and sCD14) and systemic inflammation (interleukin-6 [IL-6]) in AUD patients admitted for hospital treatment between 2013 and 2018. Clinical and laboratory parameters were obtained upon admission. IL-6, sCD163, and sCD14 were measured in frozen plasma samples. We performed logistic regression to detect associations between cocaine and cannabis use and markers of monocyte activation and inflammation in the highest quartile. RESULTS: A total of 289 patients (77.5 % male) were included (median age = 50 years). The median alcohol intake upon admission was 142 g/day. The median duration of AUD was 20 years. Of the 289 patients with AUD, 76 % were active smokers, 23.1 % and 22.1 % concomitantly used cocaine and cannabis, respectively The median levels of IL-6, sCD163, and sCD14 were 4.37 pg/mL, 759 ng/mL, and 1.68 × 106 pg/mL, respectively. We did not detect associations between cocaine use and inflammation or monocyte activation. Cannabis use was associated with a higher odds of having sCD163 levels in the highest quartile (adjusted odds ratio = 2.34, 95 % confidence interval = 1.07-5.15, p = 0.03). Cannabis use was not associated with inflammation. CONCLUSION: In this series of AUD patients the concomitant use of cannabis use was associated with sCD163 levels that were in the highest quartile, consistent with monocyte activation.

Accuracy of simple biochemical tests in identifying liver fibrosis in patients co-infected with human immunodeficiency virus and hepatitis C virus.

BACKGROUND & AIMS: We assessed the ability of 3 simple biochemical tests to stage liver fibrosis in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: We analyzed liver biopsy samples from 324 consecutive HIV/HCV-positive patients (72% men; mean age, 38 y; mean CD4+ T-cell counts, 548 cells/mm(3)). Scheuer fibrosis scores were as follows: 30% had F0, 22% had F1, 19% had F2, 23% had F3, and 6% had F4. Logistic regression analyses were used to predict the probability of significant (>or=F2) or advanced (>or=F3) fibrosis, based on numeric scores from the APRI, FORNS, or FIB-4 tests (alone and in combination). Area under the receiver operating characteristic curves were analyzed to assess diagnostic performance. RESULTS: Area under the receiver operating characteristic curves analyses indicated that the 3 tests had similar abilities to identify F2 and F3; the ability of APRI, FORNS, and FIB-4 were as follows: F2 or greater: 0.72, 0.67, and 0.72, respectively; F3 or greater: 0.75, 0.73, and 0.78, respectively. The accuracy of each test in predicting which samples were F3 or greater was significantly higher than for F2 or greater (APRI, FORNS, and FIB-4: >or=F3: 75%, 76%, and 76%, respectively; >or=F2: 66%, 62%, and 68%, respectively). By using the lowest cut-off values for all 3 tests, F3 or greater was ruled out with sensitivity and negative predictive values of 79% to 94% and 87% to 91%, respectively, and 47% to 70% accuracy. Advanced liver fibrosis (>or=F3) was identified using the highest cut-off value, with specificity and positive predictive values of 90% to 96% and 63% to 73%, respectively, and 75% to 77% accuracy. CONCLUSIONS: Simple biochemical tests accurately predicted liver fibrosis in more than half the HIV/HCV co-infected patients. The absence and presence of liver fibrosis are predicted fairly using the lowest and highest cut-off levels, respectively.

Differences in virological response to pegylated interferon and ribavirin between hepatitis C virus (HCV)-monoinfected and HCV-HIV-coinfected patients.

BACKGROUND: Suboptimal doses of ribavirin have been suggested to explain the diminished efficacy of pegylated interferon (PEG-IFN) plus ribavirin in hepatitis C virus (HCV)-HIV-coinfected patients. METHODS: A cohort of 104 coinfected patients and an age-, sex- and genotype-matched cohort of HCV-monoinfected patients (n = 104) were compared. All patients received PEG-IFN-alpha2a 180 microg/week plus ribavirin 800-1,200 mg daily (HCV genotype 2/3 patients received 800 mg daily and those with genotype 1/4 received 1,000-1,200 mg daily) for 48 weeks (24 weeks for monoinfected patients with genotypes 2/3). HCV RNA levels were determined qualitatively at weeks 4, 12, 24, 48 and 72 and quantified monthly until week 12. RESULTS: The coinfected cohort had more advanced liver disease and lower body weight. HCV genotype 1 patients coinfected with HIV showed higher levels of HCV RNA than monoinfected patients. A significantly higher proportion of coinfected patients interrupted the prescribed treatment period prematurely (84% versus 98%). During the first 12 weeks, smaller decreases in HCV RNA levels were observed in coinfected patients. Among patients with HCV genotype 1, coinfected patients achieved lower rates of early virological response (64% versus 87%), end-of-treatment response (47.3% versus 80%) and sustained virological response (SVR; 27.3% versus 56.4%), but not rapid virological response (RVR). HCV-HIV-coinfected patients with HCV genotype 2/3 achieved significantly lower rates of RVR (52% versus 88%). Multivariate analysis identified RVR, gender and liver fibrosis as independent predictors of SVR. CONCLUSIONS: Differences in efficacy of PEG-IFN-alpha2a plus ribavirin treatment between HCV-HIV-coinfected and HCV-monoinfected patients were maintained despite optimized ribavirin dose.

Hepatitis C infection substantially reduces survival of alcohol-dependent patients.

BACKGROUND: Heavy alcohol use is associated with life-threatening complications including progressive liver disease. We aimed to analyze the impact of hepatitis C virus (HCV) infection on survival and liver-related death in alcohol-dependent patients. PATIENTS AND METHODS: This is a longitudinal study in patients seeking treatment of alcohol abuse between 2000 and 2010. Information on alcohol use characteristics, alcoholic liver disease, and HCV infection were obtained at entry. Cumulated mortality and causes of death were ascertained through clinical records and death registry. RESULTS: A total of 819 patients (81.6% men) underwent ethanol detoxification; age was 44 (inter-quartile range [IQR] 38-51) years; the duration of heavy alcohol use was 14 (IQR 6-24) years; and the alcohol consumption was 190 (IQR 120-250) g/day. The prevalence of HCV infection was 15.8%. There were 129 (16.9%) deaths during 5,117 persons-year (p-y) of follow-up (median follow-up 6.4 [IQR 4.3-9.2] years); 31 (24.6%) deaths were observed among the HCV-positive patients, and 98 (15.4%) deaths were observed among the HCV-negative patients. The mortality rate was significantly (P=0.03) higher among the HCV-positive patients (3.84×100 p-y; 95% confidence interval [CI]: 2.70, 5.46) than among the HCV-negative patients (2.27×100 p-y; 95% CI: 1.86, 2.77). Survival times for the HCV infected patients were 34% shorter (time ratio relative to HCV negative: 0.66; 95% CI: 0.51, 0.86). The main causes of death in the HCV-positive and -negative patients were liver-related mortality (48.4%) and neoplasia (22.4%), respectively. The liver-related mortality was significantly higher among the HCV-positive patients (adjusted sub-distribution hazard ratio [asHR] 3.65; 95% CI: 1.72, 7.78; P=0.001). CONCLUSION: HCV infection compromises the survival of patients with alcohol abuse/dependence. The new direct antiviral agents for the treatment of HCV infection may result in better clinical outcomes.

Ultrasound findings of liver damage in a series of patients consecutively admitted for treatment of alcohol use disorder.

BACKGROUND: To analyze ultrasound findings of liver damage in alcohol use disorder (AUD) patients. METHODS: A cross-sectional analysis of detoxification patients. Clinical and laboratory parameters were obtained at admission. Analytical liver injury (ALI) was defined as at least two of the following: aspartate aminotransferase (AST) levels ≥74 < 300 U/L, AST/alanine aminotransferase (ALT) ratio >2, and total bilirubin >1.2 mg/dL. Advanced liver fibrosis (ALF) was defined as a FIB-4 score ≥3.25. Abdominal ultrasound was used to identify steatosis, hepatomegaly, heterogeneous liver, and portal hypertension. Predictors of these findings were determined by logistic regression. RESULTS: We included 301 patients (80% male) with a median age of 46 years (IQR: 39-51 years) and alcohol consumption of 180 g/day (IQR: 120-201 g). The prevalence of Hepatitis C virus (HCV) was 21.2%; AST and ALT serum levels were 42 U/L (IQR: 23-78 U/L) and 35 U/L (IQR: 19-60 U/L), respectively; 16% of patients had ALI and 24% ALF. Ultrasound findings were: 57.2% steatosis, 49.5% hepatomegaly, 17% heterogeneous liver, and 16% portal hypertension; 77% had at least one ultrasound abnormality, and 45% had ≥2. HCV infection was associated with heterogeneous liver (p = 0.046) and portal hypertension (p < 0.01). ALI and ALF were associated with steatosis (both p < 0.01) and hepatomegaly (both p < 0.01), ALI with portal hypertension (p = 0.08), and ALF with heterogeneous liver (p < 0.01). In logistic regression, ALI and ALF were associated with ≥2 abnormalities [OR (95%CI): 5.2 (2.1-12.8), p < 0.01 and 4.7 (2.2-9.7), p < 0.01; respectively]. CONCLUSIONS: Ultrasound findings of liver damage may facilitate clinical decisions and alcohol cessation in AUD patients.

Do serum markers of liver fibrosis vary by HCV infection in patients with alcohol use disorder?

INTRODUCTION: HCV infection is frequent in patients with alcohol use disorder (AUD). Ethanol and hepatitis C have a synergistic effect that increases the risk of end-stage liver disease. We aimed to assess fibrosis of the liver in patients admitted to treatment of AUD. METHODS: Data were collected in two hospital units between 2000 and 2014. Liver fibrosis was assessed by serum biomarkers APRI, FIB-4 and Forns, and Advanced Liver Fibrosis (ALF) was defined if APRI > 1.5, FIB-4 > 3.25 or Forns > 6.9. Correlations were analyzed by Pearson's coefficients and logistic regression models were used. RESULTS: 1313 patients (80% M) had complete data; age at admission was 45 years (IQR: 39-52 yrs), age of initial regular alcohol consumption was 20 years (IQR: 17-26 yrs) and the amount of alcohol consumed preceding admission was 200 g/day (IQR: 120-270 g/day). Prevalence of HCV infection was 18%. Prevalence of ALF in HCV positive patients was 40.6% by APRI, 30.6% by FIB-4, and 43.3% by Forns. Correlations were high for APRI vs. FIB-4 r = 0.906, APRI vs. Forns r = 0.710, and, FIB-4 vs. Forns r = 0.825. There was no significant difference in the APRI/FIB-4 correlation by HCV status (z = 1.35, p = 0.177). However, the APRI/Forns correlation was significantly higher in HCV positive patients (p < 0.001). Patients with HCV infection were two times more likely to present with ALF at admission (OR = 2.1, 95%CI:1.5-3.1). CONCLUSIONS: HCV infection is associated with severity of fibrosis in patients with excessive alcohol consumption. In this context, APRI and FIB-4 are highly correlated which facilitates the assessment of liver damage.

Survival of HIV-infected injection drug users (IDUs) in the highly active antiretroviral therapy era, relative to sex- and age-specific survival of HIV-uninfected IDUs.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART), it remains unclear whether human immunodeficiency virus (HIV)-infected injection drug users (IDUs) have durations of survival similar to those for comparable HIV-uninfected IDUs. The goal of this study was to compare survival durations of HIV-infected and HIV-uninfected IDUs for the period 1987-2004.Methods. Demographic data, drug use characteristics, and biological markers were obtained at the time of admission to a substance abuse treatment program. The outcome of interest was the duration of survival after admission, and the primary exposure was HIV infection. Vital status was ascertained by means of the mortality register by the end of 2004. Three calendar periods, which were defined on the basis of use of specific therapies, were considered: 1987-1991 (the antiretroviral monotherapy era), 1992-1996 (the dual combination therapy era and the era when methadone was introduced in Spain), and 1997-2004 (the era of HAART and of established methadone programs). We used Cox regression methods allowing for late entries to handle the contribution of persons who survived a given period and entered the following period with nonzero time. We compared HIV-uninfected and HIV-infected IDUs with adjustments for age, sex, and duration of follow-up after admission. RESULTS: A total of 1209 IDUs were admitted to the hospital during the period from January 1987 through December 2004, and 1181 were eligible for the study. The majority (81.3%) of patients were men. The mean age (+/- standard deviation) at admission was 27.8+/-5.6 years, and the mean duration of injection drug use (+/- standard deviation) was 7.6+/-5.0 years. The prevalences of HIV and hepatitis C virus infections were 59.0% and 92.3%, respectively, and the total duration of follow-up was 10.116 person-years. Although survival duration for HIV-uninfected IDUs in 1997-2004 was similar to the duration in earlier periods, the duration for HIV-infected IDUs improved significantly since 1997 (P<.01). Furthermore, among patients admitted in the last period, the survival durations for HIV-uninfected and HIV-infected IDUs was virtually the same (relative hazard, 0.89; 95% confidence interval, 0.44-1.81). CONCLUSIONS: The duration of survival of HIV-infected IDUs has improved substantially since 1997, reaching rates similar to the rates for HIV-seronegative IDUs who accessed the health care system in the era of HAART.

[Bacteremia in outpatients: a 10-year period follow-up]. / Bacteriemia en pacientes no hospitalizados: tendencias evolutivas en los últimos 10 años.

BACKGROUND AND OBJECTIVE: To know the incidence of bacteremia in outpatients (BO), their clinical and epidemiological characteristics and evolution. PATIENTS AND METHOD: We have analyzed the percentage of positive blood cultures and BO in a 10 year period. We have collected year, month, age, gender, first diagnosis, risk factors for bacteremia, microrganism, final diagnosis and diagnosis concordance. The bacteremia was classified by origin in: urinary tract infection, respiratory, abdominal, venous catheter (IVC), skin, endocarditis, bacteremia without an apparent focus (BWAF) and miscellaneous. We have compared the characteristics of the patients with and without diagnosis concordance. RESULTS: We have collected 283 episodes. The percentage of positive blood culture remained wi-thout changes and the percentage of BO tended to decrease. The most prevalent bacteria was Escherichia coli (56.5%) and the most frequent origin was urinary (59.7%) and BWAF (19.7%). There was no concordance between diagnoses in 37.1%. 30.3% of patients were admitted. Urinary tract infection was detected in 93.5% of the cases, IVC in 6.2% and BWAF in 0%. With regard to the risk factors of bacteremia, human immunodeficiency infection tended to decrease and neoplasm to increase during the study period. CONCLUSIONS: In our experience, BO tends to decrease. The management of urinary infection seems adequate, and IVC could be improved. The main challenge is the cases of BWAF.

Over-expression of CD8+ T-cell activation is associated with decreased CD4+ cells in patients seeking treatment of Alcohol Use Disorder.

INTRODUCTION: Harmful alcohol consumption may have an impact on the adaptive immune system through an imbalance in T cell subpopulations and changes in cell activation. We aimed to analyze profiles of CD4 and CD8T cell activation in patients with alcohol use disorder (AUD). METHODS: We used a cross-sectional study with patients seeking treatment of the disorder. Blood samples for immunophenotyping were obtained at admission. Profiles of T cell activation were defined: (I) CD38+/HLA-DR+, (II) CD38+/HLA-DR-, (III) CD38-/HLA-DR+, (IV) CD38-/HLA-DR- and compared with healthy controls. We calculated a CD8+ T cell activation indicator (AI) that was defined as the quotient of non-activated cells (CD38-/HLA-DR-) and activated cells (CD38+/HLA-DR+). RESULTS: 60 patients were eligible (83%M); median age was 49 years [IQR: 44-54] and alcohol consumption was 145g/day [IQR: 90-205]. Mean±SD of CD38+/HLA-DR- was 50.3±50.6 cells/µL in patients and 33.5±24.5 cells/µL in controls (p=0.03), for the CD38-/HLA-DR+ it was 61±62.2 cells/µL in patients and 21.2±17.3 cells/µL in controls (p<0.001) and for the CD38+/HLA-DR+ it was 20.2±15.6 cells/µL in patients and 10.8±10.3 cells/µL in controls (p<0.001). In patients, an inverse correlation was observed between absolute number and percentage of CD4+ T cells, and the percentage of CD38+/HLA-DR+CD8+ T cells (r=0.37, p=0.003; r=0.2, p=0.086, respectively). CONCLUSIONS: Patients with AUD have an increased expression of immune activation with respect to healthy individuals. This excess of activated CD8+ T cells correlates with the absolute CD4+ T cells.