To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users.
Patients admitted ...for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase.
A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27-35 years), and the median duration of drug use was 10 years (IQR 5.5-15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76-1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56-1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values.
Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Drinking alcohol is an established and normalised practice in our society, even though it can physically harm us. High-risk alcohol drinking patterns can increase the chance of negative consequences ...for the drinkers or their environment. The liver is by far the organ most affected by alcohol abuse; however, alcohol use disorder is a systemic disease which affects a wide range of organs and psychological processes. Other systems that can be affected by continued alcohol consumption include the immune, neurological, and cardiovascular systems. In addition, alcohol can lead to epigenetic alterations that may be transmitted from one generation to the next.
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 <t; .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.
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.
To analyze the differences in characteristics and prognosis between alcoholic and nonalcoholic patients with Wernicke encephalopathy (WE).
A retrospective observational cohort of 468 patients ...diagnosed with WE with at least 2 Caine criteria was selected from all patients discharged with a diagnosis of WE from 21 medical centers in Spain from January 1, 2000, through December 31, 2012. Demographic, clinical, and outcome variables were described.
Among the 468 patients, the most common risk factor was alcoholism (n=434 92.7%). More than one-third of patients (n=181 38.7%) had the classic WE triad of symptoms (ocular signs, cerebellar dysfunction, and confusion). Among 252 patients for whom magnetic resonance imaging data were available, 135 (53.6%) had WE-related lesions and 42 (16.7%) had cerebellar lesions. Of the 468 patients, 25 (5.3%) died during hospitalization. Alcoholic patients presented more frequently than nonalcoholic patients with cerebellar signs (P=.01) but less frequently with ocular signs (P=.02). Alcoholic patients had a significantly higher frequency of hyponatremia (P=.04) and decreased platelet count (P=.005) compared with nonalcoholics. Alcoholic patients were diagnosed earlier than nonalcoholics (median time to diagnosis, 1 vs 4 days; P=.001) and had shorter hospitalizations (13 vs 23 days; P=.002).
Compared with nonalcoholic patients, alcoholic patients with WE are more likely to present with cerebellar signs and less likely to have ocular signs. Diagnosis may be delayed in nonalcoholic patients. Mortality in the present series was lower than described previously.
The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness ...through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer.
In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival.
5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% 95% CI 60–79 to 87% 77–93). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia.
Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care.
European Commission.
HIV-1-infected active drug users (ADU) obtain smaller clinical benefits with antiretroviral therapy (HAART) compared to non-ADU subjects with sexually-transmitted HIV-1 infection. Therefore treatment ...strategies are required to address the specific issues arising in this challenging scenario. We describe the effectiveness of HAART provided in a drug abuse outpatient treatment facility through a comprehensive integrated care that includes medical, drug dependence, and psychosocial support.
We included all consecutive HIV-1-infected ADU admitted for drug dependency treatment and who started their first HAART. A comparator arm consisted of a control group of sexually transmitted HIV-1-infected subjects attended in a reference hospital under standard care. The strategy did not include directly observed treatment.
A total of 71 ADU and 48 matched subjects infected through sexual transmission were included. ADU had lower baseline CD4+ T-cell counts (196 vs 279 cells/μL, P=.001), and more advanced CDC stages (P=.001). The estimated probabilities of patients with virological response ( < 50 copies/mL) at weeks 48 and 96 were 92.9% (95%-CI: 87.1%-99.1%) and 87.3% (95%-CI: 78.7%-95.2% for ADU, and 93.7%(95%-CI: 84.1%-99.8%) and 87.5% (95%-CI: 77.5%-97.3%) for sexually-infected subjects (P= .1325 and .241). Kaplan-Meier estimates of time to loss of virological response did not show differences between groups (log rank test, P=.965).
An integrated multidisciplinary care of HIV-1-infected antiretroviral naïve ADU provided in a drug abuse treatment center obtains high rates of virological suppression, similar to those observed in a comparison group of sexually-transmitted HIV-1-infected subjects. This strategy should be further evaluated in public health programs and assessed in randomized trials.
•Ultrasound abnormalities are common in patients with severe alcohol use disorder.•Alcohol liver injury and advanced liver fibrosis predict having ≥2 abnormalities.•Sharing ultrasound findings with ...patients might promote abstinence from alcohol.
To analyze ultrasound findings of liver damage in alcohol use disorder (AUD) patients.
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.
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.
Ultrasound findings of liver damage may facilitate clinical decisions and alcohol cessation in AUD patients.
•Patients with alcohol use disorder (AUD) have more CD8+ immune activation than healthy individuals.•The excess of activated CD8+ T cells correlates inversely with the CD4+ T cells.•An activation ...indicator would be useful in clinical practice to identify risk of immunosuppression.
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).
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+).
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).
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.
PDF
