Ferran Bolao

Significant reductions of HIV prevalence but not of hepatitis C virus infections in injection drug users from metropolitan Barcelona: 1987–2001

OBJECTIVES To characterize trends from 1987 to 2001 in the prevalence of HIV and HCV infections among 2219 injection drug users (IDUs) starting treatment for substance abuse in two large hospitals in metropolitan Barcelona. METHODS The study population comprised IDUs with HIV tests completed from 1987 to 2001 and admitted for detoxification. Testing for HCV started in 1991 (n=1132). Characterization of temporal trends was carried out using logistic regression methods. Stratification was used to describe possible heterogeneities of the temporal trends. RESULTS The overall prevalence of HIV, HCV, and HBV (HBsAg+) was 55%, 88%, and 7%, respectively. Adjusted by duration of IDU, sex, and age at initiation, the prevalence of HIV infection declined significantly (p<0.001) from 1989 to 2004. The substantially higher prevalence of HCV showed a decline (p=0.065) of lesser magnitude. The decline of HIV infection was consistently observed among those with duration of IDU of less than 10 years. In turn, the decline of HCV was restricted to those with short duration of IDU (<4 years) because the prevalence of HCV infection was close to 100% for durations longer than 4 years in all calendar periods. CONCLUSIONS Preventive interventions and treatment for substance abuse might have contributed to the waning of the HIV epidemic in Spain. However, the extremely high levels of HCV infection and the underlying prevalence of HIV might lead to a large health burden of liver disease.

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.

Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients.

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio‐demographic and alcohol use characteristics, liver function tests for the assessment of alcohol‐related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9–50.2 years), duration of alcohol abuse was 18 years (IQR: 11–24 years), and median alcohol consumption was 200 g/day (IQR: 120–275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow‐up was 3.1 years (IQR: 1.5–5.1 years) accounting for 2,345 person‐years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05–2.80), alcohol‐related liver disease (HR = 3.55, 95%CI: 1.93–6.53) and HCV/HIV co‐infection (HR = 3.86 95%CI: 2.10–7.11) were predictors of death. Younger patients (≤43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3–7.3; P = 0.007). Among patients with alcohol‐related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders.

Markers of inflammation and mortality in a cohort of patients with alcohol dependence.

AbstractInflammation and intestinal permeability are believed to be paramount features in the development of alcohol-related liver damage. We aimed to assess the impact of 3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on mid-term mortality of patients with alcohol dependence.This longitudinal study included patients with alcohol dependence admitted for hospital detoxification between 2000 and 2010. Mortality was ascertained from clinical charts and the mortality register. Associations between markers of inflammation and all-cause mortality were analyzed with mortality rates and Cox proportional hazards regression models.We also performed a subgroup analysis of mortality rates in patients with anemia, based on their mean corpuscular volume (MCV).We included 909 consecutive patients with alcohol dependence. Patients were mostly male (80.3%), had a median age of 44 years (interquartile range [IQR]: 38–50), and upon admission, their median alcohol consumption was 192 g/day (IQR: 120–265). At admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels >4.5 mg/dL; and 365 (49.5%) had ferritin levels >200 ng/mL. At the end of follow-up (median 3.8 years [IQR: 1.8–6.5], and a total of 3861.07 person-years), 118 patients had died (12.9% of the study population). Cox regression models showed that the presence of anemia at baseline was associated with mortality (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11–2.52, P < 0.01); no associations were found between mortality and high fibrinogen or high ferritin levels.A subgroup of patients with anemia was analyzed and compared to a control group of patients without anemia and a normal MCV. The mortality ratios of patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41–7.26; P < 0.01) and 3.39 (95% CI: 1.86–6.43; P < 0.01), respectively.Patients with alcohol dependence admitted for detoxification had an increased risk of death when anemia was present at admission. More accurate markers of systemic inflammation are needed to serve as prognostic factors for poor outcomes in this subset of patients.

Hepatitis B virus serum profiles in injection drug users and rates of immunization over time in Barcelona: 1987-2006.

UNLABELLED Injection drug users are at increased risk for hepatitis B. Surveillance of the unexposed to infection and of the vaccinated is necessary to understand the impact of interventions. We aimed to analyze HBV serum profiles and rates of HBV vaccination over 20 years. METHODS Cross-sectional study in IDUs admitted to detoxification between 1987 and 2006 in two hospitals in Barcelona, Spain. Clinical data and serum samples for HBV, HCV and HIV infections were collected. HBV serostatus was assessed with HBsAg, Anti-HBs and Anti-HBc. RESULTS A total of 1223 IDUs were eligible; 80.3% were men; median age at admission was 28 years. Prevalence of HCV infection and HIV infection was 84.2% and 44.3%, respectively. There was a significant (p<0.001) increase of the rates of HBV vaccine-induced immunity from 3.7% in period 1987-1991 to 19.9% in period 2002-2006 and, a significant (p<0.001) decline of those with HBsAg from 9.3% in 1987-1991 to <2% after 1997. The rates of absence of HBV markers and of natural immunity remained stable from 1992 onwards. In multivariate logistic regression model, HBV vaccination was significantly (p<0.001) less frequent in older individuals (OR=0.61 [95% CI: 0.50-0.74] for a 5-year increase in age) and in HIV infected patients (p=0.014) (OR=0.51 [95% CI: 0.30-0.87]). CONCLUSIONS In the 20-year period from 1987 to 2006, HBV vaccine-induced immunity in IDUs has shown an upward trend, although overall prevalence remained low. More effective interventions are needed to reduce high rates of HBV infection in this population.

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.

Cannabis as Secondary Drug Is Not Associated With a Greater Risk of Death in Patients With Opiate, Cocaine, or Alcohol Dependence.

BACKGROUND The health burden of cannabis use in patients with other substance dependencies is not fully understood. OBJECTIVE To assess the impact of cannabis use as secondary drug on mortality of patients with other major substance use disorders. PARTICIPANTS Patients with opiate, cocaine, or alcohol dependence admitted to detoxification from 2001 to 2010 at a teaching hospital in Badalona, Spain. MAIN MEASUREMENTS Sociodemographic characteristics, drug use, medical comorbidities, and urine drug screens were obtained at admission. Deaths were ascertained through clinical records and a death registry. Mortality rates and Cox regression models were used to analyze the association between urinary cannabis and mortality. RESULTS A total of 474 patients (20% women) were admitted with a median age of 38 years (interquartile range: 32-44 years). The main substances that motivated admissions were opiates (27%), cocaine (24%), and alcohol (49%). Positive urinary cannabis was detected in 168 patients (35%). Prevalence of cannabis use among patients with opiate, cocaine, or alcohol dependence was 46.5%, 42.9%, and 25.5%, respectively. At admission, 110 (23.7%) patients had human immunodeficiency virus infection and 217 (46.5%) had hepatitis C virus infection. Patients were studied for a median of 5.6 years (interquartile range: 2.6-7.7 years) (2454.7 person-years), and at the end of the study, 50 patients (10.5%) had died, yielding a mortality rate of 2.04 × 100 patient-years (95% confidence interval: 1.53-2.66). There was no association between cannabis detection and overall mortality in the adjusted regression models [hazard ratio (95% confidence interval): 1.12 (0.60-2.00), P = 0.73], but acquired immune deficiency syndrome-related deaths were more frequent in those positive for cannabis (26% vs 2%, P = 0.03). CONCLUSION Positive urinary cannabis did not confer an increased risk of death in patients with severe opiate, cocaine or alcohol dependence.

Temporal trends in the survival of drug and alcohol abusers according to the primary drug of admission to treatment in Spain

BACKGROUND Mortality of alcohol and drug abusers is much higher than the general population. We aimed to characterize the role of the primary substance of abuse on the survival of patients admitted to treatment and to analyze changes in mortality over time. METHODS Longitudinal study analyzing demographic, drug use, and biological data of 5023 patients admitted to three hospital-based treatment units in Barcelona, Spain, between 1985 and 2006. Vital status and causes of death were ascertained from clinical charts and the mortality register. Piecewise regression models were used to analyze changes in mortality. RESULTS The primary substances of dependence were heroin, cocaine, and alcohol in 3388 (67.5%), 945 (18.8%), and 690 patients (13.7%), respectively. The median follow-up after admission to treatment was 11.6 years (IQR: 6.6-16.1), 6.5 years (IQR: 3.9-10.6), and 4.8 years (IQR: 3.1-7.8) for the heroin-, cocaine-, and alcohol-dependent patients, respectively. For heroin-dependent patients, mortality rate decreased from 7.3×100person-years (p-y) in 1985 to 1.8×100p-y in 2008. For cocaine-dependent patients, mortality rate decreased from 10.7×100p-y in 1985 to <2.5×100p-y after 2004. The annual average decrease was 2% for alcohol-dependent patients, with the lowest mortality rate (3.3×100p-y) in 2008. CONCLUSIONS Significant reductions in mortality of alcohol and drug dependent patients are observed in recent years in Spain. Preventive interventions, treatment of substance dependence and antiretroviral therapy may have contributed to improve survival in this population.

HIV Infection and Viral Hepatitis in Drug Abusers

The epidemiology of HIV infection and viral hepatitis among injection drug users (IDUs) is changing in western countries; reductions in the epidemic of blood-borne infections, such as HIV infection, and viral hepatitis among drug users are probably related to the generaliza‐ tion of harm-reduction interventions and to the treatment of both HIV/AIDS and substance abuse. Opioid substitution therapy for the treatment of patients with heroin dependence, needle exchange programmes, access to Highly Active Antiretroviral Therapy (HAART) and supervised injecting facilities, among other preventive interventions, have contributed to reduce the impact of the HIV epidemic among drug users.

Folate deficiency in patients seeking treatment of alcohol use disorder

INTRODUCTION Nutritional deficiency is frequent in patients with an alcohol use disorder (AUD). We aimed to analyze serum and erythrocyte folate deficiency in a case series of patients that initiated treatment of AUD. PATIENTS AND METHODS A cross-sectional study in patients admitted for detoxification between 2007 and 2015 was performed. Sociodemographic characteristics, history of alcohol consumption, type of alcohol, and medical co-morbidity were assessed at admission. Blood samples for biochemistry and hematological parameters were collected at admission. Logistic regression models were used to establish predictors of folate deficiency. RESULTS 211 patients (79.1% men) were eligible; age at admission was 46 years [IQR:40-51], and the amount of alcohol consumption was of 160g/day [IQR:120-200]. Thirty four percent of patients had macrocytosis (MCV>100fL), 12.8% had anemia, 23% of cases presented with serum folate deficiency and 7% presented with erythrocyte folate deficiency. Most (69%) of the patients with serum folate deficiency had normal erythrocyte folate levels. In univariate analysis, macrocytosis (OR=3.4, 95%CI:1.7-6.6), alcohol-related liver disease (ARLD) (OR=2.5, 95%CI:1.0-6.1) and drinking alcoholic beverages other than beer (OR=3.3, 95%CI:1.5-7.3) were associated with folate deficiency. However, only macrocytosis was significantly associated with serum folate deficiency in multivariate analysis (OR=3.1, 95%CI:1.1-8.9). Macrocytosis (P<0.001), ARLD (P=0.01) and the type of alcohol consumption (P<0.001) were factors associated with erythrocyte folate deficiency in univariate analysis. In multivariate analysis only macrocytosis remained significantly associated to erythrocyte folate deficiency (P=0.037). CONCLUSION Folate deficiency is a relatively frequent finding in contemporary, middle-aged patients with AUD, and macrocytosis is significantly associated with the deficiency.