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 (≥F2) or advanced (≥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: ≥F3: 75%, 76%, and 76%, respectively; ≥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 (≥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.
Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.
Given the overall lack of information on thiamine use for WE ...treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.
This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.
We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.
Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.
•There is extreme variability in thiamine dosages and routes used in the management of Wernicke encephalopathy.•It is essential to correct nutritional deficits in patients with alcohol use disorders and other risk factors for Wernicke encephalopathy.•Physicians should consider treating Wernicke encephalopathy in high-risk patients even in the absence of diagnostic criteria.
Abstract 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.
data regarding the association between Wernicke encephalopathy (WE) and alcoholic liver disease (ALD) are scarce in spite of alcohol consumption being the main risk factor for WE.
to describe the ...frequency of ALD in a cohort of patients diagnosed with WE and alcohol use disorders (AUDs) and to compare the characteristics of WE patients with and without ALD.
we conducted an observational study in 21 centers through a nationwide registry of the Spanish Society of Internal Medicine. WE Caine criteria were applied and demographic, clinical, and outcome variables were analyzed.
434 patients were included in the study, of which 372 were men (85.7%), and the mean age was 55 ± 11.8 years. ALD was present in 162 (37.3%) patients and we found a higher percentage of cases with tremor, flapping and hallucinations in the ALD group. A total of 22 patients (5.0%) died during admission (7.4% with ALD vs 3.7% without ALD; P = 0.087). Among the ALD patients, a relationship between mortality and the presence of anemia (Odds ratio OR=4.6 Confidence interval CI95% 1.1–18.8; P = 0.034), low level of consciousness (OR=4.9 CI95% 1.1–21.2; P = 0.031) and previous diagnosis of cancer (OR=10.3 CI95% 1.8–59.5; P = 0.009) was detected. Complete recovery was achieved by 27 patients with ALD (17.8%) and 71 (27.8%) without ALD (P = 0.030).
the association of WE and ALD in patients with AUDs is frequent and potentially linked to differences in clinical presentation and to poorer prognosis, as compared to alcoholic patients with WE without ALD.
•The association of Wernicke encephalopathy and alcoholic liver disease in patients with alcohol use disorders is frequent.•Diagnosis of Wernicke encephalopathy in patients with alcoholic liver disease can be harder due to clinical differences.•Patients with alcoholic liver disease and wernicke encephalopathy have worse prognosis.•The presence of Wernicke encephalopathy should prompt the assessment of alcoholic liver disease.
To analyze gender differences in the hepatic, nutritional and metabolic complications associated with alcoholism.
Cross-sectional study in alcoholic patients admitted to detoxification in two ...university hospitals of Barcelona between 1999 and 2006. During admission, co-morbidity prior to admission was assessed and blood samples to analyze biological markers were collected. Demographic and anthropometric data, daily alcohol consumption and other drug use characteristics were also obtained at admission.
There were 566 admissions in 480 patients (375 males). Age at admission was 43 years (IQR: 36.3-49.0 years). Overall, 68.4% showed macrocytosis (MCV > 95 fl), 81.7% GGT>40 U/L and 57.7% AST>37 U/L. Regarding liver function tests, frequency of alkaline phosphatase > 120 U/L was significantly higher in women (18.5 vs 10.5%, p=0.037). However, the prevalence of hyperferritinemia (> 90 ng/mL) was significantly higher in alcoholic men (85.7% vs 62.2%) (p=0.000). Having multiple liver function test alterations was significantly higher in men (OR: 1.64, 95% CI: 1.01-2.65) (p=0.043). Women showed significant differences regarding the prevalence of macrocytosis (77.5% vs 65.8%, p=0.026), low serum creatinine (< 0.7 mg/100mL) (28.2 vs 14.6%, p=0.001), low serum ferritin (< 30 ng/mL) (10.8 vs 3.9%, p=0.020), as well as of multiple nutritional alterations (OR: 1.59, 95% CI: 1.02-2.48) (p=0.040). However, men had higher prevalence of anemia than women (32.3 vs 21.4%, p=0.032). Prevalence of type I obesity (BMI>30 kg/m(2)) was significantly higher in alcoholic women (29.2 vs 7.9%, p=0.007).
Hepatic, nutritional and metabolic complications of alcoholism in women are frequent, thus increasing the risk of developing adverse clinical outcomes.
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. 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. 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). 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.
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.
To analyse incidence and determinants of tuberculosis in HIV-seroconverters before and after the introduction of HAART.
Data from a multicenter cohort study of 2238 HIV-seroconverters between the ...1980s and 2004 were analysed and censored by December 2004. Calendar year at risk intervals were pre-1992, 1992-1996 and 1997-2004. Incident tuberculosis was calculated as cases per 1000 person-years (p-y). Survival analyses using Kaplan-Meier and multivariate Cox regression allowing for late-entry were used. Proportional hazards assumptions were checked with tests based on Schoenfeld residuals.
Overall, 173 (7.7%) patients developed tuberculosis over 23 698 p-y at a rate of 7.3 cases per 1000 p-y 95% confidence interval (CI), 6.3-8.5. Incident tuberculosis was higher in intravenous drug-users (IDUs), 12.3 per 1000 p-y compared with persons infected sexually, 3.8 per 1000 p-y (P < 0.001), and persons with clotting disorders (PCD), 2.7 per 1000 p-y (P < 0.001). A decreasing tuberculosis incidence trend was observed from 1995 in all categories. Highest tuberculosis rates, 44 per 1000 p-y, were observed prior to 1997 in IDUs infected with HIV for 11 years. In multivariable analyses women were less likely to develop tuberculosis relative hazard (RH), 0.62; 95% CI, 0.41-0.96; P < 0.05) and IDUs were more likely to develop tuberculosis (RH, 3.0; 95% CI, 1.72-5.26, P < 0.001). In the HAART era, the hazard of developing tuberculosis was 70% lower (RH, 0.31; 95% CI, 0.17-0.54; P < 0.001). Before 1997, the risk of tuberculosis increased with time since HIV seroconversion, whereas it remained nearly constant in the HAART era.
Since the mid-1990s important decreases in tuberculosis have been observed in HIV-seroconverters that probably reflect the impact of both HAART and tuberculosis control programmes.
Introduction
Emerging non‐AIDS related causes of death have been observed in HIV‐positive subjects in industrialized countries. We aimed to analyze overall and cause‐specific excess of mortality of ...HIV‐positive patients compared to the general population and to assess the effect of prognostic factors.
Material and Methods
We used generalized linear models with Poisson error structure to estimate overall and cause‐specific excess of mortality in HIV‐positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short‐term and long‐term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data.
Results
In 9162 patients there were 363 deaths, 16.0% were non‐AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all‐cause mortality, 0.16 for liver, 0.10 for non‐AIDS malignancies and 0.03 for cardiovascular. Short‐term (first‐year follow‐up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06–6.01) and 1.47 (95% CI 0.95–2.27) for HCV coinfection; long‐term (subsequent follow‐up) eHR for baseline AIDS was 0.88 (95% CI 0.58–1.35) and 4.48 (95% CI 2.71–7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21–34.84) and in HCV‐coinfected patients (eHR: 3.85, 95% CI 0.85– 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4–12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6–13) showed a higher risk of non‐AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25–35.73).
Conclusions
Our results show overall, liver, non‐AIDS malignancies and cardiovascular excess of mortality associated with being HIV‐positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short‐term and long‐term effect of AIDS before entry and HCV coinfection was found for overall mortality.
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