Markers Of Inflammation And Mortality In A Cohort Of Patients With Alcohol Dependence

Inflammation 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 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 (interquartile 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 (3.84x100 p-y; 95% confidence interval [CI]: 2.70, 5.46) than among the HCV-negative patients (2.27x100 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

Assessment of liver disease in patients with chronic hepatitis C and unhealthy alcohol use

Hepatitis C virus (HCV) infection and unhealthy alcohol use are major drivers of the burden of liver disease worldwide and commonly co-occur. Assessment of underlying liver damage is a cornerstone of the clinical care of patients with chronic HCV infection and/or unhealthy alcohol use because many of them are diagnosed at advanced stages of disease. Early diagnosis of liver disease before decompensated liver cirrhosis becomes established is essential for treatment with direct acting antivirals and/or abstinence from alcohol consumption, which are the main therapeutic approaches for clinical management. In this review, we discuss current knowledge around the use of non-invasive methods to assess liver disease, such as abdominal ultrasound, controlled attenuation parameter, transient elastography, magnetic resonance imaging, and indices based on serum markers of liver injury

Association of hyperuricemia and gamma glutamyl transferase as a marker of metabolic risk in alcohol use disorder

Excessive alcohol consumption leads to overproduction of urates and renal function plays a critical role in serum uric acid levels. We aimed to assess associations of hyperuricemia in patients with alcohol use disorder (AUD) and comparable Glomerular Filtration Rate (GFR). A total of 686 patients undergoing treatment for AUD between 2013 and 2017 were eligible (77% men); age at admission was 47 years [interquartile range (IQR), 40-53 years], age of onset of alcohol consumption was 16 years [IQR, 16-18 years] and the amount of alcohol consumed was 160 g/day [IQR, 120-240 g/day]. Body Mass Index was 24.7 kg/m(2) [IQR, 21.9-28.4 kg/m(2)], eGFR was 105 mL/min/1.73 m(2) [IQR, 95.7-113.0 mL], 9.7% had metabolic syndrome and 23% had advanced liver fibrosis (FIB-4>3.25). Prevalence of hyperuricemia was 12.5%. The eGFR-adjusted multivariate analysis showed that relative to patients with GGT 300 U/L were 4.31 (95% CI 1.62-11.46) and 10.3 (95% CI 3.50-29.90) times more likely to have hyperuricemia, respectively. Our data shows that hyperuricemia in the context of AUD is strongly associated with serum GGT levels and suggest an increased cardio-metabolic risk in this population

Markers of Monocyte Activation, Inflammation, and Microbial Translocation Are Associated with Liver Fibrosis in Alcohol Use Disorder

Background: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. Methods: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 > 3.25. Results: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (-0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42-20.56), 1.87 (1.11-3.16), 2.99 (1.79-5.01), 1.84 (1.11-3.16), and 2.13 (1.30-3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48-4.58), p < 0.01). Conclusion: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF

Sex differences in the comorbidity of patients seeking a first treatment for Alcohol Use Disorder

Altres ajuts: acords transformatius de la UABBackground The CohRTA multicenter study aims to characterize patients undergoing a first treatment for alcohol use disorder (AUD). The objective is to analyze sex-specific differences in the comorbidity of AUD when starting the first treatment for the disorder. Methods A multicenter study was carried out between 2014 and 2021 in 6 public centers in Spain. Sociodemographic characteristics were collected, variables related to alcohol consumption, medical comorbidity according to Cumulative Illness Rating Scale-Substance Abuse (CIRS-SA), antecedent of psychiatric comorbidity, general blood test and screening for drugs in urine. Logistic regression models were used to establish associations. Results A total of 896 patients (634 M, 262 W) were included. Median age at admission was 48 years [IQR:41-56 years]. Men reported beginning regular alcohol consumption at an earlier age and drank more alcohol. The most frequent medical comorbidities were hepatic, respiratory, vascular and neurological. The median number of affected systems was three, with no differences between men and women. However, depressive disorder was more frequent in women. In the multivariate analysis, women were up to 4 times more likely to have a major depressive disorder, elevated ESR and elevated total cholesterol than men. Men started alcohol consumption earlier, had a higher body mass index (BMI), a higher probability of using cocaine and a higher frequency of GGT and bilirubin alteration than women. Conclusion Differences by sex were found among individuals beginning first treatment for AUD. These differences must be taken into account when designing specific therapeutic strategies for men and women

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

Abstract.Inflammation 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 patient

Prevalence and associations of metabolic syndrome in patients with alcohol use disorder

Excessive alcohol consumption has been associated with different components of the metabolic syndrome (MetS) such as arterial hypertension, dyslipidemia, type 2 diabetes or obesity. We aimed to analyze the prevalence and associations of MetS in patients with Alcohol Use Disorder (AUD). Cross-sectional study in heavy drinkers admitted for the treatment of AUD between 2013 and 2017. Medical comorbidity, anthropometric data, alcohol use and biological parameters were obtained. MetS was established according to the harmonized definition. A total of 728 patients (22% women) were included; median age was 47 years (IQR: 40-53.5), median alcohol consumption was 160 g/day (IQR: 115-240) and prevalence of MetS was 13.9%. The multivariate analysis showed a significant dose-response effect of estimated glomerular filtration (eGFR) and MetS: relative to patients with eGFR > 90 mL/min, those with eGFR (60-90 mL/min) and those with eGFR < 60 mL/min were 1.93 times (95% CI 1.18-3.15) and 5.61 times (95% CI 1.66-19.0) more likely to have MetS, respectively. MetS was significantly associated with hyperuricemia (OR 2.28, 95% CI 1.36-3.82) and elevated serum GGT (OR 3.67, 95% CI 1.80-7.46). Furthermore, for every increase of 1 year in age, the probability of MetS increased significantly (OR 1.03, 95% CI 1.01-1.05). MetS in heavy drinkers is independently associated with reduced kidney function and metabolic risk factors including hyperuricemia and elevated serum GGT

Author Correction : Association of hyperuricemia and gamma glutamyl transferase as a marker of metabolic risk in alcohol use disorder

Excessive alcohol consumption leads to overproduction of urates and renal function plays a critical role in serum uric acid levels. We aimed to assess associations of hyperuricemia in patients with alcohol use disorder (AUD) and comparable Glomerular Filtration Rate (GFR). A total of 686 patients undergoing treatment for AUD between 2013 and 2017 were eligible (77% men); age at admission was 47 years [interquartile range (IQR), 40-53 years], age of onset of alcohol consumption was 16 years [IQR, 16-18 years] and the amount of alcohol consumed was 160 g/day [IQR, 120-240 g/day]. Body Mass Index was 24.7 kg/m2 [IQR, 21.9-28.4 kg/m2], eGFR was 105 mL/min/1.73 m2 [IQR, 95.7-113.0 mL], 9.7% had metabolic syndrome and 23% had advanced liver fibrosis (FIB-4 > 3.25). Prevalence of hyperuricemia was 12.5%. The eGFR-adjusted multivariate analysis showed that relative to patients with GGT ≤ 50, those with GGT between 51 and 300 U/L and those with GGT > 300 U/L were 4.31 (95% CI 1.62-11.46) and 10.3 (95% CI 3.50-29.90) times more likely to have hyperuricemia, respectively. Our data shows that hyperuricemia in the context of AUD is strongly associated with serum GGT levels and suggest an increased cardio-metabolic risk in this population