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.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder.

BACKGROUND: Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. METHODS: We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. RESULTS: We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). CONCLUSIONS: In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.

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.

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.

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.

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.