The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

<div><h3>Background</h3><p>Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.</p> <h3>Methodology/Principal Findings</h3><p>OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.</p> <h3>Conclusion/Significance</h3><p>OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.</p> </div

Adaptation of controlled attenuation parameter (CAP) measurement depth in morbidly obese patients addressed for bariatric surgery

International audienceBACKGROUND AND AIM: The controlled attenuation parameter (CAP) using FibroScan (Echosens, Paris, France) M or XL probe has been developed for liver steatosis assessment. However, CAP performs poorly in patients with high body mass index. The aim of our study was to assess whether CAP is overestimated using the standard XL probe in patients with morbid obesity, and in the case of an overestimation, to reprocess the data at a greater depth to obtain the appropriate CAP (CAPa).PATIENTS AND METHODS: We conducted an observational prospective cohort study on a total of 249 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Patients had a liver biopsy performed during the surgery and a CAP measurement during the 15 days preceding biopsy. Patient files were reprocessed retrospectively by an algorithm, blinded to the patients' clinical data. The algorithm automatically assessed the probe-to-capsula distance (PCD) by analysing the echogenicity of ultrasound signals on the time-motion mode. In the case of a distance >35 mm, the algorithm automatically selected a deeper measurement for CAP (CAPa). When PCD was less than 35 mm, the measured CAP was considered as appropriated (CAPa) and no further reprocessing was performed.RESULTS: CAP recording was not performed at a sufficient depth in 130 patients. In these patients, the CAPa obtained at the adapted depth was significantly lower than CAP (298±3.9 versus 340±4.2 dB/m; p 35 mm, steatosis stage was the only parameter independently correlated with CAP values. For the diagnosis of steatosis (S≥1), moderate to severe steatosis (S≥2) and severe steatosis (S = 3), the AUROC curves of CAPa (measured CAP in patients with PCD35 mm) were 0.86, 0.83 and 0.79, respectively. The Obuchowski measure for the diagnosis of steatosis was 0.90±0.013.CONCLUSION: CAP was overestimated in a half of morbidly obese patients using an XL probe, but CAP can be performed correctly in these patients after adapting the measurement depth

Predictive score of sarcopenia occurrence one year after bariatric surgery in severely obese patients.

BACKGROUND AND AIM:Sarcopenic obesity is a risk factor of morbidity and mortality. The aim of this study was to generate a predictive score of sarcopenia occurrence one year after bariatric surgery. PATIENTS AND METHODS:We conducted an observational prospective cohort study on a total of 184 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Skeletal muscle cross-sectional area at the third lumbar vertebrae (SMA, cm2) was measured from the routinely performed computed tomography. The skeletal muscle index (SMI) was calculated as follows: SMA/height2 (cm2/m2). Sarcopenia was defined as an SMI < 38.5 cm2/m2 for women and < 52.4 cm2/m2 for men. Measurements were performed at surgery and one year later. RESULTS:Most of the included patients were female (79%), with a mean age of 42±0.9 years and body mass index of 43.2±0.5 kg/m2. Fifteen patients (8%) had sarcopenia before surgery and 59 (32%) at the one-year follow-up. Male gender (p<0.0001), SMA before surgery (p<0.0001), and SMI before surgery (p<0.0001) significantly correlated with the occurrence of sarcopenia one year after surgery by multivariate analysis. Two predictive sarcopenia occurrence scores were constructed using SMA and gender (SS1 score) or SMI and gender (SS2 score). The area under receiver operating characteristic (AUROC) curve of the SS2 score was significantly greater than that of the SS1 score for the diagnosis of postoperative sarcopenia occurrence (0.95±0.02 versus 0.90±0.02; p<0.01). A cut-off value for the SS2 score of 0.53 had a sensitivity of 90%, a specificity of 91%, a positive predictive value of 83%, and a negative predictive value of 95%. In the group of patients without baseline sarcopenia, the SS2 score had still an excellent AUROC of 0.92±0.02. A cut-off of 0.55 predicted development of sarcopenia one year after sleeve gastrectomy in these patients with a sensitivity of 87%, a specificity of 88%, and negative predictive value of 95%. CONCLUSION:The SS2 score has excellent predictive value for the occurrence of sarcopenia one year after sleeve gastrectomy. This score can be used to target early intensification of nutritional and dietetic follow-up to the predicted high-risk population

Characteristics of included patients.

<p>Characteristics of included patients.</p

Univariate analysis of baseline (before surgery) and follow-up (one year after surgery) parameters according to the presence of sarcopenia one year after sleeve gastrectomy.

<p>Univariate analysis of baseline (before surgery) and follow-up (one year after surgery) parameters according to the presence of sarcopenia one year after sleeve gastrectomy.</p

Predictive values of the <i>SS2 score</i> for the presence of sarcopenia one year after sleeve gastrectomy.

<p>Predictive values of the <i>SS2 score</i> for the presence of sarcopenia one year after sleeve gastrectomy.</p

Levels of serum OPN for diagnosis of significant fibrosis (F≥2) in cohorts of alcoholic patients.

<p>The area under the ROC curves are shown for the performance of serum OPN levels in evaluating significant fibrosis (F≥2) in estimation (109 patients) and validation (95 patients) cohorts.</p

Correlation between hepatic and adipose tissue OPN expression and hepatic steatosis, inflammation and fibrosis in alcoholic patients (the second gene group).

<p>Spearman's rank correlation test.</p

Characteristics of the Estimation, Second Gene and Validation groups.

<p>Data are expressed as Means ± SEM or N (%). AST: aspartate amino-tranferase; ALT: alanine amino-transferase; γGT: Gamma Glutamyl Transpeptidase.</p

Levels of serum OPN in patients with chronic viral hepatitis C.

<p>(<b>A</b>) The circulating levels of OPN were measured in the serum of 86 patients with chronic hepatitis C (25 F1, 34 F2, 19 F3, 8 F4) and analyzed according to the stage of fibrosis. Results were expressed as the median (25^th, 75^th percentile). The Kruskal-Wallis test was used to compare the 4 groups F1, F2, F3 and F4: <i>P</i><0.001. The Mann-Whitney test compared the two groups: &, <i>P</i>≤0.048, compared with F1; #, <i>P</i>≤0.026, compared with F2. Correlation between the serum OPN level with hepatic fibrosis was analyzed using the Spearman's rank correlation test. (<b>B</b>) The areas under the ROC curves are shown for the performance of serum OPN levels in estimating significant fibrosis (F≥2) or advanced fibrosis (F≥3) in this cohort.</p