D. Crisan

Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis

INTRODUCTION Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis. AIM Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT). PATIENTS AND METHODS 50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed. RESULTS Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT. CONCLUSION Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.

Two or more synchronous combination of noninvasive tests to increase accuracy of liver fibrosis assessement in chronic hepatitis C; results from a cohort of 446 patients.

Background The prediction of fibrosis is an essential part of the assessment and management of patients with chronic liver disease. Non-invasive tests (NITs) have a number of advantages over the traditional standard of fibrosis assessment by liver biopsy, including safety, cost-effectiveness, and widespread accessibility. Objectives The aim of this study was to determine the accuracy of certain biomarkers and transient elastography (TE) alone or in combination to predict the stage of liver fibrosis in chronic hepatitis C (CHC). Also, we examined whether the combination of certain biomarkers and TE could increase the diagnostic accuracy of liver fibrosis assessment. Patients and Method A total of 446 patients who were previously diagnosed with CHC were included in the study. In the study group, 6 blood-based scores (APRI, Forns, Fib-4, Hepascore, FibroTest, and Fibrometer) were calculated, and TE was performed to validate the stage of fibrosis, compared with liver biopsy (LB) as the standard. Results Significant fibrosis (F ≥ 2) was predicted with an AUROC of 0.727, 0.680, 0.714, 0.778, 0.688, 0.797, and 0.751 for the APRI, Forns, Fib-4, FibroTest, Hepascore, and Fibrometer scores and TE (Fibroscan), respectively. Severe fibrosis (F ≥ 3) was predicted, with AUROCs ranging between 0.705 and 0.811 for Hepascore and Fibrometer, respectively. Of the biomarkers, Fibrometer had the highest AUROC value in predicting both significant and severe fibrosis. The combination of APRI or FIB-4 with Fibrometer increased the diagnostic accuracy for significant fibrosis (from 69.07 to 82.27 for APRI, P = 0.001 and from 57.74 to 81.33, P = 0.001 for Fib-4). Combining APRI or Fib-4 with TE also increased the diagnostic accuracy (from 69.07 to 80.70%, P = 0.001 for APRI and from 57.74 to 81.33%, P = 0.001 for Fib-4) for significant fibrosis. The association that included Fibrotest was also reliable for the improvement of diagnostic accuracy. These combinations were more accurate or the assessment of severe fibrosis. Conclusions The synchronous association between a simple, inexpensive score and a complex but expensive score or TE increases the diagnostic accuracy of non-invasive methods for the assessment of liver fibrosis stage.

Non-invasive steatosis assessment in NASH through the computerized processing of ultrasound images: Attenuation versus textural parameters

Ultrasonography is a simple method in diagnosing nonalcoholic steatohepatitis (NASH), providing useful information, but it is subjective and does not accurately differentiate between steatosis grades. The computerized processing of the data that comprises the ultrasonic image (CPU) might transform ultra-sonography into an objective examination. CPU can be achieved either by methods based on the study of parenchymal echogenicity and on the attenuation of the ultrasounds (attenuation and back-scattering coefficients), or by methods based on the quantification of some textural parameters. In the present paper we set out to compare the performance of the attenuation coefficient (AC) and the textural parameters derived from the GLCM matrix 96 NASH patients and 24 healthy subjects were prospectively included in this study. We found a strong correlation between the AC and steatosis and a weak, but statistically significant one, with balooning and lobular inflammation, but not with fibrosis. The multivariate analysis showed, however, that only steatosis influences independently the AC. Of the analyzed textural parameters, only the GLCM entropy correlated weakly, but significantly, with the steatosis degree. Our study proves that the use of the attentuation coefficient computed on the ultrasonographic image can help differentiate healthy from NASH patients, as well as discriminate between various degrees of fatty load. The attenuation coefficient performs better than the textural parameters derived from the GLCM matrix. However, only GLCM entropy, of all textural parameters tested, correlates with steatosis, and even then, only for the differentiation normal vs NASH, not between steatosis grades.

Comparison between attenuation coefficient computed on the ultrasound image and a biological marker, adiponectin, in the diagnosis of steatosis in non-alcoholic fatty liver disease

The study aimed to identify the presence of steatosis and differentiate between insignificant and significant steatosis in non-alcoholic fatty liver disease (NAFLD). Thirty three patients with NAFLD proven by liver biopsy and evaluated in order to stratify the degree of steatosis were studied. The computerized processing of the data of the ultrasonic image (attenuation coefficient - LS7 slope), and a biological marker (adiponectin) were evaluated. Predictive value and AUROC curves were used to assess the accuracy of the results. Adiponectin levels was found to differentiate between controls (13435.4plusmn741.5 ng/ml) and NAFLD (4552.9plusmn2473 ng/ml) but also between insignificant (9348.4plusmn7368 ng/ml) and significant steatosis (4501plusmn2389.6 ng/ml). The AUROC for adiponectin, was 0.899 and for LS7 slope 0.952 with sensitivity, specificity, positive predictive value and negative predictive value of 84.8; 93.3; 96.5; 73.7, respectively 84.8;100;90.3 and 70.6 for the diagnosis of hepatic steatosis. The simultaneous utilization of these methods could substantial improve the identification of steatosis in NAFLD and the assessment of its grade.

Endoscopic Management of Bleeding Gastric Varices—an Updated Overview

Gastric varices (GVs) are known to bleed massively and often difficult to manage with conventional techniques. This article aims to overview the endoscopic methods for the management of acute gastric variceal bleeding, especially the advantages and limits of GV obliteration with tissue adhesives, by comparison with band ligation and other direct endoscopic techniques of approach. The results of indirect radiological and surgical techniques of GV treatment are shortly discussed. A special attention is payed to the emerging role of endoscopic ultrasound in the therapy of bleeding GV, in the confirmation of its eradication and in follow-up strategies.

Ultrasonographic diagnosis of nonalcoholic steatohepatitis based on the quantitative evaluation of the ultrasound beam behavior into the liver

Ultrasonography is a simple method in diagnosing nonalcoholic steatohepatitis (NASH), providing useful information, but it is subjective and does not accurately differentiate between steatosis grades. The computerized processing of the data that comprises the ultrasonic image might transform ultrasonography into an objective examination. We aim to study the performance of the quantitative evaluation of the ultrasound beam behavior into the liver in diagnosing NASH and in establishing the fatty load grade.

Non-invasive Steatosis Assessment through the Computerized Processing of Ultrasound Images: Attenuation versus First Order Texture Parameters

Steatosis is a frequent histological finding in patients with chronic hepatitis C virus (VHC) infection. Usual ultrasonography (US) cannot accurately detect the steatosis grade, nor can it always discriminate between steatosis and fibrosis. An improvement of usual US examination is currently under research. A possible approach might be the computerized processing of the data comprised in the US image. In the present paper we set out to compare the performance of two computerized methods for the steatosis assessment on the US images: the attenuation coefficient and the first order textural parameters (FO): Mean, Standard Deviation and Skewness. The attenuation coefficient correlated significantly with steatosis (r=-0.444, p<0.0001), but not with fibrosis (r=-0.046, p=0.395) or necroinflammatory activity (r=-0056, p=0.211). Of the FO parameters, only the FO mean correlated significantly with steatosis (r=0.300, p<0.0001), but also with necroinflammatory activity (r=0.128, p=0004). The present study proves that, in patients having chronic hepatitis C, the attenuation coefficient, but also the FO mean, can discriminate between different steatosis grades; however, the attenuation coefficient has a better performance than the FO mean, being influenced only by steatosis, not by fibrosis or necroinflammatory activity. The area under the ROC curve is significantly better for the attenuation coefficient as compared to the FO mean for the prediction of steatosis regardless of the grade (0.741 vs 0.652, p=0.001), as well as for the prediction of moderate/severe steatosis (0.791 vs 0.719, p=0.043).

Peroral endoscopic myotomy: Time to change our opinion regarding the treatment of achalasia?

Peroral endoscopic myotomy (POEM) is a new endoscopic treatment for achalasia. Compared to the classical surgical myotomy, POEM brings at least the advantage of minimal invasiveness. The data provided until now suggest that POEM offers excellent short-term symptom resolution, with improvement of dysphagia in more than 90% of treated patients, with encouraging manometric outcomes and low incidence of postprocedural gastroesophageal reflux. The effectiveness of this novel therapy requires long-term follow-up and comparative studies with other treatment modalities for achalasia. This technique requires experts in interventional endoscopy, with a learning curve requiring more than 20 cases, including training on animal and cadaver models, and with a need for structured proctoring during the first cases. This review aims to summarize the data on the technique, outcomes, safety and learning curve of this new endoscopic treatment of achalasia.

The diagnostic performance of attenuation coefficient computed on the ultrasound image compared to a biochemical marker — SteatoTest — for steatosis quantification in non-alcoholic fatty liver disease

The aim of this study was to establish the diagnostic performance and comparison of a biological marker (SteatoTest) and an innovative imagistic parameter (the attenuation coefficient-AC) to identify hepatic steatosis and to assess its degree. Seventy seven patients with NAFLD morphologicaly proven by liver biopsy were prospectively studied, compared with 16 healthy subjects. The patients were stratify according to the degree of hepatic steatosis. The computerized processing of the data offered by ultrasonic image (AC) and a blood test (SteatoTest) were determined. The diagnostic value for each method was assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and the area under the receiving operating characteristics curve (AUROC). SteatoTest was found to differentiate between controls (0.173 ± 0.079) and NAFLD controls (0.744 ± 0.166) but failed to discriminate the degree of steatosis. AC had a good diagnostic value in detection of steatosis (controls (0.320 ± 0.502) and NAFLD (−0.122 ± 0.063) and could also discriminates between grades of steatosis. In conclusions our finding suggest that AC and Steat-Test could be used for detection of steatosis. A combination of these parameters might increase the diagnostic performance.

Lyso‐phosphatidylcholine: A potential metabolomic biomarker for alcoholic liver disease?

We read with great interest the work of Michelena et al., which demonstrated that in patients with alcoholic hepatitis the presence of a systemic inflammatory response, with or without infection, precipitates development of complications and death. By identifying lipopolysaccharide (LPS) as an important player in the inflammatory response, the authors open a novel gateway for identifying the inflammatory mediators that cause this systemic response. Historic reports found an inverse association between lyso-phosphatidylcholine (LYPC) and the amount of liver fibrosis in an experimental model of alcoholic liver disease (ALD). More recently lower LYPC levels were found in nonalcoholic fatty liver disease/nonalcoholic steatohepatitis patients compared with controls. The link between LPS and LYPC is considered to be phosphatidylcholine-specific phospholipase C, the levels and activity of which are increased by LPS. Therefore, we hypothesized that LYPC may be a biomarker for severity and short-term prognosis in patients with ALD. Thirty consecutive patients admitted for ALD were included. Of them, 17 were known to have cirrhosis and 7 had previous clinical liver-related decompensation (LRD) events. Patients were followed for 30 days for the development of LRD and/or death. At inclusion 16 patients (12 of whom were known to have cirrhosis) had an alcoholic steatohepatitis test score (BioPredictive, France) 0.18, indicating at least minimal activity; the test was used in addition to clinical and biological criteria for the diagnosis of alcoholic hepatitis: recent alcohol abuse, leukocytosis, aspartate aminotransferase/alanine aminotransferase >1. Highperformance liquid chromatography-mass spectrometry was used to determine baseline levels of two LYPC serum metabolites: 16:1 and 20:4. Twelve patients decompensated during follow-up, 6 of them having multiple LRDs; 2 patients died. Both LYPCs had lower levels in patients with LRD compared to those without (0.277 [0.19520.737] versus 0.517 [0.16620.987], P 5 0.0001, and 0.564 [0.31222.116] versus 1.302 [0.795-3.492], P 5 0.008, respectively). The performance of the two LYPC metabolites to predict LRD is summarized in Table 1. They also had a good inverse correlation with Model for End-Stage Liver Disease (20.602; 20.619) (see Supporting Fig. S1); Maddrey (20.632; 20.656); and age, serum bilirubin, international normalized ratio, and serum creatinine (ABIC) (20.404; 20.529) scores and with liver stiffness by transient elastography (20.608 and 20.645). No correlation was found with daily alcohol intake (20.384 and 20.321; P 5 0.07 and 0.135, respectively).