Non-invasive laboratory, imaging and elastography markers in predicting varices with high risk of bleeding in cirrhotic patients.

Introduction. Upper digestive tract endoscopy remains the gold-standard for detecting esophageal or gastric varices and assessment of bleeding risk, but this method is invasive. The aim of the study was to identify non-invasive factors that could be incorporated into an algorithm for estimating the risk of variceal bleeding.Methods. A prospective study was performed on 130 cirrhotic patients. Tests were performed on all patients which included liver enzymes, complete blood count and coagulation parameters, abdominal ultrasound, elastography of both the liver and the spleen. Upper gastrointestinal endoscopy was performed in all patients included in the study and the results were classified, in accordance with Baveno VI into 2 outcome groups: Group 1 - patients with low bleeding risk and Group 2 - patients with varices needing treatment.Results. The study lot (130 patients) was divided into: Group I (low bleeding risk - 102 patients), and Group II (high bleeding risk - 28 patients). Parameters found to have significant differences in univariate analysis were transaminases, platelet count, spleen size, INR, portal vein diameter and both liver and spleen elastography. Calculating AUROC for each parameter identifies spleen elastography as having the best result, followed by INR, AST and platelet count. Liver elastography had the worst AUROC. Independent variables identified by logistic regression included spleen elastography, INR, platelet count, spleen diameter, ALT, age, and gender.Conclusions. Spleen stiffness is the best single parameter predicting the presence of high-risk esophageal varices.

Spleen Stiffness as Predictor of Esophageal Varices in Cirrhosis of Different Etiologies.

The purpose of this study is to determine whether esophageal varices (EV) can be identified through the evaluation of spleen stiffness (SSM) via acoustic radiation force impulse (ARFI). A total of 135 patients suffering from cirrhosis underwent a clinical exam, laboratory tests, abdominal ultrasound, liver stiffness (LSM) measurement, SSM evaluation and upper gastrointestinal endoscopy. Based on the endoscopy results, the patients were classified into three groups: those with no evident EV, those with small EV and those with varices needing treatment (VNT). Patients with EV of any grade had significantly higher average SSM values over those with no EV (3.37 m/s versus 2.79 m/s, p-value < 0.001), while patients with VNT showed an even greater difference (3.96 m/s versus 2.93 m/s, p-value < 0.001). SSM proved to be an excellent method of predicting patients with VNT.

The role of spleen stiffness using ARFI in predicting esophageal varices in patients with Hepatitis B and C virus-related cirrhosis.

INTRODUCTION: Current guidelines recommend that all patients with cirrhosis undergo upper gastrointestinal endoscopy (UGE) screening for esophageal varices (EV). Unfortunately, UGE has a lot of disadvantages, consequently various non-invasive methods of diagnosing EV have been proposed. We evaluated if spleen stiffness (SS) measured by Acoustic Radiation Force Impulse (ARFI) is a viable technique in diagnosing EV. METHODS: We recruited 178 patients with cirrhosis caused by Hepatitis B and C who underwent biochemical tests, abdominal ultrasound, UGE, LS and SS measurements using ARFI elastography. Based on the endoscopic results the patients were divided in 3 groups: without EV, with small EV (<5 mm) and with large EV (>5 mm). RESULTS: ARFI SS was the only non-invasive parameter associated with the presence of EV (2.7±0.30 vs. 3.4±0.52, p<0.001) and large EV (2.91±0.36 vs. 3.86±0.37, p=0.001) after multivariate logistic regression (p<0.001). ARFI SS for predicting EV showed an AUROC of 0.872 (CI 95%: 0.799-0.944), for a cut-off value of 2.89 m/s: Sensitivity (Se) 91.4% (CI 95%: 81-97%), Specificity (Sp) 67.7% (CI 95%: 51-85%). ARFI SS for diagnosing large EV (>5mm) had better results with an AUROC 0.969 (CI 95%:0.935-0.99), and for a cut-off of 3.30 m/s: Se 96.4% (CI 95%: 82-99.9%), Sp 88.5% (CI 95%: 78-95%). CONCLUSIONS: SS measured using ARFI is a good method of detecting EV and is an excellent method of diagnosing large EV in patients with virus-related cirrhosis.

Nonalcoholic fatty liver disease: one entity, multiple impacts on liver health.

Nonalcoholic fatty liver disease (NAFLD) is very prevalent and now considered the most common cause of chronic liver disease. Staging the severity of liver damage is very important because the prognosis of NAFLD is highly variable. The long-term prognosis of patients with NAFLD remains incompletely elucidated. Even though the annual fibrosis progression rate is significantly higher in patients with nonalcoholic hepatitis (NASH), both types of NAFLD (nonalcoholic fatty liver and nonalcoholic steatohepatitis) can lead to fibrosis. The risk for progressive liver damage and poor outcomes is assessed by staging the severity of liver injury and liver fibrosis. Algorithms (scores) that incorporate various standard clinical and laboratory parameters alongside imaging-based approaches that assess liver stiffness are helpful in predicting advanced fibrosis.

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: a retrospective multicentre study.

BACKGROUND: Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. AIM: To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. METHODS: A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. RESULTS: The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. CONCLUSION: Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.

Acoustic Radiation Force Impulse elastography for fibrosis evaluation in patients with chronic hepatitis C: an international multicenter study.

AIM: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. PATIENTS AND METHODS: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5-10 valid measurements, expressed in meters/second - m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6-10 valid measurements, expressed in kiloPascals - kPa). RESULTS: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r=0.654) was found between ARFI measurements and fibrosis (p<0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 - cut-off>1.19 m/s (AUROC=0.779), F ≥ 2 - cut-off>1.33 m/s (AUROC=0.792), F ≥ 3 - cut-off>1.43 m/s (AUROC=0.829), F=4 - cut-off>1.55 m/s (AUROC=0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r=0.728 vs. 0.689, p=0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p=0.01) and fibrosis (F ≥ 1, METAVIR) (p=0.01). CONCLUSION: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

Is ARFI elastography reliable for predicting fibrosis severity in chronic HCV hepatitis?

AIM: To determine whether acoustic radiation force impulse (ARFI) elastography is a reliable method for predicting fibrosis severity in patients with chronic hepatitis C virus (HCV) hepatitis. METHODS: We performed a multicenter study including 274 subjects with HCV chronic hepatitis in which we compared ARFI with liver biopsy (LB). In each patient we performed LB (evaluated according to the Metavir score) and ARFI measurements (using a Siemens Acuson S2000™ ultrasound system: 10 valid measurements were performed and median values were calculated and expressed in meters/second (m/s). RESULTS: A direct, strong, correlation (Spearman r = 0.707) was found between ARFI measurements and fibrosis (P < 0.0001). For predicting the presence of fibrosis (F ≥ 1 Metavir), significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4), the cut-off values of 1.19, 1.21, 1.58 and 1.82 m/s were determined, respectively, liver stiffness measurements had 73%, 84%, 84% and 91% Se respectively; 93%, 91%, 94%, 90% Sp, respectively; with AUROCs of 0.880, 0.893, 0.908 and 0.937, respectively. CONCLUSION: ARFI measurement is a reliable method for predicting the severity of fibrosis in HCV patients.

Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflammation and fibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several noninvasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. These markers are currently neither available in all centers nor validated in extensive studies. Examples include high-sensitivity C reactive protein and plasma pentraxin 3, which are associated with extensive liver fibrosis in NASH. Interleukin-6 correlates with inflammation, and cytokeratin-18 represents a marker of hepatocyte apoptosis (prominent in NASH and absent in simple steatosis). Tissue polypeptide specific antigen seems to have a clinical utility in the follow-up of obese patients with NASH.

Hepatocyte steatosis in patients infected with genotype 1 hepatitis C virus.

BACKGROUND: Recent findings suggest a higher prevalence of hepatic steatosis in patients with chronic hepatitis C, estimated at 50%. Both host and viral factors contribute to the development of steatosis in chronic hepatitis C. Steatosis is an initial stage, which promotes hepatic fibrosis through oxidative stress. AIM: To assess the pathogenic mechanism of genotype 1 hepatitis C virus in steatosis and to evaluate the correlation between the degree of steatosis and the level of oxidative stress. PATIENTS AND METHODS: The study was carried out on 50 patients (29 males, 21 females) with genotype 1 HCV and liver biopsy proven chronic hepatitis C. Patients with other etiology of chronic liver disease were excluded. We statistically correlated the degree of steatosis with clinical (age, sex, waist circumferences) and biological parameters (alaninaminotransferase, gammaglutamyltranspeptidase - GGT, insulin, ferritin, serum viral load, oxidative stress). Insulin resistance (IR) was determined by the homeostasis model assessment (HOMA) method. The oxidative stress was estimated by serum malondialdehyde (MDA) and glutathione (GSH). RESULTS: 27 patients presented steatosis (57%): 14 out of 29 men (48%) and 14 out of 21 women (66%); in two thirds of them, steatosis was moderate. Univariate analysis identified five parameters that significantly influenced steatosis: age >45 years, sex - female, IR (HOMA>2.5), BMI, central adiposity (as reflected by waist circumferences and high GGT-values). Multivariate analysis identified four significant parameters: sex - female, insulin resistance (HOMA>2.5), BMI>30 kg/m(2) and GGT>2N. No relationship was found between steatosis and viral replication. The study demonstrated a significant correlation between steatosis and IR on the one hand and between steatosis and liver fibrosis on the other hand (p<0.05). Liver fibrosis was significant correlated with the increase levels of free radicals (MDA>250 nmol/dL). CONCLUSIONS: The pathogenic mechanism of genotype 1 HCV in steatosis is independent from viral replication and it may be linked to virus induced metabolic abnormalities such as IR. More women (66%) than men (48%) developed steatosis. Increased levels of free radicals, correlated with moderate and severe steatosis suggest the intervention of oxidative stress in determining the hepatic lesions associated with steatosis.

Role of oxidative stress in the pathogenesis of chronic hepatitis C (CHC).

UNLABELLED: Oxidative stress is an important pathophysiological mechanism in chronic hepatitis with C-virus infection (CHC). Steatosis is frequently observed in CHC and seems to have a significant impact on the natural history of the disease with respect to development of fibrosis. The aim of this study was to investigate the relationship between systemic parameters of oxidative stress, insulin resistance, steatosis degree, and fibrosis in CHC. Fifty patients with chronic hepatitis C (29 men and 21 women with the average age 45 years), with or without steatosis, were tested for: oxidative stress and antioxidant status by measuring serum malondialdehyde (MDA), total blood non-proteic thiols concentration (GSH), gamma glutamyl transpeptidase (GGT) activity, lipid parameters, and liver function tests. Our results show that the prevalence of insulin resistance (IR) in chronic hepatitis with C-virus genotype 1 was 32% and the association with hepatic steatosis was in a proportion of 48%, IR is mediated by both metabolic factors as well as viral factors. Hepatic steatosis was associated with an increase of MDA, correlated with its severity, and secondary with a decrease of GSH. The activity of serum GGT was net superior, in patients with steatosis, proportional with its degree. CONCLUSIONS: In patients infected by HCV genotype 1, oxidative stress and insulin resistance contribute to steatosis, which in turn exacerbates both insulin resistance and oxidative stress and accelerates the progression of fibrosis. The induction of GGT is an adaptive response against oxidative damage elicited by lipid peroxidation and it may be critical in the progression of the disease.