Addition of Dulaglutide or Empagliflozin to Standard-of-Care Treatment: Effect on Liver Steatosis in Patients With Type 2 Diabetes Mellitus.

Background Patients with liver steatosis and diabetes mellitus can benefit from medications like glucagon-like peptide 1 receptor agonists or sodium-glucose co-transporter 2 inhibitors, as far as both hyperglycemia and fatty liver are concerned. Studies comparing members of both these families have not yet been published. We aimed to compare the effects of Empagliflozin and Dulaglutide, focusing primarily on liver steatosis. Methodology This prospective, observational, controlled study enrolled 78 patients from two centers in Athens, Greece. Adults with type 2 diabetes mellitus (DM2) and nonalcoholic fatty liver disease were assigned to one of three groups and received either Empagliflozin or Dulaglutide or any other medical treatment deemed appropriate by their physician. The primary endpoint was the reduction in liver fat fraction, assessed using magnetic resonance imaging-proton density fat fraction. Additionally, we evaluated the proportion of patients achieving a relative reduction above 30% of their initial liver fat concentration. Results The Empagliflozin group exhibited a reduction in liver fat fraction. Furthermore, the percentage of patients with a relative reduction of liver steatosis, >30%, was significantly larger in this group, compared to the Dulaglutide and Control groups. Significant body weight reduction was observed in all three groups, but no improvement in fibrosis assessing scores was noted. Conclusions Empagliflozin is effective in improving liver steatosis, while Dulaglutide does not exhibit a similar effect. Larger studies, comparing these or related agents, are necessary, to further assess benefits in patients with DM2 and nonalcoholic fatty liver.

Comparison of Visual Transient Elastography, Vibration Controlled Transient Elastography, Shear Wave Elastography and Sound Touch Elastography in Chronic liver Disease assessment using liver biopsy as 'Gold Standard'.

PURPOSE: Chronic liver disease (CLD) is considered one of the main causes of death. Ultrasound Elastography (USE) is a CLD assessment imaging method. This study aims to evaluate a recently introduced commercial alternative of USE, Visual Transient Elastography (ViTE), and to compare it with three established USE methods, Vibration Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Sound Touch Elastography (STE), using Liver Biopsy (LB) as 'Gold Standard'. METHOD: 152 consecutive subjects underwent a liver ViTE, VCTE, SWE and STE examination. A Receiver Operator Characteristic (ROC) analysis was performed on the measured stiffness values of each method. An inter- intra-observer analysis was also performed. RESULTS: The ViTE, VCTE, SWE and STE ROC analysis resulted in an AUC of 0.9481, 0.9900, 0.9621 and 0.9683 for F ≥ F1, 0.9698, 0.9767, 0.9931 and 0.9834 for F ≥ F2, 0.9846, 0.9651, 0.9835 and 0.9763 for F ≥ F3, and 0.9524, 0.9645, 0.9656, and 0.9509 for F = F4, respectively. ICC scores were 0.98 for Inter-observer and 0.97 for Intra-observer variability analysis. CONCLUSION: ViTE performance in CLD stage differentiation is comparable to the performance of VCTE, SWE and STE.

Liver Ultrasound Attenuation: An Ultrasound Attenuation Index for Liver Steatosis Assessment.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disease type in the Western countries. Ultrasound (US) is used for NAFLD and hepatic steatosis (HS) grading. The most popular US method for NAFLD assessment is the hepatorenal index (HRI), but because of its limitations, other noninvasive methods have been developed. The Resona 7 US system has recently incorporated an US attenuation-related quantitative feature, liver ultrasound attenuation (LiSA), for HS estimation. The purpose of this study is to compare LiSA's and HRI's performance on NAFLD assessment. METHODS: A total of 159 NAFLD patients having a magnetic resonance imaging-proton density fat fraction (MRI-PDFF) examination were examined by 2 radiologists, who performed LiSA and HRI measurements in the liver. Correlation of LiSA's and HRI's measurements with MRI-PDFF values was calculated through Pearson correlation coefficient (PCC). To further investigate the performance of LiSA and HRI, optimum cutoffs, provided by the literature, were used to correspond HS grades to MRI-PDFF results. Moreover, a receiver operating characteristic (ROC) analysis on LiSA measurements and steatosis grades was performed. RESULTS: Magnetic resonance imaging-PDFF was better correlated with LiSA (PCC = 0.80) than HRI (PCC = 0.67). Receiver operating characteristic analysis showed better performance range for LiSA (77.8%-91.8%) than for HRI (72.8%-85.4%) on all HS grades for all studies used for corresponding MRI-PDFF values to HS grades. CONCLUSIONS: The results indicate that LiSA is more accurate than HRI in HS differentiation and can lead to more accurate grading of HS on NAFLD patients.

Substitution treatment or active intravenous drug use should not be contraindications for antiviral treatment in drug users with chronic hepatitis C.

INTRODUCTION AND AIMS: International guidelines and routine clinical practice express concerns about antiviral treatment in intravenous drug users (IDUs). We analysed the effect of IDU and/or substitution therapy on chronic hepatitis C (CHC) treatment adherence and response. PATIENTS AND METHODS: Intravenous drug users with CHC were divided into three groups: (A) patients on a substitution programme; (B) active users; and (C) past IDUs. Patients were treated according to the standard of care and followed by a specialist team. RESULTS: A total of 175 patients (mean age 39.4±8.8) were included. One hundred and forty-four (65%) were adherent to therapy (completing treatment and 6 months of follow-up). Twenty-two patients (36%) discontinued because of side effects, 28 (46%) discontinued on their own and 11 (18%) completed treatment but did not present at follow-up. Of 142 patients with available treatment outcome, 99 (69.7%) achieved a sustained virological response (SVR), with no differences among the study groups. Patients with genotypes 2-3 and those who completed the treatment schedule had 2.78-fold (95% CI: 1.3-5.8) and 6.4-fold (95% CI: 2.6-15.6) higher probability of achieving SVR. CONCLUSION: Active use of illicit drugs and/or drug substitution do not affect the treatment outcome in patients with CHC as long as they are closely followed and remain adherent to the treatment.

Smoking is associated with steatosis and severe fibrosis in chronic hepatitis C but not B.

OBJECTIVE: The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC. MATERIAL AND METHODS: The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded. RESULTS: In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028-1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356-11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003-1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001-1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286-96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted. CONCLUSIONS: Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.

Aetiology and outcome of acute hepatic failure in Greece: experience of two academic hospital centres.

Introduction: In Western countries, the most frequent aetiology of acute liver failure (ALF) is acetaminophen overdose, while in developing countries viral infections [hepatitis A virus and hepatitis B virus (HBV)] predominate. Aim: To evaluate the epidemiology, clinical characteristics, outcome and prognostic factors of survival of patients with ALF in Greece during the last 6 years. Results: A total of 40 patients, 28 females (70%), with a median age of 37.4+/-18.6 years (range: 15-84) with ALF were studied. HBV infection was the cause in 53% of them (compared with 74% from a previous study reported in the early 1980s), drug toxicity in 15% and undetermined in 13%. The overall survival was 57.5%, including 94% with and 15% without liver transplantation. Forty-five per cent of our patients had emergency liver transplantation in European Centers within a median time of 3.3 days (1-9) from admission. The total bilirubin level at admission and the development of infections were found to be significantly associated with poor outcome. Conclusions: Hepatitis B virus still remains the most important cause of ALF in Greece, but shows a significant decrease as compared with studies in the early 1980s. Almost half of our patients needed emergency liver transplantation and had a very good survival rate. The other 15% of the patients presented spontaneous survival only with intensive medical support.

Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B).

Wilson disease (WND) is caused by mutations in the ATP7B gene and exhibits substantial allelic heterogeneity. In this study we report the results of molecular analyses of 20 WND families not described previously. When combined with our prior results, the cohort includes 93 index patients from 69 unrelated families. Twenty different mutations accounted for 86% of the WND chromosomes. The most frequent were p.H1069Q (35%), p.R969Q (12%), c.2530delA (7%), p.L936X (7%), p.Q289X (7%), and p.I1148T (3%). We also present here a detailed phenotypic assessment for patients whose molecular result was previously reported. Thirty cases were homozygous for 9 different mutations, 13 of which were homozygous for p.H1069Q, and 7 for p.R969Q. Mutations p.H1069Q and p.R969Q appeared to confer a milder disease as patients showed disease onset at a later age, and were associated with milder severity when found in trans with severe mutations. Predicted nonsense and frameshift mutations were associated with severe phenotypic expression with earlier disease onset and lower ceruloplasmin values. WND can be treated by copper-chelation therapy, particularly if the disease is diagnosed before irreversible tissue damage occurs. Our results on the effect of predicted nonsense and frameshift mutations are especially important for early medical intervention in presymptomatic infants and children with these genotypes.