Frequent Liver Disease Research Articles

Ameliorative effect of Ruzu herbal bitters on high-fat diet induced non-alcoholic fatty liver disease in Wistar rats

Context: One of the world’s most widespread and frequent liver diseases is the non-alcoholic fatty liver disease (NAFLD). Aims: To evaluate the preventives activities of Ruzu herbal bitters (RHB), which is an anti-obesity therapeutic concoction used widely in Nigeria on high–fat diet (HFD) induced NAFLD in albino Wistar rats. Methods: A total number of twenty-five rats were isolated and divided equally into five groups. Group 1, the normal control group was placed on normal rat diet and normal saline (1 mL/kg body weight daily) for twelve weeks. The remaining four groups 2-5 were placed on HFD for twelve weeks; adding to the following treatment schedules by oral gavage: group 2 received pioglitazone 4 mg/kg daily, group 3 received RHB 0.6 mL/kg daily, group 4 received normal saline 1 mL/kg daily and group 5 received fenofibrate 10 mg/kg daily (s.c). The animals were sacrificed and biochemical markers of liver function, lipid profile, glycemic index, and histopathological assessment of the liver of the rats were determined. Results: Rat treated with RHB and other treated groups significantly (p<0.05) reduced the liver index, fasting blood glucose, and activities and concentrations of liver function enzymes and molecules when compared to untreated NAFLD group. Scoring of hepatic steatosis also showed the ameliorative role of the treatment on NAFLD. Conclusions: This study reveals that RHB and other treatment options assessed could prevent HFD–induced NAFLD and could be explored as another therapeutic approach to fenofibrate and pioglitazone in NAFLD management.

Intrahepatic cholestasis of pregnancy

Die Schwangerschaftscholestase („intrahepatic cholestasis of pregnancy“, ICP) ist die häufigste schwangerschaftsspezifische Lebererkrankung. Das Leitsymptom Juckreiz sowie eine begleitende Serumkonzentrationserhöhung von Gallensäuren und/oder der Alaninaminotransferase (ALT) sind wegweisend in der Diagnosestellung. Die mütterliche Prognose ist gut. Das fetale Outcome ist abhängig von der Gallensäurenkonzentration. Die ICP ist dabei sowohl mit Frühgeburt als auch mit intrauterinem Fruchttod (IUFT) assoziiert. Dieser ist Folge einer akuten fetalen Asphyxie, nicht einer chronischen uteroplazentaren Dysfunktion. Ein prädiktives Monitoring, z. B. durch Kardiotokographie (CTG) oder Ultraschall gibt es nicht. Eine medikamentöse Therapie mit Ursodeoxycholsäure (UDCA) bessert den Juckreiz, aber beeinflusst das fetale Outcome nicht nachweislich. Eine Entbindungsindikation ist in Abhängigkeit von Gallensäurenkonzentration und Gestationsalter gegeben. In Folgeschwangerschaften besteht ein hohes Wiederholungsrisiko.

Helicobacter pylori and non-alcoholic fatty liver disease.

Helicobacter pylori is the most prevalent infection worldwide, while non-alcoholic fatty liver disease emerged as the most frequent liver disease. The common occurrence can be either by chance or due to certain pathogenetic factors. Epidemiologic studies revealed that the risk of non-alcoholic liver disease is increased in patients infected with Helicobacter pylori. DNA fragments of Helicobacter pylori were rarely identified in human samples of liver carcinoma and fatty liver. Helicobacter pylori could influence the development of non-alcoholic fatty liver either by hormonal (ghrelin? gastrin? insulin?), or by effect of pro-inflammatory cytokines (interleukin 1 and 8, tumor necrosis factor ɑ, interferon ɣ) and by changes of gut microbiome as well. Probiotic supplementation could improve some clinical parameters of non-alcoholic fatty liver disease and eradication rates of Helicobacter pylori. Regimens used for eradication can be safely administered, although non-alcoholic fatty liver increases the risk of drug-induced liver damage. Controlled studies of the effect of eradication on the development and progression of non-alcoholic fatty liver are warranted.

Bioinformatics analysis reveals novel core genes associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease and associated with a wide spectrum of hepatic disorders ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). NASH is projected to become the most common indication for liver transplantation, and the annual incidence rate of NASH-related HCC is 5.29 cases per 1000 person-years. Owing to the epidemics of NAFLD and the unclear mechanism of NAFLD progression, it is important to elucidate the underlying NAFLD mechanisms in detail. NASH is mainly caused by the development of NAFL Therefore, it is also of great significance to understand the mechanism of progression from NAFL to NASH. Gene expression chip data for NAFLD and NASH were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between NAFLD and normal controls (called DEGs for NAFLD), as well as between NASH and normal tissue (called DEGs for NASH-Normal), and between NASH and NAFL tissue (called DEGs for NASH-NAFL). For DEGs for the NAFLD group, key genes were identified by studying the form of intersection. Potential functions of DEGs for NASH were then analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction network (PPI) was constructed using the STRING database. A total of 249 DEGs and one key gene for NAFLD were identified. For NASH-Normal, 514 DEGs and 11 hub genes were identified, three of which were closely related to the survival analysis of HCC, and potentially closely related to progression from NASH to HCC. One key gene for NASH-NAFL (AKR1B10) was identified. These genes appear to mediate the molecular mechanism underlying NAFLD and may be promising biomarkers for the presence of NASH.

Involvement of Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain Containing 3 Inflammasome in the Pathogenesis of Liver Diseases.

The inflammasome is widely acknowledged for its crucial role in the pathogenesis of cancers and many neurodegenerative, metabolic, and auto-inflammatory diseases in recent years. Multiple types of inflammasomes exist. However, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most often investigated inflammasome and has come to limelight in recent studies. NLRP3 inflammasome is a multi-protein complex. Its activation can cause the cleavage of inactive pro-caspase-1 into activated caspase-1, that ultimately promotes the transformation of pro-interleukin (IL)-1β and pro-IL-18 into biologically-active IL-1β and IL-18, respectively. These processes lead to the local inflammatory responses and induce pyroptosis, causing disparaging effects. Recently, numerous studies have shown that NLRP3 inflammasome plays an important role in the pathogenesis of liver diseases, including non-alcoholic fatty liver disease, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Liver diseases have become a severe health burden worldwide, and there is adequate evidence indicating that the regulation of NLRP3 inflammasome acts as a guard against hazard to liver. In this review, we provide a straightforward overview of NLRP3 inflammasome as well as several frequent liver diseases. We then discuss the contribution and regulation of NLRP3 inflammasome during the pathogenesis of liver diseases, which may provide an important indication for the prevention and treatment of various liver diseases.

Prediction of Liver Steatosis Applying a New Score in Subjects from the Brazilian Longitudinal Study of Adult Health.

To develop a noninvasive algorithm for diagnosis of liver steatosis and to compare its diagnostic value with available predictive models. Liver steatosis represents the most frequent liver disease worldwide. This cross-sectional study analyzed data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Patients were randomly divided into training (n=6571) and validation (n=3286) cohort. Abdominal ultrasound (US), used to grade steatosis, and overnight fasting blood tests were performed at the same day. Fatty Liver Index (FLI), Hepatic Steatosis Index, and Nonalcoholic Fatty Liver Disease-Liver Fat Score were calculated. A backward stepwise multivariate logistic regression analysis was used to develop the new predictive model, Steato-ELSA. In total, 9857 subjects [58% female, age=51 (interquartile range, 45 to 58) years, body mass index=26.4 (23.9 to 29.6) Kg/m] were included. Body mass index, waist circumference, homeostasis model of assessment of insulin resistance, transaminases, and triglycerides were independently associated with steatosis in the multivariate model (Hosmer-Lemeshow P=0.279). In the validation cohort, the area under the receiver-operator characteristics (95% confidence interval) for prediction of mild and moderate steatosis were: (i) 0.768 (0.751-0.784) and 0.829 (0.810-0.848) for Steato-ELSA; (ii) 0.762 (0.745-0.779) and 0.819 (0.799-0.838) for Fatty Liver Index; (iii) 0.743 (0.727-0.761) and 0.800 (0.779-0.822) for Hepatic Steatosis Index; and (iv) 0.719 (0.701-0.737) and 0.769 (0.747-0.791) for Nonalcoholic Fatty Liver Disease-Liver Fat Score. Steato-ELSA performed significantly better than other models and yielded sensitivity (Se)/specificity (Sp) (95% confidence interval): (i) for mild steatosis (score ≥0.386): Se=65.6% (63.0-68.3) and Sp=73.7% (71.8-75.6); (ii) for moderate steatosis (score ≥0.403): Se=83.5% (80.0-86.9) and Sp=68.7% (67.0-70.4). Steato-ELSA is an accurate and inexpensive tool that uses simple parameters to identify individuals at high risk of liver steatosis.

Inhibition of receptor-interacting protein kinase 1 improves experimental non-alcoholic fatty liver disease

In non-alcoholic fatty liver disease (NAFLD), hepatocytes can undergo necroptosis: a regulated form of necrotic cell death mediated by the receptor-interacting protein kinase (RIPK) 1. Herein, we assessed the potential for RIPK1 and its downstream effector mixed lineage kinase domain-like protein (MLKL) to act as therapeutic targets and markers of activity in NAFLD. C57/BL6J-mice were fed a normal chow diet or a high-fat diet (HFD). The effect of RIPA-56, a highly specific inhibitor of RIPK1, was evaluated in HFD-fed mice and in primary human steatotic hepatocytes. RIPK1 and MLKL concentrations were measured in the serum of patients with NAFLD. When used as either a prophylactic or curative treatment for HFD-fed mice, RIPA-56 caused a downregulation of MLKL and a reduction of liver injury, inflammation and fibrosis, characteristic of non-alcoholic steatohepatitis (NASH), as well as of steatosis. This latter effect was reproduced by treating primary human steatotic hepatocytes with RIPA-56 or necrosulfonamide, a specific inhibitor of human MLKL, and by knockout (KO) of Mlklin fat-loaded AML-12 mouse hepatocytes. Mlkl-KO led to activation of mitochondrial respiration and an increase in β-oxidation in steatotic hepatocytes. Along with decreased MLKL activation, Ripk3-KO mice exhibited increased activities of the liver mitochondrial respiratory chain complexes in experimental NASH. In patients with NAFLD, serum concentrations of RIPK1 and MLKL increased in correlation with activity. The inhibition of RIPK1 improves NASH features in HFD-fed mice and reverses steatosis via an MLKL-dependent mechanism that, at least partly, involves an increase in mitochondrial respiration. RIPK1 and MLKL are potential serum markers of activity and promising therapeutic targets in NAFLD. There are currently no pharmacological treatment options for non-alcoholic fatty liver disease (NAFLD), which is now the most frequent liver disease. Necroptosis is a regulated process of cell death that can occur in hepatocytes during NAFLD. Herein, we show that RIPK1, a gatekeeper of the necroptosis pathway that is activated in NAFLD, can be inhibited by RIPA-56 to reduce not only liver injury, inflammation and fibrosis, but also steatosis in experimental models. These results highlight the potential of RIPK1 as a therapeutic target in NAFLD.

Preclinical evaluation of Endothelial Dysfunction by peripheral artery tonometry and its correlations with untargeted metabolomic profiles in NAFLD

Background: NAFLD has become one the most frequent liver disease in western countries. It is associated with Metabolic Syndrome, insulin resistance and diabetes. As well as the abovementioned conditions, it represents, a cardiovascular risk factor. Some evidences have demonstrated that Endothelial Dysfunction (ED),the pathophysiological basis of Cardiovascular Diseases (CVD),is present also in a part of NAFLD pts. ED can be evaluated in its “preclinical” status by performing vascular reactivity studies,such as Peripheral Artery Tonometry (PAT). However, not all NAFLD patients have a clinically demonstrable ED or a higher CVD risk. Untargeted Metabolomics is a novel and powerful method to discover biomarkers and give insights on diseases pathophysiology.

Comparison of the efficacy of Ursodeoxycholic acid (UDCA) versus vitamin E plus vitamin C in non-diabetic patients with nonalcoholic Steatohepatitis (NASH)

Introduction: Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which effective therapy is still lacking. Despite an important role of oxidative stress in the pathogenesis of NASH, antioxidant approaches have not been investigated sufficiently. The aim of the study was to compare ursodeoxycholic acid (UDCA) versus vitamin E plus vitamin C in non-diabetic patients with nonalcoholic steatohepatitis. Method: Patients with elevated aminotransferase levels and drinking, less than 40g alcohol/week with NASH diagnose were randomly assigned to receive either UDCA 15 mg/per kg/day (group A) or vitamin E 800 mg/day plus vitamin C 500 mg/day (group B) for 12 months and control group, which did not receive any medical treatment. Lifestyle modification was advised to all groups. The primary study end point was improvement in alanine transaminase (ALT) levels, secondary end points were improvement in steatosis score and improvement in fibrosis score. Result: 107 patients were included 35 in the group A, 52 in the group B and 20 in control group, 11 patients dropped out, non because of side effects. Baseline characteristics were not significantly different between groups. After 12 months treatment with vitamin E plus C, as compared with UDCA, was associated with a significant reduction of mean alanine aminotransferase (ALT) levels. Similarly, there was significant reduction of both mean steatosis score and fibrosis score. Conclusion: Vitamin E plus C combination is an effective, safe and inexpensive treatment option in patients with NASH and may be useful to reduce damage from oxidative stress and slow the process leading to cirrhosis

Frequency and risk factors for liver disease following pancreatitis: A population-based cohort study

Background & aimsBoth liver disease (LD) and pancreatitis pose substantial burdens. There have been no general population-based studies on frequency of LD after an episode of pancreatitis. The aim of this study was to investigate the occurrence of LD in a population-based cohort of patients following pancreatitis. MethodsNationwide data on the general population of nearly 3 million people were used to identify retrospectively diagnoses of acute pancreatitis, chronic pancreatitis (CP), LD and cirrhosis from 1998 to 2016. Acute pancreatitis was categorised as first (FAP) or recurrent (RAP) episode. Number of pancreatitis recurrences prior to LD diagnosis was determined. ResultsA total of 20,931 pancreatitis patients were included, of which 874 developed LD following pancreatitis. The incidence of LD in FAP was 115.59 (95% confidence interval 102.19–128.98), in RAP – 217.63 (95% confidence interval 173.31–261.94), and in CP – 539.43 (95% confidence interval 494.72–584.13) patients per 100,000 pancreatitis patients per year. There was a significant increase in the probability of LD with increasing number of pancreatitis recurrences and, for the same number of pancreatitis recurrences, LD was significantly more frequent after CP than RAP (hazard ratio 1.666 (95% confidence interval 1.322–2.098; p = <0.001)). ConclusionsThe frequency of LD increases from FAP to RAP to CP. While number of pancreatitis recurrences is a significant risk factor for development of LD, there is a higher probability of LD following CP than RAP even for the same number of recurrences. Interventions preventing pancreatitis and its progression may lower the burden of LD.

Clinicopathological investigation of steatohepatitic hepatocellular carcinoma: A multicenter study using immunohistochemical analysis of adenoma-related markers.

Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC). This was a retrospective multicenter study. A clinicopathological investigation was undertaken to compare 62 cases with SH-HCC features to 31 age- and sex-matched standard HCC cases, including an immunohistochemical study using markers for classification of HCA and diagnosis of HCC. The characteristic features of SH-HCC compared with standard HCC include a higher rate of complications of MS, more frequent non-alcoholic fatty liver disease as an underlying liver disease, and HCC development in non-cirrhotic liver. The rate of solitary tumors showed no difference between the two groups, but the median diameter of the main tumor was greater in SH-HCCs (45mm/20mm, P = 0.01). The HCCs were mostly moderately differentiated, and the patterns were mainly trabecular in both groups. Positive findings for serum amyloid A and C-reactive proteins, classification markers of inflammatory HCA, were significantly higher in cancerous lesions of SH-HCC cases (50%/13%, P< 0.01 and 42%/16%, respectively; P= 0.01). We confirmed that SH-HCC was strongly associated with MS and NAFLD, and found that classification markers of inflammatory HCA were significantly higher in SH-HCC. Further studies are needed to elucidate the relationship between SH-CCC and HCA for understanding the carcinogenic pathways in these diseases.

Dietary Rapeseed Oil Supplementation Reduces Hepatic Steatosis in Obese Men

Obesity is associated with nonalcoholic fatty liver disease (NAFLD) leading to increased hepatic glucose production. NAFLD is one of the most frequent liver diseases however, effective treatment is limited. Animal studies showed a reduction in hepatic steatosis with dietary alpha linoleic acid, which is highly enriched in rapeseed oil (RA). In this study we used a nutritional therapeutic approach and investigated the effect of an isocaloric diet supplemented with RA or olive oil (OL) on liver fat content, endogenous glucose production, total body insulin sensitivity and serum lipids in obese humans suffering from NAFLD. 27 obese men (BMI 30-35, age 18-65) consumed an isocaloric diet including 50 g of either RA (n=12) or OL (n=15) daily for eight weeks. Hepatic MRI, hyperinsulinemic-euglycemic clamp studies with isotope labelled glucose and blood tests were performed prior to and at the end of the study to assess liver fat content, endogenous glucose production and cholesterol and free fatty acid levels, respectively. Body fat content and BMI did not change over the time of intervention for RA and OL. At the end of the study a significant reduction in hepatic fat content (P=0.038) could be observed for RA (13.09±1.61 before vs. 11.14±1.58% after intervention) vs. OL (13.29±2.52 before vs. 15.73±2.74% after intervention). For RA, a 21% reduction (P&amp;lt;0.02) in serum free fatty acids was observed after eight weeks of oil consumption whereas no significant changes were seen for OL. Consuming RA resulted in a slight reduction in basal endogenous glucose production (1.71±0.15 before vs. 1.49±0.mg/kg/min after intervention, P=n.s.) compared to OL (1.66±0.before vs. 1.65±0.mg/kg/min after intervention, P=n.s.). There were no significant changes in total body insulin sensitivity and serum cholesterol levels in RA or OL. Our results demonstrate a beneficial effect of the fatty acid composition of RA on hepatic lipid production as shown by reduced hepatic fat content and free fatty acid levels. Disclosure M. Kruse: None. M. Kemper: None. S. Gancheva: None. D. Dannenberger: None. D.F. Markgraf: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. A.F. Pfeiffer: None.

Fulminant Hepatitis A in Children, its Incidence, Presentation, Complications and Outcome: A Study from Eastern India

Introduction: Hepatitis A is one of the most frequent infectious liver diseases affecting children worldwide. The disease is usually mild and self-limited, and complications are very rare. But sometimes hepatitis A can cause acute liver failure (ALF), a severe, life-threatening condition. The objective was to do clinicoepidemiological evaluation of hepatitis A patients who were admitted to the In patients department of our hospital along with analyze the complications seen in the disease.Materials and Methods: It was a prospective study, done in Department of paediatrics, Maharaja Krushna Chandra Gajapati from May 2014-April 2016. Total number of patients was 80. Patients having history or features of prodromal symptoms like fever, nausea, vomiting, anorexia, yellowish discoloration of urine and body, pain abdomen, change in mental status and coagulopathy with suspicion of acute hepatitis (within 8 wks) with positive IgM for hepatitis A were included in the group. Statistical analysis was done by SPSS software version 20.Results: Total number of patients was 80. Mean age of hospitalisation was 5.5 years. 90% children were having jaundice. 85% patients were having liver enzyme high. Most common complication was gallbladder wall thickening followed by ascitis, pleural effusion etc. Encephalopathy was observed in three patients. Total three patients died. Maximum death was seen in infancy with delay in hospitalisation.Conclusions: Viral hepatitis due to hepatitis A is a benign disease. But fulminant hepatic failure due to it is not uncommon. The lesser the age, presence of cardinal features like jaundice may not be apparent. So clinicians must be conscious of these lethal complications while managing a child of probable viral hepatitis. This study will raise the consciousness of urgency of vaccination for hepatitis A, which is thought to be sparingly optional for many parents as well as doctors.

Identifying risk profiles in liver transplant candidates and implications for induction immunosuppression.

Changes in recipient and donor characteristics are redefining the role of induction in liver transplant recipients. Older recipients are more common, with greater concomitant comorbidity. Moderate or severe renal dysfunction is now estimated to affect 40% of liver transplant recipients. Donors are also becoming older, and other factors such as more frequent non-alcoholic fatty liver disease (NAFLD) compromise the quality of some grafts. Rejection rates are now relatively low (~10%) but some patients have a markedly increased risk such as younger recipients and those undergoing re-transplantation. Induction immunosuppression is associated with a significant reduction in rejection risk but due to various factors universal induction is not justified. Steroid-free therapy without induction increases the risk of biopsy-proven acute rejection (BPAR) but randomized trials have shown that induction with an interleukin-2 antagonist receptor (IL-2RA) agent or with rabbit antithymocyte globulin (rATG) maintains immunosuppressive efficacy in steroid-free regimens. Delayed calcineurin inhibitor (CNI) initiation (e.g. to days 4-5 post-transplant) can prevent deterioration of renal function during the first year post-transplant, but requires induction with an IL-2RA agent or rATG to maintain early immunosuppressive efficacy. IL-2RA induction may be inadequate to ensure a low risk of rejection in a steroid-free regimen combined with delayed tacrolimus. Randomized trials of CNI withdrawal at month 1 post-transplant have only achieved an acceptable rate of BPAR when induction is administered. In terms of safety, an increased rate of infection does not seem to be a concern. The most recent large-scale analyses have not indicated any evidence for an increased risk of malignancy, or specifically post-transplant lymphoproliferative disease. In summary, the place of induction in the management of liver transplant patients is becoming established. Selective use in high-risk individuals to avoid graft rejection is still relevant, but the key rationale for induction is to facilitate steroid-sparing and CNI-sparing regimens to reduce long-term complications.

Cardiorespiratory Fitness Stipulates Presence and Normalization of NAFLD In a Community‐Based Adults Enrolled in a Lifestyle Modification Program

RATIONALENon‐alcoholic fatty‐liver disease(NAFLD) is the most frequent liver disease in western countries and has obesity as its main risk and cardiovascular mortality as worse outcome. NAFLD might be secondary to environmental factors such as energy dense food and sedentary lifestyle.PURPOSETo characterize the effects of physical activity and fitness on the presence of NAFLD in a community‐based adults submitted to a Lifestyle Modification Program(LiSM).METHODSBaseline data from 1010 individuals, selected for the LiSM, from 2005 to 2017, were cross‐sectionally analysed for medical, anthropometry, plasma biochemistry, physical activity (IPAQ version 8) and fitness(hand grip, flexibility and cardiorespiratory‐Balke's treadmill protocol). The algorithm based on BMI, waist circumference (WC), triglycerides and GGT was used to develop the “fatty liver index” (FLI), which varies between 0 and 100 with a FLI ≥ 60 ruling in the NAFLD. Longitudinal analysis were undertaken in data from 583 subjects submitted to a 10‐wk LiSM intervention with daily supervised mixed‐physical exercises(5x/wk, 80min/session/60–80% VO2max) and dietary counseling. FLI values were splitted into quartiles for comparison with co‐variables. SAS version 9.2 was used to complete ANOVA and evaluated FLI quartiles(Q1–Q4). Tukey's post hoc was applied with significance level set at p&lt;0.05.ResultsFLI quartiles were Q1(&lt;36.5), Q2(36.6–59.8), Q3(59.9–84.7) and Q4(&gt;84.8). Q4 was predominantly male, lower schooling, lower income and in (self‐ perceptive) bad health. Q4 showed also lower physical activity and lower aerobic fitness without changes in flexibility and strength. FLI correlated negatively with VO2max(r=−0.49, p&lt;0.00001)values. After LiSM, 95 subjects had reduced their FLI from ≥60(M0) to &lt;60(M1). In a (%)muscle mass dependent effect, VO2max determined the FLI responses to LiSM,ConclusionPhysical inactivity/aerobic fitness were risk factors for higher FLI, overcome by LiSM effects on aerobic conditioning.Support or Funding InformationSuported by CNPq and CAPESThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Relationship Between the Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) with the Severity of Coronary Artery Disease (CAD) in Patients Undergoing Coronary Artery Angiography: A Cross- Sectional Study

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent liver diseases worldwide. There are several common risk factors between NAFLD and coronary artery disease (CAD). Objectives: This study aims to evaluate the relationship between the prevalence of Non-alcoholic fatty liver disease (NAFLD) with severity of Coronary Artery Disease (CAD) in patients undergoing coronary artery angiography. Methods: This study was a cross-sectional, descriptive-analysis research that included 514 patients who underwent angiography. The severity of CAD was assessed by the number of vessels involved (vessel score: vd). An ultrasound was performed for all the patients also, intensity of fatty liver involvement was graded from zero (absence of steatosis) to three (severe steatosis). Results: Ultrasonographic examination proven NAFLD in 59.1% of patients with different grades. Patients with NAFLD had significantly higher body mass index (P < 0.001), waist circumference (P = 0.03), and age (P < 0.001). In addition, there were significant differences between ALT and AST within the normal group and NAFLD patients (P < 0.001). Moreover, coronary angiographic data indicated that the presence of NAFLD significantly correlated with the CAD severity score as so: 64% of people with 2vd and 60.5% of people with three-vessle lisense had fatty liver that was statistically significant (df = 4; P = 0.014). Conclusions: This study showed a high prevalence of NAFLD in patients with documented CAD. It is extremely important since knowing risk factors, designing screening programs, and early treatment of fatty liver could lead to reducing the risk of cardiovascular diseases.

The effects of Ramadan fasting on serum concentrations of vaspin and omentin-1 in patients with nonalcoholic fatty liver disease

IntroductionNonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease. Vaspin may modulate the inflammatory process, insulin resistance, and NAFLD. Omentin-1 is independently associated with hepatocyte ballooning. There is evidence of improvement in the adipokines level and histological hepatic steatosis following energy intake restriction and weight loss. The aim of the study was to evaluate the effects of Ramadan fasting on various circulating adipokines in NAFLD patients. MethodsThis study was conducted on 83 NAFLD patients, 42 cases who declared that they would fast during the month of Ramadan fasted and 41 controls who decided not to fast during Ramadan. Anthropometric parameters including weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and body fat percentage were measured before and after Ramadan. Dietary intake and physical activity levels were assessed by 24-h recall questionnaire and International physical activity questionnaire-short form (IPAQ-S), respectively. Serum adipokines including vaspin and omentin-1 were measured using commercial ELISA kit. ResultsPatients who fasted displayed a lower mean hip circumference and body mass index and considerable changes in serum vaspin and omentin-1 (p-value <0.05). The stepwise multivariate linear regression model revealed that the changes in weight, WHR, and dietary intakes were significant predictors of changes in serum adipokines. ConclusionThere is a potential for fasting in improving several anthropometric indices in NAFLD patients. Additionally, fasting during Ramadan resulted in decreased levels of adipokines including vaspin and omentin-1. Studies with longer follow-up periods are required.

Transjugular Intrahepatic Portosystemic Shunt in Patients with Portal Hypertension: Patency Depends on Coverage and Interventionalist’s Experience

Background and Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice in decompensated portal hypertension. TIPS revision due to thrombosis or stenosis increases morbidity and mortality. Our aim was to investigate patient- and procedure-associated risk factors for TIPS-revision. Patients and Methods: We retrospectively evaluated 189 patients who underwent the TIPS procedure. Only patients who required TIPS revision within 1 year (Group I, 34 patients) and patients who did not require re-intervention within the first year (Group II [control group], 54 patients) were included. Results: Out of 88 patients, the majority were male (69.3%) and mean age was 56 ± 11 years. Indications for TIPS were refractory ascites (68%), bleeding (24%), and Budd-Chiari syndrome (8%). The most frequent liver disease was alcohol-induced cirrhosis (60%). Forty-three patients (49%) received bare and 45 patients (51%) covered stents, thus resulting in reduction of hepatic venous pressure gradient (HVPG) from 19.0 to 9.0 mm Hg. When comparing patient- and procedure-related factors, the type of stent (p < 0.01) and interventionalist’s experience (number of performed TIPS implantations per year; p < 0.05) were the only factors affecting the risk of re-intervention due to stent dysfunction, while age, gender, indication, Child-Pugh, and model of end-stage liver disease score, platelet count, pre- and post-HVPG, additional variceal embolization, stent diameter, and number of stents did not significantly differ. Conclusion: Patients undergoing TIPS procedure should be surveilled closely for shunt dysfunction while covered stents and high-level experience are associated with increased ­patency.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis

Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.

Impact of Non-alcoholic Fatty Liver Disease on Chronic Hepatitis B Infection

Both chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are frequent liver diseases with substantial morbidity and mortality. How often do these two diseases occur together? Does hepatitis B virus protect or promote concurrent fatty liver? How does concurrent fatty liver influence the clinical outcomes of CHB? We summarized the latest evidence to tackle all these clinically significant questions. Concurrent fatty liver in CHB without significant alcohol intake is a common and increasingly alarming problem. Patients with CHB have a lower chance of fatty liver than the general population, but the underlying mechanism remains to be further explored. Clinical impacts of concurrent fatty liver among CHB patients, in terms of treatment response, fibrosis and cirrhosis progression, liver cancer risk, and mortality, are still debatable. Concurrent fatty liver in CHB is a common and clinically relevant condition.