Is Nonalcoholic Fatty Liver Disease in Children the Same Disease as in Adults?

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children, and can present in toddlerhood. There is a differential distribution of NAFLD in children based on race and gender. The gold standard for diagnosis and classification of pediatric NAFLD is liver biopsy although ongoing studies aim to identify and define noninvasive investigations for pediatric NAFLD. Treatments that have been shown to be successful in adult NAFLD, such as insulin sensitizers and Vitamin E, have not been proven to be as definitively successful in children with NAFLD.     

Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.     

Treatment of Nonalcoholic Fatty Liver Disease: Where do we Stand? An Overview

Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, the prevalence of which had progressively increased over the past 10 years where other liver diseases remained at the same prevalence rates or are expected to decrease as in the case of hepatitis C virus (HCV). The treatment of NAFLD is of prime concern to health care professionals and patients due to the significant mortality and morbidity it implies; the problem is further escalated by the fact that standard of care medications targeting NAFLD remain experimental and without evidence base. Treatment nowadays is focused on lifestyle modification and managing the comorbid associated diseases, with a possible role for some hepatic protective agents. This review presents all the medications that had been proposed and used for the treatment of NAFLD with or without scientific rationale and includes agents for weight loss, insulin sensitizers, drugs that reduce blood lipids, glucagon-mimetics, drugs that may reduce fibrosis, angiotensin receptor blockers, and medicines believed to reduce endoplasmic reticular stress such as vitamin E, ursodeoxycholic acid, and S-adenosyl methionine. A quick review of the newer agents that proved to be promising such as obeticholic acid and GFT505 and the medicines that are still in the pipeline is also presented.     

How Much Weight Loss is Effective on Nonalcoholic Fatty Liver Disease?

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide with no specific treatment. Weight loss is the most effective therapeutic strategy in its management; however, there is no consensus on its specifics. Thus, this study was conducted to evaluate the effects of weight loss on liver enzymes, markers of inflammation, oxidative stress and CK18-M30 (cytokeratin 18) as a biomarker of hepatocellular apoptosis.

Objectives

To study the effect of weight reduction diet as an exclusive treatment for NAFLD.

Patients and Methods

Forty four patients with NAFLD received a diet including a 500 to 1000 kcal per day intake reduction as30% fat, 15% protein, and 55% carbohydrate for six months. Anthropometric parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lipid profile, malondialdehyde (MDA), TNF-α, IL-6, CK18-M30 were measured at baseline and at the end of the study. At the end of follow up, patients were classified as adherent or nonadherent to treatment according to a weight loss of ≥ 5%, or < 5% of initial body weight, respectively.

Results

Twenty five patients were classified as adherent group and nineteen as nonadherent group (9.7% vs. 1.9% total body weight loss after 6 months, respectively). After 6 months, changes in adherent and nonadherent groups were as follows: reduction in body weight from 93.7 ± 15.8 kg to 84.2 ± 13.4 kg vs. 94 ± 16.6 kg to 92.2 ± 16.2 kg (P < 0.05), BMI from 32.7 ± 3.9 to 29.5 ± 3.2 vs.31.8 ± 5.4 to 31.1 ± 5.3 (P < 0.001), and waist circumference from 105.1 ± 12.6 cm to 97.4 ± 9.8 cm vs.106.8 ± 14.2 cm to 103.7 ± 14 cm (P < 0.001), respectively. Diastolic blood pressure was significantly decreased in adherent group (from 80.2 ± 5.1 mmHg to 76.9 ± 5 mmHg; P < 0.001). Also, total cholesterol, LDL, triglyceride, ALT, AST, GGT and CK18-M30 levels were significantly decreased in the adherent group compared to nonadherent group (P < 0.05).

Conclusions

This intervention offers a practical approach for treatment of patients with NAFLD with diet therapy.     

Innate Immune Reactivity of the Ileum–Liver Axis in Nonalcoholic Steatohepatitis

Background  

Over-proliferation and bacterial translocation of Gram-negative bacilli within the intestinal flora, and increased portal venous levels of endotoxins, are involved in nonalcoholic steatohepatitis (NASH).     

A Clinical–Morphological Study on Cholestatic Presentation of Nonalcoholic Fatty Liver Disease

To determine the association among the clinical, biochemical, and histological features of cholestasis, we analyzed all the relevant data of the patients recorded in our non-alcoholic fatty liver disease (NAFLD) database. We selected 20 NAFLD patients with abnormal transaminase levels, with both alkaline phosphatase ≥500 U/L and γ-glutamyl transpeptidase ≥250 U/L. Their histological features were compared with those of a group of patients with NAFLD matched for sex, age, and body mass index and of a group of patients matched for sex, body mass index and histological NAFLD grading/staging. Cases and controls satisfied, on histology, the criteria for NASH. The presence of cholestasis in our patients was correlated with injury of the bile duct epithelium, characterized by cholangitis, swelling, variable bile duct loss, and bile stasis. Compared to NAFLD patients of similar age, sex, and body mass index, the cholestatic group had total and severe histological liver impairment. When we analyzed the group of patients histologically identified on the basis of identical stage and grade severity, we could not find any evidence of significant bile damage, compared to cases, despite the control group’s significantly older age. NAFLD patients with biochemical cholestasis have a histological picture of bile damage; they have more advanced histological impairment than patients matched for age, sex and body mass index.     

Serum Resistin as a Biomarker in Nonalcoholic Fatty Liver Disease: Is This a Road to be Taken?

Nonalcoholic fatty liver disease (NAFLD), which encompass-es a broad spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH...