It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them?

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of fat deposits (>5%) in the liver with subsequent inflammation and fibrosis. Studies in the literature show that insulin resistance (IR) may be considered as the key mechanism in the onset and progression of NAFLD. Recently, using natural products as an alternative approach in the treatment of NAFLD has drawn growing attention among physicians. In this review, the authors present the most recent randomized controlled trials (RCTs) and lines of evidence from animal models about the efficacy of nutraceutics in alleviating NAFLD. Among the most studied substances in the literature, the following molecules were chosen because of their presence in the literature of both clinical and preclinical studies: spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, and bromelain.

Gastrointestinal peptides and nonalcoholic fatty liver disease.

PURPOSE OF REVIEW: In this review, authors have selected from literature the most recent and suggestive studies on therapy of nonalcoholic fatty liver disease (NAFLD). The selected interventions regulate the action of gastrointestinal peptides, such as gastric inhibitory polypeptide (GIP), nesfatin, peptide YY, cholecystokinin, and glucagon-like peptide 1 (GLP-1). These hormones have been found frequently modified in obesity and/or type 2 diabetes mellitus, morbidities mostly associated with NAFLD. This disease has a very high prevalence worldwide and could evolve in a more severe form, that is, nonalcoholic steatohepatitis, characterized by inflammation and fibrosis. The findings shown by this article describe the metabolic effects of new drugs, mainly but not only, as well of some old substances. RECENT FINDINGS: Recent approaches, in animal models or in humans, use synthetic GLP-1 receptor agonists, a centrally administered antibody neutralizing GIP receptor, curcumin, compound being active on nesfatin, resveratrol (antiinflammatory agent), and Ginseg, both of them acting on nesfatin, a cholecystokinin receptor analogue, and finally coffee functioning on YY peptide. SUMMARY: The implications of the presented findings, if they are confirmed in larger clinical trials, likely open the door to future application in clinical practice. In fact, nowadays, patients have only diet and article (incl abstract and keywords) exercise as well accepted recommendations. Thus, there are unmet needs to find substances that could really improve the progression of nonalcoholic steatohepatitis toward liver cirrhosis and hepatocellular carcinoma.

Reticulocyte Hemoglobin Content Helps Avoid Iron Overload in Hemodialysis Patients: A Retrospective Observational Study.

BACKGROUND/AIM: Anemia in patients suffering from end-stage renal failure is currently treated with Erythropoiesis-Stimulating Agents (ESA). This treatment needs sufficient iron supplementation to avoid an inadequate dosage of ESA. Nowadays modern analytical instruments allow to accurately calculate the content of Hemoglobin (Hb) in reticulocytes (CHr), that can be used as a guide for prescribing patients with the appropriate amount of iron. PATIENTS AND METHODS: Patients, undergoing hemodialysis, were retrospectively selected from the database and were divided in two groups: group A received intravenous (IV) iron and subcutaneously ESA, and their dosages were adjusted on the basis of the following parameters: Hb, Mean corpuscular haemoglobin (MCH), CHr with consequent MCH/CHr ratio and reticulocyte count determined by the ADVIA 120 Hematology System of Siemens; group B patients were administered IV iron and ESA monitoring iron storage, Hb and ferritin. The aforementioned parameters and the administered amount of iron and ESA were monitored at baseline, four and eight months from the begining of the study. RESULTS: For ESA supplementation, no difference was observed between the groups at the various observed times. Despite similar Hb levels, the patients of group A needed significant lower doses of IV iron (-57.8%) avoiding risks of organ toxicity and obtaining consequent cost saving of nearly 1 €/patient/month. CONCLUSION: The use of CHr and its related parameters allows the avoidance of overdosage of IV iron, which can potentially damage organs, and the reduction of health care direct and indirect costs.

Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease.

BACKGROUND: The gut microbiota is modulated by metabolic derangements, such as nutrition overload and obesity. AIM: The aim of this systematic review is to summarize the role of these gut modifiers in nonalcoholic fatty liver disease (NAFLD) and obesity. METHODS: A systematic search of MEDLINE (from 1946), PubMed (from 1946) and EMBASE (from 1949) databases through May 2014 was carried out to identify relevant articles. The search terms were 'probiotic' AND 'NAFLD', 'prebiotic' AND 'NAFLD', 'antibiotic' AND 'NAFLD', 'probiotics' AND 'obesity', 'prebiotic' AND 'obesity' or 'antibiotic' AND 'obesity'; these terms were searched as text word in 'clinical trials' and as exploded medical subject headings where possible. RESULTS: The evidence in the literature is scant, due to the scarcity of appropriately powered, randomized, controlled clinical trials, involving various centers and population of different origin. CONCLUSION: Although probiotics and prebiotics have been proposed in the treatment and prevention of patients with obesity-related NAFLD, their therapeutic use is not supported by high-quality clinical studies.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor (PPAR) α, PPARγ, sterol regulatory element-binding protein-1, carbohydrate responsive element-binding protein], impacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil, flaxseeds, olive oil) which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Is there any consensus as to what diet or lifestyle approach is the right one for NAFLD patients?

In this article, we review the current concepts about the pathogenesis of hepatic steatosis and non-alcoholic steatohepatitis and evaluate the existing diets in the context of this knowledge and the available literature. The intent is to enable clinicians to evaluate the diets of non-alcoholic fatty liver disease (NAFLD) patients and make rational decisions based on this perspective - in the absence of controlled trials - to help their patients. Finally, a tailored approach for the dietary treatment of NAFLD is offered as a way to optimize the dietary management of this condition.

Drug-induced liver injury: is it somehow foreseeable?

The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neo-substances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.

Drug-induced liver injury due to "natural products" used for weight loss: a case report.

Taking herbal-extracts to lose weight is an underestimated health hazard. Often, these products contain active agents that can cause acute liver damage. In this case report, a 22-year-old female patient, who presented with a feature of cholestatic syndrome, was so sure that the "natural products" were not dangerous that she did not inform her physicians that she had taken them, making their task that much more challenging. Clinical presentation mimicked acute cholecystitis and the patient underwent a cholecystectomy. Surgery was without any consequences and complications, although it did not completely cure the illness. She later admitted to having taken herbal remedies and this led to the correct diagnosis of phytotherapy-related hepatotoxicity and a successful therapeutic approach. The true incidence of phytotherapy-related hepatotoxicity and its pathogenic mechanisms are largely unknown. It is important to increase the awareness of both clinicians and patients about the potential dangers of herbal remedies.