MAFLD/NAFLD Biopsy-Free Scoring Systems for Hepatic Steatosis, NASH, and Fibrosis Diagnosis

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is the most prevalent liver disorder worldwide. Historically, its diagnosis required biopsy, even though the procedure has a variable degree of error. Therefore, new non-invasive strategies are needed. Consequently, this article presents a thorough review of biopsy-free scoring systems proposed for the diagnosis of MAFLD. Similarly, it compares the severity of the disease, ranging from hepatic steatosis (HS) and nonalcoholic steatohepatitis (NASH) to fibrosis, by contrasting the corresponding serum markers, clinical associations, and performance metrics of these biopsy-free scoring systems. In this regard, defining MAFLD in conjunction with non-invasive tests can accurately identify patients with fatty liver at risk of fibrosis and its complications. Nonetheless, several biopsy-free scoring systems have been assessed only in certain cohorts; thus, further validation studies in different populations are required, with adjustment for variables, such as body mass index (BMI), clinical settings, concomitant diseases, and ethnic backgrounds. Hence, comprehensive studies on the effects of age, morbid obesity, and prevalence of MAFLD and advanced fibrosis in the target population are required. Nevertheless, the current clinical practice is urged to incorporate biopsy-free scoring systems that demonstrate adequate performance metrics for the accurate detection of patients with MAFLD and underlying conditions or those with contraindications of biopsy.

Body weight and blood chemistry of wild coatis that feed on discarded human food

ABSTRACT: The coati (Nasua nasua, Linnaeus 1766) is a generalist species, feeding on often-discarded human food in dumpsters around ecological tourism sites. We investigated the body weight and some blood chemistry variables related to the diet of wild coatis from three parks: Parque Municipal das Mangabeiras (PM), Parque Nacional do Caparaó (PNC) e Estação Ecológica Água Limpa (EEAL). We tested the plasma of 53 coatis for high-density lipoprotein (HDL), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), cholesterol (Chol), triglycerides (Trig), and alkaline phosphatase (ALP). Male and female adults did not significantly differ on the weight (P > 0.05) and blood chemistry indexes (P > 0.05). The adult coatis of the PM were heavier than the adult coatis of the other two parks. There were significant differences in HDL (P < 0.04), AST (P < 0.001), ALT (P < 0.001), and GGT (P < 0.001) between adults of the three parks. Only ALT and ALP were significantly different (P < 0.05) among the young coatis. The results suggested the coatis of the three parks have different health status. The consumption of discarded human food seems to affect body weight of the PM coatis. The coatis from PNC and EEAL had blood chemistry profiles suggestive of liver disorder. We recommend carrying on environmental education programs to visitors and additional clinical investigations on coatis from these parks.

Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease

The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca2+ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca2+ is intricately compartmentalized, and the Ca2+ flow is tightly controlled by a network of Ca2+ transport and buffering proteins. Impaired Ca2+ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca2+ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca2+ signaling as a potential therapeutic approach.

The Pharmacological Study of Antidiabetatic Property of Ficus racemosa Leaves by Observing Different Aspects

Ficus racemosa is belong to the family of Moraceae.It is a famous medicinal plant in India which is used in traditional system of medicine for long period of time for the treatment of various diseases like liver disorder, diarrhora, inflamatory condition, ulcer, urinary disorder, antifungal and diabetics. This plant is very useful from ancient time of maintained in Ayurveda, Siddha, Unani and Homeopathy. Plant are one of the most important role/source in medicine. The commen name of Ficus racemosa is “Audumber” and “Umbar”. In Thervada Buddhism the plant is said to have as the tree for achived enlightenment by the 26th Loard Buddha, Konaagama. This udumbara is deciduous tree. The more information is described below and the people are moving towards ayurvedic preprations.

Evaluation of Efficacy of Phalatrikadi Ghan Vati in Patients of Non-Alcoholic Fatty Liver Disease through Reverse Pharmacology Approach – Study Protocol

Background: Non-alcoholic fatty liver disease (NAFLD), mostly diagnosed incidentally, is a rapidly emerging liver disorder. In absence of any specific treatment, current management focuses on theuse of hepatoprotective agents in addition to lifestyle modification and prevention of metabolic syndrome. Several Ayurveda agents have shown promising effects in patients over centuries of use. But this evidence needs to be assessed scientifically through reverse pharmacology approach. A polyingredient Ayurveda drug, Phalatrikadighanvati (PGV) has been selected for this study because of its long history of use and that its individual contents have shown positive results in liver disorders. Objective: Evaluation of efficacy of Phalatrikadighanvati in patients of non alcoholic fatty liver disease (NAFLD) along with its pharmaceutical and analytical study. Materials and Methods: The drug shall bepharmaceutically processed and analyzed as per pharmacopoeial standards.Present study has been designed as a randomized placebo controlled double blind clinical trial in two stages. The first stage shall be a pilot study to decide the best effective and safe dose in patients of NAFLD. The pilot study shall include two groups of 10 patients each in a dose of PGV 500mg and 1gm respectively twice a day for 12 weeks. After theselection of thebest dose, RCT will be conducted on that dose in the second stage.It shall be a Phase 2 trial with 60 patients divided equally in two groups.The patients in group one shall be given a dose as per the outcome of the pilot study twice a day and another group shall be administered placebo for a period of 12 weeks. Results: Efficacy of Phalatrikadi ghan vati will evaluated in terms of subjective and objective parameters using paired and unpaired t-test. Conclusion: PGV is expected to improve the diagnostic parameters in patients of NAFLD thus proving to be efficacious in managing NAFLDand act as a potent hepatoprotective agent.

Liver Injury and Elevated Levels of Interleukins, Interleukin-2 Receptor, and Interleukin-6 Predict the Severity in Patients With COVID-19

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.

Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles

Non-alcoholic fatty liver disease (NAFLD), mainly characterized by the accumulation of excess fat in hepatocytes, is the most prevalent liver disorder afflicting ~25% of adults worldwide. In vivo studies have shown that adult rodents with NAFLD were more sensitive to metallic nanoparticles (MNPs) than healthy MNPs. However, due to the complex interactions between various cell types in a fatty liver, it has become a major challenge to reveal the toxic effects of MNPs to specific types of liver cells such as steatotic hepatocytes. In this study, we reported the susceptibility of steatotic hepatocytes in cytotoxicity and the induction of oxidative stress to direct exposures to MNPs with different components (silver, ZrO2, and TiO2 NPs) and sizes (20–30 nm and 125 nm) in an oleic acid (OA) -induced steatotic HepG2 (sHepG2) cell model. Furthermore, the inhibitory potential of MNPs against the process of fatty acid oxidation (FAO) were obvious in sHepG2 cells, even at extremely low doses of 2 or 4 μg/mL, which was not observed in non-steatotic HepG2 (nHepG2) cells. Further experiments on the differential cell uptake of MNPs in nHepG2 and sHepG2 cells demonstrated that the susceptibility of steatotic hepatocytes to MNP exposures was in association with the higher cellular accumulation of MNPs. Overall, our study demonstrated that it is necessary and urgent to take the intracellular exposure dose into consideration when assessing the potential toxicity of environmentally exposed MNPs.

A CASE REPORT REGARDING MANAGEMENT OF KAMALA THROUGH AYURVEDA

Ayurveda is traditionally skilful in treating liver diseases for centuries. Although named Jaundice as a liver disorder was not mentioned in Ayurveda literature but based on common characteristics and Pathology, Kamala can be correlated with jaundice. Jaundice is a clinical manifestation of disorders of underlying bilirubin metabolism, hepa- tocellular dysfunction, or biliary obstruction. Jaundice occurs in settings of cholestasis or inability to effectively secrete bile as well as disorders of bilirubin metabolism and hepatocellular dysfunction. Today's lifestyle with un- hygienic and poor dietary habits and alcoholic habits, etc are responsible factors to promote hepatic damage which is clinically reflected as Kamala. This paper discusses a patient seen in the OPD of Kayachikitsa Quadra Institute of Ayurveda Roorkee Haridwar. Her chief complaints Udara shool (pain in the abdomen), Kshudha Mandhya (loss of appetite), Daurbalya (weakness), Hrullas (Nausea), Mutrapitata (yellow discolouration of urine, Vibhandha (constipation) for 15 days. This patient was effectively treated by the combination of Kutaki Churna, Triphala, Trivrita Churna, Bhunimba Churna, Arogya Vardhini Vati, Phalatrikadi Kashaya, Punarnava Mandoor and Liv 52. All the symptoms showed highly significant results. Hence it can be concluded that these medicines are very effective in patients with jaundice. Keywords: Udara shool, Kshudha mandhya, Daurbalya, Hrullas, Mutrapitata, Vibhandha.

Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers

Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is the most common liver disorder in developed countries. Although many new therapeutics for NASH are present in the drug development pipeline, there are still no approved drugs. One of the reasons that makes NASH drug development challenging is the lack of appropriate animal NASH models that resolve issues arising from inter-species differences between humans and rodents. In the present study, we developed a choline-deficient, L-amino-acid-defined, high-fat-diet (CDAHFD)-induced human NASH model using human liver chimeric mice. We demonstrated human hepatocyte injury by an elevation of plasma human alanine aminotransferase 1 in mice fed CDAHFD. Histological analysis showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. The chimeric mice fed CDAHFD were treated with a peroxisome-proliferator-activated receptor α/δ agonist, Elafibranor. Elafibranor ameliorated steatosis, ballooning of hepatocytes, and preserved fibrosis progression. We developed a novel humanized NASH model that can elucidate pathophysiological mechanisms and predict therapeutic efficacy in human NASH. This model will be useful in exploring new drugs and biomarkers in the early stages of human NASH.