Traditional Chinese Medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives.
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ABSTRACT:
SUBMITTER: Dai X
PROVIDER: S-EPMC8330116 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer. In recent years, bile acids have emerged as relevant signaling molecules that act at both hepatic and extrahepatic tissues to regulate lipid and carbohydrate metabolic pathways as well as energy homeostasis. Activation or modulation of bile acid receptors, such as the farnesoid X receptor and TGR5, and transporters, such as the ileal apical sodium-dependent bile acid transporter, appear to affect both insulin sensitivity and NAFLD/NASH pathogenesis at multiple levels, and these approaches hold promise as novel therapies. In the present review, we summarize current available data on the relationships of bile acids to NAFLD and the potential for therapeutically targeting bile-acid-related pathways to address this growing world-wide disease. (Hepatology 2017;65:350-362).
| S-EPMC5191969 | biostudies-literature
Project description:Despite more than two decades of extensive research focusing on nonalcoholic fatty liver disease (NAFLD), no approved therapy for steatohepatitis-the severe histological form of the disease-presently exists. More importantly, new drugs and small molecules with diverse molecular targets on the pathways of hepatocyte injury, inflammation, and fibrosis cannot achieve the primary efficacy endpoints. Precision medicine can potentially overcome this issue, as it is founded on extensive knowledge of the druggable genome/proteome. Hence, this review summarizes significant trends and developments in precision medicine with a particular focus on new potential therapeutic discoveries modeled via systems biology approaches. In addition, we computed and simulated the potential utility of the NAFLD polygenic risk score, which could be conceptually very advantageous not only for early disease detection but also for implementing actionable measures. Incomplete knowledge of the druggable NAFLD genome severely impedes the drug discovery process and limits the likelihood of identifying robust and safe drug candidates. Thus, we close this article with some insights into emerging disciplines, such as chemical genetics, that may accelerate accurate identification of the druggable NAFLD genome/proteome.
| S-EPMC7641575 | biostudies-literature
Project description:traditional chinese medicine Targeted loci
| PRJNA796441 | ENA
Project description:Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.
| S-EPMC8601846 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is a disease of attention because of increase in prevalence from 20% to 41%. The clinical and pathological conditions in patients with NAFLD range from steatosis alone to nonalcoholic steatohepatitis (NASH) with or without fibrosis to hepatic cancer. In the United States, NAFLD was the second-leading indication for liver transplant between 2004 and 2013. Although imaging studies such as magnetic resonance elastography and the use of diagnostic panels and scoring systems can provide a fairly accurate diagnosis of NAFLD, there are few treatment options for patients with mild to moderate disease other than lifestyle modification. Many of the currently used medical treatments have been shown to cause severe side effects and some have been shown to be associated with increased risk for certain types of cancer. In recent years, a number of traditional Chinese herbal treatments have been examined for their potential uses as treatment for NAFLD. In this review, we provide a general overview of NAFLD and a survey of Western pharmacologic drugs currently used to treat the disease as well as the results of recent studies on the effectiveness of traditional Chinese herbal remedies for managing nonalcoholic fatty liver disease.
| S-EPMC5107852 | biostudies-other
Project description:BackgroundThe prevalence and incidence of youth-onset nonalcoholic fatty liver disease (NAFLD) far exceeds other paediatric chronic liver diseases and represents a considerable public health issue globally.MethodsHere, we performed a narrative review of current knowledge regarding the epidemiology of paediatric NAFLD, selected concepts in pathogenesis, comorbidities, diagnosis, and management, and issues related to the transition to adulthood.ResultsPaediatric NAFLD has become increasingly more prevalent, especially in certain subgroups, such as children with obesity and certain races/ethnicities. The pathophysiology of paediatric NAFLD is complex and multifactorial, driven by an interaction of environmental and genetic factors. Once developed, NAFLD in childhood is associated with type 2 diabetes, hypertension, increased cardiovascular disease risk, and end-stage liver disease. This predicts an increased burden of morbidity and mortality in adolescents and young adults. Early screening and diagnosis are therefore crucial, and the development of noninvasive biomarkers remains an active area of investigation. Currently, treatment strategies are focused on lifestyle changes, but there is also research interest in pharmacological and surgical options. In the transition from paediatric to adult care, there are several potential challenges/barriers to treatment and research is needed to understand how best to support patients during this time.ConclusionsOur understanding of the epidemiology and pathophysiology of paediatric NAFLD has increased considerably over recent decades, but several critical knowledge gaps remain and must be addressed in order to better mitigate the short-term and long-term risks of youth-onset NAFLD.
| S-EPMC7576279 | biostudies-literature
Project description:Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.
| S-EPMC6514656 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the United States affecting 80-100 million Americans. NAFLD encompasses a spectrum of diseases ranging from excess liver fat (nonalcoholic fatty liver or NAFL), to necro-inflammation (nonalcoholic steatohepatitis or NASH), to fibrosis/ cirrhosis, and malignant transformation (hepatocellular carcinoma). Susceptibility to NAFLD is highly variable and it remains unclear why some patients with NAFLD exhibit NASH, whereas patients with known risk factors have NAFL only. The reasons for this variability can be a partially attributed to differences in genetic background. In the last decade, there have been multiple genome wide association studies, which have enriched our understanding of the genetic basis of NAFLD. The I148M PNPLA3 (patatin-like phospholipase domain-containing protein 3) variant has been identified as the major common genetic determinant of NAFLD. Variants with moderate effect size like TM6SF2, MBOAT7 and GCKR have also been shown to have a significant contribution. New research has uncovered major pathways leading to disease development and progression; therefore, multiple medications are being developed and tested for the treatment of advanced NAFLD. These agents target metabolic mechanisms as well as inflammation and fibrosis pathways. Several randomized clinical trials (RCTs) are evaluating the efficacy of these novel agents on histological improvement of disease severity and decreasing liver-related outcomes. FDA-approved medications for NASH and NASH-related fibrosis are expected by 2020.
| S-EPMC6230844 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease due to an increase in the prevalence of obesity. The development of NASH leads to an increase in morbidity and mortality. While the first line of treatment is lifestyle modifications, including dietary changes and increased physical activity, there are no approved pharmacological treatment agents for NAFLD and NASH currently. Due to its complex pathophysiology, different pathways are under investigation for drug development with the focus on metabolic pathways, inflammation, and slowing or reversing fibrosis. There are several agents advancing in clinical trials, and promising results have been seen with drugs that affect hepatic steatosis, inflammation, and fibrosis. This review will provide an overview on NAFLD and some of the mechanisms of disease that are being targeted with pharmacologic agents.
| S-EPMC6163009 | biostudies-other
Project description:Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. CONCLUSION:Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361-371).
| S-EPMC6508084 | biostudies-literature