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Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.

SUBMITTER: Alonso-Pena M

PROVIDER: S-EPMC10341551 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key.

Alonso-Peña Marta M Del Barrio Maria M Peleteiro-Vigil Ana A Jimenez-Gonzalez Carolina C Santos-Laso Alvaro A Arias-Loste Maria Teresa MT Iruzubieta Paula P Crespo Javier J

International journal of molecular sciences 20230627 13

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndro ...[more]

PMID: 37445895

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Project description:Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory". However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS). The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first "Achilles' heel" of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor). Recently, a new isoform of human manganese superoxide dismutase (MnSOD) was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel recombinant protein (rMnSOD) potentially represents a new and highly efficient adjuvant therapy to counteract the progression from NASH to HCC.

Project description:Background: It is unknown how perceived social support and the progression of liver damage influence the psychosocial profile of patients with non-alcoholic fatty liver disease (NAFLD). In the present study, we therefore investigated which biomarkers influence the quality of life, mental health, and coping strategies of NAFLD patients. Methods: Quality of life (SF-12 and CLDQ-NAFLD), mental health (HADS and BDI-II), and coping strategies (COPE-28) were evaluated by high or low perceived social support (MSPSS) and the presence of non-alcoholic steatohepatitis (NASH) and significant fibrosis in 492 biopsy-proven NAFLD patients. The results were compared with quality of life normality tables for the general Spanish population. We also determined whether liver histology and biopsychosocial variables predicted participants' quality of life. Results: Interactive effects were found in vitality (p = 0.05), activity (p = 0.005), anxiety (p = 0.04), and denial (p = 0.04), with NASH patients showing a higher-risk biopsychosocial profile when they perceived less social support. Furthermore, patients with low perceived social support showed lower quality of life, worse mental health, and more maladaptive coping than those with high perceived social support, regardless of NASH presence. Patients with significant fibrosis showed lower quality of life compared to those without or the general Spanish population. Patients with significant fibrosis also reported worse mental health and more maladaptive coping. Lastly, significant fibrosis, female sex, greater anxiety and depressive symptoms, and worse physical and mental health-related quality of life were found to be independent determinants of worse disease-specific quality of life in these patients. Conclusions: Low perceived social support, significant fibrosis, and female sex were independently associated with a higher-risk psychosocial profile in NAFLD. These findings support the role of psychological biomarkers based on quality of life, mental health, and coping strategies in the management of these patients and suggest the potential benefits of a psychological intervention.

Dataset Information

Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key.

Publications

Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key.

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