Research Article Details
| Article ID: | A01501 |
| PMID: | 34722019 |
| Source: | Cureus |
| Title: | Decoding the Pathophysiology of Non-alcoholic Fatty Liver Disease Progressing to Non-alcoholic Steatohepatitis: A Systematic Review. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic manifestation of metabolic syndromes, and its roots are strongly associated with obesity and insulin resistance. The excess fat induces inflammatory pathways by tissue irritation and progresses to non-alcoholic steatohepatitis (NASH), fibrosis, and has emerged as the most frequent cause of hepatocellular cancer (HCC). This systematic review was structured per the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The evidence was obtained from 13 research articles published in PubMed, Google Scholar, and Science Direct databases, including cross-sectional, case-control, prospective cohort studies, meta-analysis, and systematic reviews. The inclusion/exclusion criteria of free articles, published in English involving humans of mid-age in the last five years were applied. This review highlights findings in 7781 individuals, including non-NAFLD, NAFLD, and NASH positive individuals based on anthropometric measurement, blood samples, FibroScan, flow cytometry, and liver biopsy. The results underscored that the onset of inflammation set on the background of NAFLD starts NASH; the understanding and control of inflammation will help us design definitive biomarkers and treatment modalities. The complex pathogenesis and comparatively slow advancement but high morbidity have led investigators to understand the nuts and bolts for early management and prevention. Lipotoxicity and dysbiosis stimulate the immune system to generate cytokines and chemokines and decline in adipokines. The role of proteinase3 (PR3) and antitrypsin (ATT) ratio and biliverdin reductase (BVR) compel the exploration for non-invasive tests for definitive therapy. |
| DOI: | 10.7759/cureus.18201 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S09 | Bariatric surgery | Metabolic surgery | -- | -- | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |