Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

• Published in: Drug design, development and therapy development and therapy, 2015-01, Vol.9 (default), p.4835-4845
• Main Authors: Milic, Sandra, Mikolasevic, Ivana, Krznaric-Zrnic, Irena, Stanic, Marija, Poropat, Goran, Stimac, Davor, Vlahovic-Palcevski, Vera, Orlic, Lidija
• Format: Article
• Language: English
• Subjects: Alcohol use; Aldosterone; Algorithms; Angiotensin; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Biopsy; Cardiovascular diseases; Care and treatment; Chronic illnesses; Clinical trials; Collagen; Critical Pathways; Decision Support Techniques; Diabetes; Diabetes mellitus; Diet; Drug targeting; Fatty liver; Gastroenterology; Gastrointestinal surgery; Health risks; Hepatology; Humans; Hyperlipidemia; Hypertension; Incidence; Inflammation; Innovations; Insulin; Insulin resistance; Life Style; Lifestyles; Liver; Liver cancer; Liver diseases; Metabolic disorders; Metabolic syndrome; Microbiota; Morbidity; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - physiopathology; Non-alcoholic Fatty Liver Disease - therapy; nonalcoholic fatty liver disease; Obesity; Optimization; Organs; Pathogenesis; Patients; Pharmacology; Phlebotomy; Physical activity; Population studies; Prevalence; Public health; Renin; Renin-Angiotensin System - drug effects; Review; Risk analysis; Risk Factors; Risk Reduction Behavior; Therapy; Thiazolidinediones - therapeutic use; Tocopherol; Treatment Outcome; Tumor necrosis factor-TNF; Vitamin D; Vitamin D - therapeutic use; Vitamin deficiency; Vitamin E; Weight control
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/dddt.s64877

Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD). NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH) is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only limited clinical evidence is available regarding their long-term efficacy and safety. Vitamin D and renin-angiotensin-aldosterone system blockers are promising drugs that are currently being intensively investigated for use in NAFLD/NASH patients.