Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

Abstract

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.

Therapeutic Effect of Gypenosides on Nonalcoholic Steatohepatitis <i>via</i> Regulating Hepatic Lipogenesis and Fatty Acid Oxidation

“…1) The epidemiological data demonstrate that the NAFLD occurrence rate is 25-30% in the U.S.A., 12.6-50% in Asia (Japan, China, and South Korea), and 3-10% in children, respectively. [2][3][4][5][6] Thus, NAFLD is an increasingly common global health problem, especially in the youth population, which is caused by changes in modern lifestyles and diets. 7) NASH is presently the most rapidly growing indication for liver transplantation in hepatocellular carcinoma patients in the U.S.A., and it will become the leading indication for liver transplantation in the near future.…”

Review article: novel methods for the treatment of non-alcoholic steatohepatitis - targeting the gut immune system to decrease the systemic inflammatory response without immune suppression

“…Cenicriviroc (CVC), a dual‐CCR2/CCR5 antagonist, showed potent anti‐inflammatory and anti‐fibrotic activity in animal models, and its safety and pharmacokinetic results were recently published . This therapy is currently being tested in patients with NASH. Several additional compounds that have been tested in NASH have direct and indirect anti‐inflammatory properties, that is, fatty acid–bile acid conjugates that serve as metabolic modulators, anti‐lysyl‐oxidase 2 monoclonal antibody, which has anti‐fibrotic effects, vitamin D, an immunomodulatory molecule and renin–angiotensin–aldosterone system blockers Massive weight loss as a result of bariatric surgery results in histological improvement and partial reversal of cirrhosis .…”

“…While progress has been achieved in our understanding of the pathophysiology, diagnosis and natural history of NAFLD, no drugs have yet been approved for the treatment of NASH . Studies investigating the optimal therapy for NAFLD and NASH have not yet been able to develop a universal treatment protocol . Lack of a clear mechanism remains a major difficulty in drug development for NASH, which is caused by a complex interplay between host and environmental factors .…”

“…4 Studies investigating the optimal therapy for NAFLD and NASH have not yet been able to develop a universal treatment protocol. 5 Lack of a clear mechanism remains a major difficulty in drug development for NASH, which is caused by a complex interplay between host and environmental factors. 3 Thus, the use of pharmacological agents as an adjunctive therapy to lifestyle modification is crucial, as weight loss is a difficult task to achieve and maintain.…”

Az idült májbetegségek progressziójához vezető folyamatok

“…A csökkent inzulinérzékenység a nem alkoholos zsír-májbetegség (NAFLD) progressziójában részt vevő egyik fő mechanizmus [21]. A hyperinsulinaemia indítja be a gének átíródásának fokozását és a de novo lipogenesist a májban.…”