Nonalcoholic steatohepatitis pharmacotherapy and predictors of response: dual role of aminotransferases as biosensors of metabolism and biomarkers of histological improvement

PIROLA, CARLOS J.; SOOKOIAN, S.

Hepatobiliary Surg Nutr

AME Publishing Company

Lugar: Hong Kong; Año: 2019 vol. 8 p. 381 - 385

2304-3881

Nonalcoholic steatohepatitis (NASH)?the severehistological form of nonalcoholic fatty liver disease(NAFLD)?is regarded as a major health problemworldwide (1,2). The disease can progress to liver cirrhosisand eventually to hepatocellular carcinoma (1,3). Treatmentof NASH and NASH-fibrosis is thus increasingly beinggiven priority in the clinical field. Yet, these efforts facechallenges not only related to the design and validationof novel pharmacological agents, but also to the need tooptimize treatment options as well as improve access totherapies. In fact, while many drugs are currently beingtested for safety and efficacy, only a few approved optionsfor the treatment of NASH presently exist (4,5). It is thusexpected that, in the near future, emphasis will be given toselecting the right drug for treating NASH patients from awide spectrum of treatment choices. Hence, identificationof early predictors of treatment response represents anunmet and relevant need.Loomba and coworkers have recently published resultsyielded by a post-hoc analysis of clinical predictors ofhistologic response (6), whereby the data was sourced fromthe FLINT trial?a double-blind, placebo-controlled,randomized clinical trial conducted at multiple medicalcenters across the U.S. involving non-cirrhotic NASHpatients?to assess the treatment efficacy of obeticholicacid (OCA, a farnesoid X receptor agonist) given orally(25 mg daily) for 72 weeks (7). Specifically, the authorsaimed at identifying baseline and early on-treatmentfactors that might predict histologic response. By utilizinga multivariable-adjusted model, the authors found thatbaseline NAS (NASH activity score) >5, baseline triglyceridelevels ≤154 mg/dL, baseline international normalizedratio ≤1, baseline aspartate aminotransferase (AST) level≤49 IU/L, and a decrease in alanine aminotransferase (ALT)levels at week 24 by at least 17 IU/L were significantlyassociated with histological improvement (6). Theseinteresting and promising findings deserve some reflections.Nonalcoholic steatohepatitis pharmacotherapy and predictors of response: dual role of aminotransferases as biosensors of metabolism and biomarkers of histological improvement.