Current complications and challenges in nonalcoholic steatohepatitis screening and diagnosis

Abstract

Nonalcoholic steatohepatitis (NASH) can lead to complications such as liver failure, cirrhosis and hepatocellular carcinoma. The diagnostic gold standard for NASH is liver biopsy; however, other noninvasive methods have been developed. In this article, the authors evaluate current methods in NASH screening and diagnosis. Routine radiologic modalities were found to detect hepatic steatosis accurately, but were unable to establish the diagnosis of NASH or stage of fibrosis. Newly developed elastography based techniques seem promising to estimate liver fibrosis. Other noninvasive tests such as FibroTest, ELF, Hepascore, FIB-4, NFS, FLI and ION (biochemical panels) have AUROCs ranging between 0.80-0.98 for detecting advanced fibrosis but lack specificity for detecting mild fibrosis. Noninvasive tools, especially elastography, identify NASH associated advanced fibrosis potentially reducing liver biopsies. More research is needed to validate the clinical utility of these tests.

Translating scientific discovery: the need for preclinical models of nonalcoholic steatohepatitis

“…However, in the specific case of NASH, given that liver biopsies cannot be routinely obtained at the population level, there is an inadequate direct assessment for true incidence or prevalence rates. Therefore, given the limitation in obtaining direct data on NASH, a rough estimate of prevalence in the general population, is thought to be in the range of 1.5–6.5% [7, 8]. …”

Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

“…First, since NASH is the potentially progressive form of NAFLD, it should be the target of new therapeutic regimens. Furthermore, the severity of hepatic fibrosis (i.e., fibrosis stage) predicts liver‐related mortality in NAFLD and therefore, the development of treatment regimens for patients with significant hepatic fibrosis must be prioritized . In addition to the appropriate endpoints, it is important to consider the placebo effect on the histology of NASH patients who are treated in randomized controlled trials.…”

“…Furthermore, the severity of hepatic fibrosis (i.e., fibrosis stage) predicts liver-related mortality in NAFLD and therefore, the development of treatment regimens for patients with significant hepatic fibrosis must be prioritized. (7)(8)(9)(10) In addition to the appropriate endpoints, it is important to consider the placebo effect on the histology of NASH patients who are treated in randomized controlled trials. In fact, this placebo effect has been shown to be substantial.…”

Pediatric Non-Alcoholic Fatty Liver Disease

“…Histologically, NAFLD represents an umbrella term that incorporates an entire spectrum of pathologic severity, ranging from steatosis to steatohepatitis with or without fibrosis [27]. While there has been much progress in understanding the pathogenesis of NAFLD, there is still some debate about the pathogenic steps in the progressive form of NAFLD [6]. As previously noted, the “multi-hit hypothesis” seems the most reasonable explanation for the pathogenesis [28].…”

“…Further research has supported that Hispanic children of Mexican origin have one of the highest incidences of NAFLD, which has been associated with obesity and the PNPLA3 gene [5]. NAFLD is a metabolic disorder characterized by excessive fat deposition in the liver parenchyma, which is not associated with infection, medication, or an autoimmune process [6]. Additionally, NAFLD encompasses a spectrum of liver diseases, ranging from simple hepatic steatosis, which has also been called NAFL, to non-alcoholic steatohepatitis (NASH), which carries an increased risk of progression to fibrosis, cirrhosis, and even hepatocellular carcinoma [7,8,9].…”