The Liver Meeting in 2022 demonstrated the large amount of ongoing research that is currently taking place in nonalcoholic steatohepatitis (NASH). Outlining all of the wonderful research that has been presented this meeting would be a herculean task. In this review, I aim to concisely summarize the most interesting and clinically meaningful research topics that directly impact daily practice. 

First, the therapeutics of NASH continues to evolve. Dr. Stephen Harrison reviewed the emerging therapies under study in NASH, discussing those treatments currently in phase 3 trials. Resmetirom is thyroid hormone receptor (THR)-beta agonist which reduces liver fat, improves NASH, lowers low-density lipoprotein (LDL) and triglyceride levels, which is well tolerated. Obeticholic acid (OCA), an farnesoid X receptor (FXR) agonist, reduces lipogenesis and free fatty acids, and prevents lipotoxicity. There’s improvement in fibrosis by OCA, but it did not lead to NASH resolution. OCA can sometimes increase pruritus, worsen hyperlipidemia, and lead to cholecystitis. Lanifibranor, a pan-peroxisome proliferator–activated receptor (PPAR) agonist, improves steatosis, inflammation, and fibrosis, and is also generally well tolerated. Lastly, semaglutide, a glucagon like peptide-1 (GLP1) agonist, helps facilitate weight loss and reduces liver fat and NASH compared to placebo. Outside of some gastrointestinal disturbances, it is a well-tolerated medication.

Other potential treatments currently in phase 2 trials, including a fibroblast growth factor 21 (FGF21) agonist, may help with both NASH and alcohol-associated steatohepatitis (ASH). Dr. Harrison completed his talk by discussing the use of combination therapies to enhance long-term outcomes. One example of combination currently being studied include semaglutide with firsocostat and cilofexor, which helps target different mechanisms of action that may improve benefit. Other combinations of therapies are also currently being studied with some exciting upcoming results.

The era of noninvasive testing in liver disease to avoid liver biopsy also continues to evolve. Dr. Noureddin discussed noninvasive markers of NAFLD/NASH and the importance of identifying those with NASH and F2 fibrosis or higher, given their increased risk of NASH-related mortality. Doing this noninvasively is increasingly preferred in clinical practice as well as in trial settings. Noninvasive testing is also increasingly used to monitor response to therapy and predict major adverse liver events (MALO).

He discussed how high-risk populations, such as those with type 2 diabetes mellitus in primary care settings, should be targeted for screening pathways as recommended by the AGA and EASL. The FIB-4 can be a first test used in the algorithm for screening with some certain caveats. For instance, it may not be as reliable in those above 65 years of age, but ongoing studies continue to evaluate its accuracy and reliability in other specialized cohorts.

Often, the use of more than one test is required for confirmation of fibrosis level and to predict outcomes. Other promising noninvasive tests include but are not limited to Enhanced Liver Fibrosis (ELF) test, NIS4 score, PRO-C3 fibrosis biomarker, MASEF, FAST and MAST models, MEFIB score, and proteomic as well as machine learning models that are undergoing investigation. Imaging parameters are also very accurate in clinical pathways for steatosis and fibrosis screening in NASH. These include transient elastography, MRE, MRI-PDFF, and cT1 imaging, all of which have high area under the receiver operating characteristic curve for predicting fibrosis and/or steatosis. Dr. Noureddin also discussed the importance of using a combination of noninvasive tests to monitor response to therapy and predict clinical outcomes. Different versions of these combinations can be employed in clinical practice by treating hepatologist.

The most exciting areas in the management of NASH continue to be in the context of noninvasive testing in the background of promising treatment modalities that are emerging. The use of these measures and treatments in combination, will likely be the future of NAFLD management.