on-alcoholic fatty liver disease (NAFLD) is associated with obesity, metabolic syndrome, dyslipidemia and type 2 diabetes (T2D). NASH is the progressive form of NAFLD, defined as ≥5% hepatic steatosis with inflammation and hepatocyte injury (that is, ballooning), with or without fibrosis 1 . Despite a predicted global prevalence of 2-12% in adults 2,3 , currently there is no approved treatment. Most clinically evaluated therapeutic mechanisms target the metabolic dysfunction of hepatocytes or suppress inflammation and fibrosis 4 . However, an ideal therapeutic would treat advanced fibrosis and resolve the profibrotic milieu driven by hepatocyte death (apoptosis) associated with chronic steatosis, lipotoxicity and oxidative and endoplasmic reticulum stress.FGF21 is a key regulator of whole-body and individual organ metabolism 5 . It activates a cell membrane co-receptor complex of β-klotho and one of its cognate FGF receptors (FGFRs), FGFR1c, FGFR2c or FGFR3c. FGF21 and its analogs improve metabolic status in preclinical models of obesity, diabetes and NASH 6 , suggesting promise as a therapeutic for NASH. However, many FGF21 analogs have not fulfilled the preclinical promise of FGF21 therapeutics, with disappointing translation into the clinic. Although substantial reductions in serum triglycerides have been seen in patients with T2D and obesity, effects on high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol have been variable, with inconsistent effects on glycemic control and body weight [7][8][9] . Furthermore, in patients with NASH, liver fat reductions have been moderate 10 . Two antibody-based therapeutics that act on the FGF21 co-receptor complex are also in development. Unlike analogs of the FGF21 polypeptide, BFKB8488A (Genentech) and MK3655 (Merck Sharp & Dohme; formerly NGM313 (NGM Biopharmaceuticals)) activate only the FGFR1c/β-klotho co-receptor complex. In patients with NAFLD, the highest adequately tolerated dose of BFKB8488A reduced HFF by 38% after 12 weeks 11 but did not improve markers of glycemic control in patients with T2D 12 . After a single dose, MK3655 improved glycemic control in obese non-diabetic participants with 37% relative reduction in liver fat 36 d after administration; however, significant weight gain was seen 13 .Efruxifermin is a fusion protein of human IgG 1 Fc domain linked to a modified human FGF21 (Fc-FGF21) with balanced in vitro agonist potency at FGFR1c, FGFR2c and FGFR3c 14 . Efruxifermin is longer acting than most FGF21 analogs, with a 3-3.5-d half-life 15 . A study in patients with T2D showed improvements in lipoprotein profiles and glycemic control 15 , which supported investigation of efruxifermin in patients with NASH. This study aimed to test the safety and efficacy of weekly subcutaneous administration for 16 weeks in patients with NASH.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with insulin resistance and metabolic syndrome. The spectrum of disease ranges from simple steatosis to steatohepatitis and progression to cirrhosis. Compelling evidence over the past several years has substantiated a significant link between NAFLD and cardiovascular disease ranging from coronary artery disease to subclinical carotid atherosclerosis. Close follow up, treatment of risk factors for NAFLD, and cardiovascular risk stratification are necessary to predict morbidity and mortality in this subset of patients.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity worldwide. With the obesity pandemic, NAFLDrelated HCC is contributing to the burden of disease exponentially. Genetic predisposition and clinical risk factors for NAFLD-related HCC have been identified. Cirrhosis is a well-known and major risk factor for NAFLD-related HCC. However, the occurrence of NAFLD-related HCC in patients without cirrhosis is increasingly recognized and poses a significant challenge regarding cancer surveillance. It is of paramount importance to develop optimal risk stratification scores and models to identify subsets of the population at high risk so they can be enrolled in surveillance programs. In this review, we will discuss the risks and prediction models for NAFLDrelated HCC.

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Pancreatic fluid collections (PFCs) have conventionally been treated with surgery, percutaneous drainage, or with the more recently established endoscopic ultrasound (EUS)-guided drainage modality. Currently, endoscopic plastic or metallic stents are used for PFC drainage. Plastic stents present issues with stent migration and premature occlusion requiring frequent stent exchanges or placement of additional stents. Metallic stents are tubular and may migrate, resulting in inefficient drainage, content leakage, retrieval and replacement, and possible mucosal injury. The aim of this review was to summarize and evaluate the clinical and technical effectiveness of EUS-guided placement of the recently developed AXIOS stent, a lumen-apposing self-expandable metallic stent (LASEMS)for PFC drainage. A literature review was performed to identify the studies describing this technique. In this review article we have summarized case series or reports describing EUS-guided LASEMS placement. The indications, techniques, limitations and complications reported are discussed. A total of 298 patients were included across all studies described thus far in the literature. Overall, a 97% technical success rate and a 96% clinical success rate have been reported. Early and late complications related to the placement or removal of LASEMS have been reported, however few cases have presented life-threatening results. EUS-guided PFC drainage and LASEMS placement can be a safe and effective alternative approach in the management of selected patients.