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In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma (HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonography with or without alpha-fetoprotein (AFP) in patients with advanced fibrosis. Furthermore, the use of non-invasive tools could represent a strategy to implement surveillance performance. In this review, we analyzed the main risk factors of NAFLD-related HCC, the validated screening methods and the future perspectives.

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Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.

Background The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. Methods This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. Results 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %–93.9 %] vs. 87.8 % [95 %CI 82.1 %–92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %–96.3 %] vs. 95.5 % [95 %CI 91.4 %–98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P < 0.001). Conclusions The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.