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Background and Objectives: Prospective studies comparing EUS-guided liver biopsy (EUS-LB) to percutaneous LB (PC-LB) are scarce. We compared the efficacy and safety of EUS-LB with those of PC-LB in a prospective randomized clinical trial. Methods: Between 2020 and 2021, patients were enrolled and randomized (1:1 ratio). The primary outcome was defined as the proportion of patients with ≥11 complete portal tracts (CPTs). The sample size (n = 80) was calculated based on the assumption that 60% of those in the EUS-LB and 90% of those in the PC-LB group will have LB with ≥11 CPTs. The secondary outcomes included proportion of patients in whom a diagnosis was established, number of CPTs, pain severity (Numeric Rating Scale-Pain Intensity), duration of hospital stay, and adverse events. Results: Eighty patients were enrolled (median age, 53 years); 67.5% were female. Sixty percent of those in the EUS-LB and 75.0% of those in the PC-LB group met the primary outcome (P = 0.232). The median number of CPTs was higher in the PC-LB (17 vs 13; P = 0.031). The proportion of patients in whom a diagnosis was established was similar between the groups (92.5% [EUS-LB] vs 95.0% [PC-LB]; P = 1.0). Patients in the EUS-LB group had less pain severity (median Numeric Rating Scale-Pain Intensity, 2.0 vs 3.0; P = 0.003) and shorter hospital stay (2.0 vs 4.0 hours; P < 0.0001) compared with the PC-LB group. No patient experienced a serious adverse event. Conclusions: EUS-guided liver biopsy was safe, effective, better tolerated, and associated with a shorter hospital stay.
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BACKGROUND AND AIMS: NAFLD and its more-advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver-related, and all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant. APPROACH AND RESULTS: To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline-NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite-NASH (D-NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO2 and the rate-limiting enzyme in ß-oxidation (ß-hydroxyacyl-CoA dehydrogenase activity) were reduced by ~40%-50% with D-NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH. CONCLUSIONS: These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.