The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and approximately 25% of the global population may have NAFLD. NAFLD is associated with obesity and metabolic syndrome, but its pathophysiology is complex and only partly understood. The transsulfuration pathway (TSP) is a metabolic pathway regulating homocysteine and cysteine metabolism and is vital in controlling sulfur balance in the organism. Precise control of this pathway is critical for maintenance of optimal cellular function. The TSP is closely linked to other pathways such as the folate and methionine cycles, hydrogen sulfide (H₂S) and glutathione (GSH) production. Impaired activity of the TSP will cause an increase in homocysteine and a decrease in cysteine levels. Homocysteine will also be increased due to impairment of the folate and methionine cycles. The key enzymes of the TSP, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are highly expressed in the liver and deficient CBS and CSE expression causes hepatic steatosis, inflammation, and fibrosis in animal models. A causative link between the TSP and NAFLD has not been established. However, dysfunctions in the TSP and related pathways, in terms of enzyme expression and the plasma levels of the metabolites (e.g., homocysteine, cystathionine, and cysteine), have been reported in NAFLD and liver cirrhosis in both animal models and humans. Further investigation of the TSP in relation to NAFLD may reveal mechanisms involved in the development and progression of NAFLD.

Introduction: Abdominal ultrasound (US) and CT are important tools for the initial evaluation of patients with liver disease. Our study aimed to determine the accuracy of these methods for diagnosing cirrhosis. Methods: In all, 377 participants from 4 prospective cohort studies evaluating patients with various liver diseases were included. All patients were included between 2017 and 2022 and had undergone a liver biopsy as well as US and/or CT. Using the histological assessment as the gold standard, we calculated diagnostic accuracy for US and CT. Liver biopsies were evaluated by expert histopathologists and diagnostic scans by experienced radiologists. Results: The mean age was 54 ± 14 years and 47% were female. Most patients had NAFLD (58.3%) or alcohol-associated liver disease (25.5%). The liver biopsy showed cirrhosis in 147 patients (39.0%). Eighty-three patients with cirrhosis had Child-Pugh A (56.4% of patients with cirrhosis) and 64 had Child-Pugh B/C (43.6%). Overall, the sensitivity for diagnosing cirrhosis by US was 0.71 (95% CI 0.62–0.79) and for CT 0.74 (95% CI 0.64–0.83). The specificity was high for US (0.94, 95% CI 0.90–0.97) and for CT (0.93, 95% CI 0.83–0.98). When evaluating patients with Child-Pugh A cirrhosis, sensitivity was only 0.62 (95% CI 0.49–0.74) for US and 0.60 (95% CI 0.43–0.75) for CT. For patients with Child-Pugh B/C, sensitivity was 0.83 (95% CI 0.70–0.92) for US and 0.87 (95% CI 0.74–0.95) for CT. When limiting our analysis to NAFLD (20% with cirrhosis), the sensitivity for US was 0.45 (95% CI 0.28–0.64) and specificity was 0.97 (95% CI 0.93–0.99). Conclusion: US and CT show moderate sensitivity and may potentially overlook compensated cirrhosis underlining the need for additional diagnostic testing. Export

Objectives This study aimed to evaluate the influence of fungal infection and antifungal treatment on outcome in patients with walled-off pancreatic necrosis (WON). Methods A retrospective description of fungal infections in a cohort of consecutive patients undergoing endoscopic, transmural drainage and necrosectomy for WON, treated in a tertiary referral center was reviewed. Results Between 2005 and 2013, fungal infection in WON was documented in 57 (46%) of 123 patients. The most common isolates at first positive culture were Candida albicans (55%) and Candida glabrata (20%). Thirty-nine (70%) patients were treated with antifungals after the first fungal finding. There was no significant difference in mortality (21% vs 13%, P = 0.517) or organ failure (34% vs 33%, P = 0.903) between the group treated with adequate antifungals after the first fungal finding compared to the group not treated or treated inadequately. The in-hospital mortality was 18% (10 patients). Concomitant fungemia was found in 6 patients, of which 3 died, as opposed to 7 with fungi in the necrosis only (50% vs 14%, P = 0.027). Conclusions This study demonstrates a high incidence and associated high in-hospital mortality of fungal infection in WON, thus emphasizing the importance of fungal infections in WON.