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Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio Hep/Port , Ratio Peri/Hep , and Ratio Port/Peri ) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio Peri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio Port/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Background: Heart failure is a significant problem leading to repeated hospitalizations. Telemonitoring and hemodynamic monitoring have demonstrated success in reducing hospitalization rates, but not all studies reported significant effects. The aim of this systematic review and meta-analysis is to examine the effectiveness of telemonitoring and wireless hemodynamic monitoring devices in reducing hospitalizations in heart failure., Methods & Results: PubMed and Cochrane Library were searched up to 1 st May 2017 for articles that investigated the effects of telemonitoring or hemodynamic monitoring on hospitalization rates in heart failure. In 31,501 patients (mean age: 68 ± 12 years; 61% male; follow-up 11 ± 8 months), telemonitoring reduced hospitalization rates with a HR of 0.73 (95% CI: 0.65-0.83; P < 0.0001) with significant heterogeneity ( I 2 = 94%). These effects were observed in the short-term (≤ 6 months: HR = 0.77, 95% CI: 0.65-0.89; P < 0.01) and long-term (≥ 12 months: HR = 0.73, 95% CI: 0.62-0.87; P < 0.0001). In 4831 patients (mean age 66 ± 18 years; 66% male; follow-up 13 ± 4 months), wireless hemodynamic monitoring also reduced hospitalization rates with a HR of 0.60 (95% CI: 0.53-0.69; P < 0.001) with significant heterogeneity ( I 2 = 64%).This reduction was observed both in the short-term (HR = 0.55, 95% CI: 0.45-0.68; P < 0.001; I 2 = 72%) and long-term (HR = 0.64, 95% CI: 0.57-0.72; P < 0.001; I 2 = 55%)., Conclusions: Telemonitoring and hemodynamic monitoring reduce hospitalization in both short- and long-term in heart failure patients.