High frequency of acute decompensation and cancer in patients with compensated cirrhosis due to nonalcoholic fatty liver disease : A retrospective cohort study

The natural history of compensated cirrhosis due to nonalcoholic fatty liver disease (NAFLD) has not been completely characterized. The aim of the present study was to assess the incidence and risk factors of acute decompensation of cirrhosis, hepatocellular carcinoma, and extrahepatic cancers. This was a multicenter, retrospective, cohort study including 449 patients with compensated cirrhosis due to NAFLD. We calculated cumulative incidences and used competitive risk analysis to determine the risk factors associated with decompensation and cancer development. Over a median of 39 months of follow-up, 124 patients (28%) presented acute decompensation. The most frequent decompensation was ascites (21%) followed by hepatic encephalopathy (15%), variceal bleeding (9%), and spontaneous bacterial peritonitis (3%). Acute-on-chronic liver failure was diagnosed in 6% of patients during follow-up. Liver function parameters and specifically an albumin level below 40 g/L were independently associated with an increased risk of decompensation. The presence of ischemic heart disease was independently associated with acute decompensation. Seventy-eight patients (18%) developed hepatocellular carcinoma or extrahepatic cancers during follow-up (51 and 27, respectively). Conclusion : Patients with compensated cirrhosis due to NAFLD are at high risk of severe liver complications, such as the development of acute decompensation, in a relative short follow-up time. This population is at high risk of hepatic and extrahepatic cancers. The analysis of a large contemporary cohort of 449 patients with compensated cirrhosis due to non-alcoholic fatty liver disease shows a high frequency of acute decompensations (AD) and development of cancer during 39 months of follow-up. Almost 28% of the cohort developed acute decompensation and 18% developed hepatocellular carcinoma (HCC) or extrahepatic cancer. Predictors of decompensation are mainly related to liver function and portal hypertension

Bioelectrochemical conversion of CO2 to value added product formate using engineered Methylobacterium extorquens

The conversion of carbon dioxide to formate is a fundamental step for building C1 chemical platforms. Methylobacterium extorquens AM1 was reported to show remarkable activity converting carbon dioxide into formate. Formate dehydrogenase 1 from M. extorquens AM1 (MeFDH1) was verified as the key responsible enzyme for the conversion of carbon dioxide to formate in this study. Using a 2% methanol concentration for induction, microbial harboring the recombinant MeFDH1 expressing plasmid produced the highest concentration of formate (26.6 mM within 21 hours) in electrochemical reactor. 60 ??M of sodium tungstate in the culture medium was optimal for the expression of recombinant MeFDH1 and production of formate (25.7 mM within 21 hours). The recombinant MeFDH1 expressing cells showed maximum formate productivity of 2.53 mM/g-wet cell/hr, which was 2.5 times greater than that of wild type. Thus, M. extorquens AM1 was successfully engineered by expressing MeFDH1 as recombinant enzyme to elevate the production of formate from CO2 after elucidating key responsible enzyme for the conversion of CO2 to formate

Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe

Raw Data supporting Article: Oxidation state-dependent binding properties of the active site in a Mo-containing formate dehydrogenase

Raw Data supporting Article: Oxidation state-dependent binding properties of the active site in a Mo-containing formate dehydrogenas

Impact of the COVID-19 pandemic on the care and outcomes of patients with NAFLD-related cirrhosis

The COVID-19 pandemic has had a strong, negative impact on health systems and many chronic diseases globally. We aimed to evaluate the impact of the first year of the pandemic on the outcomes of NAFLD cirrhosis patients.Before-after study conducted in 4 University hospitals in Catalonia, Spain. Study subperiods were divided in Pre-pandemic (March/2019-February/2020) vs. Pandemic (March/2020-February/2021). Primary outcome was the rate of first liver-related events (LRE). Overall clinical outcomes (LRE plus cardiovascular plus all-cause mortality) were also assessed.354 patients were included, all of whom were compensated at the beginning of the study period but 83 subjects (23.5%) had presented a prior hepatic decompensation. Mean age was 67.3 years and 48.3% were female. Median BMI was 31.2kg/m2 and type-2 diabetes (T2D) was present in 72.8% patients. The rates of first LRE in the Pre-pandemic and Pandemic periods were 7.4% and 11.3% (p=0.12) respectively. Whilst the rate of overall events was significantly higher in the Pandemic period (9.9% vs. 17.8%; p=0.009), this was strongly associated to COVID-19-related deaths. The rate of worsened metabolic status was significantly higher in the Pandemic period (38.4% vs.46.1%; p=0.041), yet this was not associated with the risk of first LRE during the Pandemic period, whereas T2D (OR 3.77,95%CI 1.15-12.32; p=0.028), albumin2.67 (OR 15.74,95%CI 2.01-123.22; p=0.009) were identified as risk factors in the multivariable analysis.Overall, patients with NAFLD cirrhosis did not present poorer liver-related outcomes during the first year of the pandemic. Health systems preparedness seems key to ensure NAFLD cirrhotic patients receive appropriate care during health crises.Mobility restrictions and social stress induced by the COVID-19 pandemic have led to increased alcohol drinking and worsened metabolic control (e.g., weight gain, poor control of diabetes) in a large proportion of the population from many countries. We aimed at analyzing whether patients with cirrhosis due non-alcoholic fatty liver disease, whom are particularly vulnerable to such lifestyle modifications, were significantly impacted during the first year of the pandemic. With that purpose, we studied 354 patients and compared their clinical situation one year before the pandemic outbreak and one year after. We found that although metabolic control was indeed worse after the first year of the pandemic and patients presented worse clinical outcomes, the latter was mostly due to non-liver causes but rather to COVID-19. Moreover, the care provided to cirrhotic patients with NAFLD did not worsen during the first year of the pandemic.© 2022 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL)

Urinary L-FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis

Background & Aims: Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. Methods: A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. Results: Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. Conclusions: Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. Lay summary: Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis