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Chronic liver diseases, including hepatocellular carcinoma (HCC), lead to an imbalance in energy metabolism. The non-protein respiratory quotient (npRQ), which estimates energy malnutrition, can be evaluated using an indirect calorimeter; however, npRQ measurement is limited in routine work. This study aimed to investigate the relationship between the albumin–bilirubin (ALBI) score and npRQ in patients with HCC. We conducted a retrospective cohort study in 109 patients with HCC who underwent indirect calorimetry and then compared the npRQ with various clinical parameters, including liver function and tumor factors. The median npRQ was 0.82. A significant negative correlation was found between the npRQ and the ALBI score (r = −0.35, p < 0.001). The median npRQ in modified ALBI (mALBI) grades 1, 2a, 2b, and 3 were 0.84, 0.86, 0.81, and 0.79, respectively (grade 2a vs. 2b, p = 0.002). Factors associated with npRQ <0.85, which is reported to be the best cutoff value for energy malnutrition, were analyzed. On multivariate analysis, the ALBI score (cutoff value, −2.18) was the only significant independent factor (odds ratio, 7.65; p < 0.001). The proportion of HCC patients with npRQ <0.85 significantly increased among patients with an ALBI score ≥−2.18 (45/51, 88.2%) compared with those with an ALBI score <−2.18 (29/58, 50%) (p < 0.001). The ALBI score might be a useful predictor for energy malnutrition in patients with HCC. In addition, most HCC patients with mALBI grade 2b or 3 can be considered to have energy malnutrition. [ABSTRACT FROM AUTHOR]

Background & Aims: Despite abundant clinical evidence, the mechanisms by which hepatic iron overload develops in patients with hepatitis C virus (HCV)-associated chronic liver disease remain unknown. The aim of this study was to investigate how hepatic iron overload develops in the presence of HCV proteins. Methods: Male transgenic mice expressing the HCV polyprotein and nontransgenic control mice (C57BL/6) were assessed for iron concentrations in the liver, spleen, and serum and iron regulatory molecules in vivo and ex vivo. Results: Transgenic mice had increased hepatic and serum iron concentrations, decreased splenic iron concentration, and lower hepcidin expression in the liver accompanied by higher expression of ferroportin in the duodenum, spleen, and liver. In response to hepatocellular iron excess, transferrin receptor 1 expression decreased and ferritin expression increased in the transgenic liver. Transgenic mice showed no inflammation in the liver but preserved the ability to induce hepcidin in response to proinflammatory cytokines induced by lipopolysaccharide. Hepcidin promoter activity and the DNA binding activity of CCAAT/enhancer-binding protein α (C/EBP) were down-regulated concomitant with increased expression of C/EBP homology protein, an inhibitor of C/EBP DNA binding activity, and with increased levels of reactive oxygen species in transgenic mice at the ages of 8 and 14 months. Conclusions: HCV-induced reactive oxygen species may down-regulate hepcidin transcription through inhibition of C/EBPα DNA binding activity by C/EBP homology protein, which in turn leads to increased duodenal iron transport and macrophage iron release, causing hepatic iron accumulation. [Copyright &y& Elsevier]

Alcohol has long been acknowledged to be one of the main causes of hepatic disorders. In recent years, with the advancements in antiviral therapies, the relative proportion that alcoholic liver disease contributes among liver diseases has increased, necessitating the establishment of a useful model for the elucidation of the mechanism of its development. In this study, we developed a model of alcoholic liver disease using medaka, a small-sized fish known for its usefulness as a model organism. After rearing medaka in water containing ethanol for 2 months, fat deposition was observed in their livers. In addition, on the basis of the metabolomic analysis of the liver to evaluate metabolic changes resulting from ethanol administration, the increases in ethanol metabolites and changes in lipid metabolism were assessed. As minimally invasive evaluation methods, transparent medaka enabled the macroscopic evaluation of the progression of alcoholic fatty liver, while ultrasonography enabled the quantification of the fatty deposition of the liver. Furthermore, intestinal microbiota, the composition of which is important for the development of alcoholic liver disease, was evaluated. Microbiota changes similar to those of humans with alcoholic liver disease were observed. This study demonstrates that the development of liver disease and its amelioration through drugs can be easily evaluated using the present model or modifications thereof. Thus, this study is expected to be useful in the elucidation of liver disease development. [ABSTRACT FROM AUTHOR]