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1.
Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD.
Scavo, MP, Depalo, N, Rizzi, F, Carrieri, L, Serino, G, Franco, I, Bonfiglio, C, Pesole, PL, Cozzolongo, R, Gianuzzi, V, et al
Nutrients. 2022;(6)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.
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2.
Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study.
Mirizzi, A, Franco, I, Leone, CM, Bonfiglio, C, Cozzolongo, R, Notarnicola, M, Giannuzzi, V, Tutino, V, De Nunzio, V, Bruno, I, et al
Nutrients. 2019;11(11)
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Plain language summary
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic (liver) fat accumulation. Lifestyle interventions are the only known effective treatment for NAFLD. The aim of this study was to estimate associations between the consumption of some food group components with the grade of severity in NAFLD subjects. The study is a cross-sectional nutritional randomised clinical trial, which enrolled 136 subjects (79 males) with moderate or severe NAFLD. Results showed that some food group components were associated with a lower or a higher risk of developing severe NAFLD, and that, within the same food group, some components with a protective or promoter action are present. Authors conclude that their findings could help to elaborate personalised dietary counselling to treat NAFLD.
Abstract
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±10.18) with a mean BMI of 33.41 (±4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95-0.99); chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34-0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74-0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01-1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01-1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01-1.21), fats (O.R. 1.12, 95% C.I. 1.01-1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.
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Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study.
Vitale, A, Farinati, F, Noaro, G, Burra, P, Pawlik, TM, Bucci, L, Giannini, EG, Faggiano, C, Ciccarese, F, Rapaccini, GL, et al
Hepatology (Baltimore, Md.). 2018;(4):1232-1244
Abstract
UNLABELLED Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). CONCLUSION Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.
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4.
Aerobic Physical Activity and a Low Glycemic Diet Reduce the AA/EPA Ratio in Red Blood Cell Membranes of Patients with NAFLD.
Tutino, V, De Nunzio, V, Caruso, MG, Bonfiglio, C, Franco, I, Mirizzi, A, De Leonardis, G, Cozzolongo, R, Giannuzzi, V, Giannelli, G, et al
Nutrients. 2018;(9)
Abstract
Omega-6 Polyunsaturated Fatty Acids (PUFAs), through the eicosanoids derived from arachidonic acid (AA), are able to modulate the inflammatory processes, whereas omega-3 PUFAs, such as eicosapentaenoic acid (EPA), exert anti-oxidant and anti-inflammatory effects. An unbalanced AA/EPA ratio in favor of AA leads to the development of different metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the effects of different diets, alone and in combination with two physical activity programs, on the AA/EPA ratio value in erythrocyte membranes of patients with NAFLD. One hundred forty-two subjects with NAFLD were enrolled in the study and randomized into six treatment groups. AA/EPA ratio was significantly reduced after 90 days of treatment with only a program of aerobic activity. However, it appears that the combination of physical activity and a Low Glycemic Index Mediterranean Diet (LGIMD) was more efficacious in reducing AA/EPA levels, at 45 days of treatment, even if this effect was not maintained over time. The combined effect of diet and physical activity reduced the AA/EPA ratio value improving the score of steatosis. Dietary intake of omega-3 PUFAs, in association with a healthy lifestyle, may be used in the prevention protocols for many chronic diseases, including NAFLD.
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Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection.
Caradonna, L, Mastronardi, ML, Magrone, T, Cozzolongo, R, Cuppone, R, Manghisi, OG, Caccavo, D, Pellegrino, NM, Amoroso, A, Jirillo, E, et al
Current pharmaceutical design. 2002;(11):995-1005
Abstract
Endotoxins or lipopolysaccharides (LPS), major components of the cell wall of Gram-negative bacteria, once released from the bacterial outer membrane bind to specific receptors and, in particular, to a membrane-bound receptor, the CD14 (mCD14) and the toll-like receptor 4 present on monocytes/ macrophages. In turn, LPS-activated monocytes/ macrophages release in the host tissue an array of so-called proinflammatory cytokines and, among them, Tumor Necrosis Factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-12 are the major mediators. Before therapy (To) and at the end of 6-month interferon (IFN)-alpha/Ribavirin (RIB) treatment (T6), circulating endotoxin levels were measured in responder and non responder HCV+ patients. At T0, 57% of the non responders were endotoxin-positive and had, on average, 54 pg/ml of plasma LPS while in 50% of the responder patients endotoxin were found with an average of 29 pg/ml. At T6, in responders LPS were no longer detectable, while in 42% of the non responders LPS were found (average levels 45 pg/ml). In terms of serum cytokine concentration, at T6 IFN-gamma levels when compared to those detected at T0 were increased in both endotoxin-positive and endotoxin-negative patients. However, at T6 IL-10 concentration was significantly increased only in the group of endotoxin-negative subjects (responder patients), in comparison to T0 values. The origin of endotoxemia in HCV+ patients seems to be multifactorial, likely depending on impaired phagocytic functions and reduced T-cell mediated antibacterial activity. In these patients, however, one cannot exclude the passage of LPS from the gut flora to the blood stream, owing a condition of altered intestinal permeability. At the same time, a less efficient detoxification of enteric bacterial antigens at the hepatic level should be taken into consideration. Finally, novel therapeutic attempts aimed to neutralize LPS in the host are discussed.
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6.
The treatment of chronic hepatitis C not responding to interferon.
Cozzolongo, R, Cuppone, R, Manghisi, OG
Current pharmaceutical design. 2002;(11):967-75
Abstract
Approximately 60% of all patients with chronic hepatitis C (C-HCV) treated with standard interferon (IFN) treatment, i.e. combination of recombinant alpha IFN and ribavirin (RBV), are refractory to treatment. Many factors should be responsible for HCV persistence after antiviral treatment. Beside the well-known importance of some factors such as viral heterogeneity, co-infections with Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV), presence or absence of fibrosis, age, sex, iron overload, a greater attention is being paid to the study of viral kinetics. Observing the trend of the slope of viral decline, already after a few hours antiviral administration, it is possible to predict the sustained virologic response and therefore to optimize therapy. As for alternative therapeutics, re-treatment with IFN alone was excluded considering the very disappointing results, whereas it seemed that the combination IFN plus RBV could recover up to 30% of the patients. Later both randomized trials and two metanalyses have demonstrated that this option is disadvantageous from the cost-effectiveness point of view since 14 patients need to be treated to obtain one responsive. The treatment combining IFN plus RBV and amantadine seems more promising. Recently trials with pegylated IFN have started with the aim to increase the therapeutical response in this category of HCV-positive patients.