Article

Steatosi associata al virus dell'epatite C e steatosi metabolica. Patologie diverse o sovrapposte?

ABSTRACT tensione e aterosclerosi sono strettamente associati sia alla semplice steatosi che alla NASH. L'infezione cronica da virus dell'epatite C (HCV) è la più frequente nel mondo ed è la principale causa di car-cinoma epatocellulare e di cirrosi in lista d'attesa per tra-pianto di fegato 7 . Diversamente da quanto osservato nell'infezione cronica da virus dell'epatite B e nelle epa-topatie autoimmuni, l'infezione da HCV si associa a stea-tosi epatica in una percentuale significativamente più ele-vata di casi 8-10 ed è in questi un importante cofattore di ma-lattia che promuove la progressione del danno epatico 11-13 . La steatosi osservata in corso di infezione da HCV è con-siderata un'entità nosografica autonoma 14,15 . Insulino-resistenza, alterato metabolismo lipidico, lipo-perossidazione, stress ossidativo e alterazioni mitocon-driali sono meccanismi patogenetici che inducono il dan-no epatico e la sua progressione, sia nella NAFLD, che nell'infezione da HCV 16-25 . Dal versante clinico la NAFLD e l'infezione da HCV presentano le seguenti analogie: as-sociazione a fenomeni autoimmuni 26 e manifestazioni extraepatiche 27-30 ; presenza di quadro istologico severo a U.O. di Medicina Interna e Gastroenterologia (Direttore: Dr. Enrico De Micheli), Ospedale Civile di Modena, *Medicina 3 (Direttore: Prof. Nicola Carulli), Dipartimento di Medicina e Specialità Mediche, Università degli Studi di Modena e Reggio Emilia **Divisione di Medicina Interna ed Epatologia (Direttore: Prof. Giuseppe Ruggiero), Seconda Università degli Studi di Napoli Cofinanziamento: MIUR anno 2002; protocollo 2002 062883001 e COFIN 2004 061213_001.

0 Bookmarks
 · 
59 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased levels of tumor necrosis factor (TNF)-alpha and oxidative stress have been implicated as factors contributing to hepatic injury in fatty liver diseases. As steatosis is associated with an accelerated progression of fibrosis in chronic hepatitis C (HCV), we hypothesized that the messenger (m)RNA expression of genes involved with the production of reactive oxygen species, inflammation and cellular injury would be increased in liver tissue from subjects with steatosis and chronic HCV. Real-time polymerase chain reaction was performed to determine relative mRNA expression levels of collagen I, TNF-alpha, cytochrome P450 2E1 (CYP 2E1), transforming growth factor-beta1 and CD14 in liver biopsies from 38 patients with chronic HCV. The mRNA expression levels were compared between subjects with and without steatosis, fibrosis, and inflammation. Multivariate analysis demonstrated that collagen I mRNA expression was increased by 199% in steatosis (P = 0.02), 85% in moderate to severe fibrosis (P = 0.02) and 157% in inflammation (P = 0.03). Livers of patients with steatosis also had an increase in TNF-alpha mRNA expression by 50% (P = 0.03) and CYP 2E1 expression by 37% (P = 0.04) compared with non-steatotic livers. Tumor necrosis factor-alpha protein was localized to Kupffer cells, bile ducts and portal inflammatory cells by immunohistochemistry. Increased expression of TNF-alpha may be involved in the pathogenesis of liver injury and progression of fibrosis in individuals who have steatosis in association with chronic HCV.
    Journal of Gastroenterology and Hepatology 05/2003; 18(4):386-92. · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have generated a transgenic mouse with no white fat tissue throughout life. These mice express a dominant-negative protein, termed A-ZIP/F, under the control of the adipose-specific aP2 enhancer/promoter. This protein prevents the DNA binding of B-ZIP transcription factors of both the C/EBP and Jun families. The transgenic mice (named A-ZIP/F-1) have no white adipose tissue and dramatically reduced amounts of brown adipose tissue, which is inactive. They are initially growth delayed, but by week 12, surpass their littermates in weight. The mice eat, drink, and urinate copiously, have decreased fecundity, premature death, and frequently die after anesthesia. The physiological consequences of having no white fat tissue are profound. The liver is engorged with lipid, and the internal organs are enlarged. The mice are diabetic, with reduced leptin (20-fold) and elevated serum glucose (3-fold), insulin (50- to 400-fold), free fatty acids (2-fold), and triglycerides (3- to 5-fold). The A-ZIP/F-1 phenotype suggests a mouse model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome), indicating that the lack of fat can cause diabetes. The myriad of consequences of having no fat throughout development can be addressed with this model.
    Genes & Development 11/1998; 12(20):3168-81. · 12.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: GASTROENTEROLOGY 1999;117:1241-1244
    Gastroenterology 12/1999; 117(5):1241-4. · 12.82 Impact Factor

Full-text (2 Sources)

View
9 Downloads
Available from
May 20, 2014