Enhanced serum concentrations of transforming growth factor-beta1 in simple fatty liver: is it really benign?
Tóm tắt
Inside the spectrum of non-alcoholic fatty liver disease, simple fatty liver is generally thought of as being "non progressive", differently from non-alcoholic steatohepatitis, which increases in severity due to the presence of apoptosis/inflammation and fibrosis. The "benignity" of fatty liver is widely accepted but conceptually difficult to maintain because the mechanisms underlying this entity are the same ones that determine the more severe form. Findings provide evidence that iron overload is associated with increased liver damage and collagen deposition. Transforming growth factor-beta1 released by hepatic stellate cells during chronic liver injury plays a critical role in liver apoptosis and fibrogenesis. To verify whether both the forms of non-alcoholic fatty liver disease were really dissimilar, evaluating the serum profile of two key parameters, indexes of severity. A total of 123 patients (57 females) participated, forming three groups: forty five patients with fatty liver, 42 patients with non-alcoholic steatohepatitis and 36 with chronic hepatitis C. All had a biopsy-proven diagnosis. Serum concentrations of transforming growth factor-beta1 and ferritin. High concentrations of transforming growth factor-beta1 were noticed in patients suffering from both fatty liver and non-alcoholic steatohepatitis, 129.1 (45.4) versus 116.8 (42.2) ng/mL, P = 0.2; they were significantly superior to those of chronic hepatitis C patients 87.5 (39.5) ng/mL, P < 0.001. Ferritin levels were on average above normal values and similar in the three groups (P = 0.9), also when adjusted for gender (P = 0.5) and age (P = 0.3). No difference between serum concentrations of transforming growth factor-beta1 and ferritin in fatty liver and non-alcoholic steatohepatitis suggests that these forms share more common aspects, regarding their progression, than previously thought.
Tài liệu tham khảo
de Oliveira CP, de Mello ES, Alves VA, Saviero SM, Strauss E: Changes in histological criteria lead to different prevalences of nonalcoholic steatohepatitis in severe obesity. Ann Hepatol. 2007, 6: 255-61.
Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P: The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005, 129: 113-21. 10.1053/j.gastro.2005.04.014.
George J, Pera N, Phung N, Leclercq I, Yun Hou J, Farrell G: Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis. J Hepatol. 2003, 39: 756-64. 10.1016/S0168-8278(03)00376-3.
Qamar A, Sheikh SZ, Masud A, Jhandier MN, Inayat IB, Hakim W, Mehal WZ: In vitro and in vivo protection of stellate cells from apoptosis by leptin. Dig Dis Sci. 2006, 51: 1697-705. 10.1007/s10620-006-9244-8.
Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, Oren R: NAFLD and hyperinsulinemia are major determinants of serum ferritin levels. J Hepatol. 2007, 46: 700-7. 10.1016/j.jhep.2006.09.018.
Imeryuz N, Tahan V, Sonsuz A, Eren F, Uraz S, Yuksel M, Akpulat S, Ozcelik D, Haklar G, Celikel C, Avsar E, Tozun N: Iron preloading aggravates nutritional steatohepatitis in rats by increasing apoptotic cell death. J Hepatol. 2007, 47: 851-9. 10.1016/j.jhep.2007.06.018.
Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ: Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003, 125: 437-443. 10.1016/S0016-5085(03)00907-7.
Tsukada S, Westwick JK, Ikejima K, Sato N, Rippe RA: Smad and p38 MAPK signaling pathways independently regulate α1(I) collagen gene expression in unstimulated and TGF-β stimulated hepatic stellate cells. J Biol Chem. 2005, 280: 10055-64. 10.1074/jbc.M409381200.
Kanzler S, Baumann M, Schirmacher P, Dries V, Bayer E, Gerken G, Dienes HP, Lohse AW: Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. J Viral Hepat. 2001, 8: 430-7. 10.1046/j.1365-2893.2001.00314.x.
Sumida Y, Kanemasa K, Fukumoto K, Yoshida N, Sakai K: Hepatic iron accumulation may be associated with insulin resistance in patients with chronic hepatitis C. Hepatol Res. 2007, 37: 932-40. 10.1111/j.1872-034X.2007.00152.x.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28: 412-9. 10.1007/BF00280883.
Forsberg L, Halldin J, Ekman S, Rönnberg S: Screening of binge drinking among patients on an emergency surgical ward. Alcohol. 2002, 27: 77-82. 10.1016/S0741-8329(02)00202-1.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ, Nonalcoholic Steatohepatitis Clinical Research Network: Nonalcoholic Steatohepatitis Clinical Research Network Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005, 41: 1313-21. 10.1002/hep.20701.
Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN: Histological grading and staging of chronic hepatitis. J Hepatol. 1995, 22: 696-9. 10.1016/0168-8278(95)80226-6.
Yoneda M, Mawatari H, Fujita K, Iida H, Yonemitsu K, Kato S, Takahashi H, Kirikoshi H, Inamori M, Nozaki Y, Abe Y, Kubota K, Saito S, Iwasaki T, Terauchi Y, Togo S, Maeyama S, Nakajima A: High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol. 2007, 42: 573-82. 10.1007/s00535-007-2060-x.
Khan R, Sheppard R: Fibrosis in heart disease: understanding the role of transforming growth factor-beta1 in cardiomyopathy, valvular disease and arrhythmia. Immunology. 2006, 118: 10-24. 10.1111/j.1365-2567.2006.02336.x.
Martinelli AL, Ramalho LN, Zucoloto S: Hepatic stellate cells in hepatitis C patients: relationship with liver iron deposits and severity of liver disease. J Gastroenterol Hepatol. 2004, 19: 91-8. 10.1111/j.1440-1746.2004.03255.x.
Ribeiro PS, Cortez-Pinto H, Solá S, Castro RE, Ramalho RM, Baptista A, Moura MC, Camilo ME, Rodrigues CM: Hepatocyte apoptosis, expression of death receptors, and activation of NF-kappaB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am J Gastroenterol. 2004, 99: 1708-17. 10.1111/j.1572-0241.2004.40009.x.
Langer DA, Das A, Semela D, Kang-Decker N, Hendrickson H, Bronk SF, Katusic ZS, Gores GJ, Shah VH: Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species. Hepatology. 2008, 47: 1983-93. 10.1002/hep.22285.
Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A: Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001, 15: 1667-72. 10.1046/j.1365-2036.2001.01083.x.
Kunde SS, Lazenby AJ, Clements RH, Abrams GA: Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology. 2005, 42: 650-6. 10.1002/hep.20818.
Gawrieh S, Papouchado BG, Burgart LJ, Kobayashi S, Charlton MR, Gores GJ: Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation. Liver Transpl. 2005, 11: 1207-13. 10.1002/lt.20455.
Palekar NA, Naus R, Larson SP, Ward J, Harrison SA: Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease. Liver Int. 2006, 26: 151-6. 10.1111/j.1478-3231.2005.01209.x.