Histological course of nonalcoholic fatty liver disease in Japanese patients: tight glycemic control, rather than weight reduction, ameliorates liver fibrosis

Erika Hamaguchi, Toshinari Takamura, Masaru Sakurai, Eishiro Mizukoshi, Yoh Zen, Yumie Takeshita, Seiichiro Kurita, Kuniaki Arai, Tatsuya Yamashita, Motoko Sasaki, Yasuni Nakanuma, Shuichi Kaneko, Erika Hamaguchi, Toshinari Takamura, Masaru Sakurai, Eishiro Mizukoshi, Yoh Zen, Yumie Takeshita, Seiichiro Kurita, Kuniaki Arai, Tatsuya Yamashita, Motoko Sasaki, Yasuni Nakanuma, Shuichi Kaneko

Abstract

Objective: The goal of this study was to examine whether metabolic abnormalities are responsible for the histological changes observed in Japanese patients with nonalcoholic fatty liver disease (NAFLD) who have undergone serial liver biopsies.

Research design and methods: In total, 39 patients had undergone consecutive liver biopsies. Changes in their clinical data were analyzed, and biopsy specimens were scored histologically for stage.

Results: The median follow-up time was 2.4 years (range 1.0-8.5). Liver fibrosis had improved in 12 patients (30.7%), progressed in 11 patients (28.2%), and remained unchanged in 16 patients (41%). In a Cox proportional hazard model, decrease in A1C and use of insulin were associated with improvement of liver fibrosis independent of age, sex, and BMI. However, DeltaA1C was more strongly associated with the improvement of liver fibrosis than use of insulin after adjustment for each other (chi(2); 7.97 vs. 4.58, respectively).

Conclusions: Tight glycemic control may prevent histological progression in Japanese patients with NAFLD.

References

    1. Duvnjak M, Lerotic I, Barsic N, Tomasic V, Virovic Jukic L, Velagic V. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J Gastroenterol 2007; 13: 4539– 4550
    1. Sakurai M, Takamura T, Ota T, Ando H, Akahori H, Kaji K, Sasaki M, Nakanuma Y, Miura K, Kaneko S. Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease. J Gastroenterol 2007; 42: 312– 317
    1. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94: 2467– 2474
    1. Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865– 873
    1. Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology 2004; 40: 820– 826
    1. Kita Y, Mizukoshi E, Takamura T, Sakurai M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S. Impact of diabetes mellitus on prognosis of patients infected with hepatitis C virus. Metabolism 2007; 56: 1682– 1688
    1. Ota T, Takamura T, Kurita S, Matsuzawa N, Kita Y, Uno M, Akahori H, Misu H, Sakurai M, Zen Y, Nakanuma Y, Kaneko S. Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology 2007; 132: 282– 293
    1. Matsuzawa N, Takamura T, Kurita S, Misu H, Ota T, Ando H, Yokoyama M, Honda M, Zen Y, Nakanuma Y, Miyamoto K, Kaneko S. Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology 2007; 46: 1392– 1403
    1. Uno M, Kurita S, Misu H, Ando H, Ota T, Matsuzawa-Nagata N, Kita Y, Nabemoto S, Akahori H, Zen Y, Nakanuma Y, Kaneko S, Takamura T. Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis. Hepatology 2008; 48: 109– 118
    1. Bergheim I, Guo L, Davis MA, Lambert JC, Beier JI, Duveau I, Luyendyk JP, Roth RA, Arteel GE. Metformin prevents alcohol-induced liver injury in the mouse: critical role of plasminogen activator inhibitor-1. Gastroenterology 2006; 130: 2099– 2112
    1. Sugimoto R, Enjoji M, Kohjima M, Tsuruta S, Fukushima M, Iwao M, Sonta T, Kotoh K, Inoguchi T, Nakamuta M. High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase. Liver Int 2005; 25: 1018– 1026
    1. Suzuki M, Akimoto K, Hattori Y. Glucose upregulates plasminogen activator inhibitor-1 gene expression in vascular smooth muscle cells. Life Sci 2002; 72: 59– 66
    1. Takamura T, Sakurai M, Ota T, Ando H, Honda M, Kaneko S. Genes for systemic vascular complications are differentially expressed in the livers of type 2 diabetic patients. Diabetologia 2004; 47: 638– 647
    1. Takeshita Y, Takamura T, Hamaguchi E, Shimizu A, Ota T, Sakurai M, Kaneko S. Tumor necrosis factor-alpha-induced production of plasminogen activator inhibitor 1 and its regulation by pioglitazone and cerivastatin in a nonmalignant human hepatocyte cell line. Metabolism 2006; 55: 1464– 1472

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit