nach oben

Erschienen in:

01.11.2014 | Original Article—Liver, Pancreas, and Biliary Tract

Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients

verfasst von: Takashi Nakahara, Hideyuki Hyogo, Masato Yoneda, Yoshio Sumida, Yuichiro Eguchi, Hideki Fujii, Masafumi Ono, Takumi Kawaguchi, Kento Imajo, Hiroshi Aikata, Saiyu Tanaka, Kazuyuki Kanemasa, Kazuma Fujimoto, Keizo Anzai, Toshiji Saibara, Michio Sata, Atushi Nakajima, Yoshito Itoh, Kazuaki Chayama, Takeshi Okanoue, Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)

Erschienen in: Journal of Gastroenterology | Ausgabe 11/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

The prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome have been increasing worldwide. The associations between metabolic factors and the histologic severity of NAFLD have not yet been clarified. Therefore, we studied the relationships between relevant metabolic factors and the histological severity of NAFLD.

Methods

In a cross-sectional multicenter study conducted in Japan, we examined 1,365 biopsy-proven NAFLD patients. The frequencies of underlying lifestyle-related diseases and their relationships to the NAFLD histology were investigated.

Results

The hepatic fibrosis stages (Stage 0/1/2/3/4) were 22.6/34.1/26.7/14.5/2.1 (%) in the male patients, and 16.2/31.7/23.9/21.6/6.6 (%) in the female patients. Dyslipidemia was present in 65.7 % (hypertriglyceridemia, 45.3 %; increased low-density lipoprotein cholesterol, 37.5 %; decreased high density lipoprotein cholesterol, 19.5 %) of patients. Hypertension was present in 30.2 %, and diabetes mellitus (DM) in 47.3 %. The fibrosis stage increased with age, especially in postmenopausal females. The body mass index was positively correlated with the fibrosis stage. Deterioration of glucose control was positively correlated with the fibrosis stage, this correlation being more prominent in females. Multivariate analysis identified age and DM as significant risk factors for advanced fibrosis. No significant correlation of the fibrosis stage was observed with hypertension. There was a negative correlation between the serum triglyceride levels and the fibrosis stage.

Conclusions

DM appeared to be a significant risk factor for advanced fibrosis in patients with NAFLD, and would therefore need to be properly managed to prevent the progression of NAFLD.

Nur mit Berechtigung zugänglich

Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Int Med. 2005;143:722–8.PubMedCrossRef

Kojima S, Watanabe N, Numata M, Ogawa T, Matsuzaki S. Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J Gastroenterol. 2003;38:954–61.PubMedCrossRef

Amarapurkar DN, Hashimoto E, Lesmana LA, Sollano JD, Chen PJ, Goh KL, Asia-Pacific Working Party on NAFLD. How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J Gastroenterol Hepatol. 2007;22:788–93.PubMedCrossRef

Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology. 1995;22:1714–9.PubMedCrossRef

Tokushige K, Hashimoto E, Horie Y, Taniai M, Higuchi S. Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey. J Gastroenterol. 2011;46:1230–7.PubMedCrossRef

Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–9.PubMedCrossRef

James O, Day C. Non-alcoholic steatohepatitis: another disease of affluence. Lancet. 1999;353:1634–6.PubMedCrossRef

Ono M, Saibara T. Clinical features of nonalcoholic steatohepatitis in Japan: evidence from the literature. J Gastroenterol. 2006;41:725–32.PubMedCrossRef

Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50:1844–50.PubMedCrossRef

10.

Hui JM, Farrell GC. Clear messages from sonographic shadows? Links between metabolic disorders and liver disease, and what to do about them. J Gastroenterol Hepatol. 2003;18:1115–7.PubMedCrossRef

11.

Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–23.PubMedCrossRef

12.

Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.PubMedCrossRef

13.

Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43:S99–112.PubMedCrossRef

14.

Angulo P. Obesity and nonalcoholic fatty liver disease. Nutr Rev. 2007;65:S57–63.PubMedCrossRef

15.

Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology. 2010;52:913–24.PubMedCentralPubMedCrossRef

16.

Larter CZ, Chitturi S, Heydet D, Farrell GC. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol. 2010;25:672–90.PubMedCrossRef

17.

Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology. 2008;48:792–8.PubMedCrossRef

18.

Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009;7:234–8.PubMedCrossRef

19.

Hossain N, Afendy A, Stepanova M, Nader F, Srishord M, Rafiq N, et al. Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1224–9.PubMedCrossRef

20.

Yoneda M, Fujii H, Sumida Y, Hyogo H, Itoh Y, Ono M, et al. Platelet count for predicting fibrosis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46:1300–6.PubMedCrossRef

21.

Sumida Y, Yoneda M, Hyogo H, Yamaguchi K, Ono M, Fujii H, et al. A simple clinical scoring system using ferritin, fasting insulin and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46:257–68.PubMedCrossRef

22.

The World Medical Association, Inc. Declaration of Helsinki; Ethical principle for medical research involving human subject. Seoul: WMA General Assembly; 2008.

23.

Iwamoto K, Kanno K, Hyogo H, Yamagishi S, Takeuchi M, Tazuma S, et al. Advanced glycation end products enhance the proliferation and activation of hepatic stellate cells. J Gastroenterol. 2008;43:298–304.PubMedCrossRef

24.

Hyogo H, Tazuma S, Arihiro K, Iwamoto K, Nabeshima Y, Inoue M, et al. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism. 2008;57:1711–8.PubMedCrossRef

25.

Matsuzawa U, Inoue S, Ikeda Y, Sakata T, Saito Y, Sato Y, Japanese Society for the Study of Obesity, et al. New criteria of obesity (in Japanese). J Jpn Soc Study Obes. 2000;6:18–28.

26.

Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F, et al. Noninvasive in vivo quantitative assessment of fat content in human liver. Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol. 1997;27:108–13.PubMedCrossRef

27.

World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. Geneva: World Health Organization; 2006.

28.

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.PubMedCrossRef

29.

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;94:2467–74.PubMedCrossRef

30.

Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.PubMedCrossRef

31.

Paul Angulo. Nonalcoholic fatty liver disease. N Engl J Med. 2002;18:1221–31.

32.

Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–8.PubMed

33.

Liou I, Kowdley KV. Natural history of nonalcoholic steatohepatitis. J Clin Gastroenterol. 2006;40(Suppl 1):S11–6.PubMed

34.

Abdelmalek MF, Diehl AM. Nonalcoholic fatty liver disease as a complication of insulin resistance. Med Clin North Am. 2007;91:1125–49.PubMedCrossRef

35.

Kamada Y, Kiso S, Yoshida Y, Chatani N, Kizu T, Hamano M, et al. Estrogen deficiency worsens steatohepatitis in mice fed high-fat and high-cholesterol diet. Am J Physiol Gastrointest Liver Physiol. 2011;301:1031–43.CrossRef

36.

Zhu L, Brown WC, Cai Q, Krust A, Chambon P, McGuinness OP, et al. Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance. Diabetes. 2013;62:424–34.PubMedCentralPubMedCrossRef

37.

Eguchi Y, Hyogo H, Ono M, Mizuta T, Ono N, Fujimoto K, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol. 2012;47:586–95.PubMedCrossRef

38.

Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57:1441–7.PubMedCrossRef

39.

Donati G, Stagni B, Piscaglia F, Venturoli N, Morselli-Labate AM, Rasciti L, et al. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut. 2004;53:1020–3.PubMedCentralPubMedCrossRef

40.

Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodés J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–7.PubMedCrossRef

41.

Vallance P, Moncada S. Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet. 1991;337:776–8.PubMedCrossRef

42.

Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology. 2001;34:738–44.PubMedCrossRef

43.

Megyesi C, Samols E, Marks V. Glucose tolerance and diabetes in chronic liver disease. Lancet. 1967;18:1051–6.CrossRef

44.

Petrides AS, DeFronzo RA. Glucose and insulin metabolism in cirrhosis. J Hepatol. 1989;8:107–14.PubMedCrossRef

45.

Arase Y, Kobayashi M, Suzuki F, Suzuki Y, Kawamura Y, Akuta N, et al. Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C. Hepatology. 2013;57:964–73.PubMedCrossRef

Titel: Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients
verfasst von: Takashi Nakahara
Hideyuki Hyogo
Masato Yoneda
Yoshio Sumida
Yuichiro Eguchi
Hideki Fujii
Masafumi Ono
Takumi Kawaguchi
Kento Imajo
Hiroshi Aikata
Saiyu Tanaka
Kazuyuki Kanemasa
Kazuma Fujimoto
Keizo Anzai
Toshiji Saibara
Michio Sata
Atushi Nakajima
Yoshito Itoh
Kazuaki Chayama
Takeshi Okanoue
Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)
Publikationsdatum: 01.11.2014
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 11/2014
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-013-0911-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2014

The opposite prognostic significance of nuclear and cytoplasmic p21 expression in resectable gastric cancer patients

How much management is necessary? Sustaining the benefit of achieving a sustained virologic response to hepatitis C

Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients

Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study

Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes