Skip to main content
Erschienen in: Journal of Gastroenterology 1/2019

13.07.2018 | Original Article—Liver, Pancreas, and Biliary Tract

Hepatocellular carcinoma as a leading cause of cancer-related deaths in Japanese type 2 diabetes mellitus patients

verfasst von: Toshihide Shima, Hirofumi Uto, Kohjiro Ueki, Yutaka Kohgo, Kohichiroh Yasui, Naoto Nakamura, Tatsuaki Nakatou, Toshinari Takamura, Sumio Kawata, Kazuo Notsumata, Kyoko Sakai, Ryosuke Tateishi, Takeshi Okanoue

Erschienen in: Journal of Gastroenterology | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (JG 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013.

Methods

This was a longitudinal, multicenter cohort study. Of the 5642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-specific mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP.

Results

All-cancer mortality was significantly higher in T2D patients than in the GP [SMR 1.58, 95% confidence interval (CI) 1.33–1.87]. Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 2.41–5.10). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.64–3.97) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 103/μl, SMR of HCC increased from 3.57 to 6.58 (95% CI 4.34–9.58). T2D patients with platelet count > 200 × 103/μl showed no increase in mortality risk (SMR 0.68) of HCC.

Conclusions

HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 103/μl for early detection of HCC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Hotta N, Nakamura J, Iwamoto Y, et al. Causes of death in Japanese diabetics: a questionnaire survey of 18,385 diabetics over a 10-year period. J Diabetes Investig. 2010;1:66–76.CrossRefPubMedPubMedCentral Hotta N, Nakamura J, Iwamoto Y, et al. Causes of death in Japanese diabetics: a questionnaire survey of 18,385 diabetics over a 10-year period. J Diabetes Investig. 2010;1:66–76.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Nakamura J, Kamiya H, Haneda M, et al. Causes of death in Japanese patients with diabetes based on the results of a survey of 45,708 cases during 2001–2010: report of Committee on Causes of Death in Diabetes Mellitus. Diabetol Int. 2017;8:117–36.CrossRefPubMedPubMedCentral Nakamura J, Kamiya H, Haneda M, et al. Causes of death in Japanese patients with diabetes based on the results of a survey of 45,708 cases during 2001–2010: report of Committee on Causes of Death in Diabetes Mellitus. Diabetol Int. 2017;8:117–36.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Tateishi R, Okanoue T, Fujiwara N, et al. Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol. 2015;50:350–60.CrossRefPubMed Tateishi R, Okanoue T, Fujiwara N, et al. Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol. 2015;50:350–60.CrossRefPubMed
6.
Zurück zum Zitat Shima T, Uto H, Ueki K, et al. Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus. J Gastroenterol. 2012;48:515–25.CrossRefPubMed Shima T, Uto H, Ueki K, et al. Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus. J Gastroenterol. 2012;48:515–25.CrossRefPubMed
7.
Zurück zum Zitat Diabetes C, Complications Trial/Epidemiology of Diabetes I, Complications Study Research G. Mortality in type 1 diabetes in the DCCT/EDIC versus the general population. Diabetes Care. 2016;39:1378–83. Diabetes C, Complications Trial/Epidemiology of Diabetes I, Complications Study Research G. Mortality in type 1 diabetes in the DCCT/EDIC versus the general population. Diabetes Care. 2016;39:1378–83.
9.
Zurück zum Zitat Breslow NE, Day NE. Statistical methods in cancer research. Volume II—the design and analysis of cohort studies. IARC Scientific Publications No. 82. Oxford: Oxford University Press; 1987. Breslow NE, Day NE. Statistical methods in cancer research. Volume II—the design and analysis of cohort studies. IARC Scientific Publications No. 82. Oxford: Oxford University Press; 1987.
10.
Zurück zum Zitat Yoneda M, Fujii H, Sumida Y, et al. Platelet count for predicting fibrosis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46:1300–6.CrossRefPubMed Yoneda M, Fujii H, Sumida Y, et al. Platelet count for predicting fibrosis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46:1300–6.CrossRefPubMed
11.
Zurück zum Zitat Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.CrossRefPubMedPubMedCentral Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Peleg AY, Weerarathna T, McCarthy JS, et al. Common infections in diabetes: pathogenesis, management and relationship to glycaemic control. Diabetes Metab Res Rev. 2007;23:3–13.CrossRefPubMed Peleg AY, Weerarathna T, McCarthy JS, et al. Common infections in diabetes: pathogenesis, management and relationship to glycaemic control. Diabetes Metab Res Rev. 2007;23:3–13.CrossRefPubMed
13.
Zurück zum Zitat Noto H, Osame K, Sasazuki T, et al. Substantially increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis of epidemiologic evidence in Japan. J Diabetes Complications. 2010;24:345–53.CrossRefPubMed Noto H, Osame K, Sasazuki T, et al. Substantially increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis of epidemiologic evidence in Japan. J Diabetes Complications. 2010;24:345–53.CrossRefPubMed
14.
Zurück zum Zitat Noto H, Tsujimoto T, Sasazuki T, et al. Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr Pract. 2011;17:616–28.CrossRefPubMed Noto H, Tsujimoto T, Sasazuki T, et al. Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr Pract. 2011;17:616–28.CrossRefPubMed
15.
Zurück zum Zitat Sasazuki S, Charvat H, Hara A, et al. Diabetes mellitus and cancer risk: pooled analysis of eight cohort studies in Japan. Cancer Sci. 2013;104:1499–507.CrossRefPubMedPubMedCentral Sasazuki S, Charvat H, Hara A, et al. Diabetes mellitus and cancer risk: pooled analysis of eight cohort studies in Japan. Cancer Sci. 2013;104:1499–507.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Inoue M, Iwasaki M, Otani T, et al. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med. 2006;166:1871–7.CrossRefPubMed Inoue M, Iwasaki M, Otani T, et al. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med. 2006;166:1871–7.CrossRefPubMed
17.
Zurück zum Zitat Tanaka K, Tsuji I, Tamakoshi A, et al. Diabetes mellitus and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2014;44:986–99.CrossRefPubMed Tanaka K, Tsuji I, Tamakoshi A, et al. Diabetes mellitus and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2014;44:986–99.CrossRefPubMed
18.
Zurück zum Zitat Kasuga M, Ueki K, Tajima N, et al. Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer. Cancer Sci. 2013;104:965–76.CrossRefPubMedPubMedCentral Kasuga M, Ueki K, Tajima N, et al. Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer. Cancer Sci. 2013;104:965–76.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Wang C, Wang X, Gong G, et al. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer. 2012;130:1639–48.CrossRefPubMed Wang C, Wang X, Gong G, et al. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer. 2012;130:1639–48.CrossRefPubMed
20.
Zurück zum Zitat Chen Y, Wu F, Saito E, et al. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia. 2017;60:1022–32.CrossRefPubMedPubMedCentral Chen Y, Wu F, Saito E, et al. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia. 2017;60:1022–32.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Kato M, Noda M, Mizoue T, et al. Diagnosed diabetes and premature death among middle-aged Japanese: results from a large-scale population-based cohort study in Japan (JPHC study). BMJ Open. 2015;5:e007736.CrossRefPubMedPubMedCentral Kato M, Noda M, Mizoue T, et al. Diagnosed diabetes and premature death among middle-aged Japanese: results from a large-scale population-based cohort study in Japan (JPHC study). BMJ Open. 2015;5:e007736.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Sasaki A, Horiuchi N, Hasegawa K, et al. Causes of death in Japanese diabetics. A 20-year study of death certificates. J Chronic Dis. 1985;38:655–61.CrossRefPubMed Sasaki A, Horiuchi N, Hasegawa K, et al. Causes of death in Japanese diabetics. A 20-year study of death certificates. J Chronic Dis. 1985;38:655–61.CrossRefPubMed
23.
Zurück zum Zitat Koh WP, Wang R, Jin A, et al. Diabetes mellitus and risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study. Br J Cancer. 2013;108:1182–8.CrossRefPubMedPubMedCentral Koh WP, Wang R, Jin A, et al. Diabetes mellitus and risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study. Br J Cancer. 2013;108:1182–8.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Loomba R, Abraham M, Unalp A, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology. 2012;56:943–51.CrossRefPubMed Loomba R, Abraham M, Unalp A, et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology. 2012;56:943–51.CrossRefPubMed
25.
Zurück zum Zitat Porepa L, Ray JG, Sanchez-Romeu P, et al. Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ. 2010;182:E526–31.CrossRefPubMedPubMedCentral Porepa L, Ray JG, Sanchez-Romeu P, et al. Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ. 2010;182:E526–31.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Nakahara T, Hyogo H, Yoneda M, et al. 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. J Gastroenterol. 2014;49:1477–84.CrossRefPubMed Nakahara T, Hyogo H, Yoneda M, et al. 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. J Gastroenterol. 2014;49:1477–84.CrossRefPubMed
27.
Zurück zum Zitat White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(1342–59):e2. White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(1342–59):e2.
28.
Zurück zum Zitat Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–21.CrossRefPubMed Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–21.CrossRefPubMed
29.
Zurück zum Zitat Chen J, Han Y, Xu C, et al. Effect of type 2 diabetes mellitus on the risk for hepatocellular carcinoma in chronic liver diseases: a meta-analysis of cohort studies. Eur J Cancer Prev. 2015;24:89–99.CrossRefPubMed Chen J, Han Y, Xu C, et al. Effect of type 2 diabetes mellitus on the risk for hepatocellular carcinoma in chronic liver diseases: a meta-analysis of cohort studies. Eur J Cancer Prev. 2015;24:89–99.CrossRefPubMed
30.
Zurück zum Zitat Yoshimura K, Okanoue T, Ebise H, et al. Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining. Hepatology. 2016;63:462–73.CrossRefPubMed Yoshimura K, Okanoue T, Ebise H, et al. Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining. Hepatology. 2016;63:462–73.CrossRefPubMed
31.
Zurück zum Zitat Okanoue T, Ebise H, Kai T, et al. A simple scoring system using type IV collagen 7S and aspartate aminotransferase for diagnosing nonalcoholic steatohepatitis and related fibrosis. J Gastroenterol. 2018;53:129–39.CrossRefPubMed Okanoue T, Ebise H, Kai T, et al. A simple scoring system using type IV collagen 7S and aspartate aminotransferase for diagnosing nonalcoholic steatohepatitis and related fibrosis. J Gastroenterol. 2018;53:129–39.CrossRefPubMed
32.
Zurück zum Zitat Kawamura Y, Arase Y, Ikeda K, et al. Large-scale long-term follow-up study of Japanese patients with non-alcoholic fatty liver disease for the onset of hepatocellular carcinoma. Am J Gastroenterol. 2012;107:253–61.CrossRefPubMed Kawamura Y, Arase Y, Ikeda K, et al. Large-scale long-term follow-up study of Japanese patients with non-alcoholic fatty liver disease for the onset of hepatocellular carcinoma. Am J Gastroenterol. 2012;107:253–61.CrossRefPubMed
34.
Zurück zum Zitat Onitilo AA, Engel JM, Glurich I, et al. Diabetes and cancer II: role of diabetes medications and influence of shared risk factors. Cancer Causes Control. 2012;23:991–1008.CrossRefPubMedPubMedCentral Onitilo AA, Engel JM, Glurich I, et al. Diabetes and cancer II: role of diabetes medications and influence of shared risk factors. Cancer Causes Control. 2012;23:991–1008.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Walker JJ, Johnson JA, Wild SH. Diabetes treatments and cancer risk: the importance of considering aspects of drug exposure. Lancet Diabetes Endocrinol. 2013;1:132–9.CrossRefPubMed Walker JJ, Johnson JA, Wild SH. Diabetes treatments and cancer risk: the importance of considering aspects of drug exposure. Lancet Diabetes Endocrinol. 2013;1:132–9.CrossRefPubMed
36.
Zurück zum Zitat Kawaguchi T, Kohjima M, Ichikawa T, et al. The morbidity and associated risk factors of cancer in chronic liver disease patients with diabetes mellitus: a multicenter field survey. J Gastroenterol. 2015;50:333–41.CrossRefPubMed Kawaguchi T, Kohjima M, Ichikawa T, et al. The morbidity and associated risk factors of cancer in chronic liver disease patients with diabetes mellitus: a multicenter field survey. J Gastroenterol. 2015;50:333–41.CrossRefPubMed
37.
Zurück zum Zitat Johnson JA, Bowker SL. Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia. 2011;54:25–31.CrossRefPubMed Johnson JA, Bowker SL. Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia. 2011;54:25–31.CrossRefPubMed
38.
Zurück zum Zitat Goto A, Noto H, Noda M, et al. Report of the Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on Diabetes and Cancer, second report. Diabetol Int. 2016;7:12–5.CrossRefPubMedPubMedCentral Goto A, Noto H, Noda M, et al. Report of the Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on Diabetes and Cancer, second report. Diabetol Int. 2016;7:12–5.CrossRefPubMedPubMedCentral
Metadaten
Titel
Hepatocellular carcinoma as a leading cause of cancer-related deaths in Japanese type 2 diabetes mellitus patients
verfasst von
Toshihide Shima
Hirofumi Uto
Kohjiro Ueki
Yutaka Kohgo
Kohichiroh Yasui
Naoto Nakamura
Tatsuaki Nakatou
Toshinari Takamura
Sumio Kawata
Kazuo Notsumata
Kyoko Sakai
Ryosuke Tateishi
Takeshi Okanoue
Publikationsdatum
13.07.2018
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 1/2019
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-018-1494-7

Weitere Artikel der Ausgabe 1/2019

Journal of Gastroenterology 1/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

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