Abstract
It is unknown whether diabetes mellitus is a risk factor of the hepatocarcinogenesis in patients with chronic hepatitis C. Three hundred eleven anti-hepatitis C virus (HCV) -positive patients who had undergone liver biopsies were studied. Patients with histologically proven cirrhosis or withdrawing within 12 months were excluded. Thus, the remaining 279 patients were followed-up for 65.9 ± 29.4 months until the occurrence of hepatocellular carcinoma (HCC). During the observation period, HCC developed in 13 patients. Diabetes, age, sex, habitual alcohol intake, history of blood transfusion, serum α-fetoprotein level, histological findings, HCV genotype, viral load, and interferon therapy were assessed as potential risk factors. The Cox proportional hazard model identified that diabetes mellitus, histological staging, and age were independently associated with the occurrence of HCC. With multivariate analysis, only diabetes mellitus and age were associated with the occurrence of HCC. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C.
Similar content being viewed by others
REFERENCES
Okuda K, Nakashima T, Kojiro M, Kondo Y, Wada K: Hepatocellular carcinoma without cirrhosis in Japanese patients. Gastroenterology 97:140–146, 1989
Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M: Incidence of hepatocellular carcinoma in chronic hepatitis B and C: A prospective study of 251 patients. Hepatology 21:650–655, 1995
Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, Kawashima T: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328:1797–1801, 1993
Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama K, Murashima N, Kumada H: Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: A prospective observation of 2215 patients. J Hepatol 28:930–938, 1998
Benvegnu L, Fattovich G, Noventa F, Tremolada F, Chemello L, Cecchetto A, Alberti A: Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. Cancer 74:2442–2448, 1994
Bruno S, Silini E, Crosignani A, Borzio F, Leandro G, Bono F, Asti M, Rossi S, Larghi A, Cerino A, Podda M, Mondelli MU: Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Hepatology 25:754–758, 1997
Romeo R, Rumi MG, Ninno ED, Colombo M: Hepatitis C virus genotype 1b and risk of hepatocellular carcinoma. Hepatology 26:1077, 1997
Mason AL, Lau JYN, Hoang N, Qian K, Alexander GJM, Xu L, Guo L, Jacob S, Regenstein FG, Zimmerman R, Everhart JE, Wasserfall C, Maclaren NK, Perrillo RP: Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 29:328–333, 1999
La Vecchia C, Negri E, Franceschi S, D'Avanzo B, Boyle P: A case—control study of diabetes mellitus and cancer risk. Br J Cancer 70:950–953, 1994
Yu MC, Tong MJ, Govindarajan S, Henderson BE: Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asian of Los Angeles County, California. J Natl Cancer Inst 83:1820–1826, 1991
La Vecchia C, Negri E, D'Avanzo B, Boyle P, Franceschi S: Medical history and primary liver cancer. Cancer Res 50:6274–6277, 1990
Lawson DH, Gray JM, McKilop C, Clarke J, Lee FD, Patrick RS: Diabetes mellitus and primary hepatocellular carcinoma. Q J Med 61:945–955, 1986
Knodell R, Ishak G, Black W, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981
Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Sheuer PJ: Classification of chronic hepatitis: Diagnosis, grading, and staging. Hepatology 19:1513–1520, 1994
Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Sato K, Tsuda F, Miyakawa Y, Mayumi M: Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. J Gen Virol 73:673–679, 1992
Braga C, La Vecchia C, Negri E, Franceschi S: Attributable risks for hepatocellular carcinoma in northern Italy. Eur J Cancer 33:629–634, 1997
Colombo M, de Franchis R, Del Ninno E, Sangiovanni A, De Fazio C, Tommasini M: Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 325:675–680, 1991
Caronia S, Taylor K, Pagliaro L, Carr C, Pallazo U, Petrick J, O'Rahilly S, Shore S, Tom BDM, Alexander GJM: Further evidence for an association between non-insulin dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30:1059–1063, 1999
Bigam DL, Pennington JJ, Carpentier A, Wanless IR, Hemming AW, Croxford R, Greig PD, Lilly LB, Heathcote JE, Levy GA, Cattral MS: Hepatitis C-related cirrhosis: A predictor of diabetes mellitus after liver transplantation. Hepatology 32:87–90, 2000
Ikeda Y, Shimada M, Hasegawa H, Gion T, Kajiyama K, Shirabe K, Yanaga K, Takenaka K, Sugimachi K: Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection. Hepatology 27:1567–1571, 1998
Shimada M, Hasegawa H, Gion T, Shirabe K, Taguchi K, Takenaka K, Tanaka S, Sugimachi K: Risk factors of the recurrence of hepatocellular carcinoma originating from residual cancer cells after hepatectomy. Hepatogastroenterology 46:2469–2475, 1999
Allison MED, Wreghitt T, Palmer CR, Alexander GJM: Evidence for a link between hepatits C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol 21:1135–1139, 1994
Fraser GM, Harman I, Meller N, Niv Y, Porath A: Diabetes mellitus is associated with chronic hepatitis C but not chronic hepatitis B infection. Isr J Med Sci 32:526–530, 1996
Strasser SI, Watson KJR, Lee CS, Coghlan PJ, Desmond PV: Risk factors and predictors of outcome in an Australian cohort with hepatitis C virus infection. Med J Aust 162:355–358, 1995
Colombo M: Natural history and pathogenesis of hepatitis C virus related hepatocellular carcinoma. J Hepatol 31(suppl 1):25–30, 1999
Di Bisceglie AM, Goodman ZD, Ishak KG, Hoofnagle JH, Melpolder JJ, Alter HJ: Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis. Hepatology 14:969–974, 1991
Dusheiko G, Schmilovitsz-Weiss H, Brown D, McOmish F, Yap PL, Sherlock S: Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatology 19:13–18, 1994
Hagiwara H, Hayashi N, Mita E, Naito M, Kasahara A, Fusamoto H: Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease. Hepatology 17:545–550, 1993
Honda M, Kaneko S, Sakai A, Unoura M, Murakami S, Kobayashi K: Degree of diversity of hepatitis C virus quasispecies and progression of liver disease. Hepatology 20:1144–1151, 1994
Weltman MD, Brotodihardjo A, Crewe EB, Farrell GC, Bilous M, Grierson JM, Liddle C: Coinfection with hepatitis B and C or B, C and D viruses results in severe liver disease and responds poorly to interferon-alpha treatment. J Viral Hepat 2:39–45, 1995
Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 349:825–832, 1997
Ostapowicz G, Watson KJR, Locarnini SA, Desmond PV: Role of alcohol in the progression of liver disease caused by hepatitis C virus infection. Hepatology 27:1730–1735, 1998
Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K, Kumada H, Kawanishi M: A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 18:47–53, 1993
Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M: Interferon therapy reduces the risk for hepatocellular carcinoma: National surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 131:174–181, 1999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tazawa, J., Maeda, M., Nakagawa, M. et al. Diabetes Mellitus May Be Associated with Hepatocarcinogenesis in Patients with Chronic Hepatitis C. Dig Dis Sci 47, 710–715 (2002). https://doi.org/10.1023/A:1014715327729
Issue Date:
DOI: https://doi.org/10.1023/A:1014715327729