Role of diabetes mellitus on the recurrence rate of hepatocellular carcinomas after radiofrequency ablation in chronic hepatitis C patients

Abstract

Aim: The aim was to assess the impact of hyperglycemia on the recurrence of hepatocellular carcinoma (HCC) as well as evaluate survival after curative ablation by radiofrequency.

Methods: This study, which was conducted retrospectively on 107 chronic hepatitis C (CHC) patients with 159 HCCs, was presented to the Hepatology Unit of Internal Medicine Department at Tanta University Hospitals. All lesions were curatively treated by radiofrequency ablation (RFA) and the surveillance of HCC recurrence was evaluated radiologically every 3 months for periods between 6 and 36 months. Of 107 subjects, 70 were males and 37 were females, with mean age 50.4 ± 9.4 years. All patients were divided according to their glycemic state into the following three groups: Group I, which included 37 type 2 diabetic patients, with adequate maintenance of blood glucose, has 52 HCCs; Group II, which included 25 type 2 diabetic patients with inadequate maintenance of blood glucose, has 43 HCCs; and Group III, which included 45 euglycemic non-diabetic patients, has 64 HCCs.

Results: Our results showed that, there was significant increase in recurrence rate in diabetic patients with inadequate maintenance of blood glucose (Group II) compared to those in Group I and Group III (P < 0.0001). Interestingly, there was no significant difference concerning HCC recurrence between diabetic patients with adequate maintenance of blood glucose (Group I) and non-diabetic euglycemic patients (Group III). Our results also identified that, inadequate maintenance of blood glucose in diabetic patients was also a significant predictor of poor survival.

Conclusion: Inadequate maintenance of blood glucose in diabetic patients is a significant risk factor for recurrence of HCC and for poor survival after curative RFA therapy in CHC patients.

Keywords

Hepatocellular carcinoma / hyperglycemia / radio frequency ablation / recurrence / survival

References

[1] Parkin DM,Ferlay J.Global cancer statistics, 2002..CA Cancer J Clin2005;55:74-108

[2] Bosch FX,Díaz M.Primary liver cancer: worldwide incidence and trends..Gastroenterology2004;127:S5-16

[3] Gomaa AI,Toledano MB,Taylor-Robinson SD.Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis..World J Gastroenterol2008;14:4300-8 PMCID:PMC2731180

[4] Arii S,Sakamoto M,Kumada T,Yamashita T,Tanaka M,Kudo M.Management of hepatocellular carcinoma: Report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009)..Hepatol Res2010;40:667-85

[5] Minami Y.Radiofrequency ablation of hepatocellular carcinoma: current status..World J Radiol2010;2:417-24 PMCID:PMC3006479

[6] Chen MS,Zheng Y,Liang HH,Lin XJ.A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma..Ann Surg2006;243:321-8 PMCID:PMC1448947

[7] Tateishi R,Teratani T,Sato S,Fujishima T,Kawabe T.Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases..Cancer2005;103:1201-9

[8] Izumi N,Noguchi O,Kanazawa N,Himeno Y,Sakai T.Risk factors for distant recurrence of hepatocellular carcinoma in the liver after complete coagulation by microwave or radiofrequency ablation..Cancer2001;91:949-56

[9] Curley SA,Ellis LM,Vallone P.Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis..Ann Surg2000;232:381-91 PMCID:PMC1421151

[10] Poon RT,Lo CM,Wong J.Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors..Ann Surg1999;229:216-22 PMCID:PMC1191634

[11] Tung-Ping Poon R,Wong J.Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma..Ann Surg2000;232:10-24 PMCID:PMC1421103

[12] Fuke H,Shiraki K,Beppu T,Yamamoto N,Takaki H,Yamakado K,Takei Y.Predictive factors for distant recurrence of HCV-related hepatocellular carcinoma after radiofrequency ablation combined with chemoembolization..Aliment Pharmacol Ther2008;27:1253-60

[13] Hagihara H,Kobayashi Y,Nakamura S,Toshimori J,Ohnishi H,Yamamoto K.Effect of pegylated interferon therapy on intrahepatic recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma..Int J Clin Oncol2011;16:210-20

[14] Miyake Y,Iwasaki Y.Meta-analysis: interferon-alpha prevents the recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma..J Viral Hepat2010;17:287-92

[15] Wong JS,Tsoi KK,Cheung SY,Wong J,Lai PB.Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma..Aliment Pharmacol Ther2011;33:1104-12

[16] Inoue M,Otani T,Noda M.Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan..Arch Intern Med2006;166:1871-7

[17] Bugianesi E,Vanni E,Brunello F,Musso A,Capussotti L,Rizzetto M.Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma..Gastroenterology2002;123:134-40

[18] Toyoda H,Nakano S,Sugiyama K,Tanikawa M,Hisanaga Y.Impact of diabetes mellitus on the prognosis of patients with hepatocellular carcinoma..Cancer2001;91:957-63

[19] Huo TI,Lui WY,Lee PC,Chang FY.Differential mechanism and prognostic impact of diabetes mellitus on patients with hepatocellular carcinoma undergoing surgical and nonsurgical treatment..Am J Gastroenterol2004;99:1479-87

[20] Komura T,Kita Y,Takata Y,Yamashita T,Shimizu K,Honda M,Kaneko S.Impact of diabetes on recurrence of hepatocellular carcinoma after surgical treatment in patients with viral hepatitis..Am J Gastroenterol2007;102:1939-46

[21] Chen WT,Lin CC,Lin SM.Diabetes may not affect outcomes in hepatocellular carcinoma after radio-frequency ablation..Hepatogastroenterology2011;58:551-7

[22] Aizawa N,Imanishi H,Iwata Y,Ikeda N,Takashima T,Moriwaki E,Iijima H,Nishiguchi S.Elevation of the glycated albumin to glycated hemoglobin ratio during the progression of hepatitis C virus related liver fibrosis..World J Hepatol2012;4:11-7 PMCID:PMC3272076

[23] Association American Diabetes.Diagnosis and classification of diabetes mellitus..Diabetes Care2010;31:S62-9

[24] Youkou A,Suzuki K,Sakagami T,Arakawa M,Narita I.Influence of obesity on control in asthmatic Japanese patients defined by the Japanese definition of obesity..Intern Med2011;50:1911-6

[25] Hosokawa T,Tsuchiya K,Muraoka M,Tamaki N,Nakata T,Suzuki S,Nakanishi H,Takahashi Y.Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy..World J Gastroenterol2013;19:249-57 PMCID:PMC3547569

[26] Davila JA,Shaib Y,El-Serag HB.Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study..Gut2005;54:533-9 PMCID:PMC1774454

[27] Lai MS,Chiu YH.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection..Hepatology2006;43:1295-302

[28] El-Serag HB,Javadi F.The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence..Clin Gastroenterol Hepatol2006;4:369-80

[29] Hassan MM,Hatten CJ,Li D,Beasley P.Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus..Hepatology2002;36:1206-13

[30] Liu H,Li J.High glucose promotes cell proliferation and enhances GDNF and RET expression in pancreatic cancer cells..Mol Cell Biochem2011;347:95-101

[31] Okumura M,Sakuma H,Maruyama T,Cooper DR.Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression..Biochim Biophys Acta2002;1592:107-16

[32] Yamamoto M,Taggart J,Cooper DR.A shift from normal to high glucose levels stimulates cell proliferation in drug sensitive MCF-7 human breast cancer cells but not in multidrug resistant MCF-7/ADR cells which overproduce PKC-betaII..Int J Cancer1999;83:98-106

[33] Nishikawa T,Du XL,Matsumura T,Yorek MA,Oates PJ,Giardino I.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage..Nature2000;404:787-90

[34] akahashi H,Eguchi Y,Kuwashiro T,Isoda H,Iwane S,Anzai K,Fujimoto K.Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C..J Gastroenterol2011;46:790-8

[35] Monnier L,Ginet C,Villon L,Colette C.Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes..JAMA2006;295:1681-7

[36] Fisher WE,Schirmer WJ.Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors..J Surg Res1996;63:310-3