Metabolic Factors and Risk of Hepatocellular Carcinoma by Chronic Hepatitis B/C Infection: A Follow-up Study in Taiwan

Background 95% CI, 1.38–12.4) among anti-HCV–seropositive subjects and a 2-fold risk (RRa, 2.36; 95% CI, 0.91–6.17) in persons without HBV and HCV infections, after controlling for other metabolic components, but not in HBsAg-seropositive subjects (RRa, 1.36; 95% CI, 0.64–2.89). Diabetes was associated with HCC in all 3 groups, with the highest risk in those with HCV infection (RRa, 3.52; 95% CI, 1.29–9.24) and lowest in HBV carriers (RRa, 2.27; 95% CI, 1.10–4.66). We found more than 100-fold increased risk in HBV or HCV carriers with both obesity and diabetes, indicating synergistic effects of metabolic factors and hepatitis. Conclusions: The finding that both obesity and diabetes are predictors of HCC risk, possibly differently depending on HBV and HCV infection status, may shed some light in preventing HCC. Background 95% CI, 1.38–12.4) among anti-HCV–seropositive subjects and a 2-fold risk (RRa, 2.36; 95% CI, 0.91–6.17) in persons without HBV and HCV infections, after controlling for other metabolic components, but not in HBsAg-seropositive subjects (RRa, 1.36; 95% CI, 0.64–2.89). Diabetes was associated with HCC in all 3 groups, with the highest risk in those with HCV infection (RRa, 3.52; 95% CI, 1.29–9.24) and lowest in HBV carriers (RRa, 2.27; 95% CI, 1.10–4.66). We found more than 100-fold increased risk in HBV or HCV carriers with both obesity and diabetes, indicating synergistic effects of metabolic factors and hepatitis. Conclusions: The finding that both obesity and diabetes are predictors of HCC risk, possibly differently depending on HBV and HCV infection status, may shed some light in preventing HCC. See CME quiz on page 293. The incidence of liver cancer is increasing in several developed countries and would continue to increase for some decades.1Bosch F.X. Ribes J. Diaz M. et al.Primary liver cancer: worldwide incidence and trends.Gastroenterology. 2004; 127: S5-S16Abstract Full Text Full Text PDF PubMed Scopus (2139) Google Scholar The estimated attributable risk for the combined effects of hepatitis B and C viral infections accounts for more than 80% of liver cancer cases worldwide.1Bosch F.X. Ribes J. Diaz M. et al.Primary liver cancer: worldwide incidence and trends.Gastroenterology. 2004; 127: S5-S16Abstract Full Text Full Text PDF PubMed Scopus (2139) Google Scholar Obesity and diabetes have been found to be associated with an increased risk of hepatocellular carcinoma (HCC) in several epidemiologic studies.2Moller H. Mellemgaard A. Lindvig K. et al.Obesity and cancer risk: a Danish record-linkage study.Eur J Cancer. 1994; 30A: 344-350Abstract Full Text PDF PubMed Scopus (398) Google Scholar, 3Wolk A. Gridley G. Svensson M. et al.A prospective study of obesity and cancer risk (Sweden).Cancer Causes Control. 2001; 12: 13-21Crossref PubMed Scopus (506) Google Scholar, 4Rapp K. Schroeder J. Klenk J. et al.Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria.Br J Cancer. 2005; 93: 1062-1067Crossref PubMed Scopus (270) Google Scholar, 5Calle E.E. Rodriguez C. Walker-Thurmond K. et al.Overweight, obesity and mortality from cancer in a prospective studied cohort of US adults.N Engl J Med. 2003; 348: 1625-1638Crossref PubMed Scopus (5870) Google Scholar, 6Samanic C. Gridley G. Chow W.H. et al.Obesity and cancer risk among white and black United States veterans.Cancer Causes Control. 2004; 15: 35-43Crossref PubMed Scopus (263) Google Scholar, 7Nair S. Mason A. Eason J. et al.Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?.Hepatology. 2002; 36: 150-155Crossref PubMed Scopus (286) Google Scholar Five large population studies, 3 in Europe2Moller H. Mellemgaard A. Lindvig K. et al.Obesity and cancer risk: a Danish record-linkage study.Eur J Cancer. 1994; 30A: 344-350Abstract Full Text PDF PubMed Scopus (398) Google Scholar, 3Wolk A. Gridley G. Svensson M. et al.A prospective study of obesity and cancer risk (Sweden).Cancer Causes Control. 2001; 12: 13-21Crossref PubMed Scopus (506) Google Scholar, 4Rapp K. Schroeder J. Klenk J. et al.Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria.Br J Cancer. 2005; 93: 1062-1067Crossref PubMed Scopus (270) Google Scholar and 2 in the United States,5Calle E.E. Rodriguez C. Walker-Thurmond K. et al.Overweight, obesity and mortality from cancer in a prospective studied cohort of US adults.N Engl J Med. 2003; 348: 1625-1638Crossref PubMed Scopus (5870) Google Scholar, 6Samanic C. Gridley G. Chow W.H. et al.Obesity and cancer risk among white and black United States veterans.Cancer Causes Control. 2004; 15: 35-43Crossref PubMed Scopus (263) Google Scholar observed that obesity is associated with an increase in HCC incidence2Moller H. Mellemgaard A. Lindvig K. et al.Obesity and cancer risk: a Danish record-linkage study.Eur J Cancer. 1994; 30A: 344-350Abstract Full Text PDF PubMed Scopus (398) Google Scholar, 3Wolk A. Gridley G. Svensson M. et al.A prospective study of obesity and cancer risk (Sweden).Cancer Causes Control. 2001; 12: 13-21Crossref PubMed Scopus (506) Google Scholar, 4Rapp K. Schroeder J. Klenk J. et al.Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria.Br J Cancer. 2005; 93: 1062-1067Crossref PubMed Scopus (270) Google Scholar, 6Samanic C. Gridley G. Chow W.H. et al.Obesity and cancer risk among white and black United States veterans.Cancer Causes Control. 2004; 15: 35-43Crossref PubMed Scopus (263) Google Scholar and mortality,5Calle E.E. Rodriguez C. Walker-Thurmond K. et al.Overweight, obesity and mortality from cancer in a prospective studied cohort of US adults.N Engl J Med. 2003; 348: 1625-1638Crossref PubMed Scopus (5870) Google Scholar but a study conducted in an Asian country failed to obtain similar results.8Lai M.S. Hsieh M.S. Chiu Y.H. et al.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection.Hepatology. 2006; 43: PubMed Scopus Google Scholar A of and cohort have diabetes to a 2-fold increased risk of M.S. Hsieh M.S. Chiu Y.H. et al.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection.Hepatology. 2006; 43: PubMed Scopus Google Scholar, Chow W.H. et risk of liver cancer in with diabetes PubMed Scopus Google Scholar, Gridley G. et incidence in a cohort of with diabetes in PubMed Scopus Google Scholar, C. A. et and the risk of liver J Cancer. PubMed Scopus Google Scholar, H. et of diabetes in the of hepatocellular PubMed Scopus Google Scholar, The of diabetes in hepatocellular carcinoma: a study among United States J 2001; PubMed Google Scholar, Diabetes the risk of liver and hepatocellular 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, et the risk of hepatocellular carcinoma in the United a population 2005; PubMed Scopus Google Scholar, et factors for hepatocellular carcinoma: of with viral hepatitis and diabetes 2002; 36: PubMed Scopus Google Scholar, H. et and cancer risk in and 2005; PubMed Scopus Google Scholar, E.E. et a of cancer mortality in a large cohort of US J 2004; PubMed Scopus Google Scholar, S. K. et of diabetes, and viral hepatitis on risk of hepatocellular carcinoma in and in the 2004; PubMed Scopus Google Scholar, M. M. et and the risk of cancer: from a cohort study in Med. 2006; PubMed Scopus Google Scholar, H. The diabetes and hepatocellular carcinoma: a of epidemiologic 2006; Full Text Full Text PDF PubMed Scopus Google Scholar large cohort study in M.S. Hsieh M.S. Chiu Y.H. et al.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection.Hepatology. 2006; 43: PubMed Scopus Google Scholar studies, 3 M.S. Hsieh M.S. Chiu Y.H. et al.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection.Hepatology. 2006; 43: PubMed Scopus Google Scholar, et the risk of hepatocellular carcinoma in the United a population 2005; PubMed Scopus Google Scholar, S. K. et of diabetes, and viral hepatitis on risk of hepatocellular carcinoma in and in the 2004; PubMed Scopus Google Scholar whether diabetes and HCC hepatitis infection status, but investigated the of a of hepatitis on the increasing prevalence of obesity and diabetes, is to the 2 factors other metabolic and and HCC hepatitis B and is a risk factor for is to whether metabolic factors are associated with HCC differently depending on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection We conducted the using from a J. et of hepatocellular carcinoma a of hepatitis B virus 2006; PubMed Scopus Google Scholar, et B antigen and the risk of hepatocellular Engl J Med. 2002; PubMed Scopus Google Scholar, J. et risk on the of hepatitis B viral 2006; Full Text Full Text PDF PubMed Scopus Google Scholar that been followed up for more than in Taiwan and in cohort hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) at We to whether obesity and diabetes other metabolic factors are independently associated with stratified by HBV and HCV to the possible joint influence of obesity/diabetes and HBV/HCV infections on the risk of HCC to the the in HCC risk is associated with is the study that the obesity/diabetes other metabolic factors and risk of HCC by and serostatus, the of HBV and HCV A of the and and was J. et of hepatocellular carcinoma a of hepatitis B virus 2006; PubMed Scopus Google Scholar, et B antigen and the risk of hepatocellular Engl J Med. 2002; PubMed Scopus Google Scholar, J. et risk on the of hepatitis B viral 2006; Full Text Full Text PDF PubMed Scopus Google Scholar and residents of that the and of Taiwan were to in a cancer and a total of and to with on and factors was via a by were at and on hepatitis B HBV and were using and J. et of hepatocellular carcinoma a of hepatitis B virus 2006; PubMed Scopus Google Scholar, et B antigen and the risk of hepatocellular Engl J Med. 2002; PubMed Scopus Google Scholar, J. et risk on the of hepatitis B viral 2006; Full Text Full Text PDF PubMed Scopus Google Scholar All to in and the were and by the of the of Taiwan The metabolic factors for obesity, of diabetes and and of total and The of obesity was by of mass index kg/m2) and obesity was a for and for to in the Asian S. et the of the metabolic to 2004; PubMed Scopus Google Scholar was to to and on the for the Asian index for Asian and for and 2004; Scholar A of diabetes and was from the of and were to be of on and were at study positive for or for liver cancer via was national were to with the national cancer in Taiwan to HCC cases and liver cancer identified linkage to the national cancer or from or at were from the The cancer was in in and in not all liver to the national cancer were on liver cancer cases in carriers to the HCC a all HCC cases in at of the by at 2 or for were from the of to the of HCC or were and not with HCC were on factors that may be associated with both metabolic factors and HCC in a and that were 3 All analyses were stratified by of and and persons were both and positive and were from the to of HCC cases The relative risk and 95% confidence interval were estimated by Cox proportional hazards models. and obesity obesity and of diabetes were in the with for and to whether the of HBV or HCV infections the obesity/diabetes and HCC risk in a to the joint of obesity, diabetes, and of or was estimated by the of HCC cases with metabolic factor and viral risk factor diabetes and that was to the of attributable to the combined of J PubMed Scopus Google Scholar The of from was estimated from the 95% of an on the by of attributable to the combined of J PubMed Scopus Google Scholar and the of indicating with both HBV and HCV infections were the was on of of or diabetes and both factors in with were for both and and A of metabolic obesity, and of diabetes and were among those without HBV and HCV infections to whether the was associated with increasing HCC risk in a of were by the of a the of the and other HCC risk an using a with a was HBV HCC of liver and the metabolic factors obesity, and of diabetes and were all in to the of and HCC after for the effects of other metabolic All analyses were using Scholar All analyses were without a of liver at and the the indicating that may not be for the HCC cases that of may be but at and and of metabolic factors may be to HCC. We analyses HCC cases of and the the The that HCC cases may be and with metabolic and may influence the risk be the of to the was found to have with and to the in increased HCC on to all study subjects in the the in the the was for both and were for and were for at The or of HCC risk factors in 3 is in for were were in were and the highest of diabetes and of liver HBsAg-seropositive were were in and of and the lowest of and and to be than the other 2 were for both the highest total and the highest with and A total of HCC cases were identified the The HCC was similar in 2 with HBV or HCV infection and but in the with an incidence of HCC of and of for HCC by HBV and HCV and positive and and at high or at total in and in of diabetes of at at of liver HCC in and in in a without HBV and HCV infections and or were associated with an increased risk of HCC. Extreme obesity and of diabetes were associated with an increased risk of HCC 95% CI, for ≥30 95% CI, for HBsAg-seropositive and or were associated with an increased risk of HCC. Diabetes was associated with a relative HCC risk of (95% CI, obesity were to HCC was associated with a risk of HCC 95% CI, in HBsAg-seropositive and of Incident HCC in to by HBV and HCV and positive and and positive (95% (95% (95% at high or at total for in and in of diabetes of at at in and in in a anti-HCV–seropositive subjects a HCC risk factor but not was associated with a relative HCC risk of (95% CI, and were associated with HCC but not Obesity 95% CI, for ≥30 obesity 95% CI, and of diabetes 95% CI, were associated with the risk of HCC in anti-HCV–seropositive 3 the relative HCC risk associated with metabolic factors after for other and stratified by and and obesity were were in models. were for both and of the metabolic factors were associated with HCC risk a 2-fold HCC risk observed for obesity 2.36; 95% CI, for ≥30 and diabetes 95% CI, HBsAg-seropositive of diabetes was the HCC risk factor with an of (95% CI, obesity was associated with a increased risk of HCC 95% CI, was found with increasing was associated with a risk of HCC 95% CI, anti-HCV–seropositive obesity was associated with an of (95% CI, and was associated with an increasing HCC risk in a with the highest of (95% CI, for Diabetes was associated with a increased risk of HCC in both 95% CI, 3.52; 95% CI, and were associated with HCC risk in but not of HCC in to by HBV and HCV and positive and and positive total ≥30 for obesity of diabetes of All are (95% are for in at at and high and in a All are (95% are for in at at and high and the effects of the of obesity, diabetes, and HBV and HCV infections on HCC risk, with the of HBV and HCV infections, diabetes, and The relative HCC risk was (95% CI, for the of and obesity and (95% CI, for the of and The was (95% CI, for the of and diabetes and (95% CI, for the of and all factors the relative HCC risk was high (95% CI, for HBsAg-seropositive subjects with obesity and diabetes and (95% CI, for anti-HCV–seropositive subjects with obesity and of HCC by and Extreme and of hepatitis (95% for and at high and of diabetes of and for and at high and obesity ≥30 of and for and at high and of and was HCC for and at high and of diabetes of and for and at high and obesity ≥30 of and for and at high and of and was HCC in a the of synergistic effects in an of diabetes on both 95% CI, and 95% CI, obesity HCC risk to 95% CI, but not to 95% CI, to of the were in for without HBV and HCV infections, the of metabolic factors obesity, and of diabetes and was associated with increasing HCC risk in a 95% CI, for metabolic risk The was (95% CI, the was to the and of Incident HCC in to of HBV and HCV of of for in at at and high and of metabolic factors for to those than at of metabolic factors for for in at at and high and in a analyses were to whether were associated with factors to liver and metabolic the HBV and found a of HBV and of with those for was an HBV and those with the highest HBV on were with HCC at than those not HCC All other at obesity, obesity, and of diabetes and were associated with of and of at and of HBV and of in to HCV HBV were subjects with viral obesity of diabetes of for in at and high and were subjects with viral in a for in at and high and prospective the several metabolic factors and risk of HCC was on HBV and HCV obesity and obesity ≥30 kg/m2) were independently associated with 2-fold and 4-fold increased risk of HCC among Extreme obesity was associated with 2-fold increased risk in those without HBV and HCV infections, was HBV was not associated with HCC Diabetes was associated with to increased risk of of HBV and HCV The risk was highest among those with HCV infection and lowest in HBV carriers and not in those without those without HBV and HCV infections, of metabolic factors were to for the to HCC and were We found more than 100-fold increased risk of HCC among HBV or HCV carriers with both obesity and diabetes, with those without all indicating synergistic effects of metabolic factors and hepatitis have that obesity is associated with an increased risk of H. Mellemgaard A. Lindvig K. et al.Obesity and cancer risk: a Danish record-linkage study.Eur J Cancer. 1994; 30A: 344-350Abstract Full Text PDF PubMed Scopus (398) Google Scholar, 3Wolk A. Gridley G. Svensson M. et al.A prospective study of obesity and cancer risk (Sweden).Cancer Causes Control. 2001; 12: 13-21Crossref PubMed Scopus (506) Google Scholar, 4Rapp K. Schroeder J. Klenk J. et al.Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria.Br J Cancer. 2005; 93: 1062-1067Crossref PubMed Scopus (270) Google Scholar, 5Calle E.E. Rodriguez C. Walker-Thurmond K. et al.Overweight, obesity and mortality from cancer in a prospective studied cohort of US adults.N Engl J Med. 2003; 348: 1625-1638Crossref PubMed Scopus (5870) Google Scholar, 6Samanic C. Gridley G. Chow W.H. et al.Obesity and cancer risk among white and black United States veterans.Cancer Causes Control. 2004; 15: 35-43Crossref PubMed Scopus (263) Google Scholar, 7Nair S. Mason A. Eason J. et al.Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?.Hepatology. 2002; 36: 150-155Crossref PubMed Scopus (286) Google Scholar but 2 of failed to for other metabolic factors and HCC risk factors to of H. Mellemgaard A. Lindvig K. et al.Obesity and cancer risk: a Danish record-linkage study.Eur J Cancer. 1994; 30A: 344-350Abstract Full Text PDF PubMed Scopus (398) Google Scholar, 3Wolk A. Gridley G. Svensson M. et al.A prospective study of obesity and cancer risk (Sweden).Cancer Causes Control. 2001; 12: 13-21Crossref PubMed Scopus (506) Google Scholar study observed a increased risk among the population in with the H. Mellemgaard A. Lindvig K. et al.Obesity and cancer risk: a Danish record-linkage study.Eur J Cancer. 1994; 30A: 344-350Abstract Full Text PDF PubMed Scopus (398) Google Scholar the incidence for liver cancer was (95% CI, in in A. Gridley G. Svensson M. et al.A prospective study of obesity and cancer risk (Sweden).Cancer Causes Control. 2001; 12: 13-21Crossref PubMed Scopus (506) Google Scholar of liver cancer among kg/m2) was with of in a large US E.E. Rodriguez C. Walker-Thurmond K. et al.Overweight, obesity and mortality from cancer in a prospective studied cohort of US adults.N Engl J Med. 2003; 348: 1625-1638Crossref PubMed Scopus (5870) Google Scholar et S. Mason A. Eason J. et al.Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?.Hepatology. 2002; 36: 150-155Crossref PubMed Scopus (286) Google Scholar that obesity was an independent risk factor for HCC in with 95% CI, for kg/m2) and 95% CI, but not in with HCV HBV and hepatitis. of to increased risk of HCC associated with of diabetes was with M.S. Hsieh M.S. Chiu Y.H. et al.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection.Hepatology. 2006; 43: PubMed Scopus Google Scholar, Chow W.H. et risk of liver cancer in with diabetes PubMed Scopus Google Scholar, Gridley G. et incidence in a cohort of with diabetes in PubMed Scopus Google Scholar, C. A. et and the risk of liver J Cancer. PubMed Scopus Google Scholar, H. et of diabetes in the of hepatocellular PubMed Scopus Google Scholar, The of diabetes in hepatocellular carcinoma: a study among United States J 2001; PubMed Google Scholar, Diabetes the risk of liver and hepatocellular 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, et the risk of hepatocellular carcinoma in the United a population 2005; PubMed Scopus Google Scholar, et factors for hepatocellular carcinoma: of with viral hepatitis and diabetes 2002; 36: PubMed Scopus Google Scholar, H. et and cancer risk in and 2005; PubMed Scopus Google Scholar, E.E. et a of cancer mortality in a large cohort of US J 2004; PubMed Scopus Google Scholar, S. K. et of diabetes, and viral hepatitis on risk of hepatocellular carcinoma in and in the 2004; PubMed Scopus Google Scholar, M. M. et and the risk of cancer: from a cohort study in Med. 2006; PubMed Scopus Google Scholar, H. The diabetes and hepatocellular carcinoma: a of epidemiologic 2006; Full Text Full Text PDF PubMed Scopus Google Scholar of H. The diabetes and hepatocellular carcinoma: a of epidemiologic 2006; Full Text Full Text PDF PubMed Scopus Google Scholar et the risk of hepatocellular carcinoma in the United a population 2005; PubMed Scopus Google Scholar a HCV and diabetes with an of (95% CI, for those with HCV and diabetes, with those without factor in a large study in the United study found a similar with an of (95% CI, for those with HCV and diabetes, was than the of diabetes 95% CI, and HCV 95% CI, but the not S. K. et of diabetes, and viral hepatitis on risk of hepatocellular carcinoma in and in the 2004; PubMed Scopus Google Scholar synergistic effects of diabetes and viral hepatitis with an of (95% CI, but combined hepatitis B and C a study by et M.S. Hsieh M.S. Chiu Y.H. et al.Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection.Hepatology. 2006; 43: PubMed Scopus Google Scholar found that 2 diabetes increased risk of HCC in those were HCV 95% CI, or 95% CI, The may be to HCV persons with HBV infections and to the risk from The synergistic of kg/m2) and diabetes on the risk of HCC been We found that kg/m2) not increase HCC risk to an with diabetes a synergistic in the not This is with the from that is not associated with increased risk of HCC in the with obesity ≥30 kg/m2) in to diabetes, the synergistic to in the in The of of with risk of HCC among those with HBV or HCV infections were with 2 other H. et of diabetes in the of hepatocellular PubMed Scopus Google Scholar, M. et in with hepatocellular Med. 2001; Google Scholar We HBV in a and a was observed of HBV and The and was by study conducted in Chiu Y.H. et al.A study the metabolic and hepatitis infection study J 2006; Scholar but been a on the of HBV and liver is to increase the risk of would that be associated with of the have the that may the and HCC risk study and the study by et Chiu Y.H. et al.A study the metabolic and hepatitis infection study J 2006; Scholar is associated with HBV been that in HBV may the of is the of the et hepatitis B virus of B by the of 2004; PubMed Scopus Google Scholar of B B would in of all the in the was to viral increasing of viral M. B virus is by and 2005; PubMed Scopus Google Scholar This to be with of a and viral The obesity/diabetes and HCC may be by that increase the of and to factors and risk for hepatocellular 2004; 127: Full Text Full Text PDF PubMed Scopus Google Scholar have that liver may be the factor obesity/diabetes and risk of K. K. et carcinoma in 2001; PubMed Scopus Google Scholar, et the of from to hepatocellular 2002; Full Text Full Text PDF PubMed Scopus Google Scholar been that obesity/diabetes increase the risk of HCC with liver may to M. A. et the of liver of hepatitis C and with HCV and 2001; PubMed Scopus Google Scholar the of liver been to K. K. K. et is a risk factor for hepatocellular carcinoma in with hepatitis C virus 2003; PubMed Scopus (286) Google Scholar of HCC to those at high risk to the infection of is the on of diabetes the of diabetes a without of or We diabetes from a of be of a study found and for of et and was for diabetes, and but not for 2004; Full Text Full Text PDF PubMed Scopus Google Scholar and is to that is to the or of HCC the was and more to the were to metabolic not have on and but not a metabolic factors and HCC. The of HCC cases with obesity in some stratified may the from but the all and were at and HCC cases was identified study and All risk factors were on at enrollment, and may the of the in risk and the possible in HCC risk factors over is and with HCC observed in study be to the that metabolic factors some in the of obesity and diabetes among on the HCV HCV and obesity/diabetes with risk of HCC is The mass of hepatitis B the mortality and of liver to HBV infection in et B and hepatocellular carcinoma in and PubMed Scopus Google Scholar, et hepatitis B in in the after was 2006; PubMed Scopus Google Scholar not in developed countries the United of HBV infection are and may be in to the increase in the prevalence of other risk factors hepatitis C infection and metabolic Mason incidence of hepatocellular carcinoma in the United Engl J Med. Scholar, et increase in the incidence of hepatocellular carcinoma in the United an Med. 2003; PubMed Scopus Google Scholar The of metabolic obesity and diabetes, to HCC risk differently depending on HBV and HCV infections may shed some light in preventing HCC after of hepatitis B and C. been to liver in with and liver in are associated with 2006; PubMed Scopus Google Scholar may be for of HCC. the of obesity ≥30 kg/m2) in study may to the Asian for other more are to The obesity/diabetes and HCC may not be to the but to the metabolic The S. of of for on and of the PDF