The Association Between Diabetes and Hepatocellular Carcinoma: A Systematic Review of Epidemiologic Evidence
Clinical Gastroenterology and HepatologyPublished 1 March 2006Open access
Hashem B. El‐Serag, Howard Hampel, Fariba Javadi
Citations813
SJR quartileQ1
SJR score3.51
SNIP2.89
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Diabetes is associated with an increased risk for HCC, however, more research is required to examine issues related to the duration and treatment of diabetes, and confounding by diet and obesity.
Abstract
Diabetes is associated with an increased risk for HCC. However, more research is required to examine issues related to the duration and treatment of diabetes, and confounding by diet and obesity.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
New England Journal of MedicineOverweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults
7,717 Citations2003Eugenia E. Calle, Carmen Rodríguez +2 more
Current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women, and increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
GastroenterologyThe Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
2,873 Citations2005Leon A. Adams, James Lymp +5 more
Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis, although the absolute risk is low.
New England Journal of MedicineRising Incidence of Hepatocellular Carcinoma in the United States
2,863 Citations1999Hashem B. El‐Serag, Andrew C. Mason
The incidence of hepatocellular carcinoma increased significantly among younger persons (40 to 60 years old) during the period from 1991 to 1995 as compared with earlier periods, and the age-specific incidence of this cancer has progressively shifted toward younger people.
HepatologyNonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome
2,678 Citations2003Giulio Marchesini, Elisabetta Bugianesi +9 more
The presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease and the increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades.
HepatologyIndependent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis
1,611 Citations1999Paul Angulo, Jill C. Keach +2 more
Older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis, and this is the subgroup of patients who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.
GastroenterologyExpanding the natural history of nonalcoholic steatohepatitis: From cryptogenic cirrhosis to hepatocellular carcinoma
1,435 Citations2002Elisabetta Bugianesi, Nicola Leone +9 more
Features suggestive of NASH are more frequently observed in HCC arising in patients with CC than in age- and sex-matched HCC patients of well-defined viral or alcoholic etiology.
GastroenterologyDiabetes increases the risk of chronic liver disease and hepatocellular carcinoma
1,235 Citations2004Hashem B. El‐Serag, Thomas Tran +1 more
Among men with diabetes, the risk of chronic nonalcoholic liver disease and hepatocellular carcinoma is doubled, independent of alcoholic liver disease, viral hepatitis, or demographic features.
HepatologyFatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors
1,209 Citations1990Ian R. Wanless, John S. Lentz
Statohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass, and incidence of steatosis and steatohePatitis correlated with the degree of obesity.
JAMAFasting Serum Glucose Level and Cancer Risk in Korean Men and Women
981 Citations2005Sun Ha Jee
In Korea, elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers, and the risk tends to increase with an increased level offasting serum glucose.
Journal of HepatologyThe histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies
912 Citations2004Leon A. Adams, Schuyler O. Sanderson +2 more
Fibrosis in NAFLD progresses slowly over time with considerable variability in the rate of changes among patients, and changes of aminotransferases do not parallel changes in fibrosis stage.
American Journal of EpidemiologyDiabetes Mellitus as a Predictor of Cancer Mortality in a Large Cohort of US Adults
809 Citations2004Steven S. Coughlin, Eugenia E. Calle +3 more
The findings suggest that diabetes is an independent predictor of mortality from cancer of the colon, pancreas, female breast, and, in men, of the liver and bladder.
HepatologyRisk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus
762 Citations2002Manal M. Hassan, Lu-Yu Hwang +6 more
A significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis in high‐risk individuals.
GutDiabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study
701 Citations2005Jessica A. Davila, Robert O. Morgan +3 more
Findings from this population based study suggest that diabetes is an independent risk factor for HCC, regardless of the presence of other major HCC risk factors.
JNCI Journal of the National Cancer InstituteCancer Incidence in a Population-Based Cohort of Patients Hospitalized With Diabetes Mellitus in Denmark
630 Citations1997Louise Wideroff, Gloria Gridley +6 more
Patients hospitalized with a diagnosis of diabetes appear to be at higher risk of developing cancers of the liver, biliary tract, pancreas, endometrium, and kidney, however, the elevated risks of endometrial and kidney cancers may be confounded by obesity.
Clinical Gastroenterology and HepatologyNonalcoholic fatty liver disease in patients with type 2 diabetes
446 Citations2004Zobair M. Younossi, Terry Gramlich +3 more
The potential role of insulin resistance in the development of poor clinical outcomes in patients with NAFLD and DM is supported, as markers of hepatic dysfunction were the only independent predictors of increased mortality.
Archives of Internal MedicineRisk Factors for the Rising Rates of Primary Liver Cancer in the United States
419 Citations2000Hashem B. El‐Serag, Andrew C. Mason
Hepatitis C virus infection accounts for most of the increase in the number of cases of primary liver cancer among US veterans and the rates ofPrimary liver cancer associated with alcoholic cirrhosis and hepatitis B virus infection have remained stable.
JNCI Journal of the National Cancer InstituteExcess Risk of Primary Liver Cancer in Patients With Diabetes Mellitus
374 Citations1996Hans‐Olov Adami, W.-H. Chow +7 more
It is suggested that patients with diabetes are at increased risk of developing primary liver cancer and perhaps cancers of the biliary tract.
CancerHepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection
319 Citations2003Kazuyuki Ohata, Keisuke Hamasaki +12 more
The objective of this study was to determine the relation between hepatic steatosis and hepatocarcinogenesis in patients with chronic HCV infection.
JNCI Journal of the National Cancer InstituteCancer Incidence in Patients With Type 1 Diabetes Mellitus: A Population-Based Cohort Study in Sweden
277 Citations2003Kazem Zendehdel
Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes, including liver, pancreatic, kidney, and endometrial cancer.
CancerSynergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S.
276 Citations2004Jian‐Min Yuan, Sugantha Govindarajan +2 more
Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma, but to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse.
The American Journal of GastroenterologyThe role of diabetes in hepatocellular carcinoma: a case-control study among United States veterans
266 Citations2001Hashem B. El‐Serag, Peter Richardson +1 more
DM increased the risk of PLC only in the presence of other risk factors such as hepatitis C or B or alcoholic cirrhosis, and without markers of chronic liver disease the adjusted OR for diabetes and PLC was not significantly increased.
Liver TransplantationObesity and diabetes as a risk factor for hepatocellular carcinoma
227 Citations2004Jean Marc Regimbeau, Magali Colombat +7 more
Patients with chronic liver disease who underwent resection for HCC were assessed for obesity, diabetes mellitus, and histological features of the tumor and the adjacent liver parenchyma to examine the incidence of risk factors for nonalcoholic fatty liver disease (NAFLD).
Journal of Chronic DiseasesSubsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus
226 Citations1982Mark W. Ragozzino, L. Joseph Melton +2 more
Subsequent cancer incidence was determined in the population-based incidence cohort of Rochester, Minnesota, residents diagnosed with diabetes mellitus between 1945 and 1969 and the potential biases of increased medical surveillance among diabetics and exacerbation of subclinical diabetes by occult malignancy did not appear to be important.
JNCI Journal of the National Cancer InstituteCancer Mortality Among Diabetics<xref ref-type="fn" rid="FN2">2</xref>
217 Citations1970Irving I. Kessler
JNCI Journal of the National Cancer InstituteNonviral Risk Factors for Hepatocellular Carcinoma in a Low-Risk Population, the Non-Asians of Los Angeles County, California
193 Citations1991M C Yu, B. E. Henderson +2 more
The data suggest that cigarette smoking, alcohol consumption, and use of oral contraceptives are major risk factors for hepatocellular carcinoma among non-Asian residents of Los Angeles County.
Pathology InternationalHepatocellular carcinoma arising in non‐alcoholic steatohepatitis
176 Citations2001Yoh Zen, Kazuyoshi Katayanagi +4 more
This case suggests that HCC could be a late complication of NASH, and one nodule was pathologically diagnosed as a pseudolymphoma, while three other nodules were moderately differentiated HCC, well‐differentiated HCC and dysplastic nodule (11 years later), suggesting multicentric occurrence of HCC.
JNCI Journal of the National Cancer InstituteRole of Diabetes Mellitus in the Etiology of Hepatocellular Carcinoma
159 Citations2000Παγώνα Λάγιου
A large case–control study of HCC in Athens, Greece, in which information on medical history and life-style variables has been collected and chronic infection with HBV and/or HCV has been assessed.
International Journal of CancerDiabetes mellitus and the risk of primary liver cancer
143 Citations1997Carlo La Vecchia, Eva Negri +2 more
A history of diabetes mellitus could explain about 8% (95% CI 5–11) of cases of liver cancer in this population of patients in Italy, and the potential pathogenic mechanisms include liver alteration—and consequent cell proliferation—in subjects with diabetes.
Seminars in Liver DiseaseHepatitis C and Hepatocellular Carcinoma
135 Citations1995Adrian M. Di Bisceglie
HCV appears to represent a major underlying cause of HCC in southern Europe and Japan, regions where HCC incidence is intermediate, whereas its impact is smaller in sub-Saharan Africa and China.
Journal of Internal MedicineCancer and diabetes ‐ a follow‐up study of two populationbased cohorts of diabetic patients
128 Citations1997Henrik Hjalgrim, Morten Frisch +4 more
Cancer and diabetes ‐ a follow‐up study of two population‐ based cohorts of diabetic patients.
The American Journal of GastroenterologyNonalcoholic Steatohepatitis and Hepatocellular Carcinoma: Natural History?
119 Citations2000Helma Pinchemel Cotrim, Raymundo Paraná +2 more
It isstrated that the gastric mucous cells gain entry into the blood stream after gastric biopsy by using the glycosyltransferase,a4GnT as a cell-specific marker for gastric gland mucous Cells.
CancerA case-control study of primary hepatocellular carcinoma in Taiwan
110 Citations1988Sheng‐Nan Lu, T. Lin +5 more
The variables such as cigarette smoking, alcohol drinking, peanut consumption, frequent intake of raw fish, heart diseases, peptic ulcer, malaria, hypertension, diabetes, color blindness, G‐6‐PD deficiency, surgical operation, blood transfusion, and liver diseases of parents and children were not found to be associated with PHC.
International Journal of CancerA case‐control study of hepatitis B and C virus infections in the etiology of hepatocellular carcinoma
85 Citations1995Stephanos J. Hadziyannis, Edward Tabor +6 more
Comparisons with previous work in a similar population demonstrated that, when second‐generation anti‐HCV assays are applied to sera stored for 7–15 years, confirmatory assays or a higher diagnostic cut‐off point may be necessary to ensure that the testing is specific.
QJMDiabetes Mellitus and Primary Hepatocellular Carcinoma
84 Citations1986D. H. Lawson, James M. Gray +4 more
A four-fold excess of diabetic patients among the group with hepatocellular carcinoma and the association was strongest in patients receiving drug treatment for diabetes, but the data were insufficient to determine whether any specific anti-diabetic agent could be responsible.
Diabetes/Metabolism Research and ReviewsProspective study of diabetes mellitus and liver cancer in Japan
81 Citations2001Yoshihisa Fujino, Tetsuya Mizoue +2 more
The purpose of the present study was to examine the association between diabetes and liver cancer in view of the trend and the interaction.
Digestive Diseases and SciencesDiabetes Mellitus May Be Associated with Hepatocarcinogenesis in Patients with Chronic Hepatitis C
80 Citations2002Junichi Tazawa, Manabu Maeda +6 more
European Journal of CancerAttributable risks for hepatocellular carcinoma in Northern Italy
61 Citations1997C Braga, Carlo La Vecchia +2 more
Even if available information on hepatitis and dietary factors was limited, and the AR estimates were based on several arbitrary assumptions, available knowledge could, in principle, reduce the burden of the disease in Italy from 3300 deaths to approximately 750 for males, and from 1600 to approximately 500 for females.
Alcoholism Clinical and Experimental ResearchAnalysis of Risk Factors for Hepatocellular Carcinoma in Patients With HBs Antigen‐ and Anti‐HCV Antibody‐Negative Alcoholic Cirrhosis: Clinical Significance of Prior Hepatitis B Virus Infection
53 Citations2003Shinichiro Uetake, Masayoshi Yamauchi +4 more
It is suggested that heavy cumulative alcohol intake and prior exposure to HBV infection are risk factors for the development of HCC in patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis.
Japanese Journal of Cancer ResearchA Hospital‐based Case‐Control Study on Hepatocellular Carcinoma in Fukuoka and Saga Prefectures, Northern Kyushu, Japan
51 Citations1993Katsuhiro Fukuda, Akira Shibata +4 more
Multivariatc analyses based on a conditional logistic regression model without an interaction term revealed that hepatitis B surface antigen (HBsAg) positive status and anti‐hepatitis C virus antibody by c100‐3 antigen positive status had a statistically significant OR for HCC in both sexes.
Journal of EpidemiologyA Case-Control Study on Male Hepatocellular Carcinoma Based on Hospital and Community Controls
29 Citations1998Akira Shibata, Katsuhiro Fukuda +3 more
A case control study on male primary hepatocellular carcinoma and hepatitis B or C virus and some potential risk factors, e.g. blood transfusion, aldehyde dehydrogenase 2(ALDH2) genotype and drinking habits, was performed using two controls in Fukuoka and Saga Prefectures.
The Kurume Medical JournalAssociation between Diabetes Mellitus and Hepatocellular Carcinoma: Results of a Hospital- and Community-based Case-control Study
26 Citations2003MICHIYO MATSUO
Investigating the relationship between diabetes mellitus (DM) and primary hepatocellular carcinoma (HCC) in Kyushu, Japan revealed that DM might be a risk factor for HCC.