The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a well‐recognized cause of cirrhosis and has been increasingly associated with the development of hepatocellular carcinoma (HCC). The aims of this study were to (1) estimate the incidence of HCC in patients with NASH‐related cirrhosis, (2) compare incidence in NASH‐related cirrhosis with hepatitis C virus (HCV)‐related cirrhosis, and (3) identify risk factors of HCC in patients with NASH‐related cirrhosis compared with HCV‐related cirrhosis. Adult patients with cirrhosis secondary to chronic HCV (n = 315) or NASH (n = 195) were evaluated at our hepatobiliary clinic between 2003 and 2007. To assess for HCC development, all patients were monitored using serial abdominal computed tomography and serum alpha‐fetoprotein every 6 months. Kaplan‐Meier analysis was performed to estimate the cumulative incidence of HCC. Descriptive statistics were computed for all factors. Univariate and multivariate Cox regression analysis were used to assess associations between HCC and factors of interest. The median follow‐up was 3.2 years (25th percentile [P25], 75th percentile [P75]: 1.7, 5.7) during which 25/195 (12.8%) of NASH‐cirrhotic and 64/315 (20.3 %) of HCV‐cirrhotic patients developed HCC (P = 0.03). Yearly cumulative incidence of HCC was found to be 2.6% in patients with NASH‐cirrhosis, compared with 4.0% in patients with HCV cirrhosis (P = 0.09). Multivariate regression analysis revealed that older age (P = 0.006) and alcohol consumption (P = 0.002) were independent variables associated with development of HCC in patients with NASH‐cirrhosis. Compared with nondrinkers, patients who reported any regular alcohol consumption were at greater risk for HCC development (hazard ratio: 3.6; P25, P75: 1.5, 8.3). Conclusion: Patients with NASH cirrhosis have a greatly increased risk of liver cancer. Alcohol consumption, a modifiable risk factor, appears to be the most significant factor associated with risk of HCC development in our study population. (Hepatology 2010;)

[1]  M. Kedda,et al.  The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks. , 1997, Gastroenterology.

[2]  J. Marrero,et al.  NAFLD may be a common underlying liver disease in patients with hepatocellular Carcinoma in the United States , 2002, Hepatology.

[3]  R. Groszmann,et al.  American association for the study of liver diseases , 1992 .

[4]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.

[5]  H. El‐Serag,et al.  Rising incidence of hepatocellular carcinoma in the United States. , 1999, The New England journal of medicine.

[6]  P. Giral,et al.  Survival, liver failure, and hepatocellular carcinoma in obesity‐related cryptogenic cirrhosis , 2002, Hepatology.

[7]  K. Wakasa,et al.  Hepatocellular Carcinoma Arising from Nonalcoholic Steatohepatitis: Report of Two Cases , 2005, Surgery Today.

[8]  J. Bruix,et al.  Management of hepatocellular carcinoma , 2005, Hepatology.

[9]  P. Macfarlane,et al.  Metabolic Syndrome With and Without C-Reactive Protein as a Predictor of Coronary Heart Disease and Diabetes in the West of Scotland Coronary Prevention Study , 2003, Circulation.

[10]  K. McGlynn,et al.  The Continuing Increase in the Incidence of Hepatocellular Carcinoma in the United States: An Update , 2003, Annals of Internal Medicine.

[11]  C. la Vecchia,et al.  The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  S. Caldwell,et al.  Cryptogenic cirrhosis: Clinical characterization and risk factors for underlying disease , 1999, Hepatology.

[13]  H. El‐Serag,et al.  Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. , 2007, Gastroenterology.

[14]  S. Porru,et al.  Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. , 2002, American journal of epidemiology.

[15]  A. Feldstein,et al.  Diabetes Mellitus Is Associated with Impaired Response to Antiviral Therapy in Chronic Hepatitis C Infection , 2009, Digestive Diseases and Sciences.

[16]  Jian-Min Yuan,et al.  Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. , 2004, Cancer.

[17]  R. Carithers,et al.  Practice Guidelines : Evaluation of the Patient for Liver Transplantation , 2005 .

[18]  J. Olsen,et al.  Obesity and cancer risk: a Danish record-linkage study. , 1994, European journal of cancer.

[19]  M. Taniai,et al.  Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis , 2009, Journal of Gastroenterology.

[20]  R O Morgan,et al.  Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study , 2005, Gut.

[21]  Robert A Fisher,et al.  Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C , 2006, Hepatology.

[22]  H. El‐Serag,et al.  The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[23]  Jian-Min Yuan,et al.  Environmental factors and risk for hepatocellular carcinoma. , 2004, Gastroenterology.

[24]  Teruaki Kimura,et al.  Hepatocellular carcinoma with nonalcoholic steatohepatitis , 2004, Journal of Gastroenterology.

[25]  E. Abdalla,et al.  Obesity and diabetes as a risk factor for hepatocellular carcinoma , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[26]  M. Kudo Hepatocellular carcinoma and NASH , 2004, Journal of gastroenterology.

[27]  J. Fraumeni,et al.  Cigarette smoking and liver cancer among US veterans , 1990, Cancer Causes & Control.

[28]  Michael J Thun,et al.  Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. , 2003, The New England journal of medicine.

[29]  B. Henderson,et al.  Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. , 1989, Cancer research.

[30]  A. Zuckerman,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans , 1995, IARC monographs on the evaluation of carcinogenic risks to humans.

[31]  R. Poon Angiogenesis in Hepatocellular Carcinoma , 2000 .

[32]  H. Adami,et al.  A prospective study of obesity and cancer risk (Sweden) , 2004, Cancer Causes & Control.

[33]  J. Marrero,et al.  Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. , 2005, Journal of hepatology.

[34]  Mauro Salizzoni,et al.  Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. , 2002, Gastroenterology.

[35]  C. O. Zein,et al.  Predictors and Noninvasive Identification of Severe Liver Fibrosis in Patients with Chronic Hepatitis C , 2007, Digestive Diseases and Sciences.