Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection

Brad Q. Starley; Christopher J. Calcagno; Stephen A. Harrison

doi:10.1002/hep.23594

journal article May 01, 2010

Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection

Brad Q. Starley Christopher J. Calcagno Stephen A. Harrison

Hepatology Vol. 51 No. 5 pp. 1820-1832 · Ovid Technologies (Wolters Kluwer Health)

View at Publisher Save 10.1002/hep.23594

Abstract

Hepatocellular carcinoma (HCC) is a common and deadly malignancy that is increasing in incidence in developed countries. The emergence of hepatitis C virus (HCV) accounts for about half of this increase in HCC, although the etiology of HCC in 15%-50% of new HCC cases remains unclear. The most common form of chronic liver disease in developed countries is nonalcoholic fatty liver disease (NAFLD), which encompasses a broad spectrum of histopathology. The prevalence of NAFLD, including the more aggressive nonalcoholic steatohepatitis (NASH), is increasing with the growing epidemics of diabetes and obesity. NASH can progress to cirrhosis and its related complications. Growing evidence suggests that NASH accounts for a large proportion of idiopathic or cryptogenic cirrhosis, which is associated with the typical risk factors for NASH. HCC is a rare, although important complication of NAFLD. Diabetes and obesity have been established as independent risk factors for the development of HCC. New evidence also suggests that hepatic iron deposition increases the risk of HCC in NASH-derived cirrhosis. Multiple case reports and case reviews of HCC in the setting of NASH support the associations of diabetes and obesity with the risk of HCC, as well as suggest age and advanced fibrosis as significant risks. Insulin resistance and its subsequent inflammatory cascade that is associated with the development of NASH appear to play a significant role in the carcinogenesis of HCC. The complications of NASH, including cirrhosis and HCC, are expected to increase with the growing epidemic of diabetes and obesity. (Hepatology 2010;51:1820–1832)

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References

130

[1]

Gomaa "Hepatocellular carcinoma: epidemiology, risk factors, and pathogenesis." World J Gastroenterol (2008) 10.3748/wjg.14.4300

[2]

Parkin "Global cancer statistics in the year 2000." Lancet Oncol (2001) 10.1016/s1470-2045(01)00486-7

[3]

ElSerag "Hepatocellular carcinoma: epidemiology and molecular carcinogenesis." Gastroenterology (2007)

[4]

Bosch "Primary liver cancer: worldwide incidence and trends." Gastroenterology (2004) 10.1053/j.gastro.2004.09.011

[5]

ElSerag "Rising incidence of hepatocellular carcinoma in the United States." N Engl J Med (1999)

[6]

Bugianesi "Nonalcoholic steatohepatitis and cancer." Clin Liver Dis (2007) 10.1016/j.cld.2007.02.006

[7]

Sass "Nonalcoholic fatty liver disease: a clinical review." Dig Dis Sci (2005) 10.1007/s10620-005-1267-z

[8]

Clark "The prevalence and etiology of elevated aminotransferase levels in the United States." Am J Gastroenterol (2003) 10.1111/j.1572-0241.2003.07486.x

[9]

Browning "Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity." HEPATOLOGY (2004) 10.1002/hep.20466

[10]

Schaffner "Nonalcoholic fatty liver disease." Prog Liver Dis (1986)

[11]

Hamaguchi "The metabolic syndrome as a predictor of nonalcoholic fatty liver disease." Ann Intern Med (2005) 10.7326/0003-4819-143-10-200511150-00009

[12]

Suzuki "Chronological development of elevated aminotransferases in a nonalcoholic population." HEPATOLOGY (2005) 10.1002/hep.20543

[13]

Shen "Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey World." J Gastroenterol (2003)

[14]

Omagari "Fatty liver in nonalcoholic nonoverweight Japanese adults: incidence and clinical characteristics." J Gastroenterol Hepatol (2002) 10.1046/j.1440-1746.2002.02846.x

[15]

Nomura "Prevalence of fatty liver in a general population of Okinawa, Japan." Jpn J Med (1988) 10.2169/internalmedicine1962.27.142

[16]

Ground "Liver pathology in aircrew." Aviat Space Environ Med (1982)

[17]

Hilden "Liver histology in a normal populationexaminations of 503 consecutive fatal traffic casualties." Scand J Gastroenterol (1977) 10.3109/00365527709181339

[18]

Epidemiology of Fatty Liver in a Hospital-based Study in Taiwan

Shih-Wei Lai, CHEE-KEONG TAN, KIM-CHOY NG

Southern Medical Journal 2002 10.1097/00007611-200295110-00012

[19]

Nonumura "Clinicopathologic study of alcohollike liver disease in nonalcoholics: nonalcoholic steatohepatitis and fibrosis." Gastroenterol Jpn (1992)

[20]

Bedogni "Prevalence of and risk factors for nonalcoholic fatty liver disease: the dionysos nutrition and liver study." HEPATOLOGY (2005) 10.1002/hep.20734

[21]

Torres "Diagnosis and therapy of nonalcoholic steatohepatitis." Gastroenterology (2008) 10.1053/j.gastro.2008.02.077

[22]

Daniel "Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients." Am J Gastroenterol (2000)

[23]

Skelly "Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology." J Hepatol (2001) 10.1016/s0168-8278(01)00094-0

[24]

Fan "Prevalence of and risk factors for fatty liver in a general population of Shanghai, China." J Hepatol (2005) 10.1016/j.jhep.2005.02.042

[25]

Weston "Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease." HEPATOLOGY (2005) 10.1002/hep.20554

[26]

Caldwell "Is NASH underdiagnosed among African Americans?" Am J Gastroenterol (2002) 10.1111/j.1572-0241.2002.05795.x

[27]

Nonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome

Giulio Marchesini, Elisabetta Bugianesi, Gabriele Forlani et al.

Hepatology 2003 10.1053/jhep.2003.50161

[28]

Ludwig "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease." Mayo Clin Proc (1980) 10.1016/s0025-6196(24)00530-5

[29]

Pagano "Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association." HEPATOLOGY (2002) 10.1053/jhep.2002.30690

[30]

CortezPinto "Nonalcoholic fatty liver: another feature of the metabolic syndrome?" Clin Nutr (1999)

[31]

Chitturi "NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome." HEPATOLOGY (2002) 10.1053/jhep.2002.30692

[32]

Harrison "The natural history of nonalcoholic fatty liver disease: a clinical histopathological study." Am J Gastroenterol (2003) 10.1111/j.1572-0241.2003.07659.x

[33]

Adams "The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies." J Hepatol (2005) 10.1016/j.jhep.2004.09.012

[34]

Fassio "Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies." HEPATOLOGY (2004)

[35]

Lindor "Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial." HEPATOLOGY (2004) 10.1002/hep.20092

[36]

Ong "Nonalcoholic fatty liver disease (NAFLD)two decades later: are we smarter about its natural history?" Am J Gastroenterol (2003) 10.1111/j.1572-0241.2003.07667.x

[37]

Argo "Epidemiology and natural history of nonalcoholic steatohepatitis." Clin Liver Dis (2009) 10.1016/j.cld.2009.07.005

[38]

Hui "Longterm outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C." HEPATOLOGY (2003) 10.1053/jhep.2003.50320

[39]

Adams "The natural history of nonalcoholic fatty liver disease: a populationbased cohort study." Gastroenterology (2005) 10.1053/j.gastro.2005.04.014

[40]

Ratziu "Survival, liver failure, and hepatocellular carcinoma in obesityrelated cryptogenic cirrhosis." HEPATOLOGY (2002) 10.1053/jhep.2002.33324

[41]

Siegel "Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link." Cancer (2009) 10.1002/cncr.24687

[42]

Ekstedt "Longterm followup of patients with NAFLD and elevated liver enzymes." HEPATOLOGY (2006) 10.1002/hep.21327

[43]

Ong "Increased overall mortality and liverrelated mortality in nonalcoholic fatty liver disease." J Hepatol (2008)

[44]

Rafiq "Longterm followup of patients with nonalcoholic fatty liver." Clin Gastorenterol Hepatol (2009)

[45]

Bugianesi "Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma." Gastroenterology (2002) 10.1053/gast.2002.34168

[46]

Caldwell "Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease." HEPATOLOGY (1999) 10.1002/hep.510290347

[47]

Poonawala "Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a casecontrol study." HEPATOLOGY (2000) 10.1053/jhep.2000.17894

[48]

Powell "The natural history of nonalcoholic steatohepatitis: a followup study of fortytwo patients for up to 21 years." HEPATOLOGY (1990) 10.1002/hep.1840110114

[49]

Abdelmalek "Two cases from the spectrum of nonalcoholic steatohepatitis." J Clin Gastroenterol (1995) 10.1097/00004836-199503000-00011

[50]

Ong "Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease." Liver Transpl (2001) 10.1053/jlts.2001.24644

Showing 50 of 130 references

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Details

Published: May 01, 2010
Vol/Issue: 51(5)
Pages: 1820-1832
License: View

Authors

B

Brad Q. Starley

C

Christopher J. Calcagno

S

Stephen A. Harrison

From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) — all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié–Salpêtrière, Assistance Publique–Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutr...

Cite This Article

Brad Q. Starley, Christopher J. Calcagno, Stephen A. Harrison (2010). Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection. Hepatology, 51(5), 1820-1832. https://doi.org/10.1002/hep.23594

Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection

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