Obesity and hepatocellular carcinoma

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GASTROENTEROLOGY

November 2004, Supplement . Volume 127 . Number 5

Obesity and hepatocellular carcinoma

H. Caldwell * *

Deborah M. Crespo ?

Hyon Kang *

Abdullah M.S. Al-Osaimi *

Epidemiological studies have shown that obesity is a risk factor for

hepatocellular carcinoma. Similar studies further indicate that diabetes is

also a major risk factor. Both obesity and diabetes are frequently

associated with nonalcoholic fatty liver disease, and case reports have

shown progression of nonalcoholic fatty liver disease to cirrhosis and

hepatocellular carcinoma. Although no study has clearly tied all of these

variables together, it is likely that the association of hepatocellular

carcinoma with obesity represents the progression of underlying nonalcoholic

fatty liver disease to cirrhosis. The mechanism most likely involves

replicative senescence of steatotic mature hepatocytes and compensatory

hyperplasia of progenitor (oval) cells as a reaction to chronic injury due

to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis.

Growth factors associated with chronic inflammation, type 2 diabetes, and

DNA mutations as a result of lipid peroxidation probably play significant

roles in clonal expansion and hepatocellular carcinoma progression. It

remains unclear whether cirrhosis is a prerequisite for the development of

hepatocellular carcinoma or whether hepatocellular carcinoma can develop in

fatty liver in the absence of cirrhosis. However, well-documented case

reports suggest that most cases of hepatocellular carcinoma arise in the

setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy

aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular

carcinoma remains to be shown. Prophylactic measures and the role of cancer

surveillance have not been adequately investigated, but current evidence

suggests a risk for hepatocellular carcinoma in nonalcoholic

steatohepatitis-related cirrhosis that rivals that of hepatocellular

carcinoma in hepatitis C virus-related cirrhosis, particularly in older male

patients.

Publishing and Reprint Information

*Division of Gastroenterology and Hepatology, University of Virginia,

Charlottesville, Virginia

?Nucleo de Estudos e Pesquisas em Hepatologia da Amazonia, Belem-Para,

Brazil

None of the authors has affiliations or private industry affiliations

relevant to this work.

*Address requests for reprints to: H. Caldwell, MD, Division of

Gastroenterology and Hepatology, University of Virginia Health System, P.O.

Box 800708, Charlottesville, Virginia 22908-0708. fax: (434) 924-0491

Email address: shc5c@... ( H. Caldwell)

Copyright © by American Gastroenterological Association

doi: 10.1053/j.gastro.2004.09.021

[Guest guest]

GASTROENTEROLOGY

November 2004, Supplement . Volume 127 . Number 5

Obesity and hepatocellular carcinoma

H. Caldwell * *

Deborah M. Crespo ?

Hyon Kang *

Abdullah M.S. Al-Osaimi *

Epidemiological studies have shown that obesity is a risk factor for

hepatocellular carcinoma. Similar studies further indicate that diabetes is

also a major risk factor. Both obesity and diabetes are frequently

associated with nonalcoholic fatty liver disease, and case reports have

shown progression of nonalcoholic fatty liver disease to cirrhosis and

hepatocellular carcinoma. Although no study has clearly tied all of these

variables together, it is likely that the association of hepatocellular

carcinoma with obesity represents the progression of underlying nonalcoholic

fatty liver disease to cirrhosis. The mechanism most likely involves

replicative senescence of steatotic mature hepatocytes and compensatory

hyperplasia of progenitor (oval) cells as a reaction to chronic injury due

to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis.

Growth factors associated with chronic inflammation, type 2 diabetes, and

DNA mutations as a result of lipid peroxidation probably play significant

roles in clonal expansion and hepatocellular carcinoma progression. It

remains unclear whether cirrhosis is a prerequisite for the development of

hepatocellular carcinoma or whether hepatocellular carcinoma can develop in

fatty liver in the absence of cirrhosis. However, well-documented case

reports suggest that most cases of hepatocellular carcinoma arise in the

setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy

aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular

carcinoma remains to be shown. Prophylactic measures and the role of cancer

surveillance have not been adequately investigated, but current evidence

suggests a risk for hepatocellular carcinoma in nonalcoholic

steatohepatitis-related cirrhosis that rivals that of hepatocellular

carcinoma in hepatitis C virus-related cirrhosis, particularly in older male

patients.

Publishing and Reprint Information

*Division of Gastroenterology and Hepatology, University of Virginia,

Charlottesville, Virginia

?Nucleo de Estudos e Pesquisas em Hepatologia da Amazonia, Belem-Para,

Brazil

None of the authors has affiliations or private industry affiliations

relevant to this work.

*Address requests for reprints to: H. Caldwell, MD, Division of

Gastroenterology and Hepatology, University of Virginia Health System, P.O.

Box 800708, Charlottesville, Virginia 22908-0708. fax: (434) 924-0491

Email address: shc5c@... ( H. Caldwell)

Copyright © by American Gastroenterological Association

doi: 10.1053/j.gastro.2004.09.021

[Guest guest]

GASTROENTEROLOGY

November 2004, Supplement . Volume 127 . Number 5

Obesity and hepatocellular carcinoma

H. Caldwell * *

Deborah M. Crespo ?

Hyon Kang *

Abdullah M.S. Al-Osaimi *

Epidemiological studies have shown that obesity is a risk factor for

hepatocellular carcinoma. Similar studies further indicate that diabetes is

also a major risk factor. Both obesity and diabetes are frequently

associated with nonalcoholic fatty liver disease, and case reports have

shown progression of nonalcoholic fatty liver disease to cirrhosis and

hepatocellular carcinoma. Although no study has clearly tied all of these

variables together, it is likely that the association of hepatocellular

carcinoma with obesity represents the progression of underlying nonalcoholic

fatty liver disease to cirrhosis. The mechanism most likely involves

replicative senescence of steatotic mature hepatocytes and compensatory

hyperplasia of progenitor (oval) cells as a reaction to chronic injury due

to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis.

Growth factors associated with chronic inflammation, type 2 diabetes, and

DNA mutations as a result of lipid peroxidation probably play significant

roles in clonal expansion and hepatocellular carcinoma progression. It

remains unclear whether cirrhosis is a prerequisite for the development of

hepatocellular carcinoma or whether hepatocellular carcinoma can develop in

fatty liver in the absence of cirrhosis. However, well-documented case

reports suggest that most cases of hepatocellular carcinoma arise in the

setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy

aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular

carcinoma remains to be shown. Prophylactic measures and the role of cancer

surveillance have not been adequately investigated, but current evidence

suggests a risk for hepatocellular carcinoma in nonalcoholic

steatohepatitis-related cirrhosis that rivals that of hepatocellular

carcinoma in hepatitis C virus-related cirrhosis, particularly in older male

patients.

Publishing and Reprint Information

*Division of Gastroenterology and Hepatology, University of Virginia,

Charlottesville, Virginia

?Nucleo de Estudos e Pesquisas em Hepatologia da Amazonia, Belem-Para,

Brazil

None of the authors has affiliations or private industry affiliations

relevant to this work.

*Address requests for reprints to: H. Caldwell, MD, Division of

Gastroenterology and Hepatology, University of Virginia Health System, P.O.

Box 800708, Charlottesville, Virginia 22908-0708. fax: (434) 924-0491

Email address: shc5c@... ( H. Caldwell)

Copyright © by American Gastroenterological Association

doi: 10.1053/j.gastro.2004.09.021

[Guest guest]

GASTROENTEROLOGY

November 2004, Supplement . Volume 127 . Number 5

Obesity and hepatocellular carcinoma

H. Caldwell * *

Deborah M. Crespo ?

Hyon Kang *

Abdullah M.S. Al-Osaimi *

Epidemiological studies have shown that obesity is a risk factor for

hepatocellular carcinoma. Similar studies further indicate that diabetes is

also a major risk factor. Both obesity and diabetes are frequently

associated with nonalcoholic fatty liver disease, and case reports have

shown progression of nonalcoholic fatty liver disease to cirrhosis and

hepatocellular carcinoma. Although no study has clearly tied all of these

variables together, it is likely that the association of hepatocellular

carcinoma with obesity represents the progression of underlying nonalcoholic

fatty liver disease to cirrhosis. The mechanism most likely involves

replicative senescence of steatotic mature hepatocytes and compensatory

hyperplasia of progenitor (oval) cells as a reaction to chronic injury due

to ongoing nonalcoholic steatohepatitis and resultant hepatic fibrosis.

Growth factors associated with chronic inflammation, type 2 diabetes, and

DNA mutations as a result of lipid peroxidation probably play significant

roles in clonal expansion and hepatocellular carcinoma progression. It

remains unclear whether cirrhosis is a prerequisite for the development of

hepatocellular carcinoma or whether hepatocellular carcinoma can develop in

fatty liver in the absence of cirrhosis. However, well-documented case

reports suggest that most cases of hepatocellular carcinoma arise in the

setting of nonalcoholic steatohepatitis with cirrhosis. Whether therapy

aimed at nonalcoholic fatty liver disease reduces the risk of hepatocellular

carcinoma remains to be shown. Prophylactic measures and the role of cancer

surveillance have not been adequately investigated, but current evidence

suggests a risk for hepatocellular carcinoma in nonalcoholic

steatohepatitis-related cirrhosis that rivals that of hepatocellular

carcinoma in hepatitis C virus-related cirrhosis, particularly in older male

patients.

Publishing and Reprint Information

*Division of Gastroenterology and Hepatology, University of Virginia,

Charlottesville, Virginia

?Nucleo de Estudos e Pesquisas em Hepatologia da Amazonia, Belem-Para,

Brazil

None of the authors has affiliations or private industry affiliations

relevant to this work.

*Address requests for reprints to: H. Caldwell, MD, Division of

Gastroenterology and Hepatology, University of Virginia Health System, P.O.

Box 800708, Charlottesville, Virginia 22908-0708. fax: (434) 924-0491

Email address: shc5c@... ( H. Caldwell)

Copyright © by American Gastroenterological Association

doi: 10.1053/j.gastro.2004.09.021