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Carcinogenesis and NAFLD
CARCINOGENESIS AND THE SPECTRUM OF HEPATIC
TUMORS IN NASH
Augusto Villanueva
Icahn School of Medicine at Mount Sinai,
New York, NY, The United States
Email: augusto.villanueva@mssm.edu
Take home messages
• There is compelling epidemiological evidence of a casual link between NAFLD/NASH and HCC.
• It remains unclear what is the risk of HCC in patients with NAFLD or non-cirrhotic NASH. The
role of HCC surveillance in these populations remains to be determined.
• Potential mechanisms involved in NAFLD/NASH HCC involve inflammation pathways (e.g. NF-
kB), metabolic disarray (e.g. PTEN) and oxidative stress (e.g. SAM).
• In terms of chemoprevention, no drug has been able to prevent disease progression and HCC
development in NASH patients. The alleged protective role of metformin needs to be confirmed in
controlled studies.
Introduction
At a global scale, mortality due to liver cancer has increased by more than 50% in the last 20 years. It
remains as one of the deadliest malignancies with a high ratio of mortality to incidence of 0.95. Since
2012, liver cancer is the second most common cause of death from cancer worldwide. In the US, recent
data estimated that in 2014 there would be 33,190 new cases of liver cancer. Overall, patients’ 5-year
survival is 16%, which is second only to pancreatic cancer. Altogether, these data confirm that disease
burden due to liver cancer is increasing in the US as well as worldwide.The AACR 2013 report confirms
how liver cancer has become the leading cause of increased cancer mortality in the US in the last 20
years.
Different reports suggest that patients with NAFLD-HCC tend to be older, with tumors diagnosed
at more advanced stages, but these assumptions are not supported by strong data. To increase the
controversy, there are also studies indicating that NAFLD/NASH tumors are less aggressive compared
with hepatitis-related HCC. In terms of clinical management, there is no evidence suggesting that
NAFLD-HCC should be managed differently to other etiologies. Recommended management of HCC
is extensively described in the 2012 EASL-EORTC guidelines [1]. In terms of early HCC detection
and surveillance, guidelines recommend abdominal ultrasound every 6 months in at-risk populations.
These are broadly cirrhotic patients of any etiology, and certain subgroups of patients with non-cirrhotic
hepatitis B or C. Based on the available data, screening is not recommended in patients with NAFLD/
NASH who haven’t developed cirrhosis. Regarding prognostic prediction, the BCLC algorithm is
endorsed as a general roadmap to classify patients and guide treatment decision-making. There are
five treatment modalities that are recommended based on their ability to improve survival, including
potentially curative options (i.e. resection, transplantation and ablation) and palliative treatments (i.e.
transarterial chemoembolization and sorafenib). Following the approval of sorafenib in 2007, all phase
3 clinical trials testing new drugs in patients with advanced stages have been negative.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 77
CARCINOGENESIS AND THE SPECTRUM OF HEPATIC
TUMORS IN NASH
Augusto Villanueva
Icahn School of Medicine at Mount Sinai,
New York, NY, The United States
Email: augusto.villanueva@mssm.edu
Take home messages
• There is compelling epidemiological evidence of a casual link between NAFLD/NASH and HCC.
• It remains unclear what is the risk of HCC in patients with NAFLD or non-cirrhotic NASH. The
role of HCC surveillance in these populations remains to be determined.
• Potential mechanisms involved in NAFLD/NASH HCC involve inflammation pathways (e.g. NF-
kB), metabolic disarray (e.g. PTEN) and oxidative stress (e.g. SAM).
• In terms of chemoprevention, no drug has been able to prevent disease progression and HCC
development in NASH patients. The alleged protective role of metformin needs to be confirmed in
controlled studies.
Introduction
At a global scale, mortality due to liver cancer has increased by more than 50% in the last 20 years. It
remains as one of the deadliest malignancies with a high ratio of mortality to incidence of 0.95. Since
2012, liver cancer is the second most common cause of death from cancer worldwide. In the US, recent
data estimated that in 2014 there would be 33,190 new cases of liver cancer. Overall, patients’ 5-year
survival is 16%, which is second only to pancreatic cancer. Altogether, these data confirm that disease
burden due to liver cancer is increasing in the US as well as worldwide.The AACR 2013 report confirms
how liver cancer has become the leading cause of increased cancer mortality in the US in the last 20
years.
Different reports suggest that patients with NAFLD-HCC tend to be older, with tumors diagnosed
at more advanced stages, but these assumptions are not supported by strong data. To increase the
controversy, there are also studies indicating that NAFLD/NASH tumors are less aggressive compared
with hepatitis-related HCC. In terms of clinical management, there is no evidence suggesting that
NAFLD-HCC should be managed differently to other etiologies. Recommended management of HCC
is extensively described in the 2012 EASL-EORTC guidelines [1]. In terms of early HCC detection
and surveillance, guidelines recommend abdominal ultrasound every 6 months in at-risk populations.
These are broadly cirrhotic patients of any etiology, and certain subgroups of patients with non-cirrhotic
hepatitis B or C. Based on the available data, screening is not recommended in patients with NAFLD/
NASH who haven’t developed cirrhosis. Regarding prognostic prediction, the BCLC algorithm is
endorsed as a general roadmap to classify patients and guide treatment decision-making. There are
five treatment modalities that are recommended based on their ability to improve survival, including
potentially curative options (i.e. resection, transplantation and ablation) and palliative treatments (i.e.
transarterial chemoembolization and sorafenib). Following the approval of sorafenib in 2007, all phase
3 clinical trials testing new drugs in patients with advanced stages have been negative.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 77
