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Carcinogenesis and NAFLD
LIVER CANCER IN NAFLD: MAGNITUDE OF THE
PROBLEM
Jean-François Dufour
University Clinic for Visceral Surgery and Medicine,
University of Bern, Bern, Switzerland
Email: jf.dufour@ikp.unibe.ch
Take home messages
• HCC in NAFLD is associated with cryptogenic cirrhosis, obesity and diabetes.
• HCC in NAFLD occurs often without cirrhosis.
• Cirrhotic patients with metabolic syndrome or NAFLD should undergo surveillance. In non-cirrhotic
individuals, the risk of HCC development should be better stratified.
• The therapeutic algorithm used in HCC patients should be applied to patients with HCC due to
NAFLD.
• The proportion of patients with HCC due to NAFLD is increasing.
HCC in NAFLD: association with cryptogenic cirrhosis, obesity and diabetes
HCC is one of the most serious complications of chronic liver disease. This is certainly the case for
NAFLD. But HCC in the context of NAFLD has several specific features.
The predominant risk factor for HCC is cirrhosis, regardless of the underlying liver disease. The
incidence of HCC has been determined for several etiologies. The incidence of HCC for hepatitis
B-induced and hepatitis C-induced cirrhosis is estimated at 3-8%/year and 3-5%/year, respectively. In
a prospective cohort of 68 NASH cirrhotic patients the 5-year HCC rate was 11%, which was 3 times
lower than the 30% 5-year HCC rate observed in 69 HCV cirrhotics [1]. In a prospective US study the
risk of development of HCC was similarly 2.5 fold lower in NASH cirrhotics than in HCV-cirrhotics [2].
A substantial fraction of patients with cryptogenic cirrhosis have in fact a ‘burn-out NASH’. This is
partly due to the fact the NASH-induced cirrhosis is not only an exclusion diagnosis (similarly to NASH
which is an exclusion diagnosis), but also a default diagnosis since some of the histological features of
NASH disappear when the disease reaches a cirrhotic stage. Patients with a cryptogenic cirrhosis and
HCC present clinical characteristics associated with NAFLD, namely obesity and T2DM. Among 641
cases of cirrhosis-associated HCC, 44 patients with cryptogenic cirrhosis were retrospectively identified.
These patients had a higher prevalence of obesity and T2DM [3]. In a French series of HCC patients
undergoing surgical resection, 9% had cryptogenic cirrhosis. These patients had a higher prevalence
of obesity compared to alcohol- or virus-related cirrhotics (50% vs. 17% vs. 14%, respectively) and a
higher prevalence of diabetes (56% vs. 17% vs. 11%, respectively) (P<0.0001 for each) [4]. Patients
with cryptogenic cirrhosis are at risk of developing HCC. In a French retrospective analysis, HCC was
detected in 27% of obese patients with cryptogenic cirrhosis vs. 21% in hepatitis C induced cirrhosis,
resulting in a similar age cumulated incidence [5].
Obesity and T2DM are both risk factors for HCC. Obesity increases mortality due to many types
of cancer, but this is particularly the case for HCC. In obese individuals, the relative risk of death
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 81
LIVER CANCER IN NAFLD: MAGNITUDE OF THE
PROBLEM
Jean-François Dufour
University Clinic for Visceral Surgery and Medicine,
University of Bern, Bern, Switzerland
Email: jf.dufour@ikp.unibe.ch
Take home messages
• HCC in NAFLD is associated with cryptogenic cirrhosis, obesity and diabetes.
• HCC in NAFLD occurs often without cirrhosis.
• Cirrhotic patients with metabolic syndrome or NAFLD should undergo surveillance. In non-cirrhotic
individuals, the risk of HCC development should be better stratified.
• The therapeutic algorithm used in HCC patients should be applied to patients with HCC due to
NAFLD.
• The proportion of patients with HCC due to NAFLD is increasing.
HCC in NAFLD: association with cryptogenic cirrhosis, obesity and diabetes
HCC is one of the most serious complications of chronic liver disease. This is certainly the case for
NAFLD. But HCC in the context of NAFLD has several specific features.
The predominant risk factor for HCC is cirrhosis, regardless of the underlying liver disease. The
incidence of HCC has been determined for several etiologies. The incidence of HCC for hepatitis
B-induced and hepatitis C-induced cirrhosis is estimated at 3-8%/year and 3-5%/year, respectively. In
a prospective cohort of 68 NASH cirrhotic patients the 5-year HCC rate was 11%, which was 3 times
lower than the 30% 5-year HCC rate observed in 69 HCV cirrhotics [1]. In a prospective US study the
risk of development of HCC was similarly 2.5 fold lower in NASH cirrhotics than in HCV-cirrhotics [2].
A substantial fraction of patients with cryptogenic cirrhosis have in fact a ‘burn-out NASH’. This is
partly due to the fact the NASH-induced cirrhosis is not only an exclusion diagnosis (similarly to NASH
which is an exclusion diagnosis), but also a default diagnosis since some of the histological features of
NASH disappear when the disease reaches a cirrhotic stage. Patients with a cryptogenic cirrhosis and
HCC present clinical characteristics associated with NAFLD, namely obesity and T2DM. Among 641
cases of cirrhosis-associated HCC, 44 patients with cryptogenic cirrhosis were retrospectively identified.
These patients had a higher prevalence of obesity and T2DM [3]. In a French series of HCC patients
undergoing surgical resection, 9% had cryptogenic cirrhosis. These patients had a higher prevalence
of obesity compared to alcohol- or virus-related cirrhotics (50% vs. 17% vs. 14%, respectively) and a
higher prevalence of diabetes (56% vs. 17% vs. 11%, respectively) (P<0.0001 for each) [4]. Patients
with cryptogenic cirrhosis are at risk of developing HCC. In a French retrospective analysis, HCC was
detected in 27% of obese patients with cryptogenic cirrhosis vs. 21% in hepatitis C induced cirrhosis,
resulting in a similar age cumulated incidence [5].
Obesity and T2DM are both risk factors for HCC. Obesity increases mortality due to many types
of cancer, but this is particularly the case for HCC. In obese individuals, the relative risk of death
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 81
