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INTRODUCTION
 The incidence of HCC is increasing globally.
 HCC is the fifth leading cause of death from
cancer worldwide in men and seventh in
women.
 Chronic hepatitis B virus (HBV) and hepatitis C
virus (HCV) are responsible for 78% of cases of
HCC globally

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INTRODUCTION
 HBV for HCC in heavily populated sub-Saharan
Africa and south east Asia
 In Egypt, viral hepatitis is hyperendemic with
the highest prevalence of HCV in the world at
10% to 20% of the general population.
 In the United States, the incidence of HCC is
increasing at an alarming rate primarily caused
by HCV and nonalcoholic steatohepatitis
(NASH).

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RISK FACTORS
 The most important risk factor for the
development of HCC is a background of chronic
liver disease, for example, liver cirrhosis,
regardless of the cause.
 Hepatotropic viruses and excessive alcohol
intake are the leading risk factors.

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RISK FACTORS
 Viral Hepatitis
 Alcoholic (Laennec) Cirrhosis
 Obesity and Diabetes
 Fatty liver disease (FLD)
 Iron Storage Disease
 Biliary Disease
 Schistosomiasis
 Venous Occlusive Disease
 Liver Adenoma
 Aflatoxin
 Tobacco
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Viral Hepatitis
 Viral hepatitis, both B and C
 The chronicity of infection and progression to liver
cirrhosis is oncogenic
 A chronic hepatitis B state increases the incidence
of HCC 20- to 100-fold more than noncarriers
 HBV vaccine is the first vaccine that prevents
cancer.
 In Taiwan, vaccination of newborns has reduced
the incidence of HCC among Taiwanese children
with a parallel decrease in the HBsAg carrier state
and the incidence of HBV 6
Viral Hepatitis
 HCV is the major underlying cause of HCC in
Japan, the United States, and Egypt
 Hepatitis A and E are not implicated in the
development of HCC.
 Hepatitis D virus occurs as a coinfection with
hepatitis B but its role in development of HCC is
controversial

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Viral Hepatitis
 Liver cirrhosis, regardless of the underlying
cause, encourages hepatocarcinogenesis
 Hepatotropic viruses also have direct
carcinogenicity. In patients with HBV, a
significant number of HCCs arise in noncirrhotic
livers

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Alcoholic (Laennec) Cirrhosis
 Excessive intake of alcohol is a significant risk
factor for HCC.
 There is a synergistic relationship between
drinking alcohol (>60 g/d) and both HBV and
HCV infection in increasing the risk of HCC by
approximately 2-fold

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Obesity and Diabetes
 Epidemiologic studies have shown that obesity
and diabetes mellitus are risk factors for HCC in
nonalcoholic steatohepatitis (NASH)
 They are also the main cause of cryptogenic
cirrhosis

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Fatty Liver Disease (FLD)
 FLD is a wide spectrum of liver disease that
includes nonalcoholic FLD (NAFLD) and
nonalcoholic steatohepatitis (NASH)
 The initial insult is accumulation of fat in
hepatocytes.
 The second insult that ignites the inflammation,
steatohepatitis, leads to cirrhosis and
oncogenesis
 In NASH, 20% of patients progress to liver
fibrosis or cirrhosis, whereas, in NAFLD, only
3% of patients develop fibrosis or cirrhosis
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Iron Storage Disease
 Hemochromatosis, iron overload, and the HFE
mutations C282Y of H63D are associated with
increased risk of HCC, about 200-fold compared
with the normal population.
Biliary Disease
 Primary sclerosing cholangitis and primary biliary
cirrhosis are precursors of HCC
Schistosomiasis
 Schistosoma mansoni increased the risk of HCC
only in the presence of HCV
Venous Occlusive Disease
 Budd-Chiari syndrome secondary to vena cava
obstruction leads to an increase in hepatocyte
turnover. There have been case reports of HCC in
livers affected by Budd-Chiari syndrome
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Liver Adenoma
 The risk of malignant transformation in solitary
and multiple liver adenomas is 10%. Multiple
adenomas are typically seen in women on oral
contraceptives
Aflatoxin
 Aflatoxin is produced by the fungi Aspergillus
flavus in poorly stored grains such as rice and
corn and in nuts.
 In a meta-analysis of aflatoxin
hepatocarcinogenesis, the population
attributable risk of aflatoxin-related HCC was
found to be 23%. 13
Tobacco
 Epidemiologic studies have shown that the
association between tobacco smoking and
increased incidence of HCC is independent of
HBV or alcohol abuse.

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SURVEILLANCE
 Serum a-fetoprotein (AFP) and liver
ultrasonography (US) are the most frequently
used tests for screening
 Liver US is the recommended primary
surveillance test for HCC.

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DIAGNOSIS
 Once HCC is diagnosed on surveillance based
on US, CT and/or MRI become necessary to
confirm the diagnosis and stage the tumor
 The role of [18F]fluoro-2-deoxy-D-glucose
(FDG)-positron emission tomography (PET)
remains controversial due to its low sensitivity
(50%–55%); HCC is inconsistent in
accumulating FDG
 The role of tumor biopsy in HCC is limited to
lesions that cannot be safely characterized by
the imaging modalities
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STAGING
 The classic Child-Pugh score remains reliable
and reproducible to stratify the post
hepatectomy risk of liver failure

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BCLC 2016

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BCLC 2016

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TREATMENT OPTIONS
 Liver Resection
 Liver Transplantation
 Tumor Ablation
 Radiofrequency ablation
 Alcohol injection
 Microwave coagulation therapy (MCT)
 Laser
 Cryoablation
 TACE
 Radiation Therapy
 Transarterial radiotherapy
 Three-dimensional conformal radiotherapy
 Proton beam radiotherapy
 Combined Locoregional Therapies
 Systemic Chemotherapy
 Molecular Targeted Therapies
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FUTURE THERAPIES UNDER
INVESTIGATION
 Select Approaches of Molecular Targeted
Therapies
 c-MET inhibitors (Tivantinib)
 Epidermal growth factor receptor inhibitors
 Irreversible Electroporation (NanoKnife)
 Gene Therapy
 Circulating Tumor Cells

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SUMMARY
 Management of HCC is a rapidly evolving field
 In the past decade, with advances in liver
surgery and transplantation, curative treatment
can be offered to patients with HCC in
compensated livers who are diagnosed early or
to those who are within transplant criteria.
 For those tumors not amenable to resection or
transplantation, several locoregional therapies
are available.
 For advanced tumors, molecular targeted
therapies are yielding promising results.
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