Nguyen Thị Tu Linh, PhD 5/20/24

VNU-University of Sciences

Hepatitis & Liver cancer

Hepatitis Viruses

• Viral hepatitis is a systemic disease with primary

inflammation in the liver
• There are 6 hepatitis viruses: Hepatitis A, B, C, D,
E & G viruses
• Hepatitis B is a DNA virus while A, C, D, E, and G
contain RNA genome

Hepatitis A Viruses (HAV)

• HAV is a 27 nm non-enveloped
single-stranded RNA virus with an
icosahedral symmetry
• It belongs to the picornavirus family
• The HAV enters the body by oral
route
• The large majority of infections are
asymptomatic
• The clinical disease has 2 stages:
the prodromal or pre-icteric & icteric
stages

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Hepatitis B Viruses (HBV)

• HBV belongs to the family
Hepadnaviridae
• It is a complex 42 nm double
shelled particle
• The outer surface or envelope of
virus contains hepatitis B Surface
antigen (HBsAg)

• It encloses a 27nm nucleocapsid (core) which contains

hepatitis B core antigen (HBcAg)
• Inside the core is the genome, a circular double-stranded
DNA, and a DNA polymerase

Hepatitis B Viruses (HBV)

There are 3 important modes of transmission of HBV infection
1. Parenteral transmission
2. Perinatal transmission
3. Sexual transmission

• The course of acute HBV infection can be

divided into 3 phases:
a) Preicteric phase
b) Icteric phase
c) Convalescent phase

Hepatitis C Viruses (HCV)

• HVC belongs to the family
Flaviviridae
• It is a 50-60nm virus with a
linear single-stranded RNA
• It is transmitted by use of
contaminated needles &
syringes, transfusion of injected
blood & blood products, and
sexual intercourse

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Hepatitis D Viruses (HDV)

• The HDV is a defective virus as it
is dependent on the helper
function of HBV for it replication
and expression
• It belongs to the genus Deltavirus
• It is spherical, 36-38nm diameter
• RNA particle surrounded by
HBsAg envelop

• The genome is a single-stranded small circular molecule of

RNA
• HBV is necessary for the production of HDV virions

Hepatitis E Viruses (HEV)

• HEV belongs to the family
Calciviridae, genus Calcivirus
• They are spherical, non-enveloped,
27-38 nm in diameter
• They possess single-stranded RNA
genome, which is surrounded by
icosahedral capsid
• It is primarily associated with the ingestion of faecally
contaminated drinking water
• HEV has be known to occur in epidemic, endemic and sporadic
forms almost exclusive in developing countries

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Hepatitis G Viruses (HGV)

• It appears to be a blood-borne virus
resembling HCV
• HGV RNA has been found in
patients with acute, chronic and
fulminant hepatitis, haemophiliacs,
patients with multiple transfusions,
blood donors and intravenous drug
addicts

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Can viruses lead to cancer?

• Viruses are made up of a small number of genes in the
form of DNA or RNA surrounded by a protein coating
• A virus must enter a living cell and take over the cell’s
machinery to reproduce and make more viruses.
• Some viruses do this by inserting their own DNA (or RNA)
into that of the host cell. When the DNA or RNA affects the
host cell/s genes, it can push the cell toward becoming
cancer

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Can viruses lead to cancer?

Hepatitis B Virus (HBV)
• Hepatitis B is a leading cause of liver cancer
• HBV is spread through infected blood, semen and other
body fluids
• The hepatitis B vaccine if recommended for all children
and adults
Hepatitis C Virus (HCV)
• Hepatitis B is a leading cause of liver cancer and can
cause non-Hodgkin’s lymphoma
• HCV is spread through infected blood
• There is no vaccine against hepatitis C, but it is highly
treatable

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HEPATITIS B

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Anatomy

• The largest organ in the

body (1200 – 1500g)
• Lies in the right upper
quadrant
• Pyramid like shape
• Has a double blood
supply: portal vein and
hepatic artery

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Function of the liver

n Metabolism
• anabolism of protein, cholesterol, etc.
• catabolism of protein, fat, etc.
n Nutrient storage and supply
n Detoxification
n Bile production and excretion
n Regulation of circulating blood volume

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Liver cirrhosis

Normal liver

The small finely nodular liver The glossy distorted coarsely nodular
of micronodular cirrhosis liver of macronodular cirrhosis

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Histology of cirrhotic liver

Normal liver tissue: HE stain Cirrhotic liver tissue: HE stain

Collagens are stained in blue

http://www.kanazawa-med.ac.jp Cirrhotic liver tissue: Azan stain

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Macroscopic types of HCC

Single nodular type Multiple nodular type

Massive type Diffuse type

Classification of Primary Liver Cancer: Liver Cancer Study Group of Japan

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Histology of HCC

Well-differentiated Moderately differentiated

Poorly differentiated Undifferentiated

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Classification of Liver Cancer

n Primary liver cancer

– Hepatocellular Carcinoma (HCC)
– Intrahepatic Cholangiocarcinoma (CCC) –
Combined HCC & CCC
– Cystadenocarcinoma
– Hepatoblastoma
• Metastatic Liver cancer
– Colon, Rectum, Breast etc

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Background
• Liver cancer
• Fifth most common cancer
• Second most frequent cause of cancer-related death
globally
• 854,000 new cases and 810,000 deaths per year
• 7% of all cancers

• HCC (hepatocellular carcinoma)

• Accounts for approximately 90% of primary liver
cancers

• Constitutes a major global health problem

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Incidence of primary liver cancer in Europe

Incidence rates per 100,000
Total number per country

Italy 10,733 The Netherlands 475

Germany 9,202 Croatia 466
France (metropolitan) Republic of Moldova 448
8,332 Slovakia 398
Russian Federation 6,812 Belarus 327
Spain 5,522 Bosnia Herzegovina 314
United Kingdom 4,186 Denmark 311
Romania 2,214 Ireland 239
Poland 1,998 Slovenia 216
Ukraine 1,567 Norway 190
Greece 1,054 Lithuania 175
Portugal 1,004 Albania 171
Austria 955 Latvia 154
Czech Republic, 919 FYR Macedonia 135
Switzerland 811 Luxembourg 68
Serbia 799 Estonia 64
Belgium 645 Cyprus 56
Bulgaria 640 Montenegro 51
Hungary 630 Malta 19
Finland 620 Iceland 10
Sweden 490

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Main risk factors for primary liver cancer

worldwide*
n ~90% of HCCs are of known underlying aetiology1
n Most frequently HCV, HBV, alcohol and aflatoxin exposure

Alcohol (%) HBV (%) HCV (%) Others (%)

Europe
Western 32 13 44 10
Central 46 15 29 10
Eastern 53 15 24 8
North America 37 9 31 23
Andean Latin America 23 45 12 20
Asia
East Asia 32 41 9 18
Asia-Pacific 18 22 55 6
South-East Asia 31 26 22 21
Africa
North Africa, Middle East 13 27 44 16
Southern (sub-Saharan) 40 29 20 11
Western (sub-Saharan) 29 45 11 15

*C ontribution of hepatitis B , C , alcohol and other causes on absolute liver cancer deaths, both sexes, globally and by region 2015. D ata refer to all prim ary liver cancers
(H C C , intrahepatic C C A and liver cancer of m ixed differentiation)
1. A kinyem iju T , et al. JA M A O ncol 2017;3:1683–91;
E A S L C P G H C C . J H epatol 2018; doi: 10.1016/j.jhep.2018.03.019

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Nguyen Thị Tu Linh, PhD 5/20/24
VNU-University of Sciences

Epidemiology and risk factors

n Incidence of HCC has been rising
n Driven by increases in chronic viral infections and lifestyle-related risk factors
n Cirrhosis is an important risk factor for HCC
n Multiple causes, including viral hepatitis, chronic alcohol use, NAFLD
n Up to 90% of HCC arises on a background of cirrhosis in the Western world 1

Recommendations Level of evidence Grade of recommendation

The incidence of HCC is increasing both in Europe and worldwide; it is amongst the leading
causes of cancer death globally High

Chronic liver disease should be treated to avoid progression High Strong

1. F orner A , et al. Lancet 2018;391:1301–1314;

E A S L C P G H C C . J H epatol 2018; doi: 10.1016/j.jhep.2018.03.019

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Prevention
n Primary prevention of HCC can be achieved with universal vaccination against
HBV
n Progression to cirrhosis and HCC can be prevented by:
n Antiviral treatment in patients with chronic hepatitis B and C*
n Adoption of healthy lifestyle measures

Recommendations Level of evidence Grade of recommendation

Vaccination against hepatitis B reduces the risk of HCC and is recommended for all
newborns and high-risk groups High Strong

Governmental health agencies should implement policies that:

• Prevent HBV/HCV transmission
• Counteract chronic alcohol abuse Moderate Strong
• Promote lifestyles that prevent obesity and metabolic syndrome
In patients with chronic hepatitis, use antiviral therapies to:
• Maintain HBV suppression in chronic hepatitis B High Strong
• Maintain SVR in chronic hepatitis C

*Level of evidence high, grade of recom m endation strong

E A S L C P G H C C . J H epatol 2018; doi: 10.1016/j.jhep.2018.03.019

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HCC preventive interventions

F ujiw ara N , et al. J H epatol 2018;68:526–49

E A S L C P G H C C . J H epatol 2018; doi: 10.1016/j.jhep.2018.03.019

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