BB2803 coursework

Background information
Hepatitis C

Clinical history of patient X

- No response to treatment

- Male: 45
- Drug addict
- Jaundice

Diagnosis: hepatitis C

Normal

Anti-HCV
treatment for
42 weeks

No treatment for 2 Y and 3 M

Liver and GIT

colon

Rectum

colon

colon

Small intestine

Functions of Liver
Amino acid synthesis
Carbohydrate metabolism
- Glycogenesis (the formation of glycogen from
glucose)
- Glycogenolysis (the breakdown of glycogen into
glucose)
- Gluconeogenesis (the synthesis of glucose from
certain amino acids, lactate or glycerol)
Fat metabolism: cholesterol synthesis , the production
of triglycerides (fats).
Protein synthesis: he liver produces, albumin,
coagulation factors I (fibrinogen), II (prothrombin), V, VII,
IX, X and XI,
The liver breaks down hemoglobin, creating metabolites
that are added to bile as pigment (bilirubin and biliverdin).
The liver breaks down or modifies toxic substances (e.g.,

Bilirubin metabolism
Haem
bilirubin

Haemoglobin
released from RBC

Bilirubin
Hemolysis
Liver
diseases
Bile flow
obstruction

80% of the daily bilirubin production (250 to 400 mg in

adults) is derived from haemoglobin under normal ( removal
of aged cells) or abnormal destruction of RBC (intravascular

The liver function tests using blood sample

Albumin: normal range: 3.9 to 5.0 g/dL
Total bilirubin: normal range: 0.11.2 mg/dL. It is raised in prehepatic,
hepatic and post hepatic abnormalities
- Direct bilirubin (conjugated bilirubin)
(normal range: 00.3 mg/dL, elevated in bile duct
obstruction and hepatic cause)
Alanine transaminase (ALT): normal range 9 to 60 IU/L, elevated when
liver cells are damaged
Aspartate transaminase (AST): normal range 10 to 40 IU/L, It is raised in
acute liver damage, but is also present in red blood cells, and cardiac and
skeletal muscle and is therefore not specific to the liver.
Alkaline phosphatase (ALP): normal range 30 to 120 IU/L. ALP levels in
plasma will rise with large bile duct obstruction, intrahepatic cholestasis
or infiltrative diseases of the liver. ALP is also present in bone and
placental tissue.
Gamma glutamyl transpeptidase (GGT): normal range 0 to 51 IU/L. It is
reasonably specific to the liver and a more sensitive marker for
cholestatic damage than ALP. GGT is raised in alcohol toxicity (acute and
chronic).

Hepatitis
(inflammation of the liver)
Can have many causes
drugs
toxins
alcohol
viral infections (A, B, C, D, E)
other infections (parasites,
bacteria)
physical damage

Hepatitis A virus (RNA virus)

Clinical Features:
After an incubation period of 3 to 6 weeks,
persons infected with HAV develop
nonspecific symptoms, including fever,
malaise, and anorexia.
Most infections with HAV are anicteric
(without jaundice)and remain undetected
Hepatitis A never pursues a chronic course.
There is no carrier state, and infection
provides lifelong immunity. Fatal culminant
hepatitis occurs only rarely.

Hepatitis A virus

Hepatitis A
Diagnosis and Treatment
Anti-HAV IgM suggest acute infection
Anti-HAV IgG suggest past infection and is common
over the age of 50
ALT and AST may be raised
Stool test for virus
No medicine or treatment t is required
Rest, fluids intake, treatment of symptoms
Most people recover completely and become immune
to reinfection

Hepatitis B (DNA virus)

Hep B infection can cause a serious
disease. Can cause lifelong infection,
cirrhosis (liver scarring), liver cancer,
liver failure and death

Incubation period
60-90 days on average (range 45-180
days)
infectious weeks before getting ill and
for variable period after acute infection
chronic carriers remain infectious

Hepatitis B Virus

Possible outcomes of infection with the

hepatitis B virus (HBV)

Hepatitis B

Diagnosis and Treatment

Blood test:

- The hepatitis B surface antigen (HBsAg) is most

frequently used to screen for the presence of this infection.

-

The presence of HBeAg in a host's serum is associated with

much higher rates of viral replication and enhanced
infectivity
PCR tests have been developed to detect and measure the
amount of HBV DNA, called the viral load, in clinical specimens
-

There is no cure for chronic hepatitis B

Interferon/Ribavirin, lamivudine (Epivir), adefovir (Hepsera),
tenofovir (Viread), telbivudine
Prevention: recombinant HBsAg vaccine

Hepatitis C
Epidemiology
World population: 3%
European countries; 0.5-2%
Egypt; 20%
Unites States: 2.5%
India: 2%
Route of transmission

(Source, CDC)

HEPATITIS C
15%

Chronically infected
Clear the infection

85%

Structure of hepatitis C virus particle

HVR2

(E1 and E2)

HVR1

E1: fusogenic protein

E2: receptor binding protein

5 NTR has Ribosomal

binding site

Ion Channel

(protease)

Genotype (HCV): 1-7

Pathogenesis of hepatitis by HCV

Nucleus

Hepatocyte

nesis of HCV: HCV is not directly pathogenic to live cells. Liver injury has
d due to CD8 T cell (cytotoxic T cell) responses to virally infected hepat
active B cell (antibody mediated) and T cell responses against all viral p
ient display persistent viremia. The mechanism by which HCV persists h
clarified

Natural history of hepatitis C

Hepatitis C
infection
15%
Spontaneous
resolution

85% Chronic
hepatitis

25%
Cirrhosis of
liver

1-4%
Hepatocellul
ar carcinoma

Clinical course of hepatitis C. Typical serologic events in two distinct

outcomes. (Top panel) About 20% of the patients with acute hepatitis C
have a self-limited infection that resolves in a few months. Anti-HCV
appears at the end of the clinical course and persists. (Bottom panel) The
remaining patients with hepatitis C develop chronic illness, with
exacerbations and remissions of clinical symptoms. The development of

Diagnosis:
Anti-HCV antibodies can be detected in 80%
of patients within 15 weeks after exposure, in
>90% within 5 months after exposure, and in
>97% by 6 months after exposure.
All persons with positive anti-HCV antibody
tests must undergo additional testing for the
presence of the hepatitis C virus (RNA of virus
by PCR) to determine whether current
infection is present.
If infected, liver enzyme tests or a liver
biopsy to check liver function

Treatment
- The hepatitis C virus (HCV) induces chronic infection in
50%-80% of infected persons. Approximately 50% of
these do not respond to therapy
- Current treatment is a combination of
Pegylated interferon-alpha-2a or
Pegylated interferon-alpha-2b and the antiviral drug
ribavirin for a period of 24 or 48 weeks, depending on
hepatitis C virus genotype
- Sustained cure rates (sustained viral response) of 75%
or better are seen with treatment in people with HCV
genotypes 2 and 3 with 24 weeks of treatment.
- In patients with HCV genotype 1, the above treatment
does not produce a 2-log viral load reduction or
complete clearance of RNA after 12 weeks. This
treatment need to be continued for 12 months.

WHAT IS CIRRHOSIS ?
Characterized by fibrosis
and structurally
abnormal nodules with
loss of function
Liver function test may
be abnormal due to a
decrease in the number
of normal liver.

Liver nodue

Connective tissue

Normal liver

Portal circulation

Formation of oedema in cirrhosis of liver