HEPATITIS C

By
Dr Faiza Samad
 HISTORY
• 400 B.C.
• Campaign Jaundice
• Hippocrates described a condition he called
“epidemic jaundice.” In the 8th century A.D.
• 1960s
• Hepatitis B Is Accidentally Discovered
• Baruch Blumberg was researching genetic links to
disease susceptibility. During this time, he
accidentally discovered the hepatitis B (HBV)
virus in the blood sample of an Australian
Aborigine. This discovery led to the development
of a test to screen people for HBV. This also led to
an effective vaccine for the disease. In 1976,
Blumberg was awarded the Nobel Prize for his
work.
• 1973
• Hepatitis A Is Discovered
• Led by Steven Feinstone, scientists at the
National Institutes of Health identified the
virus responsible for hepatitis A (HAV). The
virus was discovered in fecal samples from
prisoner volunteers. Noted microbiologist
Maurice Hilleman developed the first effective
vaccine for HAV in 1981
 HISTORY
• 1975
• A Previously Unrecognized Hepatitis Is Found
• American and British researchers identified a type of
hepatitis that didn’t test positive for the proteins found
with HAV or HBV. Both teams conclude that a
previously unrecognized human hepatitis virus is the
likely cause.
• 1989
• Hepatitis C Virus Is Identified
• The Centers for Disease Control and Prevention and
Chiron came together to identify the hepatitis C (HCV)
virus. There isn’t a vaccine for HCV at this time.
 HEPATITIS C VIRUS
This is caused by an RNA flavivirus
Eighty per cent of individuals exposed to the
virus become chronically infected and late
spontaneous viral clearance is rare
Hepatitis C is the cause of what used to be
known as ‘non-A, non-B hepatitis’
Although most individuals remain
asymptomatic until progression to cirrhosis
occurs, fatigue can complicate chronic
infection and is unrelated to the degree of
liver damage
 TRANSMISSION

Blood products
– Blood transfusions before 1992
– Other blood products before 1987
– Current transfusions no longer a major risk
factor
Injection (IV) drug use – 60% of all new
infections
 TRANSMISSION
HCV is transmitted by direct blood-to blood
contact.
Needles used for tattooing, body piercing,
acupuncture.
Sharing personal items such as razors,
toothbrushes, or nail files is a less likely, but
still possible, transmission route.(! any items
that might contain blood)
 TRANSMISSION
Snorting cocaine or other drugs
Occupational exposure
From pregnant mother to child
Non-sexual household contacts (rare)
Sexual transmission
– Low risk in monogamous relationship
Unknown
 “HIGH RISK” GROUPS
Gay men, sex workers, people with multiple
sex partners, people with STDs
Healthcare workers are at risk for HCV
infection because of needle stick accidents
Perinatal transmission from mothers with HCV
to their infants before or during birth occurs in
about 6% of births
 NOT TRANSMITTED
HCV is not transmitted by casual contact such
as sneezing, coughing, hugging, or sharing
eating utensils and drinking glasses
 RISK FACTORS FOR THE ACQUISITION OF CHRONIC
HEPATITIS C INFECTION

• Intravenous drug misuse (95% of new cases in the UK)

• Unscreened blood products

• Vertical transmission (3% risk)

• Needlestick injury (3% risk)

• Iatrogenic parenteral transmission (i.e. contaminated

vaccination needles)

• Sharing toothbrushes/razors
 Investigations

Serology and virology

The HCV protein contains several antigens that
give rise to antibodies in an infected person
and these are used in diagnosis. It may take 6–
12 weeks for antibodies to appear in the
blood following acute infection such as a
needlestick injury. In these cases, hepatitis C
RNA can be identified in the blood as early as
2–4 weeks after infection
 ANTI-HCV ANTIBODIES

Anti-HCV antibodies persist in serum even

after viral clearance, whether spontaneous or
post-treatment.
 MOLECULAR ANALYSIS

• There are six common viral genotypes, the

distribution of which varies worldwide
• Genotype 1 is most common in northern
Europe and is less easy to eradicate than
genotypes 2 and 3 with traditional pegylated
interferon alfa/ ribavirin-based treatments.
 LIVER FUNCTION TESTS

LFTs may be normal or show fluctuating

serum transaminases between 50 and
200 U/L. Jaundice is rare and only usually
appears in end-stage cirrhosis.
 LIVER HISTOLOGY

Serum transaminase levels in hepatitis C are a

poor predictor of the degree of liver fibrosis
and so a liver biopsy is often required to stage
the degree of liver damage. The degree of
inflammation and fibrosis can be scored
histologically. The most common scoring
system used in hepatitis C is the Metavir
system, which scores fibrosis from 1 to 4, the
latter equating to cirrhosis.
 DISEASE PROGRESSION AND MORBIDITIES

Morbidities associated with chronic HCV infection1,2

• Cirrhosis
• Decompensated cirrhosis: Ascites, varices,
Encephalopathy
• Hepatocellular carcinoma (HCC)

1. O’Leary 2008; 2. Perz 2006;

 MANAGEMENT

The aim of treatment is to eradicate infection.

Until recently, the treatment of choice was
dual therapy with pegylated interferon-alfa
given as a weekly subcutaneous injection,
together with oral ribavirin, a synthetic
nucleotide analogue The main side-effects of
ribavirin are haemolytic anaemia and
teratogenicity.
 SUSTAINED VIROLOGICAL RESPONSE, OR SVR

Virological relapse can occur in the first 3

months after stopping treatment, and cure is
defined as loss of virus from serum 6 months
after completing therapy (sustained virological
response, or SVR).
 PROGNOSIS

The length of treatment and efficacy depend

on viral genotype (12 months’ treatment for
genotype 1 results in a 40% SVR, whereas 6
months’ treatment for genotype 2 or 3 leads
to an SVR in > 70%)
 PROGNOSIS

Response to treatment is better in patients

who have an early virological response, as
defined by negativity of HCV-RNA in serum 1
month after starting therapy, and it may be
possible to shorten the duration of therapy in
this patient group.
• The addition of ribavirin to pegylated
interferon-alfa therapy improves the overall
sustained virological response from 33% to
55%.’

Manns MP, et al. Lancet 2001; 358:958–965.

Hadziyannis SJ, et al. Ann Intern Med 2004;
140:346–553.
 NEW DRUGS

The recent availability of triple therapy with

the addition of protease inhibitors such as
telaprevir and boceprevir to standard
pegylated interferon/ribavirin has provided a
significant advance in therapy, with SVR rates
for genotype 1 individuals comparable to
those previously only achieved in genotypes 2
and 3.
 PROGNOSIS

Liver transplantation should be considered

when complications of cirrhosis occur, such as
diuretic-resistant ascites. Unfortunately,
hepatitis C almost always recurs in the
transplanted liver and up to 15% of patients
will develop cirrhosis in the liver graft within 5
years of transplantation.
 PROGNOSIS

Progression from chronic hepatitis to cirrhosis

occurs over 20–40 years. Risk factors for
progression include male gender,
immunosuppression (such as co-infection with
HIV), prothrombotic states and heavy alcohol
misuse. Not everyone with hepatitis C
infection will necessarily develop cirrhosis but
approximately 20% do so within 20 years
 PROGNOSIS
Once cirrhosis has developed, the 5- and 10-
year survival rates are 95% and 81%
respectively
 PROGNOSIS

One-quarter of people with cirrhosis will

develop complications within 10 years and,
once complications like ascites have arisen,
the 5-year survival is around 50%. Once
cirrhosis is present, 2–5% per year will
develop primary hepatocellular carcinoma.
 HCV TREATMENT GOALS

 Viral eradication (undetectable viral load)

 Delay progression of fibrosis
 Prevent decompensation, HCC, and death

Best indicator of successful treatment is

sustained virologic response (SVR)
 HCV THERAPEUTIC DEVELOPMENT

The development of two distinct classes of

hepatitis C antiviral agents:
1)Direct-acting antivirals (DAAs)
2)Host-targeting antivirals (HTAs)
 INTERFERON

The first interferon was discovered in 1957 by Alick Isaacs and

Jean Lindenmann, the two scientists found that virus-
infected cells secrete a special protein that causes both
infected and noninfected cells to produce other proteins
that prevent viruses from replicating. They named the
protein interferon because it interferes with infection
Interferons are members of a larger class of proteins
called cytokines (proteins that carry signals between cells).

World of Microbiology and Immunology. 2003. Encyclopedia.com. 15 May. 2016<http://www.encyclopedia.com>.

 RECOMMENDATIONS FOR WHEN AND IN WHOM TO
INITIATE TREATMENT

Treatment is recommended for all patients with

chronic HCV infection, except those with short life
expectancies that cannot be remediated by
treating HCV, by transplantation, or by other
directed therapy. Patients with short life
expectancies owing to liver disease should be
managed in consultation with an expert.
Rating: Class I, Level A

http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy Updated
February 24, 2016
 GENOTYPE 2 TREATMENT-NAÏVE PATIENTS WITHOUT
CIRRHOSIS

• Recommended regimens .
■ Daily sofosbuvir (400 mg) and weight-based
RBV for 12 weeks is a Recommended regimen for
treatment-naïve patients with HCV genotype 2
infection who do not have cirrhosis.
Rating: Class I, Level A
■ Daily daclatasvir (60 mg) plus sofosbuvir (400
mg) for 12 weeks is a Recommended regimen for
treatment-naïve patients with HCV genotype 2
infection who do not have cirrhosis and who are
not eligible to receive RBV
 GENOTYPE 2 TREATMENT-NAÏVE PATIENTS WITH
COMPENSATED CIRRHOSIS

Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 16

weeks to 24 weeks is a Recommended regimen for
treatment-naïve patients with HCV genotype 2
infection who have compensated cirrhosis and who
are not eligible to receive RBV. Rating: Class IIa, Level B
■ Daily sofosbuvir (400 mg) and weight-based RBV for
16 weeks to 24 weeks is a Recommended regimen for
treatment-naïve patients with HCV genotype 2
infection who have compensated cirrhosis. Rating:
Class IIa, Level C

http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy Updated February 24, 2016

 GENOTYPE 3 TREATMENT-NAÏVE PATIENTS WITHOUT
CIRRHOSIS

• - Recommended regimens are listed in groups by level

of evidence, then alphabetically.
■ Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for
12 weeks is a Recommended regimen for treatment-
naïve patients with HCV genotype 3 infection who do
not have cirrhosis. Rating: Class I, Level A
■ Daily sofosbuvir (400 mg) and weight-based RBV plus
weekly PEG-IFN for 12 weeks is a Recommended
regimen for treatment-naïve patients with HCV
genotype 3 infection who do not have cirrhosis and
who are eligible to receive PEG-IFN. Rating: Class I,
Level A
 GENOTYPE 3 TREATMENT-NAÏVE PATIENTS WITH
COMPENSATED CIRRHOSIS
Recommended regimens are listed in groups by level of
evidence, then alphabetically.
■ Daily sofosbuvir (400 mg) and weight-based RBV plus
weekly PEG-IFN for 12 weeks is a Recommended regimen
for treatment-naïve patients with HCV genotype 3 infection
who have compensated cirrhosis and who are eligible to
receive PEG-IFN. Rating: Class I, Level A
■ Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24
weeks with or without weightbased RBV is a
Recommended regimen for treatment-naïve patients with
HCV genotype 3 infection who have compensated cirrhosis
Rating: Class IIa, Level B
http://www.hcvguidelines.org/full-report/when-and-whom-
initiate-hcv-therapy Updated February 24, 2016
 contd
Daily sofosbuvir (400 mg) and weight-based RBV
for 24 weeks is an Alternative regimen for
treatment-naïve patients with HCV genotype 3
infection, regardless of cirrhosis status, who
are daclatasvir and IFN ineligible.
Rating: Class I, Level A
• http://www.hcvguidelines.org/full-
report/when-and-whom-initiate-hcv-therapy
Updated February 24, 2016
THANK YOU!