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‫بسم ال الرحمن الرحيم‬

Chronic Hepatitis C

Dr : Walid
El -
Sherbiny

Tropical Medicine
Mansoura University
Incidence
Hepatitis C infect 200 million people
worldwide
HCV is a major Epidemic problem in
Egypt. Many data suggest that the
Overall incidence in Egypt is 15% of
population. The highest prevalence in
Northern Delta 28% The lowest
prevalence in Cairo and Alexandria
9% and 6 % respectively.
Virology

Single stranded, enveloped RNA virus.


There are 6 genotypes: 1 in USA . 2,3 in
Europe
& 4 in Egypt

Genotypes 2 &3 has the best response to


Interferon Therapy

Genotypes 1 & 4 has the least response to


interferon therapy
Pathology

Ranges from minimal periportal lymphocytic


inflammation to active hepatitis with bridging
fibrosis, hepatocyte necrosis and frank cirrhosis.

Activity / Fibrosis score

Steatosis, lymphoid aggregates and bile duct


damage are frequently found in the liver biopsy in
patient with HCV infection
Methods Of Transmission
1-Iatrogenic medical and dental procedure
(most important)
2-Injection drug use
3-Blood transfusion and organ
transplantation
4-Occupational exposure to blood (Medical
and paramedical)
5-Sexual and perinatal exposure (probably
low)

- The campaign of treatment of Bilharziasis using


Tartar Emetics with same needle used for all
patients Play an important role in transmission
of HCV
Clinical Manifestations
Chronic hepatitis C means HCV infection for
more than 6 months.

Usually asymptomatic, accidentally


discovered but it may be presented with
Fatigue, weight loss, muscle pain,
intermittent low grade fever and flu like
symptoms or GIT symptoms.

Hepatitis C (PCR) is detectable in the blood


within 1 to 3 weeks after infection, and
antibodies to the virus within 3 to 12 weeks
Extra-hepatic manifestations
Pathogenesis
a- Mediators of autoimmunity
b- Immune complex formation
c- Virus invasion and replication

Includes: 1- Strongly associated


1-Mixed cryoglobulinemia
2-Membrenoproliferative
glomerulonephritis
3-Porphyria cutenea tarda
4-Sjogren syndrome
5-Lymphoproliferative disorders
6-Leukocytoclastic vasculitis
2- Possibly associated

 1-Lichen planus
 2-Autoimmune thrombocytopenia
 3-Thyroid disease
 4-Type 2 diabetes
 5-Corneal ulcers (Mooren ulcers)
 6-Pulmonary fibrosis
 7-Systemic vasculitis (polyarteritis nodosa
 8-Arthralgia, myalgia, polyarthritis
Vasculitis
Vetiligo
Psoriasis
Psoriasis
Pyoderma Gangrenosum (early
lesion with necrotic centre)
Pyoderma
Gangrenosum
Pyoderma
Gangrenosum
Systemic Lupus Erythematosus
Sjogren’s Syndrome
Idiopathic pulmonary
fibrosis
Prevention
1-Avoid sharing drug needles
2-Avoid unsanitary tattooing, Acupuncture
and body piercing
3-Avoid needle stick injury, sharing
personal items such as razors, nail clippers
and teeth brush
4-Use latex condoms correctly in those
with multiple sexual partners
5-Screening of blood & blood products for
viral markers
6-Strilization

No vaccine available to protect against


Treatment
Standard treatment is a combination of
Pegylated Interferon and Ribavirin.

All patients with measurable level of HCV RNA


and liver biopsy shows bridging fibrosis along
with at least with moderate inflammation and
necrosis should be considered potential candidate
for therapy.

In the absence of contraindications, treatment is


recommended because patients are at risk of
developing liver cirrhosis and Hepatocellular
Investigations before INF
1-Anti HCV antibody & HB markers
2-CBC
3-Liver function tests
4-Quantitaive PCR
5-Pregnancy test
6-Serum T.S.H
7-Serum alfa feto protein
8-Autoimmune markers
9-IHA for Bilharziasis
10-Random blood sugar and creatinine

11-ECG
12-Fundus Examination
13-Abdominal U/S
14-Liver Biopsy
15-Upper GIT endoscopy (in patients with portal
Pegylated Interferon
Attachment of polyethylene glycol to a
protein

(pegylation) reduces its rate Of absorption


following

subcutaneous injection, reduces renal


clearance and

decrease immunogenicity of protein with


resulting
Duration of Therapy

Differs according to genotype.

For Genotypes 2 & 3 require 24 weeks of


Peg INF. alfa + ribavirin 800 mg/d while
Genotypes 1 & 4 require 48 weeks of INF
alfa + ribavirin 1000-1200 mg/d.

Failure to decrease the viral load by 2


Logs after 12 w. of treatment is highly
predictive of failure of treatment in naïve
patient who has genotype 1
Time to Do PCR
-Basal PCR (before start of treatment)
-After 4 weeks (Quantitative), if responder (Super

response)
-After 12 weeks (Quantitative): If responder (early

virologic response) then continue, if Non


responder stop
-After 24 w. (Qualitative), if Non responder stop.

-After 48 weeks (Qualitative, if responder it is end

treatment response.
Predictor of Non response To HCV
treatment:

1-Infection with Genotype 1


2-High viral load (800,000 IU/ml)
3-Advanced fibrosis stage 5 or cirrhosis
stage 6
4-High body mass index
5-age more than 40 years
6-African American race
7-Coinfection HIV with HCV
Absolute contraindications to hepatitis C
therapy
- Active psychiatric illnesses, such as
major depression, schizophrenia, or
bipolar disorder that is not controlled

- Having undergone renal, heart, or lung


transplant

- autoimmune hepatitis

- Untreated hyperthyroidism

- Pregnancy OR Breast feeding


 Severe concurrent disease:
severe uncontrolled hypertension, heart
failure, considerable coronary artery disease,
poorly controlled diabetes mellitus, severe
chronic obstructive pulmonary disease

 Known hypersensitivity to INF or Ribavirin

 Inability to practice birth control

Relative contraindications:
a- pancytopenia
b- Seizure disorders
Adverse effects of Hepatitis c therapy:

1-Flu like symptoms


2-Neutropenia and
Thrombocytopenia
3-Depression and Psychosis
4-HTN and Diabetes
5- thyroid
6-fall of hair
7-With Ribavirin, the most
prominent side effect is
heamolysis while the most
serious is teratogenicity
Two forms of contraceptions must be used
during therapy and for 6 months following
treatment cessation.

Anemia associated with IFN/RBV therapy is


treated by Epotein alfa once weekly S.C.
with OR without reduction of Ribavirin
dose

Leucopenia is treated with granulocyte


stimulating factor s.c.
Experimental treatment:

1-Viramidine is a prodrug of the Ribavirin


that has better targeting of the liver (Phase
3 trials). It will be used in conjunction with
interferon as an alternative to Ribavirin

2-Protease inhibitors (VX 950) Known as


Telaprevir is currently in Phase 3 trials