Hepatitis C and its Treatment

2. Presented by: MOHEER FATIMA (07)Presented by: MOHEER FATIMA (07)
M.Phill PharmacologyM.Phill Pharmacology
University of SargodhaUniversity of Sargodha
Presented to: Dr.Shoaib AkhtarPresented to: Dr.Shoaib Akhtar
Professor ofProfessor of
PharmacologyPharmacology
University of SargodhaUniversity of Sargodha

3. Hepatitis:Hepatitis:
 Hepatitis (plural: hepatitides) is a medical condition defined by
the inflammation of the liver caused by a viral infection and
characterized by the presence of inflammatory cells in the
tissue of the organ
 The word commonly is from Greek “Hepato” meaning Liver
and suffix “itits” meaning inflammation.
It can also be caused by:
 Genetic diseases
 Medications (including over-
the-counter)
 Alcohol
 Hepatitis viruses (A,B,C,D,E)

4. Many viruses cause hepatitis. Of these, six
medically important viruses are commonly described as
“hepatitis viruses” because their site of infection is Liver.
These six are,
1) Hepatitis A virus (HAV) Picornaviridae
2) Hepatitis B virus (HBV) Hepadnaviridae
3) Hepatitis C virus (HCV) Flaviviridae
4) Hepatitis D virus (HDV) Delta
5) Hepatitis E virus (HEV) Caliciviridae
6) Hepatitis G virus (HGV) Flaviviridae

5. Factors Hepatitis
A
Hepatitis
B
Hepatitis
C
Hepatitis
D
Hepatitis
E
Hepatitis
F
Hepatitis
G
Source of
Transmissio
n
Feacal oral
route
Blood
Body fluids
Blood
Body fluids
Blood
Body
fluids(Co
infect with
HBV.
Feacal Oral
Route
Feacal
Oral route
Blood and
BY sexual
contact
Chronic
Infection
No Yes Yes Yes No - yes
Diagonostic
s Tests
Anti-HAV-
IgM-positive
in acute
hepatitis; IgG-
positive after
infection
HBV-DNA,
anti-HBc-IgM,
HbeAg, anti
HBsAg
Anti-HCV or
anti-HDV,
HCV RNA
HDAg-
positive (anti-
HDV), HDV
RNA serum
Anti-HEV - Anti-HGV
Sighn and
symptoms
Dark
Urine,jaundi
ce,Headach
e,Fatigue
Arthralgias ,
Rash
Similar to
HBV,Less
severe
Similar to
HBV
Similar to
HAV.Very
severe in
pregnant
women
_
Similar to
Hcv
Prevention
and
treatment
Pre Post
exposure
immunizatio
n
Alfa
interferon
and vaccine
is available
Blood donor
Screening,
Peginterfer
on,Ribavirin
,Sofsobuvir
Pre Post
exposure
Immunizatio
n
Ensure safe
Drinking
Water.No
vaccine and
no antiviral
therapy
No
treatment
Available
No
treatment
available,on
ly bed
rest ,avoid
alcohol

7.  Hepatitis C Virus
Hepatitis C is caused by
single-stranded RNA
virus. Its size is 60nm and
incubation period is 6 to 7
weeks.
 Hepatitis C virus (formerly
non-A, non-B virus); may
be more than 1 virus

8.  The virus can survive outside the body at room temperature,
on environmental surfaces, for at least 16 hours but no longer
than 4 days.
 The virus is an RNA virus and uses liver cells to create copies
of itself, killing those cells in the process.
 It is an infectious form of hepatitis. Hepatitis C is more likely
then other forms of hepatitis to result in chronic hepatitis.
Having hepatitis C also increases the risk of developing liver
cancer.

9.  Many infected people do not know they have the
virus because for most, there will be no symptoms
and for others, the symptoms may not show up for
decades
 You may not know you have this infection until
damage has already been done to your liver
 There is no vaccine

10.  Sharing needles, pipes, straws, filters, ties, or water for drug
use.
 Piercing or tattooing equipment (including ink) used on
someone else.
 Hygiene/grooming such as razors, nail clippers and
toothbrushes.
 Unprotected sex.
 Reusing medical equipment that was not properly sterilized.
 Pre-1992 blood transfusions.
 HCV also can be passed from mother to unborn child.

12.  Sneezing
 Coughing
 Sharing drinking
glasses or eating
utensils
 Breast feeding
 Food and water
 Handshakes
 Holding hands
 Hugging
 Kissing on the cheek
 Playing with children

13. What
Does
Our Liver
Do????

17.  Infection and Inflammation:
 Fibrosis:
 Cirrhosis:
the virus enters the bloodstream and is carried to the
liver to infect the liver cells . infected liver cells
become damaged and some cells die causing the liver
to swell.
Continuous Inflammation of the Liver caused by
Hepatitis C can lead to fibrosis.The formation of scar
tissue within the liver.
Extensive scarring can block the flow of blood through
the liver and cause liver function to deteriorate over
time .this is called cirrhosis.

18.  Hepatocellular carcinoma:
 Liver Transplant:
Hepatitis C is the leading Cause of Liver cancer ,The
formation of malignant tumor in the liver and
ultimately liver stops working and liver failure occur.
May be needed for patients who develop liver failure
or liver cancer
About 50% of all U.S. liver transplants result from
liver damage caused by hepatitis C

20.  Cover open wounds.
 Tell people not to touch your blood.
 Clean blood spills yourself or inform others to use latex
gloves.
 Dispose of needles/materials properly.
 Do not inject drugs
 Avoid sharing contaminated articles like Razors,
toothbrushes, or other personal care items.
 Practice safe sex

21. Acute Hepatitis
Itis a short-term illness
that occurs within the first 6
months after someone is
exposed to the Hepatitis C
virus. For most people,
acute infection leads to
chronic infection.
Chronic Hepatitis
is a long-term illness that
occurs when the Hepatitis C
virus remains in a person’s
body. Hepatitis C virus
infection can last a lifetime and
lead to serious liver problems,
including cirrhosis (scarring of
the liver) or liver cancer.

22. Acute phase
70-80% of people experience NO
SYMPTOMS
20-30 % may experience:
 fatigue
 flu-like symptoms
 nausea
 yellowing of the eyes and skin
 low appetite
 rash
 abdominal pain
 bruise or bleed easily
 dark-coloured urine
 light or clay-coloured stools
Chronic phase
Can take decades for these signs to
appear:
 fatigue
 nausea
 yellowing of the eyes
 blood in stool or vomit
 dry or itchy skin
 sleep disturbances
 depression
 weight loss

23. Blood Testing:
 HCV antibody Test
 HCV RNA test
 Viral genotyping test
LFTs
Parameter Normal Ranges
ALT or SGPT male:10-40U/L
Female:7-35U/L
AST or SGOT Male:14-20U/L
Female:10-36U/L
Billirubin Direct bilirubin: 0 to 0.3 mg/dL
Total bilirubin: 0.3 to 1.9 mg/dL
Total cholestrol 180-200mg/dl
Prothrombin Time and INR 11-13seconds and 0.8 -1.1.
Total protein 60 to 80g/L or 6 to 8g/dL

25. Primary Goal :
Eradicate HCV infection .
Secondary Goals:
Slow disease progression
Improve histology
Reduce risk of Hepatocellular Carcinoma
Improve health related Quality of life

26. Prevention:
No vaccine for the prevention of HCV .
Never share needles.
Avoid direct exposure to blood or blood products.
Don't share personal care items.
Choose tattoo and piercing parlors carefully.
Practice safe sex.
Avoiding alcohol and drugs that can damage the liver,it
may help slow the rate of progression of the disease.

27. Treatment of Acute Hepatitis:
 Treatment of acute hepatitis C Include Alpha and Beta
interferon Monotherapy.
It significantly decreases the number of patients that
become chronic carriers.
Acute Hepatitis C Treatment
Genotype 1,2,3,4 Interferon Monotherapy
Interferon+Ribavirin
Peginterferon Monotherapy
Peginterferon+Ribavirin

28. Interferon :
Given by shot, usually 3 times a week
Dose: Interferon-alpha 3 MIU TIW SC
Pegylated interferon:
Long-acting, taken once a week
Drug Form
Recommended
Treatment
Regimn
Pegylated
interferon alfa-2b
(PEG-Intron)
Pen injection
system
1.5 mcg per kg
subcutaneously
once weekly
Pegylated
interferon alfa-2a
(Pegasys)
Prefilled syringe 180 mcg
subcutaneously
once weekly

29.  Combination therapy:
 Interferon (standard or pegylated) taken with
antiviral drug ribavirin (Virazole) is the treatment of
choice for chronic hepatitis C.
Drug Form
Recommended
Treatment
Regimn
Ribavirin
(Rabetol)
For viral genotype 1
Capsule Weight 75 kg (165 lb) or
greater: three 200-mg
capsules twice daily (total
daily dose of 1,200 mg)
Weight less than 75 kg: two
200-mg capsules every
morning and three 200-mg
capsules every evening (total
daily dose of 1,000 mg)
For genotype 2,3 All weights: two 200 mg
capsules twice daily (total
daily dose of 800 mg)

30. Interferon alone:
10 – 15% chance of clearing the virus from the
blood
Interferon & ribavirin:
Up to 40% chance of clearing the virus
Pegylated interferon alone:
About the same as interferon & ribavirin 40%
Pegylated interferon & ribavirin:
Up to 50% chance of clearing the virus

31.  These are the proteins ,synthesized by host cells in
response to various inducers and in turn cause
biochemical changes leading to an antiviral state in
cells.
Types:
 Alpha,Beta and Gamma

33. Interferons are the potent cytokines that possess
Antiviral
Antiproliferative
Immunomodulatory activity.
Adverse effects:Adverse effects:
Doses >1 to 2 MU cause Influenza like syndrome.
Symptoms include:
Fever
Myalgia,Arthralgia
Chills
Headache
N/V ,Diarrhoea

34.  HCV treatment improved again in 2001 with FDA
approval of pegylated interferon.
 Attaching the polyethylene glycol (PEG) molecule
to interferon (a process called pegylation) keeps
the drug in the bloodstream longer and makes it
more effective against HCV.
Types:
 peginterferon-alpha-2a
 peginterferon-alpha-2b.

36.  Peginterferon alpha is indicated for the treatment of
patients with chronic hepatitis C who have compensated
liver disease.
 Advantages over conventional Interferons:
 They have slower absorption
 Reduced distribution
 lower elimination rate
 Greater therapeutic efficacy
 The current recommendations include the use of a
combination therapy with pegylated IFNalfa and ribavirin
as the standard treatment.

37.  Pegylated interferons have improved
pharmacokinetics profile,and it reduce the extent
of their adverse events.
But it cause Ocular toxicity including
 Retinopathy
 Optic neuropathy
 Ocular loss

38.  It is an antiviral drug,a purine nucleoside analogue
with a modified base and D-Ribose sugar.
 It inhibits the replication of wide range of RNA and
DNA viruses.

40. Monotherapy:
For 6-12 months
It decreases aminotransferase elevations to normal but
does not effect HCV RNA level.
Combination therapy:

Oral Ribavirin + Injection of pegIFN alfa 2a or 2b
This treatment used for chronic HCV infection.
In HCV/HIV co-infected patients.
Used in recurrent HCV infection after liver transplantation.
Ribavirin aerosol is used for Bronchiolitis and Pneumonia
in hospitalized children .

41. Aerosolized Ribavirin may cause
conjunctival irritation
Rash
Transient wheezing
Systemic Ribavirin cause
Dose related Anemia
Oral Ribavirin cause
Fatigue
Insomnia
Depression
Teratogenic

42. Boceprevir & Telaprevir:
Boceprevir and Telprevir are Pretease inhibitor.
Developed in May of 2011, boceprevir and
telprevir were the first drugs to act directly on
the HCV virus.
Boceprevir and teleprevir increased the cure rate
for HCV genotype 1 to 70%.
A treatment regime with boceprevir or telaprevir,
with interferon and ribavirin lasts 24-48 weeks.

44.  Boceprevir and Telaprevir in combination with
pegylated interferon alpha and Ribavirin are
appreved for genotype 1 HCV infection.
ADRs:ADRs:
 Anemia,Rash ,Pruritis

Hepatitis C Treatment
protocol
Treatment
lasts
Cure
Rates
Genotype 1 Telaprevir+in
terferon+
Ribavirin
24 to 48
weeks 70-75%
Boceprevir+I
nterferon+Ri
bavirin
28-48 weeks
80%

45. Sofsobuvir(Sovaldi):
SOVALDI is a hepatitis C virus (HCV) nucleotide
analog NS5B polymerase inhibitor among the
second generation of protease inhibitors that
directly attack the Hep C virus cell..
Sofosbuvir was
approved by FDA at 6th
December 2013.

46.  One 400 mg tablet taken once daily with or without food.
 Should be used in combination with ribavirin or in combination with
pegylated interferon and ribavirin for the treatment of HCV.
 Should be used in combination with ribavirin in patients with
hepatocellular carcinoma awaiting liver transplantation for up to 48
weeks or until liver transplantation, whichever occurs first.
Patient population Treatment Duration
Genotype 1,4 SOLVADI+peginterfer
on alfa +Ribavirin
12 weeks
Genotype 2 SOLVADI+Ribavirin 12 weeks
Genotype 3 SOLVADI+Ribavirin 24 weeks

48.  Indicated for the treatment of genotype 1, 2, 3 or 4
chronic hepatitis C virus (HCV).
 It is the first drug that has demonstrated safety and
efficacy to treat certain types of HCV infection without
the need for co-administration of interferon
ADRs:ADRs:
In combination with Ribavirin
 Fatigue ,Headache
In combination with peginterferon alfa
 Insomnia,Anemia,Fatigue

49. Generic NameGeneric Name
Trade NameTrade Name
(manufacturer)(manufacturer)
DosingDosing
Interferon alfa-2aInterferon alfa-2a RoferonRoferon®®
-A (Roche)-A (Roche) 3 MIU SC TIW3 MIU SC TIW
Interferon alfa-2bInterferon alfa-2b
Intron AIntron A®®
(Schering-(Schering-
Plough)Plough)
3 MIU SC TIW3 MIU SC TIW
Interferon alfacon-1Interferon alfacon-1 InfergenInfergen®®
(InterMune)(InterMune)
99 µµg SC TIWg SC TIW
1515 µµg SC TIWg SC TIW**
Peginterferon alfa-2aPeginterferon alfa-2a PegasysPegasys®®
(Roche)(Roche) 180180 µµg SC QWg SC QW
Peginterferon alfa-2bPeginterferon alfa-2b
Peg-IntronPeg-Intron®®
(Schering-(Schering-
Plough)Plough)
1.01.0––1.51.5 µµg/kg SC QWg/kg SC QW
Ribavirin**Ribavirin**
CopegusCopegus®®
(Roche)(Roche)
RebetolRebetol®®
(Schering-(Schering-
Plough)Plough)
RibasphereRibasphereTMTM
(Three(Three
Rivers)Rivers)
0.80.8––1.2 g/day, PO1.2 g/day, PO††
0.80.8––1.2 g/day, PO1.2 g/day, PO††
0.80.8––1.2 g/day, PO1.2 g/day, PO††

50. Acetaminophen (Tylenol® and others):
 No more than four extra strength or six regular strength
tablets per day
Ibuprofen and other anti-inflammatory medications
(Motrin®, Advil®, Aleve®, and others)
Hepatitis C patients with cirrhosis should NOT take any
Iron supplements.They may increase the rate of liver
scarring
Coadministration of amiodarone with SOVALDI in
combination with another DAA may result in serious
symptomatic bradycardia.
Drugs that are intestinal P-gp inducers
 (e.g., rifampin, St. John’s wort) may alter the

51.  A medicine with the ability to protect liver cells from damaging by
poisons and viruses is referred to as a hepatoprotective.
 The herbal remedies help in supporting the immune systems
efforts to fight off the virus.
 It must be pointed out that herbal treatments are not designed for
acute stages of hepatitis.
 In this case bed rest and low fat diet, along with gentle herbal
diaphoretics such as elderflowers (Sambucus nigra) and
catnip (Nepeta cataria) are the limit of treatment recommended.

52.  The more widespread and longer lasting chronic stages of hepatitis
lend themselves to treatments with herbal remedies and other natural
therapies.
 Herbalists believe strongly in the need for bitter compounds as foods
and medicines in order to stimulate production of gastric juices and
bile from the liver.

53.  Also known as milk thistle it is a common weed of
pastures in Australia as well as in Europe and North
America. It is regarded as the standard amongst
hepatoprotective drugs.
Constituents:
 Flavonolignans. These are unusual
polyphenolic compounds referred
to collectively as silymarin.

54. Action:
Early studies demonstrated the dual effect of the flavonolignans from
Silybum on the liver.
i.e.
 A membrane stabilizing effect (protecting liver cells from destruction
from toxins) via anti-oxidant action.
 And protein synthesis enhancing effect, whereby the protected cells
act as regeneration centers for new cells.
Uses:
Thistle seed preparations are ideal for chronic and post-acute stages of
hepatitis. It is also used in fatty degeneration and even cirrhosis of the
liver.

55.  Known as Reishi mushroom in china.
Constituents:
 Triterpenes including ganoderic acid; polysaccharides; organic
germanium; adenosine.
Action and Use:Action and Use:
 Antiviral; antioxidant; antitumor; immuno-stimulant; hypoglycaemic;
cardiotonic; anti-inflammatory.
 Hepatitis patients show improved symptoms and
less tiredness in clinical trials.
 In China it is frequently used for chronic
hepatitis.
 It can be obtained in the dried form or
in tablets. Daily doses range between 2

56.  Phyllanthus are low shrubs common across southern Asia
and Australia. In parts of India the herb is renowned for its
success in treating hepatitis and jaundice.
 Constituents:
 Ellagitannins including lignans- phyllanthin
; flavanoids; alkaloids.
Actions and Uses:
 Astringent; diuretic; antiviral; hepatoprotective.
 In India fresh roots are considered the
most effective for jaundice.

57.  This study was conducted to evaluate the
hepatoprotective effects of aqueous acetone extract of
Sida alba.
 It is a herbal plant used in Burkina Faso to treat Hepatitis
in albinos Wistar rats.

58.  Male and female adult albinos Wistar rats (260-265 g)were used.
 The animals were housed in cage under controlled conditions of 12-
h light/12-h dark cycle at 25ºC.
 They received pellets food enriched with protein and water.
Group=5
n =6
Group 2
(control )
Received only
water and 35%
ethanol for 28
days daily
Group 3,4,5
Received
different doses of
aqueous acetone
extracts of Sida
alba. (75, 100,
150 mg/kg)
suspended in 35%
ethanol for 28
days daily
Group = 1
(control)
Received only
Water for 28
days daily .

59. Conclusion:Conclusion:
Administration of 35% ethanol for 28 days increase liver marker
enzymes (AST,ALT, ALP), glucose, triglycerides, total cholesterol,
total bilirubin and direct bilirubin in serum as compared with rats
which received water (control water).
However, administrations of 35% ethanol along with
Aqueous acetone extract decreased the activities of liver markers
enzyme in serum comparatively to the control water
Group.
We noticed that extract at a dose of 150 mg/kg was
highly effective than 75 and 100mg/kg body weight compared to
the control water group
This study revealed that Sida alba presents a
hepatoprotective activity.

60. 1. Laurence Brunton , Bruce Chabner, Bjorn Knollman, Goodman and Gilman's The
Pharmacological Basis of Therapeutics, Twelfth Edition 12th Edition,page
no.1610,11,12,13,14.
2. Chaterjee, T.K., 2000. Medicinal Plants with Hepatoprotectve Properties. Herbal
Options.Books and A llied (P) Ltd., Calcutta, pp: 155.
3.1K. Konaté, 2A. Souza, 3R.R.R. Aworet Samseny, 4B. Batchelili, Hepatoprotective
Effect of Aqueous Acetone Extract of Sida alba L. (Malvaceae)Against Alcohol Induced
Liver Damage in albinos Wistar Rats, Published: February 10, 2011.
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