The document discusses hepatitis C virus (HCV), including its structure, genome, genotypes, epidemiology, pathogenesis, diagnosis, and management. Some key points: - HCV is a single-stranded RNA virus of the Flaviviridae family with a genome encoding both structural and nonstructural proteins. - It exists as different genotypes globally, with genotypes 1, 2, 3 being most common. Genotype helps determine treatment duration and response. - HCV is a major cause of liver disease worldwide and is transmitted through blood exposure. Diagnosis involves HCV antibody and RNA testing. - Treatment aims to eradicate the virus and involves use of pegylated interferon and ribavirin

1. HEPATITIS C
DIAGNOSIS AND
MANAGEMENT
Chair person- Dr P Chandrasekhara
Presenter- Dr Amar Patil

2. • Hepatitis C virus, which, before its identification was
labeled “non-A, non-B hepatitis,” is a linear, single-
strand, 9600-nucleotide protein molecule.
• RNA virus, the genome of which is similar in
organization to that of flaviviruses and pestiviruses;
HCV is the only member of the genus Hepacivirus in
the family Flaviviridae.

3. • The 5′ end of the genome consists of an
untranslated region (containing an internal
ribosomal entry site, IRES) adjacent to the genes
for three structural proteins, the nucleocapsid core
protein, C, and two structural envelope
glycoproteins, E1 and E2.
STRUCTURE

4. HEP C GENOME
• The 3′ end of the genome also includes an untranslated region
and contains the genes for seven nonstructural (NS) proteins,
p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B. p7 is a
membrane ion channel protein necessary for efficient assembly
and release of HCV

5. • Because HCV does not replicate via a DNA
intermediate, it does not integrate into the host
genome. HCV tends to circulate in relatively low
titer, 103−107 virions/mL, visualization of the 50- to
80-nm virus particles remains difficult. Still, the
replication rate of HCV is very high, 1012 virions per
day; its half-life is 2.7 h.

6. HCV
• 11 genotypes (90 sub-types) , (1a, 1b, 2a, 3b
etc):
• Genotype 1 (subtypes 1a, 1b, and 1c) 70%–75%.
• Genotypes 2 (subtypes 2a, 2b, and 2c) and 3 (3a
and 3b) are less common
• Genotype 4 is common
• Genotype 2, 5 and 6 are least common
• In India Gen 3 is commonest.
Genotype helps determine therapy
duration and likelihood of responding to
therapy

7. EPIDEMIOLOGY
• Worldwide seroprevalence 3% based upon anti- HCV)
up to 180 million people infected chronically.
• Variation in distribution 0.4% to 1.1% in North
America to 9.6% to 13.6% in North Africa.
• A primary cause of death from liver disease
• Responsible for 85% of cases associated with post
transfusional NANB hepatitis.
• HCV carrier rate in India is around 1-2%, around
15million people are infected with this virus. And is
responsible for 20-30% of patients with chronic liver
disease.

8. • Occurs among persons of all ages, highest between
20 to 39 years, with a male predominance.
• The biggest risk factor is among the baby boomer
population, mainly because of their high illicit drug
usage and sexual practices during the 1980s.

9. Transmission

10. PATHOGENESIS
• Direct cell injury due to viral replication
• Genotype 1 is associated with higher viral
replication, and infection with the type 1b
genotype is associated with more progressive
liver disease
• Immune mediated cell injury:
• CD8+ and CD4+ lymphocytes in portal, peri-
portal, and lobular areas in patients with HCV
infection

11. COURSE OF DISEASE
• Associated with Acute and Chronic Infections
Feb, 17, 2015
Dr. Armaan Singh 11

12. DIAGNOSIS
• Serum anti-HCV antibodies: 99% sensitivity and
specificity
• Serum HCV RNA: “Viral Load”
• Quantitative: used for
• Confirmation of Diagnosis
• Monitoring response to therapy
• Qualitative:
• 50 IU/ml: 100 copies/mL to confirm diagnosis 98%
specificity

13. DIAGNOSIS-CONT
• A specific serologic diagnosis of hepatitis C can be
made by demonstrating the presence in serum of
anti-HCV.
• When contemporary immunoassays are used, anti-
HCV can be detected in acute hepatitis C during
the initial phase of elevated aminotransferase
activity and remains detectable after recovery (rare)
and during chronic infection (common).

14. DIAGNOSIS-CONT
• Assays for HCV RNA are the most sensitive tests
for HCV infection and represent the “gold standard”
in establishing a diagnosis of hepatitis C.
• HCV RNA can be detected even before acute
elevation of aminotransferase activity and before
the appearance of anti-HCV in patients with acute
hepatitis C.

15. • Amplification techniques are required to detect
HCV RNA, and two types are available.
1 Branched-chain complementary DNA (bDNA)
assay.
2 The other involves target amplification (i.e.,
synthesis of multiple copies of the viral genome ) by
PCR or TMA(Transcription mediated amplification).

16. DIAGNOSIS
• Both can be used as quantitative
assays and a measurement of relative
“viral load”; PCR and TMA, with a
sensitivity of 10–102 IU/mL, are more
sensitive than bDNA, with a
sensitivity of 103 IU/mL.

17. DIAGNOSIS

18. GENOTYPE TESTING
• Looking at Nucleotide Patterns
• Test is a simple blood draw test. The test is able to
look at very selected parts of the genetic makeup of
the virus, called nucleotides.
• By looking at that pattern, the ability to see whether
or not that specific nucleotide pattern, almost like a
fingerprint, is for genotype 1, 2, or 3.
• By being able to do that at the molecular basis, the
test will be able to provide details with the type of
genotype that patient has if they are infected with
Hepatitis C.

19. INDICATIONS FOR SCREENING
• Persons who have IV drugs abuse in the recent and
remote past.
• Persons with conditions of a high prevalence of HCV
infection including:
• With HIV infection
• With hemophilia who received clotting factor prior.
• Who have ever been on hemodialysis.
• With unexplained abnormal aminotransferase
levels.
• Immigrants from countries with a high prevalence
of HCV infection.

20. • Children born to HCV-infected mothers
• Health care, emergency medical and public safety
workers after a needle stick injury or mucosal
exposure to HCV-positive blood
• Current sexual partners of HCV-infected persons

21. PREVENTION
• No Vaccine is available
• Risk factor modification
• Intravenous drug abuse: treatment with oral
methadone
• Sexual contact: appropriate barrier contraception
• Avoid blood exposure: Occupational (universal
precautions) or other contact
• Avoid body piercing, sharing razors or receiving a
tattoo.
• HAV and HBV vaccine to prevent further
progression of liver disease

22. TREATMENT KINETICS
Responders Non Responders
Null Responders
Partial Responders
Rapid Virologic Response (RVR)
Early Virologic Response (EVR)
Complete EVR
End Treatment Response (ETR)

23. TREATMENT KINETICS
• Null responders: HCV RNA reduction < 2log10
IU/mL
• Partial Responders: HCV RNA reduction > 2log10
IU/mL but not suppressed to undetectable by week
24.
• Rapid virologic response (RVR): HCV RNA
undetectable within 4 weeks.
• Early virologic response (EVR): HCV RNA reduction
> 2log10 IU/mL with:
1. HCV RNA undetectable at 12 weeks – complete EVR
2. HCV RNA undetectable at 48 weeks – End treatment response
(ETR)

24. GOALS OF THERAPY
• Eradicate HCV infection in acute.
• Decrease HCV associated morbidity and mortality.
• Attain Sustained Virologic Response (SVR).
• Undetectable HVC RNA, 24 weeks after therapy completion
• Normalize biochemical markers.
• Improve clinical symptoms.
• Prevent progression to cirrhosis an HCC.
• Prevent development of end stage liver disease.
• To prevents the development of chronic HCV infection.
These goals
are partly achieved by
Pharmacotherapy

25. INDICATIONS FOR ANTIVIRAL
THERAPY
• Patients with chronic hepatitis C who have detectable
HCV RNA in serum, whether or not aminotransferase
levels are increased, and chronic hepatitis of at least
moderate grade and stage (portal or bridging fibrosis)
are candidates for antiviral therapy.
• Patients who have relapsed after, or failed to respond to
a course of IFN monotherapy are potential candidates
for retreatment with PEG IFN plus ribavirin.
• Compensated liver disease, acceptable hemoglobin (13
g/dL men, 12 g/dL women) and neutrophils (more than
1500/mm3), SCr less than 1.5 mg/dL .

26. ACUTE HCV INFECTION
• In typical cases of acute hepatitis C, recovery is
rare, progression to chronic hepatitis is common.
• Meta-analyses of some small clinical trials suggest
that antiviral therapy with interferon α
monotherapy (3 million units SC three times a
week) is beneficial, reducing the rate of chronicity
considerably by inducing sustained responses in
30–70% of patients.
• Treatment can be delayed for 8-12 weeks for to
assess for spontaneous resolution.

27. • Although treatment of acute hepatitis C is
recommended, the optimum regimen, duration of
therapy, and time to initiate therapy remain to be
determined.
• Many authorities now opt for a 24-week course
(beginning within 2–3 months after onset) of long-
acting pegylated interferon plus the nucleoside
analogue ribavirin.(value of adding ribavirin has not been
demonstrated)

28. TREATMENT OF CHRONIC
HCV INFECTION
• Contraindications to treatment
• Major uncontrolled depressive disorder .
• Solid-organ transplantation (renal, heart, lung)
• Autoimmune hepatitis or other autoimmune
conditions
• Untreated thyroid disease .
• Pregnant or unwilling to adhere to adequate
contraception.
• Severe concurrent medical disease (hypertension,
heart failure, coronary heart disease, poorly controlled
diabetes mellitus, chronic obstructive pulmonary
disease)
• Age younger than 2 years.
• Hypersensitivity to IFN or ribavirin.

29. TREATMENT OF CHRONIC HCV
INFECTION
• Difficult patient population: individualized
consideration
• Advanced liver disease (fibrosis or decompensated
cirrhosis)
• Recurrence after liver transplantation.
• Patients younger than 18 years .
• Co-infection with HIV or HBV.
• Chronic Kidney Disease.
• Non responders or relapses.

30. TREATMENT
• When first approved, IFN-α was administered via
subcutaneous injection three times a week for 6
months but achieved a sustained virologic response
(SVR) (a reduction of HCV RNA to undetectable
levels by PCR when measured ≥6 months after
completion of therapy) below 10%.
• Doubling the duration of therapy—but not
increasing the dose or changing IFN preparations—
increased the SVR rate to ~20%, and addition to the
regimen of daily ribavirin, an oral guanosine
nucleoside, increased the SVR rate to 40%.

31. Treatment
⚫ First-line treatment for acute HCV includes pegylated interferon plus
ribavirin.
⚫ once-weekly PEG-IFN and a daily oral dose of ribavirin in two divided doses
Genotype Pegylated-
IFN Dose
weight
1 Peginterferon
α2a 180 mcg/wk
Peginterferon
α2b
1.5 mcg/wk
Less than 75 K
More than 75
2,3 Peginterferon á2a
180 mcg/wk
Peginterferon
α2b
1.5 mcg/wk
At week 1, 2, 4 and then interval of 4-8 weeks monitor:
• Symptom of Disease
• Side Effects of therapy
• Blood count
• Aminotransferases.

32. FOLLOW UP
• Genotype-1:AT week 12
- Retest HCV RNA level
If Negative or decreased by 2log 10 unit Continue for full 48 wk.
Monitor for :Symptoms, Blood count, ALT at 4-8 week
interval
STOP therapy
• If RNA hasn’t fallen by 2log 10 Units:
• Genotype 2, 3
Retest HCV RNA level at 24 weeks.
• After therapy:
Assess ALT 2, & 6 months.
Repeat HCV RNA, 6 months after stopping treatment.

33. RIBAVIRIN ADVERSE EFFECT
MONITORING
• Oral nucleoside analog
• Available as 200-mg tablets (Copegus) or capsules (Rebetol)
• Adverse Effect
• Hemolytic anemia:
• Upto 10% of patients (usually within 1–2 weeks of
initiating therapy).
• decrease dose to 600 mg/day when hemoglobin drops
to 10 g/dL or less, and discontinue when hemoglobin
drops to 8.5 g/dL or less.
(J Clin Gastroenterol 2005;39:S9-S13)

34. • May worsen underlying cardiac disease.
• Monitor complete blood cell count (CBC) at
baseline, 2 weeks, 4 weeks.
• Decrease dose to 600 mg/day if hemoglobin drops
more than 2 g/dL in any 4-week period during
treatment.
• May use erythropoetin or darbepoetin to stimulate
red blood cell production, improve anemia.
(J Clin Gastroenterol 2005;39:S9-S13

35. RIBAVIRIN ADVERSE EFFECT
MONITORING
• Teratogenicity:
• Requires a negative pregnancy test at baseline and every month
up to 6 months after treatment,
• Use of two forms of barrier contraception during treatment
and for 6 months after treatment.
• Contraindicated in patients with a creatinine clearance
(CrCl) less than 50 mL/minute
• pancreatitis, pulmonary dysfunction (dyspnea,
pulmonary infiltrate, and pneumonitis), insomnia,
irritability or depression, and pruritus.

36. INTERFERON: ADVERSE
EFFECTS
• Most Common:
• influenza-like symptoms (e.g., fever, headache,
myalgia, fatigue),
• Hematologic abnormalities: neutropenia,
thrombocytopenia,
• Neuropsychiatric disorders (e.g., depression 40 %
and anxiety),
• injection site reactions,
• diarrhea, nausea, insomnia, alopecia, pruritis, and
anorexia.

37. • Less common but serious adverse
• severe psychiatric (i.e., suicidal ideation),
• cardiovascular (i.e., myocardial infarction),
• Endocrine (e.g., thyroid dysfunction, diabetes
mellitus),
• immune (e.g., psoriasis, lupus),
• pancreatitis, colitis, and other serious infections.

38. MANAGING THE ADVERSE EFFECTS
OF INTERFERON
• Hematological:
• Anemia: common reason for discontinuation and
dose reduction (upto 23% of patients)
• Tx: Erythropoitic growth factor:
• Epoitin Alfa: 40-6000 units weekly
• Darbepoitin alfa 3 mcg every 2 weeks
• IFN induced neutropenia:
• Recombinant granulocyte colony stimulating factor
(filgrastim) is safe and effective.
• Thrombocytopenia:
• Eltrombopag, an orally active thrombopoietin receptor
agonist that received FDA approval for chronic ITP
(hepatotoxic).

39. MANAGING THE ADVERSE EFFECTS
OF INTERFERON
• Neuropsychiatric:
• Prompt recognition and early treatment required
• Depression: 44% during first 3 months.
• Treatment:
• Close monitoring and follow up by a team of
health care providers including psychiatrist
• Prophylactic anti-depressants are debated
• Uncontrolled psychiatric symptoms:
contraindication for treatment.

40. TREATMENT CHALLENGES
• High viral load
• HCV RNA greater than 800,000 IU/mL
• Advanced fibrosis and cirrhosis,
• Continued drug and/or alcohol use,
• Psychiatric conditions,
• Coinfection with HBV or HIV, advanced age,
• Immunosuppression (e.g., liver transplantation recipients),
• African American race,
• Obesity and insulin resistance,
• Previous treatment with suboptimal therapy

41. DEALING WITH THE CHALLENGES:
NEW ANTIVIRALS
• Direct Acting Antiviral Drugs (DAA)
• The NS3 protease inhibitors : Telaprevir and Boceprevir
• In 2011, telaprevir and boceprevir used in combination with
PEG IFN and ribavirin were approved for the treatment of
hepatitis C genotype 1 in adults with stable liver disease, both
in patients who have not been treated before or who have
failed previous treatment.
• Because resistance develops rapidly, both telaprevir and
boceprevir must be used in combination with a PEG IFN and
ribavirin-based regimen and should never be used alone.
An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011
practiceguideline by the American Association for the Study of Liver Diseases

42. • All current telaprevir and boceprevir regimens consist of
periods of triple therapy (protease inhibitor plus PEG
IFN plus ribavirin) and periods of dual therapy (PEG
IFN plus ribavirin).
• Telaprevir regimens begin with 12 weeks of triple
therapy followed by dual therapy of a duration based on
HCV RNA status at weeks 4 and 12 (“response guided
therapy”) and prior treatment status.
• Boceprevir-based regimens consist of a 4-week lead-in
period of dual (PEG IFN–ribavirin) therapy followed by
triple therapy and, in some instances, a further
extension of dual therapy, with duration of response-
guided therapy based on HCV RNA status at weeks 4, 8,
and 24 and prior treatment status

43. HCV GENOTYPE 1
• TREATMENT-NAIVE (telaprevir and boceprevir) and PRIOR
RELAPSERS (telaprevir)
• PEG IFN-α2a 180 μg weekly plus weight-based ribavirin 1000
mg/d (<75 kg) to 1200 mg/d (≥75 kg) or
• PEG IFN-α2b 1.5 μg/kg weekly plus weight-based ribavirin
800 mg/d (≤65 kg), 1000 mg/d (>65–85 kg), 1200 mg/d (>85–
105 kg), or 1400 mg/d (>105 kg)
• Plus response-guided therapy with a protease inhibitor
consisting of either:
• Boceprevir 800 mg three times daily with food started after a
lead-in treatment of 4 weeks with PEG IFN–ribavirin or
• Telaprevir 750 mg three times daily with fatty food started at
the beginning of therapy without a PEG IFN–ribavirin lead-in

44. Boceprevir Regimen

45. TELAPREVIR REGIMEN

46. HCV GENOTYPES 2 AND 3
• 24 weeks of therapy
• PEG IFN-α2a 180 μg weekly plus ribavirin 800
mg/d or
• PEG IFN-α2b 1.5 μg/kg weekly plus ribavirin 800
mg/d (for patients with genotype 3 who have
advanced fibrosis and/or high-level HCV RNA, a
full 48 weeks of therapy may be preferable)

47. HCV GENOTYPE 4
• 48 weeks of PEG IFN–ribavirin therapy
• PEG IFN-α2a 180 μg weekly plus weight-based
ribavirin 1000 mg/d (<75 kg) to 1200 mg/d (≥75 kg) or
• PEG IFN-α2b 1.5 μg/kg weekly plus weight-based
ribavirin 800 mg/d (≤65 kg), 1000 mg/d (>65–85 kg),
1200 mg/d (>85–105 kg), or 1400 mg/d (>105 kg)
• Treatment should be discontinued in patients who do
not achieve an early virologic response at week 12.
• Patients who do achieve an early virologic response
should be retested at week 24, and treatment should be
discontinued if HCV RNA remains detectable.

48. ADVERSE EFECTS
• Both protease inhibitors have potential toxicities.
Telaprevir is associated with a severe, generalized
(trunk and extremities), often confluent,
maculopapular, pruritic rash in ~6% of treated
patients.
• Other common side effects include pruritus, rectal
burning, nausea, diarrhea, fatigue, and anemia, which
may be relatively refractory occasionally requiring
transfusion.
• Complete blood counts should be obtained at baseline
and then at 2, 4, 8, and 12 weeks after starting
telaprevir.

49. • Anemia can occur in half of boceprevir-treated
patients, as can neutropenia in up to 30% and
thrombocytopenia in 3–4%. Complete blood counts
should be obtained at baseline and then at 4, 8, and
12 weeks after starting boceprevir.
• Other side effects of boceprevir include fatigue,
nausea, headache, dysgeusia (altered or unpleasant
taste), dry mouth, vomiting, and diarrhea

50. NEW ANTIVIRALS
SOFOSBUVIR
• Dose -400mg tablet once daily for 12-24 wks
• It’s a prodrug Metabolized to active triposphate . This
triphosphate serves as a defective substrate of
NS5B protein(viral RNA polymerase)
• Thus inhibit viral RNA synthesis.
• Plasma Half life: 0.48 ‐ 0.75 h (sofosbuvir).

51. • The following points should be considered when
initiating treatment with Sofosbuvir:
• Monotherapy of Sofosbuvir is not recommended for
treatment of CHC.
• Treatment regimen and duration are dependent on
both viral genotype and patient population
• Treatment response varies based on baseline host
and viral factors
• The recommended dose of Sofosbuvir is one 400 mg
tablet, taken orally, once daily with or without food
• Sofosbuvir should be used in combination with ribavirin
or in combination with pegylated interferon and
ribavirin for the treatment of CHC in adults

52. • In the FISSION study, among patients receiving
sofosbuvir–ribavirin, response rates were lower among
patients with genotype 3 infection than among those
with genotype 2 infection (56% vs. 97%) and were lower
for patients with cirrhosis than for those without
cirrhosis (47% vs. 72%).
Alessandra Mangia, M.D et al:Sofosbuvir for Previously Untreated Chronic
Hepatitis C Infection. May 16, 2013 DOI: 10.1056/NEJMoa1214

53. • In NEUTRINO trial the efficacy and safety of
sofusbuvir in previously treatment-naïve hepatitis c
patients with or without cirrhosis(gen 1, 4, 5,6) was
studied.
• 99% of patients with gen 1,4,5 or 6 achieved RVR,
and 90% achieved a SVR12.
• Patients with cirrhosis had a slightly lower rate of
SVR(80% compared with that 92% in patients
without cirrhosis.

54. • In ATOMIC trial, the efficacy of sofosbuvir with
peg-interferon and ribavirin in treatment naïve
patients with chronic hepatitis C(Gen 1,4 or 6
without cirrhosis) was studied.
• Results of this study showed very high SVR in all
three genotypes.

55. SIMEPREVIR
• A FDA approved hepatitis C virus protease inhibitor
• A NS3/4A protease inhibitor
• thus preventing viral maturation through inhibition of
protein synthesis.
• Simeprevir is administered as one capsule once daily with
pegylated interferon and ribavirin for the treatment of
genotype 1 or genotype 4 chronic hepatitis C.

56. • The recommended dose 150 mg taken orally OD with food
Should be used in combination with peg interferon alfa
and ribavirin.
• Adverse reactions: Rash, itching, nausea,
• Muscle pain, and indigestion
• Embryo-Fetal toxicity
• Photosensitivity
• contraindications
• In pregnant or may become pregnant women
• Men whose female partners are pregnant because of the
risk for birth defects and fetal death.

57. • Pooled data from the Phase III QUEST- 1 and QUEST-2
trials demonstrated that SMV 150mg QD administered
for 12 weeks in combination with pegIFN alpha-2a/RBV
or PegIFN alpha-2b/RBV resulted in:
• Overall SVR at 12 wk rate of 80% , significantly higher
than placebo.
• 88% of patients able to shorten treatment to 24 weeks,
with 88% among them achieving SVR at 12wk.
Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV
genotype 1 infection in treatment-naïve patients: efficacy in difficult-to-treat patient
sub-populations in the QUEST-1 and 2 Phase III trials

58. INTERFERON FREE REGIMENS
• The revolution in therapy came with the
introduction of directly acting drugs(DAA) like
sofusbuvir, simeprevir and ledipasvir in 2012 and in
2014.
• All oral drugs for hepatitis c was approved by the
FDA. In India, all oral medicines was introduced in
april 2015 and the interferon free ribavirin free
regimen in treatment naïve patients involving
sofosbuvir-ledipavir and sofosbuvir-daclatasvir was
approved for use in India in December 2015.
• Combination of DAA in various forms as ‘Drug
cocktails’ is useful.

59. INTERFERON FREE REGIMENS
• European guidelines (EASL)2015 HCV genotype 1
treatment naïve
• If patient is intolerant to RBV, or if there is adverse
outcome the combination has to be extended for
24wks.
Combination drugs No cirrhosis
(SVR12)
Compensated
cirrhosis
Sofosbuvir +
Ledipasvir 12wk
100% 97%
Sofosbuvir +
Ledipasvir
+Ribavarin
12wks
100% 100%
Sofosbuvir +
Ledipasvir 24wks
99% 97%

60. Combination drugs No cirrhosis Compensated
cirrhosis
Sofusbuvir+daclatasvi r
for 12wks
94%
Sofusbuvir+daclatasvi
r+RBV 24wks
100% 88%
Sofusbuvir+daclatasvi r
24wks
100% 63%

61. •HCV GENOTYPE 1 TREATMENT EXPERINCED
(Failed PEG-INF+ RBV+Boceprovir/telaprevir)
COMBINATION OF
DRUGS
PESPONSE RATE SVR12
Sofusbuvir+ledipasvir
12wks
93%
Sofusbuvir+ledipasvir+
ribavirin 12wks
96%
Sofusbuvir+ledipasvir
24wks
100%
Compensated
cirrhosis

62. HIV/HCV COINFECTION
• In patients with HCV/HIV co-infection, hepatitis C is
more progressive and severe than in HCV-
monoinfected patients.
• Four large national and international trials of
antiviral therapy among patients with HCV/HIV co-
infection have shown that PEG IFN (both α2a and
α2b) plus ribavirin (daily doses ranging from flat-
dosed 600−800 mg to weight-based 1000/1200 mg) is
superior to standard IFN regimens.

63. • However, SVR rates were lower than in HCV-
monoinfected patients, ranging from 14 to 38% for
patients with genotypes 1 and 4 and from 44 to 73%
for patients with genotypes 2 and 3.
• An alternative recommendation for ribavirin doses
was issued by a European Consensus Conference
and consisted of standard, weight-based ribavirin
1000−1200 mg for genotypes 1 and 4, but 800 mg
for genotypes 2 and 3.

64. • A head-to-head trial of combination PEG IFN–ribavirin
therapy in HCV/HIV co-infection demonstrated
statistically indistinguishable efficacy of the two types of
PEG IFN, despite a small advantage for PEG IFN-α2a.
• For PEG IFN-α2b and -α2a, SVRs occurred in 28%
versus 32%, respectively, of patients with genotypes 1
and 4.
and in 62% versus 71%, respectively, of patients with
genotypes 2 and 3.

65. • Although data are limited and recommendations
pending, protease inhibitors may be used for
genotype 1.
• However, because of potential drug-drug
interactions between HCV protease inhibitors and
HIV antiretroviral drugs (especially in ritonavir-
boosted HIV protease inhibitors), HCV protease
inhibitors should be used cautiously in HCV-HIV
co-infected patients.
• If protease inhibitors are used, a full 48-week
course is recommended without response-guided
therapy.

66. • In HCV/HIV-infected patients, ribavirin can
potentiate the toxicity of didanosine (e.g., lactic
acidosis) and the lipoatrophy of stavudine, and
zidovudine can exacerbate ribavirin-associated
hemolytic anemia; therefore, these drug
combinations should be avoided.

67. • Photon study( photon 1 trial)
• This study showed that combination of
sofosbuvir+RBV for 12 or 24 wks achieved high
rates of SVR12 without any deleterious effects.
Genotype Treatment naïve
SVR12
%
Treatment
experience
d SVR12 %
1 76
2 88 92
3 67 94
Sulkowski MS, Naggie et al: sofosbuvir and RBV for HEP C in patients
with HIV coinfection.JAMA 2014;312.

68. DAA IN CKD PATIENTS
• The overall prevalence of HCV infection in CKD
patients on maintenance haemodialysis is 13.5%.
• Positive anti-HCV serologic ststus after kidney
transplantation is implicated in the pathogenesis of
acute glomerulopathy, i.e graft HCV-associated
nephropathy.

69. • A study investigated the safety and efficacy of
sofusbuvir+ RBV in HCV infectetd patients with
severe renal impairement(GFR<30ml/min).
• Ten patients were enrolled and have been treated
for 12-24wks, All patients experienced RVR similar
to those with normal renal function and full dose
sofosbuvir+ RBV. There were no patients with
virologic breakhrough.
Ferenci P. treatment of HEP C in difficult to treat patients.Nat Rev
Gasteroenterol Hepatol.2015;12(5).

70. CONCLUSION
• The era of DAA theray in the treatment of hepatitis
C is evolving rapidly.
• The proof of concept that HCV infection can be
cured without INF to showing that cure can be
attained in an extraordinarily high proportion of
patients has occurred more quickly than most
observers had anticipated.

71. COST OF TREATMENT

73. COST OF TREATMENT
• Cost of treatment :
• $84,000 = Rs. 50.4 lacks for 24 weeks
• In September 2014, Gilead announced that it
would permit generic manufacturers to sell
sofosbuvir in 91 developing countries
• New price now is:
• About $1,800 = Rs. 1.1lacks (less than an
IVIG course for GB)

76. Thank you