HEPATITIS C

 Hepatitis C -infection of the liver

 Caused by RNA virus
 2 TYPES:
• ACUTE: refers to first 6 months of HCV infection
following presumed HCV exposure. Less than half of
people who get hepatitis C are able to clear the virus
in the first 6 months after infection without treatment.
• CHRONIC: Most people will develop a chronic, or
lifelong, infection. Left untreated, chronic hepatitis C
can cause serious health problems including liver
disease, liver failure, liver cancer.
EPIDIOMOLOGY

 Globally- 50 million people have chronic hepatitis C

virus infection
 ~1.0 million new infections occurring per year
 WHO estimated that in 2022: ~ 242,000 people died
from hepatitis C (mostly from cirrhosis and
HCC(primary liver cancer).
 INDIA: Second largest viral hepatitis burden globally-
(3.5 crore)11.6% total disease burden- out of which:
55 lakh of hepatitis C
VIRUS

 FAMILY: Flaviviridae
 GENUS: Hepacivirus
 Linear, single-stranded, RNA
Virus
 Icosahedral envelope with
glycoprotein spikes
 50-60nm
 6 major distinct genotypes
 Genotype- India- 1b and 3a
REPLICATION
 TRANSMISSION
 Parenteral transmission
 I/v drug abusers
 Surgical/dental procedures
 Transfusion of blood and blood products
 Contaminated syringes/ needles
 Razors/ blades and other sharp instruments
 Organ transplants
 Vertical transmission (<5%)
 Sexual transmission (<3%)
HIGH RISK

 Health care workers

 Multiple blood transfusions- Haemophiliacs and
thallasaemics
 Household and sexual contacts of infected patient
 IV drug abusers
 Tattooing and ear-piercing
 Male homosexuals or prostitutes
 Vertical transmission in infants
PATHOGENESIS
HCV induces hepatocellular injury by cell mediated immune
mechanism :
 It is possible that the host lymphoid cells are infected by HCV.
 HCV-activated CD4+ helper T lymphocytes stimulateCD8+ T
lymphocytes via cytokines elaborated by CD4 + helper T cells.
 The stimulated CD8+ T lymphocytes, in turn, elaborate antiviral
cytokines against various HCV antigens
 Further support to this T- cell mediated mechanism comes from
the observation that immune response is stronger in those HCV-
infected persons who recover than those who harbour chronic
HCV infection.
 There is some role of certain HLA alleles and innate
immunity in rendering variable response by different
hosts to HCV infection
 Natural killer (NK) cells also seem to contribute to
containment of HCV infection
 In as subset of patients, there is cross reactivity
between viral antigens of HCV and host
autoantibodies to liver-kidney microsomal antigen
(anti-LKM) which explains the association of
autoimmune hepatitis and HCV hepatitis.
 It inhibits interferon, which is responsible for chronic
infections.
CLINICAL MANIFESTATIONS
 Acute infections- asymptomatic  yellowing of the skin or
mostly (~2/3rd patients ) eyes (jaundice)
 symptoms develop 2 -26 wks  fever,
after exposure to HCV, (mean
onset – 7-8 wks)  fatigue,
 acute illness lasts or 2 -12 wks.  loss of appetite,
 Fulminant hepatic failure due to  nausea,
acute HCV infection is very rare
but may be more common in  vomiting,
patients with underlying chronic
 abdominal pain- RUQ
hepatitis B virus infection
 dark urine
EXTRA-HEAPATIC
MANIFESTATIONS
 cryoglobulinaemia,
 glomerulonephritis,
 thyroiditis
 Sjogren syndrome,
 insulin resistance, type 2 diabetes,
 skin disorders such as porphyria cutanea tarda and
lichen planus.
LABORATORY FINDINGS
 Aminotransferase levels >10-20 times the upper limit
 elevated total bilirubin levels
 Anti HCV Antibodies
 HCV RNA
ASSESSMENT
 Clinical evaluation for features of cirrhosis and evidence of
decompensation,
 Liver function tests
 prothrombin time;
 CBC
 ultrasonography and alpha-fetoprotein (AFP) measurement
for periodic surveillance for HCC (q6 months)
 endoscopy for varices in persons with cirrhosis.
FIBROSIS
 TRANSIENT ELASTOGRAPHY
 APRI

 FIB-4
 In Patients with Cirrhosis: CTP score is evaluated.
 Liver biopsy: to ascertain the degree of necro-
inflammation and fibrosis, and to help guide the
decision to treat
 Though liver biopsy remains the gold standard, non-
invasive methods for assessing the stage of liver
disease are supplanting it due to the limited availability
and accessibility to liver biopsy
MANAGEMENT
WHOM TO TREAT

 Any individual diagnosed to have infection with

hepatitis C virus (viremia +) needs treatment.
 Duration of treatment will depend on :
 cirrhosis versus non-cirrhosis,
 presence of decompensation (ascites, variceal
bleeding, hepatic encephalopathy, or infection(s),
 treatment naïve versus treatment experienced
GOAL OF THERAPY

 Thegoal of antiviral therapy in patients with

chronic hepatitis C virus (HCV) is to eradicate
HCV RNA, which is predicted by attainment of a
sustained virologic response (SVR), defined as an
undetectable RNA level 12 weeks following the
completion of therapy.
DIRECT ANTIVIRAL AGENTS
 DAAs are the recommended first line treatment in India.
 well tolerated.
 Certain regimens -safe for use in patients with decompensated liver
cirrhosis and post liver transplantation. close monitoring in specialized
centres is recommended
 Daclatasvir: ADRs: fatigue, headache and nausea, seen in studies that
have either used the drug in combination with sofosbuvir with or without
ribavirin.
 Sofosbuvir with or without ledipasvir: well tolerated by patients.ADRs:
Fatigue, headache, insomnia and nausea. Bradyarrhythmias in patients
also taking amiodarone and therefore contraindicated
 Sofosbuvir with Velpatasvir: well tolerated by patients. ADRs: Headache,
fatigue, anemia, nausea, insomnia, diarrhea, weakness, rash and
depression
HCV/HIV CO-INFECTION
 Persons with HIV/HCV co-infection – more rapid progression of
liver fibrosis, especially those with a CD4 cell count of <200
cells/mm3
 Even among patients in whom ART leads to successful control
of HIV infection (i.e. undetectable HIV viral load), the risk of
hepatic decompensation among co-infected patients is higher
than among patients with HCV mono infection.
 For these reasons, all persons with HIV/HCV co-infection
should be considered for HCV treatment.
PATIENTS WITH CKD

 No dose adjustment in direct-acting antivirals is required when

using recommended regimens.
HBV/HCV COINFECTION

 It is important to check for the presence of HBV infection before

starting HCV treatment.
 HBV and HCV co-infection may result in an accelerated disease
course; HCV is considered to be the main driver of disease.
 treated with antiviral therapy for HCV; SVR rates are likely to be
similar to those in HCV-mono infected persons.
 During treatment and after HCV clearance, there is a risk of
reactivation of HBV, and this may require treatment with
concurrent anti-HBV antiviral therapy.
HCV+TUBERCULOSIS

 concurrent treatment of HCV infection and TB should be avoided.

Active TB should generally be treated before commencing
therapy for HCV
PREGNANCY
 Women of reproductive age with HCV should be counseled about the
benefit of antiviral treatment prior to pregnancy to improve the health
of the mother and eliminate the low risk of mother-to-child transmission
 There are no large-scale clinical trials evaluating the safety of direct-
acting antivirals (DAAs) in pregnancy.
 Ribavirin is contraindicated in pregnancy due to its known
teratogenicity. In addition, the risk for teratogenicity persists for up to 6
months after ribavirin cessation and applies to women taking ribavirin
and female partners of men taking ribavirin.
PREVENTION AND CONTROL
 There is no effective vaccine against hepatitis C. The best way to prevent the
disease is to avoid contact with the virus.
 Extra care should be used in healthcare settings and for people with a higher
risk of hepatitis C virus infection.
 Ways to prevent hepatitis C include:
 safe and appropriate use of healthcare injections
 safe handling and disposal of needles and medical waste
 harm-reduction services for people who inject drugs, such as needle
exchange programs, substance use counselling and use of opiate agonist
therapy (OAT)
 testing of donated blood for the hepatitis C virus and other viruses
 training of health personnel
 practicing safe sex by using barrier methods
HEALTHCARE PROFESSIONALS-
POST EXPOSURE GUIDELINES
 The source patient should be tested for either HCV RNA (preferred method) or anti-
HCV followed by reflexive HCV RNA if positive (alternative method) within 48 hours
of an occupational exposure.
 The HCP should undergo anti-HCV testing within 48 hours of an occupational
exposure to assess for preexisting HCV infection.
 Follow-up testing of HCP is recommended if the source patient is HCV RNA positive
or has an unknown HCV RNA status, including cases where the source patient
cannot be tested.
 Initial follow-up testing for HCP should be performed using a NAT for HCV RNA at 3
to 6 weeks postexposure.
 If the HCV NAT is negative at 3 to 6 weeks, a final test for anti-HCV at 4 to 6 months
postexposure is recommended for HCP.
 If the HCP tests positive for HCV RNA, they should be referred for treatment of acute
HCV.
NATIONAL PROGRAMME

 National Viral Hepatitis Control Program’ was launched in 2018 to

combat hepatitis and achieve countrywide elimination of
Hepatitis C by 2030,
 achieve significant reduction in the infected population, morbidity
and mortality associated with Hepatitis A,B, C and E.
REFERENCES

 https://nvhcp.mohfw.gov.in/common_libs/diagnosis-management-
viral-hepatitis.pdf
 https://www.hcvguidelines.org/
 https://www.hepatitisc.uw.edu/