Hepatitis C

(Non A, Non B- Hepatitis)

• Hepatitis C virus (HCV) is a member of Flaviviridae family Single stranded RNA

virus, enveloped.
• (HCV) is transmitted via blood, or body fluids.
• 1- Blood transfusion
• 2- Parenteral transmission
• Sharing needles IDU (80% ) infected with HCV)
• 3- Sexual transmission
• 4- Perinatal transmission
• 5- Other methods of transmission: Hemodialysis, tattooing, body piercing, and
acupuncture
• In 30% of the cases the source of HCV is not known.
• However there is a delay of about 70-80 day till the appearance of detectable
HCV antibodies, and about 1 in 100,000 transfusion can still result in infection.
• In USA 25 days (PCR).
• The virus does not kill the cell , but immune reaction can damage the liver cell.
 Hepatitis C
(Non A, Non B- Hepatitis)
• There is one serotype but at least Six different genotypes (genetic variation),
besides it is difficult to be cultured , complicate the search for a vaccine.
• The genotypes are important because the treatment response depends upon
the infecting genotype. Furthermore, genotypes and subtypes are important
epidemiological tools as some are geographically limited in their distribution.
• In the UK most of the infections are due to genotype 1a, 1b, 2 and 3.
• Genotype 1 is predominant in the United States. HCV has a high mutation rate,
which allows it to escape the immune response and persist in the host.
• In Egypt genotype 4 predominates.
• Egypt has a high rate of HCV infection because of the reported reuse of needles
during the national vaccination campaign to eliminate Schistosomiasis
(bilharzias), a parasitic infection
• Codes for the nucleocapsid core protein (C) and the envelope proteins (E1 and
E2/NS1) and nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B).
 Hepatitis C
• Incubation period
• Hepatitis C virus does not usually cause acute symptoms, but very occasionally
patients experience acute hepatitis. The average incubation period from exposure
to development of infection is 2–6 weeks, but may be as long as 3 months.
• Acute HCV infection is usually asymptomatic, and is only very rarely associated
with life-threatening disease.
• Produces symptoms of acute hepatitis in only about 20 percent of cases
• About 15–45% of infected persons spontaneously clear the virus within 6 months of
infection without any treatment.
• The remaining 55–85% of persons will develop chronic HCV infection. (majority of
cases)
• Of those with chronic HCV infection, the risk of cirrhosis or cancer of the liver is
15–30% within 20 years.
• Symptoms similar to Hepatitis B including jaundice, coke-colored urine, and clay-
colored stool.
• Symptoms may take 20 years to appear.
• Detected during routine testing.
• HCV can survive outside the body at room temp. for up to 3 weeks.
 Hepatitis C
• Reservoir, source, and transmission of infection
• Hepatitis C is exclusively a human disease. Patients who are infected with the
virus are the important reservoir of infection
Transmission is via blood or body fluids.
• Hepatitis C is transmitted mainly by exposure to contaminated blood, with
Intravenous drug use being the main source of infection.
• Blood transfusion was also a major source of infection before
• Other risk factors for acquiring hepatitis C include organ transplantation
• Chronic hemodialysis;
• Possibly intranasal cocaine use, body piercing, and tattooing.
• Sexual transmission of HCV is thought to be less common but is higher in
those who have had multiple sex partners or a history of sexually transmitted
diseases.
• Perinatal transmission has been estimated to occur at a rate of about 6
percent
• The prevalence rates are reported to be as high as 22% in Egypt due to use of
parenteral antischistosomal therapy
 Hepatitis C
• Because HCV is a difficult virus to culture, demonstration of the infection has relied on
other laboratory methods.
• Both serological tests and molecular tests have been developed to identify persons with
HCV infection.
• Serological tests are used in the screening of blood and organ donors for HCV infection
and in the initial diagnosis of symptomatic patients
• This testing involves detection of HCV IgG antibody
• Diagnosis of hepatitis is made by biochemical assessment of liver function
• HCV infection is diagnosed serologically in 2 steps:
• Screening for anti-HCV antibodies with a serological test identifies people who have been
infected with the virus.
• If the test is positive for anti-HCV antibodies, a nucleic acid test for HCV RNA is needed to
confirm chronic HCV infection because about 15–45% of people infected with acute HCV
• Although no longer infected, they will still test positive for anti-HCV antibodies.
• SO SEROLOGY ALONE IS NOT ???????
• After a person has been diagnosed with chronic hepatitis C infection, they should have an
assessment of the degree of liver damage (fibrosis and cirrhosis).
• This can be done. Those persons should have a laboratory test to identify the genotype of
the hepatitis C strain.
 Hepatitis C
• Improvements in the serological assays for anti-HCV over the years have enabled antibodies to be
detected earlier than previous methods— about 4 to 6 weeks after infection.
• The traditional confirmatory method was the recombinant immunoblot assay (RIBA), which detects
antibodies to different HCV antigens that have been immobilized onto a nitrocellulose strip by a
colorimetric reaction.
• However, RIBA has been replaced in many laboratories by molecular methods, which are more sensitive
and less labor-intensive
• Molecular assays that detect HCV RNA have been developed as qualitative and quantitative tests.
• Qualitative tests
• Distinguish between the presence or absence of HCV RNA in a clinical sample and are used to confirm
infection
• in HCV-antibody-positive patients, to detect infection in antibody-negative patients who are suspected of
having HCV, to screen blood and organ donors for HCV, and to detect perinatal infections in babies born
to HCV-positive mothers.
• The most commonly used qualitative method is reverse transcriptase polymerase chain reaction (RT-
PCR), but a highly sensitive transcription mediated amplification (TMA) test has recently been developed
as well.
• These tests can detect HCV infection within 1 to 3 weeks after exposure—much earlier than serological
methods
• Quantitative tests are performed by RT-PCR, real-time PCR, or branched DNA amplification (bDNA). They
are used to monitor the amount of HCV RNA, or “viral load,” carried by patients before, during, and after
antiviral therapy in chronically infected individuals
• Another type of molecular assay for HCV is the genotyping test, which determines the exact genotype
 Laboratory Tests for HCV
Serology:
Hepatitis C diagnosis depends on demonstration of anti-HCV detected by an EIA.
Anti-HCV is generally not detectable in patients with initial signs or symptoms of
hepatitis C.
Anti-HCV develop in acute infection generally between 2 and 8 weeks after evidence of
liver injury.
Some persons may not test positive for 6-9 months after onset of illness.
Hepatitis C viremia may be detected by RT-PCR within days after infection.
• Tests are not yet available to distinguish acute from chronic HCV infection.
• Positive anti-HCV IgM levels are found in 50-93% of patients with acute hepatitis C
and in 50-70% of patients with chronic hepatitis C.
• Therefore, anti-HCV IgM cannot be used as a reliable marker of acute HCV infection.
• To date, the clinical and diagnostic significance of IgM response in HCV infection is still
unclear. In fact, IgM antibodies to HCV have been found in a variable (54 to 91%)
percentage of patients with chronic HCV infection.
• An EIA test for HCV core-antigen detection has been established and appears to be
suitable for large-scale screening of blood donations, whilst its use in clinical
monitoring remains to be determined
 Laboratory Tests for HCV
• 1- Clinical indication
• Screening for acute or chronic HCV infection
• Test :Hepatitis C antibody
• Positive result indicates infection, initial screen
• MUST be confirmed by repeat testing.
• There is no HCV specific IgM test available to distinguish acute from chronic infection
• 2- For establishing infection status of patient
• Hepatitis C PCR for HCV RNA.
• Mostly quantitative (viral load) assay.
• Positive result indicates either acute or chronic infection.
• Negative result indicates clearance of infection either naturally or post-treatment
• 3- Assessment of infected patient for treatment
• Hepatitis C genotype determination
• HCV genotype will guide treatment decisions including duration of treatment
• Clearance of the infection may occur spontaneously or may require treatment with
antiviral drugs, the standard treatment involving a combination of pegylated
interferon- and ribavirin.
 Treatment
• Interferon & ribavirin.( Guanine inhibitor)
• Oral directly acting antiviral agent (DAAs) therapies
(targeted against viral protein, (protease)
• Hepatitis C virus is probably the major reason for Liver
transplantation. WHY??????
• Prevention is limited to minimizing exposure to sharing of
items such as razors, toothbrushes, & nail clippers.
• Person with HCV should be vaccinated against HAV,HBV
(Twinrix). Havrix is a HAV vaccine.
• Having had hepatitis C once does not make you
"immune" from getting hepatitis C again
• No vaccine
 Hepatitis D
Hepatitis D virus (HDV).
Hepatitis D (Hepatitis delta) has a circular single strand of RNA,
• Hepatitis D or delta is a defective RNA virus and requires the hepatitis B surface
antigen (which it uses as its outer protein coat) so it can enter the cells to infect
and replicate.
• As it cannot replicate without the help of HBV, delta infection cannot occur in
patients who are not HBV infected.
• Two types of infection are described:
• Co-infection: Where a person who is susceptible to HBV is exposed to someone
who is co-infected with HBV and delta virus, this results in acute co-infection
with both viruses at the same time.
• Super-infection: When an HBV carrier is exposed to infected blood from co-
infected patients then the exposure results in super-infection of the existing HBV
infection with delta virus; this may result in development of acute hepatitis (due
to delta virus) in an HBV chronic carrier.
• Delta infection can clear up after an acute episode or, like HBV, delta virus may
persist to cause chronic infection. There is evidence that chronic co-infection or
delta virus super-infection of chronic HBV infection has a worse prognosis.
 Hepatitis D
It becomes infectious when an external envelop HBsAg,(HBV)
whose formation is controlled by the genome of HBV , cover the
HDV protein core (the delta antigen).
In chronic HBV, chronic HDV was often accompanied by
progressive liver damage and fatality rate several times that of
people infected with HBV alone.
• Infection is diagnosed by screening blood for delta virus IgG;
although delta virus IgM is not always present in acute infection a
positive result is useful in confirming acute delta virus infection.
• In the UK, delta virus infection is seen only in those who use
recreational intravenous drugs.
• Fortunately, as delta virus requires HBV to infect and replicate,
protecting individuals for HBV through vaccination is effective in
protecting against delta virus infection as well.
 Hepatitis E

• Hepatitis E virus (HEV) is an RNA virus, caliciviruses.

• Non-enveloped
• There are at least four genotypes of the virus,
• Epidemiology & Route of spread
• Hepatitis E is spread by the fecal–oral route, Most HEV infections are related to
consumption of faecally contaminated drinking water in developing regions of Africa, the
Middle East, Southeast Asia, and Central Asia, all of which have poor sanitation
conditions.
• Person-to-person spread may occur but is uncommon.
• Waterborne outbreaks occur commonly in countries where infection is endemic.
• Similar to HAV, but not related serologically.
• Following an incubation period of 3 to 8 weeks
• Mild, prolonged infection.
• Does not cause chronic liver disease.
• Cause mortality rate (20%) in pregnant women?
• Fulminant hepatitis, associated with rapidly progressing disease and a high mortality
rate, occurs more commonly in pregnant women. The reason is not totally clear, but is
presumably due to changes in the immune response that occur during pregnancy. Like
 Hepatitis E

Laboratory diagnosis of hepatitis E infection.

• Because HEV is not easily cultured, diagnosis of it relies on serology.
• Acute infection is indicated by the presence of IgM anti-HEV, which is
detectable at clinical onset but declines rapidly in the early recovery period.
• These antibodies are typically identified by highly sensitive enzyme
immunoassays that use recombinant and synthetic HEV antigens.
• Specificity of the assays may be increased by testing for IgA anti-HEV along
with the IgM assays.
• In patients who are suspected of having hepatitis E but who yield a negative
IgM test, molecular testing for HEV RNA can be performed, typically by RT-
PCR.
• These assays should be performed on stool samples collected within 3
weeks of clinical onset.
• Immunoassays for IgG anti-HEV, which persists longer, may be performed
to determine previous exposure and seroprevalence of the infection
 Other types of Hepatitis

There is evidence of the existence of hepatitis types of G and F.

• HGV is an enveloped, single-stranded RNA virus in the
Flaviviridae family.
• It is transmitted by the bloodborne route, perinatal route, and
possibly through sexual contact.
• Detection of the virus has been based primarily on RT-PCR
methods, which amplify HGV RNA
Hepatitis G (HGV)
1) Similar to HCV in how it infects.
2)About 20% of HCV patients have HGV.
3) Prevalent throughout the world in persons with or without
clinical hepatitis, but his role as etiologic agents of hepatitis
remains under debate.