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A 22 year old boy presented with the complains of low
grade fever and dry cough.Examination revealed
palpable submental and submandibular lymph nodes
alongwith rash all over his body.Oral examination
showed erythematous posterior pharyngeal wall.Lab
showed HB 12.5, TLC 13; N 25,L 75, PLT 335,ALT
95IU,LDH330,Viral serology for A,B,C,E and Dengue were
all negative
1:What is most likely cause of raised ALT?
2:What is other name of this virus?
3:Diagnostic test of choice in this case?
Hepatitis G
Dr Ali Mehdi
• Anumber of viruses may be hepatotropic in that viremia is occasionally
associated with elevations in serum ALT levels and viral replication may
occure in hepatocytes, but little, if any liver diseases ensures.
• Such Viruses Include
• Hepatitis G Virus and The GB Agents
• TT Virus (torque teno)
• Sanban VirusA
• Yonban Virus
• SEN Virus and TTV-Like mini Viruses
INTRODUCTI
ON
• During the long search for the cause of Transfusion-associated
Non-A, Non-B hepatitis, The GB virus and HGV were discovered
in 1996 by Simons and Linnen
• Later shown to be 2 Isolates of same virus
• Analysis of Marmosets infected with derivations of GB serum led
to identification of two distics viruses, labeled GBV-Aand GBV-B
• A third virus closely related to the GB agents was subsequently
identified by the same investigators from a human sample and
was classified as GBV-C
Hepatitis G Virus
Virus Hepatitis G
Family Flavivirus
Genus Unnamed
Virion 60nm, Spherical
Envelop Yes
Genome ssRNA
Stability Ether-sensitive
Transmission Parenteral
Prevalence Moderate
Chronic Disease Yes
Virology
• GBV-C,classified as member of Flaviviridea family,is a Positive
Strand RNA virus with a genome of 9400 nucleotides encoding
approximately 2900 amino acids
• It shares 44% and 28% nucleotide homology with GBV-A
andGBV-B respectively
• Has five known genotypes
• However GBV-C shares only 27% nucleotide homology with
HCV
EPIDEMIOLOGY
• GBV-C is found worldwide
• At least five genotypes have been identified,each with a specific
geographic distribution
• Genotype 1: West Africa
• Genotype 2:Europe and USA
• Genotype 3:Asia
• Genotype 4:Southeast Asia
• Genotype 5:South Africa
• GBV-C genome is organised like that of HCV
• One long open reading frame encodes a single large
polyprotein
• With structural proteins encoded at 5’ aminoterminus and non-
structural proteins encoded at 3’carboxyterminus
• A nontranslated region at 5’end serves at internal ribosomal
entery site (IRES), allowing translation of uncapped messenger
RNA
• The structural proteins between HCV and GBV-C
• Two glycoproteins E1 and E2 predicted to compose GBV-C viral
envelop are cleaved from the polyprotein,likely by a host cell
signal peptidase
• Whereas HCV E1 and E2 have 5 and 11 N-linked glycosylation
sites
• GBV-C’s E1 and E2 have only 1 and 3 such sites respectively
• GBV-C genome doesnot encode a core protein but biophysical
and elecrtron microscopic studies suggest that virus does have a
nucleocapsid structure,presumably with a core protein
• Another important difference between GBV-C and HCVmay be
tissue tropism
• Negative strand RNA (indicating the presence of active viral
replication) has been demonstrated in liver tissue duing HCV
infection,implying hepatotropism,But has not been clearly
demonstrated during GBV-C infection
• The development of GBV-C E2 antibodies correlates with loss of
GBV-C viremia and suggests past exposure and clearance of
GBV-C infection
• Evidence of past and current GBV-Cinfection is found frequently
in persons with parenteral risk factors and also common amon
volunteer blood donors
MODES OF TRANSMISSION
• HGV is transmitted via following routes
• Transfusion of contaminated blood or blood products
• Sexual exposure
• Mother to child
• GBV-C transmission is not prevented by exclusion of donors
with normal ALT value
Studies Regarding Transmission From
Mother To Child
• In Sweden,three studies investigated vertical
transmission,including one study of HIV infected mothers.Of
seven infants born to motehrs not infected with HIV,One infant
became HGV RNA positivein serum at 3 months with persistent
viremia during 42 months of follow up with no evidence of liver
disease
• The role of breastfeedig in transmission was investigated in one
study documenting the lack of detectable HGV RNA in breast
milk of 15 viremic women.so breast feeding should not be
discouraged in HGV infected women
• Because GBV-C and HCV are transmitted parenterally, co-infection is
common
• GBV-C viremia is present in about 20% of HCV infected persons and
80% of remaining subjects are seropositive for antibodies to E2
• These findings suggest that rate of natural clearance of GBV-C is
Higher (>75%) than that for HCV (>25%)
CLINICAL FEATURES
• Detected in many patients with NON-A to Non-E acute and
chronic hepatitis and may persist for years
• It doesnot appear to cause liver disease even in
immunocompromised persons.
• It does not appear to modulate the course or response to
treatment of chronic HBV or HCV infection
• It does not affect the outcome of Liver Transplantation,even
though LT recepients have high Viral load
• The duration of infection may depend on immune status and
age of host
HGV INFECTION IN HIV PATIENTS
• HIV-infected persons are also more likely than NON-HIV
infected persons to develop chronic HGV infection
• A german study showed that HGV infection may slow the viral
replication of HIV,the authors suggested that HGV may
interfere with a classic shift from a Th1 to Th2 pattern that is
seen in many people with disease progression.however no
evidence was provided.
DIAGNOSIS
• Because GBV-C rarely causes disease in human
beings,diagnostic tests are not widely available and generally
are preserved for research purposes.
• GBV-C RNA can be detected by using PCR with commercially
available primers
• A test for GBV-C antibody,to document past infection is also
available
TREATMENT
• Because GBV-C is not associated with clinical liver disease,No
treatments have targeted GBV-C specifically
• In HIV-HCV-GBV-C Co-infected persons, Peg Interferon and
Ribavirin treatment led to sustained GBV-C clearance in 31% of
patients,with no observable subsequent effect on course of
HCV or HIV infection
• In patients Co-infected with GBV-C and HCV who were treated
with interferon and ribavirin,GBV-C RNA disappeared from
serum during the therapy but reappeared in all patients
following discontinuation of therapy
• Importantly no effect of GBV-C infection was observed on
response to treatment of HCV infection
THANK YOU

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hepatitis G

  • 1. A 22 year old boy presented with the complains of low grade fever and dry cough.Examination revealed palpable submental and submandibular lymph nodes alongwith rash all over his body.Oral examination showed erythematous posterior pharyngeal wall.Lab showed HB 12.5, TLC 13; N 25,L 75, PLT 335,ALT 95IU,LDH330,Viral serology for A,B,C,E and Dengue were all negative 1:What is most likely cause of raised ALT? 2:What is other name of this virus? 3:Diagnostic test of choice in this case?
  • 3. • Anumber of viruses may be hepatotropic in that viremia is occasionally associated with elevations in serum ALT levels and viral replication may occure in hepatocytes, but little, if any liver diseases ensures. • Such Viruses Include • Hepatitis G Virus and The GB Agents • TT Virus (torque teno) • Sanban VirusA • Yonban Virus • SEN Virus and TTV-Like mini Viruses INTRODUCTI ON
  • 4. • During the long search for the cause of Transfusion-associated Non-A, Non-B hepatitis, The GB virus and HGV were discovered in 1996 by Simons and Linnen • Later shown to be 2 Isolates of same virus • Analysis of Marmosets infected with derivations of GB serum led to identification of two distics viruses, labeled GBV-Aand GBV-B • A third virus closely related to the GB agents was subsequently identified by the same investigators from a human sample and was classified as GBV-C
  • 5. Hepatitis G Virus Virus Hepatitis G Family Flavivirus Genus Unnamed Virion 60nm, Spherical Envelop Yes Genome ssRNA Stability Ether-sensitive Transmission Parenteral Prevalence Moderate Chronic Disease Yes
  • 6. Virology • GBV-C,classified as member of Flaviviridea family,is a Positive Strand RNA virus with a genome of 9400 nucleotides encoding approximately 2900 amino acids • It shares 44% and 28% nucleotide homology with GBV-A andGBV-B respectively • Has five known genotypes • However GBV-C shares only 27% nucleotide homology with HCV
  • 7. EPIDEMIOLOGY • GBV-C is found worldwide • At least five genotypes have been identified,each with a specific geographic distribution • Genotype 1: West Africa • Genotype 2:Europe and USA • Genotype 3:Asia • Genotype 4:Southeast Asia • Genotype 5:South Africa
  • 8. • GBV-C genome is organised like that of HCV • One long open reading frame encodes a single large polyprotein • With structural proteins encoded at 5’ aminoterminus and non- structural proteins encoded at 3’carboxyterminus • A nontranslated region at 5’end serves at internal ribosomal entery site (IRES), allowing translation of uncapped messenger RNA
  • 9. • The structural proteins between HCV and GBV-C • Two glycoproteins E1 and E2 predicted to compose GBV-C viral envelop are cleaved from the polyprotein,likely by a host cell signal peptidase • Whereas HCV E1 and E2 have 5 and 11 N-linked glycosylation sites • GBV-C’s E1 and E2 have only 1 and 3 such sites respectively • GBV-C genome doesnot encode a core protein but biophysical and elecrtron microscopic studies suggest that virus does have a nucleocapsid structure,presumably with a core protein
  • 10. • Another important difference between GBV-C and HCVmay be tissue tropism • Negative strand RNA (indicating the presence of active viral replication) has been demonstrated in liver tissue duing HCV infection,implying hepatotropism,But has not been clearly demonstrated during GBV-C infection
  • 11. • The development of GBV-C E2 antibodies correlates with loss of GBV-C viremia and suggests past exposure and clearance of GBV-C infection • Evidence of past and current GBV-Cinfection is found frequently in persons with parenteral risk factors and also common amon volunteer blood donors
  • 12. MODES OF TRANSMISSION • HGV is transmitted via following routes • Transfusion of contaminated blood or blood products • Sexual exposure • Mother to child • GBV-C transmission is not prevented by exclusion of donors with normal ALT value
  • 13. Studies Regarding Transmission From Mother To Child • In Sweden,three studies investigated vertical transmission,including one study of HIV infected mothers.Of seven infants born to motehrs not infected with HIV,One infant became HGV RNA positivein serum at 3 months with persistent viremia during 42 months of follow up with no evidence of liver disease • The role of breastfeedig in transmission was investigated in one study documenting the lack of detectable HGV RNA in breast milk of 15 viremic women.so breast feeding should not be discouraged in HGV infected women
  • 14. • Because GBV-C and HCV are transmitted parenterally, co-infection is common • GBV-C viremia is present in about 20% of HCV infected persons and 80% of remaining subjects are seropositive for antibodies to E2 • These findings suggest that rate of natural clearance of GBV-C is Higher (>75%) than that for HCV (>25%)
  • 15. CLINICAL FEATURES • Detected in many patients with NON-A to Non-E acute and chronic hepatitis and may persist for years • It doesnot appear to cause liver disease even in immunocompromised persons. • It does not appear to modulate the course or response to treatment of chronic HBV or HCV infection • It does not affect the outcome of Liver Transplantation,even though LT recepients have high Viral load • The duration of infection may depend on immune status and age of host
  • 16. HGV INFECTION IN HIV PATIENTS • HIV-infected persons are also more likely than NON-HIV infected persons to develop chronic HGV infection • A german study showed that HGV infection may slow the viral replication of HIV,the authors suggested that HGV may interfere with a classic shift from a Th1 to Th2 pattern that is seen in many people with disease progression.however no evidence was provided.
  • 17. DIAGNOSIS • Because GBV-C rarely causes disease in human beings,diagnostic tests are not widely available and generally are preserved for research purposes. • GBV-C RNA can be detected by using PCR with commercially available primers • A test for GBV-C antibody,to document past infection is also available
  • 18. TREATMENT • Because GBV-C is not associated with clinical liver disease,No treatments have targeted GBV-C specifically • In HIV-HCV-GBV-C Co-infected persons, Peg Interferon and Ribavirin treatment led to sustained GBV-C clearance in 31% of patients,with no observable subsequent effect on course of HCV or HIV infection
  • 19. • In patients Co-infected with GBV-C and HCV who were treated with interferon and ribavirin,GBV-C RNA disappeared from serum during the therapy but reappeared in all patients following discontinuation of therapy • Importantly no effect of GBV-C infection was observed on response to treatment of HCV infection