hepatitis G

A number of new hepatitis viruses (G, TT, SEN) were discovered late in the past century. We review the data available in the literature and our own findings suggesting that the new hepatitis G virus (HGV), disclosed in the late 1990s

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?

2. Hepatitis G Dr Ali Mehdi

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 Virus A Yonban Virus SEN Virus and TTV-Like mini Viruses INTRODUCTION

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

20. THANK YOU