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Known as Infectious Hepatitis. In 1973 this virus was detected in stool. In following years specific serologic assay & isolation of HAV in cell culture were done to study the epidemiology & prevention. Commonly transmitted by fecal-oral route via contaminated food or water. Incubation period is 2-6 weeks. In developing countries due to poor hygiene standard the incidence is high. Infection causes no clinical signs in >90% of children & offers lifelong immunity having special significance in indigenous population.It does not have a chronic stage & does not cause permanent liver damage. Vaccine is helpful in controlling out break.
Belongs to Picornaviridae family with genus Hepatovirus. HAV is icosahedral in shape without envelope, having diameter of 27- 28 nm. HAV survives exposure to ether, acid at pH 3, heat exposure at 60o C for 60 minutes but inactivated at 85 o C for 1 minute. HAV is capable of surviving sea water (4%), dried faeces at room temperature for 4 weeks(17%),in live oysters for 5 days(12%).Only one serotype of HAV is known & there is no antigenic cross-reactivity with B,C,D,E,F,& G. The HAV genome consists of positive sense RNA which is single stranded & linear. The HAVRNA has a long open reading frame consisting of 6681 nucleotides & covalently linked to a 5’ terminal protein& a 3’ terminal polyadenosine tract. HAV replication in cell culture takes weeks to months depending on metabolic activity of host cell. In the life cycle of the virus the 1st step is attachment to cell surface receptors, the location & function determine tissue tropism .Though exact mechanism of entry of HAV in to cell is not known probably through surrogate-receptor binding mechanism. A surface glycoprotein named HAVcr-1 has been identified as receptor for HAV. Experimental data suggest that HAVcr-1 not only serves as an attachment receptor but may facilitate un coating of HAV& its entry to hepatocytes. After entry of HAV the viral RNA is un coated , cell host ribosome bind to viral RNA forming polysomes & HAV is translated to large polyproteins which are organized to 3 regions:P1,P2,P3.The P1 encodes structural proteins VP1,VP2,VP3 &VP4.P2 & P3 encode non structural proteins associated with viral replication.
Numerous strains of HAV exists with variability of nucleotide sequences Human HAV strain have 4 genotypes (I,II,III,VII) where as simian have IV,V,VI genomes. But despite heterogeneity of nucleotide sequence the antigenic structure is maintained. HAV VP1/2 & 2C are thought to be responsible for virulence. Among many strains of HAV HM175 &CR326 are important as they are used for production of vaccine. Variation of HAV genome are responsible for fulminant hepatic failure (FHF) during acute HAV infection.
HAV can be inactivated by Chlorine treatment, formalin(0.35% 37C,72 hours),peracetic acid(2%,4 hours)beta-propiolactone(0.25%,1 hour), UV radiation(2µw/cm2/min)
In US the annual calculated rate is 93,000.The highest rate is among children between 5-14 years. But it can occur in any age. The epidemiological risk factors in US-unknown (57%), sexual or household contact (12%),
International travel(9%),male homosexual(8%),injection drug users(5%),child or employee in day care(1%),food & water borne(1%),other contacts(7%).
HAV infection usually follows one of the three epidemiologic patterns:-
1. In poor sanitary conditioned countries most children at an early age are infected showing 100% Anti-HAV antibody in their serum indicating sub clinical infection. Symptomatic infections has risen to 5 years & older groups. Differs in income groups. About 95% children of low income families are infected.
2. Second pattern is seen in industrialized countries where prevalence of Anti-HAV in children is 10% & adults 37%.
3. Third pattern is seen in closed or semi closed communities like South pacific. HAV infects entire population, which then become immune. Only new borne become susceptible.
The primary route of transmission is fecal-oral route by either person to person contact or ingestion of contaminated food or water.
Rare routes:- Parenteral after blood transfusion, Injection users & non injection illicit drug users
Homosexual males
Detection of HAV & infectivity of secretions & excretions
Stool:- HAV detected during incubation & for several weeks after onset. HAV is found in 45% & 11% during 1st & 2nd weeks respectively. HAV-RNA (by PCR) is detectable up to 4-5 months.
Blood:- Viraemia present during incubation. Blood collected 3-11 days prior to onset causes post transfusion, Infection.
Bile:- Detected in Chimpanzees.
Urine:- Detected in viraemia phase. Urine contaminated with blood is infectious.
Nasopharyngeal secretion:- Unknown to human.
Semen, vaginal fluid:-Uncertain. HAV detected in viraemia phase.
Virus spread is common in poor sanitation & over crowding. Common source (e.g. water, restaurant) outbreaks are typical.
HAV once ingested survives gastric acid, pass to mucosa of small intestine & reaches liver via portal vein. Entering into hepatocytes by uncertain mechanism replicate in the cytoplasm (seen by E/M as fine granules) but not in the nucleus. HAV is distributed through out the liver. Though antigen is detected in lymphnodes, spleen, kidney they exclusivey replicate in hepatocytes. Once the virus is mature it reaches the systemic circulation via hepatic sinusoids & released to billiary tree through bile cannaliculi, pass into intestine & faeces. The hepatocyte injury is not clear as HAV is not cytopathic. Immunologically mediated cell damage is more likely. The anti HAV could result in hepatic necrosis duringmmunologically mediated elimination of HAV.
Incubation period is 2-4 weeks, rarely up to 6 weeks.
Course is usually acute self limiting, prolonged or relapsing, cholestatic phase but chronic infection does not occur. Mortality is low in healthy persons & morbidity is high in adults & older children.
More in men in all age groups.
HAV infection usually presents in 5 different clinical presentations:-
1.-Asymptomatic without jaundice
2.-Symptomatic with jaundice & self limited-8 weeks
3.-Cholestatic with jaundice lasting 10 weeks or more
4.-Relapsing with 2 or more bouts of acute infection over 6-10 weeks
Children below 2 years are usually asymptomatic jaundice in 20%. Children over 5 years or more are symptomatic (80%).Symptoms are more in adolescent or adults. Cholestatic type is a rare variant where jaundice persists for long period & subjected to invasive diagnostic procedures. Relapsing course is observed in 10% cases where shedding of HAV in stool is detected. This variant is benign & resolve ultimately. Neither cholestatic nor relapsing variant has greater mortality & treatment is symptomatic. Unlike Hepatitis-E, HAV has no higher mortality in pregnant women.
Usual prodromal symptoms are fatigue, weakness, anorexia, nausea, vomiting, abdominal pain. Less common symptoms are fever, headache, arthralgia, myalgia, diarrhea. Dark urine precedes symptoms (90%).Symptoms may last for few days to 2 weeks & decrease after onset of jaundice. Right hypochondriac pain & mild tender hepatomegaly (85%), splenomegaly (15%), cervical lymphadenopathy (15%) may be noted.
Complete clinical recovery in 2 months (60%) & in 6 months (100%).
Overall prognosis is good in healthy adults.
Fulminant hepatic failure (FHF):-
FHF is rare in children, adolescent or young adults.
Case fatality in aged >49 years is 1.8%.
Usually manifest in 1st week of illness (55%) & first 4 weeks (90%).Rare after 4 weeks.
It is higher in hyperendemic area like India.
The increased among elderly, associated CLD.
Extra hepatic manifestations:-
Less frequent than HBV. Consists of evanescent rash(14%), arthralgia(11%), leukocytoclastic vasculitis, glomerulonephritis, arthritis which are due to immune complex mechanism.Cutaneous vasculitis are seen in legs & buttocks.Skin biopsy reveal presence of IgM anti HAV & complement in vessel wall. Vasculitis & arthritis are associated with cryoglobulinemia where cryoglobulin contains IgM antiHAV. Other extrahepatic manifestations include toxic epidermal necrolysis, fatal myocarditis, renalfailure,optic neuritis, transverse myelitis,polyneuritis, cholecystitis, thrombocytopenia, aplastic amaemia, red cell aplasia.
Auto immune hepatitis (AIH) after HAV: - HAV rarely trigger the onset of Type-1 AIH.
Acute HAV is to be differentiated from other causes of viral hepatitis, AIH & other causes of hepatitis by serological tests. Many times it may be difficult due to associated chronic HBV or HCV infection.
In acute HAV IgM-antiHAV antibody is positive from the onset of symptoms & usually remains +ve up to 4 months.In some low levels may be detected up to 1 year.IgG antiHAV antibody is detected at the onset & remain +ve through out life indicating a marker of previous infection.
HAV-RNA (by PCR) has been detected in stool, blood &liver. HAV-RNA is usually undetectable in FHF than non-fulminant hepatitis. It is suggested that detection of IgM antiHAV coupled with nondetectable or low titer of HAV-RNA may signal ominous prognosis & require liver transplant.
During acute phase the liver enzyme ALT is high.
High risk populations are targeted for vaccination. Childhood vaccination have a +ve effect in reducing incidence.
High risk groups:--
Healthy persons traveling to endemic area, occupation likelihood of exposure, family members of
Infected person, adopt infant or child from endemic area.
Persons with CLD.
Persons who are HIV +ve.
Homosexual man.
Users of injection & illicit drugs.
Clotting factor disorders.
Persons living in high or intermediate rate of HAV infection.
No specific treatment. Symptomatic treatment is the rule. Advise rest, avoid fatty food & alcohol, take balanced diet & proper hydration.
Attention of proper sanitation.
Role of Immune Globulin (IG):-Use of pre exposure prophylaxis is unnecessary due to availability of vaccine. In post exposure prophylaxis IG should be given within 2 weeks of exposure in a dose of 0.02 ml/kg IM.IG can cause fever, myalgia. IG can safely be given along with vaccine.
HAV vaccine: - Two inactivated HAV vaccine are available ,to be given IM in deltoid area.
HAVRIX & VAQTA are 2 vaccines derived from HAV grown in cell culture. They are purified, formalin inactivated & contains Alum as adjuvant. HAVRIX is prepared from HM175 strain & VAQTA from CR326 strain of HAV virus, Both are safe & immunogenic. Immunity lasts for 20 years or longer.
Common side effects are soreness at injection site (56%), headache (14%),malaise(7%). Some unexplained adverse reactions are neurologic, haematologic, &autoimmune syndrome.
A combination formula of HAV &HBV is available with excellent safety &efficacy (TWINRIX).
Dosing schedule-----
HAVRIX - 2-18 years 0.5ml 0,6-12 months.
>18 years 1 ml 0, 6-12 months.
VAQTA- 2-18 years 0.5 ml 0, 6-18 months.
>18 years 1 ml 0, 6-18 months.
TWINRIX- ≥ 18 years 1 ml 0, 1, 6 months.
Death usually occurs if patient is already suffering from other hepatitis like B,C & AIDS. Young children experience mild form whereas adults much severe form.


Hepatitis D(delta) virus was discovered by Rizzetto in 1977 as an unique nuclear antigen in hepatocytes of patients infected with HBV, when he observed a new antigen other than surface, core, & e antigen.
Distributed worldwide.5% of HBV carriers are infected with HDV with a burden of 15-20 millions. Highest prevalence in South America & Mediterranean basin. The incidence of HDV is declining in some countries due to screening of blood donors for HBsAg. However HDV remains among injection drug users. Among 3 genotypes of HDV(I,II,III) genotype-I is prevalent in Mediterranean countries, Africa, Europe, North –America. Different subtypes within this genotypes are seen in Africa. Genotype-II is seen in Japan &Taiwan with mild liver disease. Genotype -III is seen in South America associated with high mortality & a lesion in liver cell is called morula cells. Various genotypes of HDV & HBV may interact though their effect on HDV is not clear. But infection with HDV genotype III&HBV genotype F cause severe hepatitis. The mode of transmission of HDV is closely linked to HBV mainly parenteral route. Sexual transmission & familial clustering seen in endemic areas. In Asian population it is primarily in injection drug users. It is not clear why HDV is so frequent & lethal in Amazon basin, nonexistent in Asia & fairly benign in Greece & South pacific. Researchers suspect different HDV genotypes cause varying degrees of liver damage.
The 1.7 kb single strand negative sense HDV-RNA genome shares many features with plant viroids.Unlike plant viroids HDVRNA encodes a protein hepatitis delta antigen (HDAg). The virion consists of HDV genome complexed with 70 copies of HDVAg in an envelope protein composed of lipid & HBsAg .The protein envelope contributed by HBV protects HDV-RNA-HDAg complex. Once HDV with its HBV envelope protein enters the host the HDV-RNA-HDAg complex migrates to the nucleus. Viral replication proceeds in the nucleus.
During translation two forms of HDAg are formed, short form (HDAg-S),long form(HDAg-L) the later having 19-20 more amino acids. The long & short forms have opposite effects on viral replication, the short form as facilitator, the long form as inhibitor. In states of high replication HDAg-S is produced.
HDV is classified as a single separate genus of Deltaviridae family. The consensus is that HDV is a satellite virus, which is a sub viral particle carrying distinct nucleic acid, usually RNA, requires helper virus for transmission & multiplication, differ in nucleic acid of helper virus. No other animal virus ha been identified as satellite virus. It is the smallest virus, unique virus & most virulent. The genetic information is stored in RNA where as in others it is stored in DNA.
Through blood & blood products like HBV. Unlike HBV sexual transmission is less though it can be transmitted by barrier free sexual activity. Homosexuals are prone but less than injection drug users. Vertical transmission is rare.
Mechanism is not clear. HDV is not directly cytotoxic. Combined infection of HBV &HDV may have a direct cytotoxic effect or an enhanced immune response against two viruses. HDV may be related to immunological response s evidenced by presence of antibodies to liver-kidney microsome (anti-LKM), thymocytes, nuclear lamin C. The ability of HDV to cause hepatic necrosis is by expression of HBV. Blood is potentially infectious in all phases of acute & chronic infection, but most infectious prior to onset of illness & symptoms.
The incubation period varies from 21-90 days. Depending on HBV two types of HDV occurs.
1. Coprimary infection-Simultaneous infection of HDV &HBV.
2. Superinfection-HDV is superimposed on chronic HBV.
HDV infection has a varying influence on the course of HBV. The severity of HDV infection may vary with frequency of HDV in a population, with level of HBV viremia, with interaction of specific HBV &HDV genotypes.
Co primary infection:-Most often in injection drug users. As both resolve in most cases chronicity is <5%. Some data suggest enhanced risk of fulminant hepatitis & death.
Super infection:-Can lead to severe hepatitis & acute decompensation. There occur high levels of HDV viremia. As HDV replication inhibits HBV replication there occurs decline of HBV-RNA. Rarely disappearance of HBsAg & appearance of antiHBs occurs. Chronic HDV infection frequently occurs than confection (70%), characterized by persistent of HDV viremia & detectable HDV-RNA in serum. The persistent replication of HBV &HDV lead to progressive hepatitis & cirrhosis within years. More rapid course lead to end stage liver disease.
The clinical course of a triple infection HBV,HDV&HCV is dominated by HCV.The patients often have severe episode of acute hepatitis. The chronic stage slowly progress like HDV or HBV.
Co infection typically manifest as self limiting acute hepatitis. Some show double peak of serum aminotransferase due to delay in HDV replication after HBV replication. Detectable serum IgM antiHBc, IgM antiHDV, HDV-RNA, HBV-DNA, HBsAg are seen. The enzymes return to normal after infection resolves.
HDV super infection manifest as acute hepatitis in a stable HBV carrier, mimicking spontaneous flare up of HBV infection. But presence of HDV-RNA and IgM anti HDV is the marker for super infection. As IgM anti HDV is seen in both co infection and super infection serologic finding of IgM anti HBc indicates co infection of HBV.
In association of HBV complicate acute liver failure, develop liver cancer and chronic infection. Combined mortality is 20%.Symptoms are similar to other viral infection, like fever, jaundice anorexia, malaise, dark urine, rash, nausea,arthralgia. But patients are more ill than HBV alone. Cirrhosis develops in 60-70% (higher than B or C ).
The useful markers are HDAg, antibody to HDAg(Anti HDV) , HDV RNA, and immunohistochemical starting of HDAg in liver.
• Detection of HDV-RNA by reverse transcriptase PCR(RT-PCR) is most reliable with 100% sensitively and earliest marker seen during the course without any other markers and high level is associated in severe cases. It also indicates efficacy of treatment and viral eradication. HDV RNA can be detected in liver by hybridization technique which is less sensitive than RT-PCR.
• HDAg is demonstrated in Liver cells by immunohistochemical staining but reliability decreases as disease become chronic. Presence of neutralizing antibody also interfere its detection.
• Detection of AntiHDV does not confer protection against HDV. Either IgM or IgG AntiHDV is detected. IgM appears in serum early and IgG later. IgM persists into chronic HDV infection and a marker of serious infection. As the disease turn to chronic the IgM changes from monomeric(S) form to multimeric (19S). IgG persists for a long time in immunocompetent person indicating chronic or previous infection.
Treatment of HDV is disappointing. Interferon is the only promising drug. Nucleoside analogs are not effective for HDV. Several clinical trials evaluated the efficacy of interferon in treating chronic HDV. Pegylated interferon treatment has not been reported. Nucleoside analogs like Lamivudine have not shown influence on HDV replication and not recommended. Co infections with HIV or HCV have poor rates of response. Usually Interferon alfa 9 million unites 3 times weekly for 1 year is recommended. Treatment for longer duration may be beneficial but to be considered on the basis of histologic severity, HDV-RNA response, and patient tolerability. Use of Pegylated interferon needs further study.
Advanced molecular biology may help to identify specific inhibitor of HDV replication. Prenylation (addition of prenyl lipid like farnesyl) of HDAg-L is a critical determinant of HDV particle assembly. In vitro it is shown that prenylation can abolish particle production.
Vaccination against HBV confers protection against HDV. Groups showing high rate of HDV infection should be vaccinated. Once HBV are eliminated HDV can not replicate without HBs antigen and also disappear. No vaccine is available against HDV. Super infection can be reduced by safer sex practice, avoiding blood or blood product contact and not sharing needles.

Hepatitis-E is a form of acute, icteric, self limited viral hepatitis caused by HEV. It was recognized in 1980 during epidemics at Delhi, Kashmir. Subsequently the virus and genomic sequence were identified. In retrospect study similar enterically transmitted hepatitis occurred in Europe in 18th and 19th centuries.
It is a small RNA virus , 32-34 nm in diameter, unenveloped and icosahedral shape. HEV-RNA is 7.2 kilo bases in length, single and positive stranded 5-’capped and polyadenylated. It contains 3 open reading frames (ORSs). ORF1 encodes nonstructural protein, ORF2 encodes the viral capsid protein and ORF3 encodes a protein of unknown function. HEV attachment and entry to hepatocytes, its replication and release mechanism in unknown. The virus is classified to genus Hepatitis-E like virus and phylogenetically related to Togavirus. Geographically various isolates of HEV are isolated like genotype1 (Asian Strain), type-2(Mexico Strain). All genotypes share at least one major serologically cross-reactive epitope. Swine HEV is genetically different from Human HEV in India but similar in other parts.
Several epidemics have been found in different parts of the world. Overall attack rate is 1-15%, higher in adults (3-30%) than children (0.2-10%). The male female ratio varies from 1:1 to 4:1. High attack and mortality rate occur in Pregnant women. The nature of epidemics range from single peaked, short lived outbreaks to prolonged, multipeaked lasting for more than 1 year.
Classification of HEV genotypes:-
Genotype Geographical Origin
1 Asia
1A India, Myanmar, Nepal
1B China, Pakistan, Soviet Union
1C Africa
1D India
2 Mexico, Africa
3 U.S
4 China, Taiwan
5 Italy
6 ,7 Greece
8 Argentina
Prevalence rates of antiHEV, which is detectable in all geographical areas are higher among endemic (10-40%) than nonendemic (1-5%).
Reservoir:-Domestic animals like pigs have been reported. A number of rodents has also been identified. The disease is thought to be a zoonosis as animals like pigs & deer are the sourse.
Predominantly through fecal-oral route. Outbreaks usually occur following heavy rain or flood & in Summer due to increased contamination. Person to person contact is uncommon & secondary attack among household contact is 0.7-2.2%. Maintenance of continuous virus in endemic area are due to sub clinical HEV infection, animal reservoir harboring HEV- like viral agents & prolonged fecal shedding of virus. Sporadic hepatitis which is demographically & clinically similar to epidemic form accounts for 50-70% of acute cases in endemic areas. Some are related to travel to endemic areas. Occasionally it can be due to undercooked meat. One study shows HEV transmission through blood but data is inadequate. No evidence of parenteral or sexual transmission.
Entering through oral route virus reaches liver through unknown mechanism. HEV can be detected in stool 1 week before the onset of illness & up to 2 weeks there after. HEVRNA is detected in serum for 2 weeks after the onset of illness in all patients. HEV antigen (HEVAg)is expressed in hepatocytes as early as 7 days after infection in >50% of cells. But the number decreases sharply when serum ALT is increased. The onset of elevation of ALT & histopathologic changes in liver correspond to the appearance of antiHEV (IgG,IgM) in serum. This suggests the liver injury may be due to immune mediated specially lymphocytes infiltrating liver have a cytotoxic/suppression immunophenotypes. Like other forms of hepatitis there occurs ballooned hepatocytes, acidophilic bodies, focal parenchymal necrosis, inflammatory infiltrates in the lobules, enlarged portal tracts. About 50% have cholestatic hepatitis characterized by canalicular bile stasis & gland like transformation of parenchymal cells with less marked hepatic degeneration & necrosis. In severe cases sub massive or massive necrosis & collapse of parenchyma are seen.
The incubation period is 2—10 weeks.There are varying clinical presentations.
1.Acute icteric hepatitis:-Onset is insidious. Prodromal phase(1-4days) have flulike symptoms, fever, mild chill, abdominal pain, anorexia, nausea, vomiting aversion to smoking, clay coloured stool, dark urine, diarrhea, arthralgia, asthenia & transient macular rash.Prodromal symptoms disappears with onset of jaundice except dark urine, clay stool, & itching. On examination there is jaundice, soft tender mild hepatomegaly & splenomegaly. Laboratory tests show bilirubinuria, conjugated hyperbilirubinemia, marked elevation of aminotransferase &gamma glutamyl transpeptidase. Elevation of ALT may precede the onset & level does not correlate the degree of hepatic injury. Mild leucopenia with lymphocytosis occurs. Serum ALT & bilirubin normalize by 6 weeks. Ultrasonography shows mild hepatomegaly with increased parenchymal echogenicity, gall bladder edema, prominent portal venules &mild splenomegaly. Acute infection usually self limited. The case fatality is 0.5-4%. Chronic hepatitis or cirrhosis do not occur.
2. Cholestatic hepatitis:-In some cases there is persistent jaundice (2-6 months), itching, marked elevation of enzymes. Ultimately spontaneous resolution occurs.
3. Anicteric hepatitis:-Some have nonspecific viral like symptoms with raised enzymes without jaundice.
4. Asymptomatic & anicteric:-Occurs frequently in younger age groups.
5. Fulminant hepatic failure:-In small cases sub acute or fulminant hepatic failure occurs mostly in endemic areas.
Pregnant women particularly 2nd & 3rd trimester are frequently affected. Fulminant hepatic failure, abortion, stillbirth, neonatal deaths are increased. The cause of high incidence is unknown.
1. Detection of HEV-RNA-Detected in stool & serum using PCR.
2. ELISA to detect immunoglobulin’s (IgM,IgG)-Presence of IgM antiHEV where as IgG antiHEV indicate convalescent phase or past infection. IgM appears early, lasting for 4-5 months, detected in 80-100% of cases during outbreaks. IgG appears few days after IgM and titer increases in convalescent phase & remain for 1-5 years.
Acute infection is usually self limited requiring supportive treatment. In fulminant cases requires measures to decrease cerebral edema or liver transplant. In pregnancy no proved benefit of terminating pregnancy is seen. Hemorrhage due to deranged coagulation can be treated with fresh frozen plasma.
PREVENTION-In endemic areas depends on supplying clean water& strict sewage disposal. Boiling of water may reduce risk. Isolation is not indicated.
Role of immunoglobulin given in pre or post exposure is not proved. Occurrence of epidemics in endemic areas indicate that anti HEV is not fully protective or the antibody declines with time to non protective level.
Various trials of vaccine are in the process. An experimental HEVDNA vaccine tried in primates. Prospect of vaccine even having short term protection is needed for travelers & pregnant women.
It is a hypothetical virus linked to hepatitis. Several cases emerged in 1990 but reports not substantiated. In 1994 viral particles detected in stool of post transfusion nonA-nonE hepatitis and injection of these materials to Indian rhesus monkey caused hepatitis & named as hepatitis F or Toga virus. Further investigation failed to confirm the existence and it was delisted.

Hepatitis G virus (HGV)& GB agents(GBV) are isolates of same virus. GBV has been identified as 3 different types e.g. GBV type A(GBV-A), GBV type B(GBV-B), GBV type C(GBV-C).About 96% homology of genome occurs between HGV&GBV-C indicating two strains of same virus. The term hepatitis G virus is questioned due to lack of association between GBV-C/HGV & acute or chronic hepatitis. For clarity GBV-C/HGV is referred as GBV-C.
GBV-C is a positive strand RNA virus genome containing 9400 nucleotides encoding about 2900 amino acids, classified as a member of Flaviviridae family. GBV-C shares 44% &28% homology with GBV-A &GBV-B respectively. Though GBV-C is similar to HCV it is clearly distinct. One long open reading frame encodes a single large polyprotein with structural protein encoded at 5’ amino terminus & nonstructural protein encoded at 3’ carboxyl terminus. The structural proteins differ in GBV-C &HCV. Though there are 2 glycoproteins E1&E2 of GBV-C the difference of polymorphism inE2 accounts for less chronic viremia in GBV-C infection (25%) than HCV(50-70%). In contrast the nonstructural proteins of HCV &GBV-C are similar. HCV &GBV-C differ in tissue tropism. In contrast toHCV, GBV-C does not show hepatotropism. But like HCV it shows lymphotropic property as negative strand RNA are found in mononuclear cells, bone marrow & spleen. Due to its interaction inside lymphocytes there is some interaction between HIV &GBV-C.
GBV-C is found world wide(2-5%). At least 5 genotypes identified according to geographical distribution.Genotype1 (West Africa), genotype2 (Europe, US), genotype3 (Asia), genotype4 (Southeast Asia), genotype5 (South Africa).
The development of antibodies to GBV-CE2 correlates with loss of viremia & suggest past exposure and clearance of GBV-C infection. Current & past infection is found among parenteral risk factors & voluntary blood donors. Frequent blood exposed patients are viremic and seropositive toE2 antibodies (50-70%). Past or current GBV-C infection may show normal ALT, posing a risk for transfusion transmission (raised ALT-exclusion criteria for donors). It can be transmitted sexually & vertically more frequently than HCV. Infected babies have no evidence of hepatitis or other sequlae. As
HCV& GBV-C are transmitted parentrally co infection is common. GBV-C viremia is seen in 20% of HCV infected persons where the rest 80% are seropositive toE2 antibodies. This suggests the high rate of natural clearance of GBV-C (75%) than HCV (25%). The virus can not be contacted through saliva, semen or any other body fluids other than blood.
Though GBV-C is detected in many patients with non A to E acute or chronic hepatitis & may persists for years it does not cause liver (or any other) disease, even in immunocompromised patients. It does not modulate the course, response to therapy in HCV, HBV patients. It does not interfere liver transplant though the rate of viremia is more due to frequent transfusion. The duration of infection depends on age & immune status of the host. Childhood acquisition leads to chronic infection. In immunocompetent adults rapid viral clearance occurs. Chronic GBV-C hepatitis occurs in HIV patients. In contrast to HCV the development of antibodies toGBV-CE2 protects against reinfection. There is no clear association between GBV-C infection & HCC, nonHodgkins lymphoma, aplastic anemia, porphyria cutanea tarda or lichen planus.

As it rarely causes human disease the diagnostic tests are reserved for research only. GBV-VRNA is detected by PCR. A test for antibody detection is also available.
GBV-C & HIV-It was observed that in HIV infected patients slow progression to AIDS & death correlated to GBV-C viremia. Co infected patients have better prognosis than HIV mono infected cases. In addition better antiretroviral therapy, rapid rise of CD4 count observed. The explanation of better response though not exactly known may be this virus prevents HIV from replicating frequently, thus extending the life span by inhibiting damage to the immune system.
As not associated with clinical disease, no treatment required. Those who are co infected with HCV treatment with interferon and ribavirin cause disappearance of GBV-CRNA from serum but reappeared in all cases after therapy completed.

INTRODUCTION:-Identified in 1977 from a patient (initial-TT) in Japan who had acute post transfusion non A to G hepatitis.
VIROLOGY: TTV is a non enveloped, single stranded, negative polarity, circular DNA virus related to family of animal virus Circoviridae. The TTV genome is 3695 nucleotide long & contains at least 3 ORFs. Three messenger RNA (mRNA) are expressed by TTV. The protein product of largest mRNA (3kb long) functions as capsid protein. At least 16 genotypes have been identified with greater than 30% sequence divergence. TTV is believed to be hepatotropic as high viral level is seen in liver than serum. It also replicates in PBMCs and bone marrow cells.
EPIDEMIOLOGY & TRANSMISSION:-Found world wide & very common. Prevalence among blood donors are high.
Transmitted by all parenteral routes & high among hemophiliacs, IV drug users, haemodialysis & organ transplants. Also transmitted enterically (fecal-oral).
CLINICAL FEATURES:-In the first reported case there was acute hepatitis, viremia was detected 6 weeks after exposure &2 weeks before the rise of serum ALT.DNA was documented by PCR and ALT subsequently returned to normal. Viremia may persist for years in both immunocompetent & immunosuppressed persons. Most cases don’t have biochemical or histologic evidence of liver disease. It does not alter the natural history or response to treatment of HCV or HBVcases.
TREATMENT:--Protocol not studied. In a co infected HCV case treatment with PegIFN 6 of 10 cases cleared TTV viremia by end of therapy but majority relapsed within 6 months.

After discovery of TTV in 1997 similar viruses with small DNA genomes isolated in Japan. Sanban, Yonban and TLMV have been divided into 29 genotypes with diverge sequences. They are transmitted by parenteral & fecal oral route. None has been clearly associated with human liver disease so far.
In 1999 another virus identified in a HIV patient (initial SEN) which is a small, non enveloped, single stranded DNA virus, transmitted by parenteral &fecal oral routes. Vertical transmission may occur. No chronic infection occurs. Prevalence is high with parenteral risk factors particularly HCV co infection. Clinical significance of SEN virus is not clear. Fulminant course or CLD do not occur.
Most studies show no association between these viruses & human disease, nor any effect on course and response to treatment of chronic viral hepatitis.

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