VIRAL HEPATITIS
The term VIRAL HEPATITIS is usually used to describe infections caused by agents whose primary tissue tropism is the liver.
To date, at least five hepatitis viruses have been recognised, and these have been named:-
Hepatitis A, B, C, D and E.
Acute hepatitis may also occur as part of the clinical course of a number of viral infections, including
human cytomegalovirus, Epstein-Barr virus, herpes simplex virus, yellow fever virus and rubella.
Viral hepatitis can be classified according to mode of transmission
ENTERICALLY TRANSMITTED HEPATITIS: A and E
PARENTERALLY TRANSMITTED HEPATITIS B , C , D and G
HEPATITIS A VIRUS
Virology
RNA Picornavirus
o Single serotype worldwide
o Acute disease and asymptomatic infection
· No chronic infection
o Protective antibodies develop in response to infection - confers lifelong immunity
Hepatitis A is caused by HAV, a 27-nm ribonucleic acid (RNA) agent that is classified as a picornavirus. Only one serotype has been observed among HAV isolates collected from various parts of the world. HAV causes both acute disease and asymptomatic infection. HAV does not cause chronic infection. Total antibody to HAV develops in response to infection and confers lifelong immunity from future HAV infection.
Mode of transmission:
Feces can contain up to 108 infectious virions per milliliter and are the primary source of HAV. Viremia occurs during the preclinical and clinical phases of illness, and HAV has been transmitted by transfusion (before screening of blood and blood products for HAV was initiated) and by injection drug use. Virus has also been found in saliva and urine during the incubation period in experimentally infected animals, but transmission by saliva or urine has not been reported to occur.
HEPATITIS A VIRUS TRANSMISSION
· Close personal contact (e.g., household contact, sex contact, child day-care centers)
· Contaminated food, water (e.g., infected food handlers)
· Blood exposure (rare) (e.g., injection drug use, rarely by transfusion)
Transmission of HAV generally occurs when susceptible persons put anything in their mouths that has been contaminated with the feces of an infected person. Close personal contact is the most common mode of HAV transmission, as demonstrated by infections among household and sex contacts of persons with hepatitis A and among children in day-care center outbreaks. Contaminated food and water can also serve as vehicles of HAV transmission. HAV transmission can occur when an infected food handler directly handles uncooked or cooked foods. Outbreaks have also been reported in association with foods contaminated before wholesale distribution, such as fresh vegetables contaminated at the time of harvesting or processing. HAV transmission can occur as a result of blood exposures such as injecting drug use or blood transfusion because viremia can occur prior to the onset of illness in infected persons. Screening of blood products for HAV has essentially eliminated the already extremely low risk associated with transfusion.
Incubation Peroid:
The average incubation period for hepatitis A is 30 days, with a range of 15 to 50 days.
Clinical Picture:
Patients characteristically have abrupt onset of symptoms which can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice. The severity of clinical disease associated with HAV infection increases with increasing age; jaundice occurs among less than 10% of children younger than 6 years of age, 40%-50% of older children, and 70%-80% of adults.
Complications of hepatitis A include fulminant hepatitis, in which the case fatality rate can be greater than 50% despite medical interventions such as liver transplantation; cholestatic hepatitis, with very high bilirubin levels that can persist for months; and relapsing hepatitis, in which exacerbations can occur weeks to months after apparent recovery. Chronic infection does not occur following HAV infection.
Laboratory Diagnosis Of Hepatitis A
-The diagnosis of acute HAV infection is confirmed during the acute or early convalescent phase of infection by the presence of IgM antibodies to HAV (IgM anti-HAV). IgM anti-HAV is generally present 5-10 days before the onset of symptoms and is no longer detectable in the vast majority of patients 6 months later.
- anti-HAV IgG, which also appears early in the course of infection, remains detectable for the lifetime of the individual and confers lifelong protection against infection. Commercial tests are available for the detection of IgM and total (IgM and IgG) anti-HAV in serum.
-In infected persons, HAV replicates in the liver, is excreted in bile, and is shed in the stool. Peak infectivity occurs during the 2-week period before onset of jaundice or elevation of liver enzymes, when the concentration of virus in stool is highest. The concentration of virus in stool declines after jaundice appears. Children and infants can shed HAV for longer periods than adults, up to several months after the onset of clinical illness. Chronic shedding of HAV in feces does not occur; however, shedding can occur in persons who have relapsing illness. Viremia occurs soon after infection and persists through the period of liver enzyme (alanine aminotransferase [ALT]) elevation.
HAV RNA can be detected in the blood and stool of most persons during the acute phase of infection by using nucleic acid amplification methods, such as PCR, and nucleic acid sequencing has been used to determine the relatedness of HAV isolates. These methods, however, are available in only a limited number of research laboratories and are not used generally for diagnostic purposes.
-Elevated liver function tests begin from 4th weeks of infection and reach maximum elevation in 8th weeks after infection and return to normal within 12th weeks after infection notice that jaundice incidence differs according to age of infection-
· Jaundice by age group: <6 yrs
6-14 yrs
>14 yrs
<10%
40%-50%
70%-80%
PREVENTING HEPATITIS A
· Hygiene (e.g., hand washing)
· Sanitation (e.g., clean water sources)
· Hepatitis A vaccine (pre-exposure)
· Immune globulin (pre- and post-exposure)
Notes:
Good hygienic practices and adequate sanitation are important elements in the prevention of HAV infection, particularly in the developing world. However, hepatitis A vaccine is the key component in the overall strategy to prevent HAV infection in the United States. Immune globulin is also available for pre-exposure and post-exposure prophylaxis.
PREPARATION OF INACTIVATED
HEPATITIS A VACCINES
· Cell culture adapted virus grown in human fibroblasts
· Purified product inactivated with formalin
· Adsorbed to aluminum hydroxide adjuvant
Notes:
In the United States, highly immunogenic and efficacious inactivated hepatitis A vaccines were first licensed in 1995 by the Food and Drug Administration (FDA). These vaccines are prepared by methods similar to those used for inactivated poliovirus vaccine. Cell culture-adapted virus is propagated in human fibroblasts, purified from cell lysates by ultrafiltration and exclusion gel chromatography or other methods, inactivated with formalin, and adsorbed to an aluminum hydroxide adjuvant.
DURATION OF PROTECTION AFTER HEPATITIS A VACCINATION
· Persistence of antibody
o At least 5-8 years among adults and children
· Efficacy
o No cases in vaccinated children at 5-6 years of follow-up
· Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years
· Other mechanisms, such as cellular memory, may contribute
Notes:
Among adults and children, studies have demonstrated that detectable antibody persists for at least 5-8 years after completing the vaccination series. Although data regarding long-term efficacy are limited, no cases among vaccinated children were observed in one community at 5-6 years of follow-up. Estimates of antibody persistence derived from mathematical models of antibody decline indicate that protective levels of anti-HAV persist for at least 20 years. Whether other mechanisms such as cellular memory also contribute to long-term protection is unknown.
FACTORS ASSOCIATED WITH DECREASED IMMUNOGENICITY TO HEPATITIS A VACCINE
· Decreased antibody concentration:
o Concurrent administration of IG
o Presence of passively-transferred maternal antibody
o Age
o Chronic liver disease
· Decreased seroconversion rate:
o HIV infection
o May be related to degree of
immunosuppression
o Liver transplantation
Notes:
The presence of anti-HAV at the time of vaccination appears to blunt the immune response. Administration of immune globulin (IG) concurrently with the first dose of hepatitis A vaccine did not decrease the proportion of adults who developed protective levels of antibody compared with adults who had been administered hepatitis A vaccine alone, but the geometric mean antibody concentrations (GMCs) among adults who received IG were lower 1 month after completion of the vaccination series than the GMCs of any adults who had been administered hepatitis A vaccine alone. The reduced immunogenicity of hepatitis A vaccine that occurs with concurrent administration of IG does not appear to be clinically significant. IG and hepatitis A vaccine can be given concurrently if indicated.
Reduced vaccine immunogenicity also has been observed in infants who had passively-transferred antibody because of prior maternal HAV infection and were administered hepatitis A vaccine according to a number of different schedules. In most studies, all infants developed protective levels of antibody, but the final GMCs were approximately 1/3 to 1/10 those of infants born to anti-HAV-negative mothers.
Based on limited data, final antibody concentrations might be lower among older vaccinated persons.
Vaccination of adults with chronic liver disease of viral or nonviral etiology produced seroprotection rates similar to those observed in healthy adults. Final antibody concentrations, however, were substantially lower for each group of patients with chronic liver disease than for healthy adults.
Hepatitis B
HBV(DNA) from Hepadna virus
Incubation Peroid:
6 weeks-6 months
Mode Of Transmission:
Parenreral, sexual, vertical
Clinical Course:
Prolonged and more severe than A
Laboratory Diagnosis:
-Elevated ALT,AST from 10-100 folds Acute infection with resolution
-Viralantigens:
1) Surface antigen (HBsAg) is secreted in excess into the blood as 22 nm spheres and tubules. Its presence in serum indicates that virus replication is occurring in the liver
2) 'e' antigen (HBeAg) secreted protein is shed in small amounts into the blood. Its presence in serum indicates that a high level of viral replication is occurring in the liver
3) core antigen (HBcAg) core protein is not found in blood
-Antibody response:
1) Surface antibody (anti-HBs) becomes detectable late in convalescence, and indicates immunity following infection. It remains detectable for life and is not found in chronic carriers (see below).
2) e antibody (anti-HBe) becomes detectable as viral replication falls. It indicates low infectivity in a carrier.
3) Core IgM rises early in infection and indicates recent infection
4) Core IgG rises soon after IgM, and remains present for life in both chronic carriers as well as those who clear the infection. Its presence indicates exposure to HBV.
Figure: Acute Hepatitis B Infection
Chronic hepatitis B
Persistance of surface antigen and prolonged persistence of e antigen.
Figure: Chronic Hepatitis B Infection
Hepatitis C Virus:
HCV(RNA) from Togavirus related to the Flavi and Pesti viruses.
Features of Hepatitis C Virus Infection
Incubation period Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice) Mild (≤20%)
Case fatality rate Low
Chronic infection* 60%-85%
Chronic hepatitis* 10%-70% (most asx)
Cirrhosis* <5%-20%
Mortality from CLD 1%-5%
*Age related
Exposures Known to be Associated With HCV Infection
· Injecting drug use
· Transfusion, transplant from infected donor
· Occupational exposure to blood
- Mostly needle sticks
- Case reports of transmission from blood splash to eye; one from exposure to non-intact skin
-Prevalence 1-2% among health care workers
Lower than adults in the general population
10 times lower than for HBV infection
· Iatrogenic (unsafe injections)
· Birth to HCV-infected mother
Average rate of infection 4%
Higher (19%) if woman co-infected with HIV
Role of viral titer unclear
No association with
Delivery method
Breastfeeding
Infected infants do well
Severe hepatitis is rare
Sex with infected partner
· Household Transmission of HCV
· Rare but not absent
· Could occur through percutaneous/mucosal exposures to blood
o Contaminated equipment used for home therapies
§ IV therapy, injections
o Theoretically through sharing of contaminated personal articles (razors, toothbrushes)
Laboratory Diagnosis Of Hepatitis C:
-Mild elevation of ALT,AST
-With fluctuation in AST(surrogate Marker of chronic hepatitis C).
1) Serology
.
1-HCV-specific IgG indicates exposure, not infectivity
2) PCR detects viral genome in patient's serum
3) Quantitative PCR to detect viral load response to therapy
Hepatitis D
HDV is a defective single-stranded RNA virus that requires the helper function of HBV to replicate. HDV requires HBV for synthesis of envelope protein composed of HBsAg, which is used to encapsulate the HDV genome.
Hepatitis D - Clinical Features
· Coinfection
o severe acute disease
o low risk of chronic infection
· Superinfection
o usually develop chronic HDV infection high
o risk of severe chronic liver disease
Notes:
HDV infection can be acquired either as a co-infection with HBV or as a superinfection of persons with chronic HBV infection. Persons with HBV-HDV co-infection may have more severe acute disease and a higher risk of fulminant hepatitis (2%-20%) compared with those infected with HBV alone; however, chronic HBV infection appears to occur less frequently in persons with HBV-HDV co-infection. Chronic HBV carriers who acquire HDV superinfection usually develop chronic HDV infection. In long-term studies of chronic HBV carriers with HDV superinfection, 70%-80% have developed evidence of chronic liver diseases with cirrhosis compared with 15%-30% of patients with chronic HBV infection alone.
Hepatitis D Virus Modes of Transmission
· Percutanous exposures
o injecting drug use
· Permucosal
o exposures sex contact
Notes:
The modes of HDV transmission are similar to those for HBV, with percutaneous exposures the most efficient. Sexual transmission of HDV is less efficient than for HBV. Perinatal HDV transmission is rare.
The serologic course of HDV infection varies depending on whether the virus is acquired as a co-infection with HBV or as a superinfection of a person with chronic HBV infection.
In most persons with HBV-HDV co-infection, both IgM antibody to HDV (anti-HDV) and IgG anti-HDV are detectable during the course of infection.
However, in about 15% of patients the only evidence of HDV infection may be the detection of either IgM anti-HDV alone during the early acute period of illness or IgG anti-HDV alone during convalescence.
Anti-HDV generally declines to sub-detectable levels after the infection resolves and there is no serologic marker that persists to indicate that the patient was ever infected with HDV. Hepatitis Delta antigen (HDAg) can be detected in serum in only about 25% of patients with HBV-HDV co-infection. When HDAg is detectable it generally disappears as HBsAg disappears and most patients do not develop chronic infection. Tests for IgG anti-HDV are commercially available in the United States. Tests for IgM anti-HDV, HDAg and HDV RNA by PCR are only available in research laboratories.
In patients with chronic HBV infection who are super-infected with HDV several characteristic serologic features generally occur, including: 1) the titer of HBsAg declines at the time HDAg appears in the serum, 2) HDAg and HDV RNA remain detectable in the serum because chronic HDV infection generally occurs in most patients with HDV superinfection, unlike the case with co-infection, 3) high titers of both IgM and IgG anti-HDV are detectable, which persist indefinitely.
Hepatitis E
Recently identified cause of enterically transmitted non-A, non-B (NANB) hepatitis
ClinicalFeatures
Incubation period 30-40 days
Acute, self limiting hepatitis, no chronic carrier state
Age: predominantly young adults, 15-40 years
Complications
Fulminant hepatitis in pregnant women. Mortality rate is high (up to 40%).
Virus cannot be cultured in vitro.
1) Calicivirus-like particles in the stool, by electron microscopy
2)Specific IgM in serum
3) PCR HEV-specific sequences in stool
Need more
visit
http://www.amazon.com/Lectures-applied-clinical-microbiology-ebook/dp/B004Y0XF54
The term VIRAL HEPATITIS is usually used to describe infections caused by agents whose primary tissue tropism is the liver.
To date, at least five hepatitis viruses have been recognised, and these have been named:-
Hepatitis A, B, C, D and E.
Acute hepatitis may also occur as part of the clinical course of a number of viral infections, including
human cytomegalovirus, Epstein-Barr virus, herpes simplex virus, yellow fever virus and rubella.
Viral hepatitis can be classified according to mode of transmission
ENTERICALLY TRANSMITTED HEPATITIS: A and E
PARENTERALLY TRANSMITTED HEPATITIS B , C , D and G
HEPATITIS A VIRUS
Virology
RNA Picornavirus
o Single serotype worldwide
o Acute disease and asymptomatic infection
· No chronic infection
o Protective antibodies develop in response to infection - confers lifelong immunity
Hepatitis A is caused by HAV, a 27-nm ribonucleic acid (RNA) agent that is classified as a picornavirus. Only one serotype has been observed among HAV isolates collected from various parts of the world. HAV causes both acute disease and asymptomatic infection. HAV does not cause chronic infection. Total antibody to HAV develops in response to infection and confers lifelong immunity from future HAV infection.
Mode of transmission:
Feces can contain up to 108 infectious virions per milliliter and are the primary source of HAV. Viremia occurs during the preclinical and clinical phases of illness, and HAV has been transmitted by transfusion (before screening of blood and blood products for HAV was initiated) and by injection drug use. Virus has also been found in saliva and urine during the incubation period in experimentally infected animals, but transmission by saliva or urine has not been reported to occur.
HEPATITIS A VIRUS TRANSMISSION
· Close personal contact (e.g., household contact, sex contact, child day-care centers)
· Contaminated food, water (e.g., infected food handlers)
· Blood exposure (rare) (e.g., injection drug use, rarely by transfusion)
Transmission of HAV generally occurs when susceptible persons put anything in their mouths that has been contaminated with the feces of an infected person. Close personal contact is the most common mode of HAV transmission, as demonstrated by infections among household and sex contacts of persons with hepatitis A and among children in day-care center outbreaks. Contaminated food and water can also serve as vehicles of HAV transmission. HAV transmission can occur when an infected food handler directly handles uncooked or cooked foods. Outbreaks have also been reported in association with foods contaminated before wholesale distribution, such as fresh vegetables contaminated at the time of harvesting or processing. HAV transmission can occur as a result of blood exposures such as injecting drug use or blood transfusion because viremia can occur prior to the onset of illness in infected persons. Screening of blood products for HAV has essentially eliminated the already extremely low risk associated with transfusion.
Incubation Peroid:
The average incubation period for hepatitis A is 30 days, with a range of 15 to 50 days.
Clinical Picture:
Patients characteristically have abrupt onset of symptoms which can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice. The severity of clinical disease associated with HAV infection increases with increasing age; jaundice occurs among less than 10% of children younger than 6 years of age, 40%-50% of older children, and 70%-80% of adults.
Complications of hepatitis A include fulminant hepatitis, in which the case fatality rate can be greater than 50% despite medical interventions such as liver transplantation; cholestatic hepatitis, with very high bilirubin levels that can persist for months; and relapsing hepatitis, in which exacerbations can occur weeks to months after apparent recovery. Chronic infection does not occur following HAV infection.
Laboratory Diagnosis Of Hepatitis A
-The diagnosis of acute HAV infection is confirmed during the acute or early convalescent phase of infection by the presence of IgM antibodies to HAV (IgM anti-HAV). IgM anti-HAV is generally present 5-10 days before the onset of symptoms and is no longer detectable in the vast majority of patients 6 months later.
- anti-HAV IgG, which also appears early in the course of infection, remains detectable for the lifetime of the individual and confers lifelong protection against infection. Commercial tests are available for the detection of IgM and total (IgM and IgG) anti-HAV in serum.
-In infected persons, HAV replicates in the liver, is excreted in bile, and is shed in the stool. Peak infectivity occurs during the 2-week period before onset of jaundice or elevation of liver enzymes, when the concentration of virus in stool is highest. The concentration of virus in stool declines after jaundice appears. Children and infants can shed HAV for longer periods than adults, up to several months after the onset of clinical illness. Chronic shedding of HAV in feces does not occur; however, shedding can occur in persons who have relapsing illness. Viremia occurs soon after infection and persists through the period of liver enzyme (alanine aminotransferase [ALT]) elevation.
HAV RNA can be detected in the blood and stool of most persons during the acute phase of infection by using nucleic acid amplification methods, such as PCR, and nucleic acid sequencing has been used to determine the relatedness of HAV isolates. These methods, however, are available in only a limited number of research laboratories and are not used generally for diagnostic purposes.
-Elevated liver function tests begin from 4th weeks of infection and reach maximum elevation in 8th weeks after infection and return to normal within 12th weeks after infection notice that jaundice incidence differs according to age of infection-
· Jaundice by age group: <6 yrs
6-14 yrs
>14 yrs
<10%
40%-50%
70%-80%
PREVENTING HEPATITIS A
· Hygiene (e.g., hand washing)
· Sanitation (e.g., clean water sources)
· Hepatitis A vaccine (pre-exposure)
· Immune globulin (pre- and post-exposure)
Notes:
Good hygienic practices and adequate sanitation are important elements in the prevention of HAV infection, particularly in the developing world. However, hepatitis A vaccine is the key component in the overall strategy to prevent HAV infection in the United States. Immune globulin is also available for pre-exposure and post-exposure prophylaxis.
PREPARATION OF INACTIVATED
HEPATITIS A VACCINES
· Cell culture adapted virus grown in human fibroblasts
· Purified product inactivated with formalin
· Adsorbed to aluminum hydroxide adjuvant
Notes:
In the United States, highly immunogenic and efficacious inactivated hepatitis A vaccines were first licensed in 1995 by the Food and Drug Administration (FDA). These vaccines are prepared by methods similar to those used for inactivated poliovirus vaccine. Cell culture-adapted virus is propagated in human fibroblasts, purified from cell lysates by ultrafiltration and exclusion gel chromatography or other methods, inactivated with formalin, and adsorbed to an aluminum hydroxide adjuvant.
DURATION OF PROTECTION AFTER HEPATITIS A VACCINATION
· Persistence of antibody
o At least 5-8 years among adults and children
· Efficacy
o No cases in vaccinated children at 5-6 years of follow-up
· Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years
· Other mechanisms, such as cellular memory, may contribute
Notes:
Among adults and children, studies have demonstrated that detectable antibody persists for at least 5-8 years after completing the vaccination series. Although data regarding long-term efficacy are limited, no cases among vaccinated children were observed in one community at 5-6 years of follow-up. Estimates of antibody persistence derived from mathematical models of antibody decline indicate that protective levels of anti-HAV persist for at least 20 years. Whether other mechanisms such as cellular memory also contribute to long-term protection is unknown.
FACTORS ASSOCIATED WITH DECREASED IMMUNOGENICITY TO HEPATITIS A VACCINE
· Decreased antibody concentration:
o Concurrent administration of IG
o Presence of passively-transferred maternal antibody
o Age
o Chronic liver disease
· Decreased seroconversion rate:
o HIV infection
o May be related to degree of
immunosuppression
o Liver transplantation
Notes:
The presence of anti-HAV at the time of vaccination appears to blunt the immune response. Administration of immune globulin (IG) concurrently with the first dose of hepatitis A vaccine did not decrease the proportion of adults who developed protective levels of antibody compared with adults who had been administered hepatitis A vaccine alone, but the geometric mean antibody concentrations (GMCs) among adults who received IG were lower 1 month after completion of the vaccination series than the GMCs of any adults who had been administered hepatitis A vaccine alone. The reduced immunogenicity of hepatitis A vaccine that occurs with concurrent administration of IG does not appear to be clinically significant. IG and hepatitis A vaccine can be given concurrently if indicated.
Reduced vaccine immunogenicity also has been observed in infants who had passively-transferred antibody because of prior maternal HAV infection and were administered hepatitis A vaccine according to a number of different schedules. In most studies, all infants developed protective levels of antibody, but the final GMCs were approximately 1/3 to 1/10 those of infants born to anti-HAV-negative mothers.
Based on limited data, final antibody concentrations might be lower among older vaccinated persons.
Vaccination of adults with chronic liver disease of viral or nonviral etiology produced seroprotection rates similar to those observed in healthy adults. Final antibody concentrations, however, were substantially lower for each group of patients with chronic liver disease than for healthy adults.
Hepatitis B
HBV(DNA) from Hepadna virus
Incubation Peroid:
6 weeks-6 months
Mode Of Transmission:
Parenreral, sexual, vertical
Clinical Course:
Prolonged and more severe than A
Laboratory Diagnosis:
-Elevated ALT,AST from 10-100 folds Acute infection with resolution
-Viralantigens:
1) Surface antigen (HBsAg) is secreted in excess into the blood as 22 nm spheres and tubules. Its presence in serum indicates that virus replication is occurring in the liver
2) 'e' antigen (HBeAg) secreted protein is shed in small amounts into the blood. Its presence in serum indicates that a high level of viral replication is occurring in the liver
3) core antigen (HBcAg) core protein is not found in blood
-Antibody response:
1) Surface antibody (anti-HBs) becomes detectable late in convalescence, and indicates immunity following infection. It remains detectable for life and is not found in chronic carriers (see below).
2) e antibody (anti-HBe) becomes detectable as viral replication falls. It indicates low infectivity in a carrier.
3) Core IgM rises early in infection and indicates recent infection
4) Core IgG rises soon after IgM, and remains present for life in both chronic carriers as well as those who clear the infection. Its presence indicates exposure to HBV.
Figure: Acute Hepatitis B Infection
Chronic hepatitis B
Persistance of surface antigen and prolonged persistence of e antigen.
Figure: Chronic Hepatitis B Infection
Hepatitis C Virus:
HCV(RNA) from Togavirus related to the Flavi and Pesti viruses.
Features of Hepatitis C Virus Infection
Incubation period Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice) Mild (≤20%)
Case fatality rate Low
Chronic infection* 60%-85%
Chronic hepatitis* 10%-70% (most asx)
Cirrhosis* <5%-20%
Mortality from CLD 1%-5%
*Age related
Exposures Known to be Associated With HCV Infection
· Injecting drug use
· Transfusion, transplant from infected donor
· Occupational exposure to blood
- Mostly needle sticks
- Case reports of transmission from blood splash to eye; one from exposure to non-intact skin
-Prevalence 1-2% among health care workers
Lower than adults in the general population
10 times lower than for HBV infection
· Iatrogenic (unsafe injections)
· Birth to HCV-infected mother
Average rate of infection 4%
Higher (19%) if woman co-infected with HIV
Role of viral titer unclear
No association with
Delivery method
Breastfeeding
Infected infants do well
Severe hepatitis is rare
Sex with infected partner
· Household Transmission of HCV
· Rare but not absent
· Could occur through percutaneous/mucosal exposures to blood
o Contaminated equipment used for home therapies
§ IV therapy, injections
o Theoretically through sharing of contaminated personal articles (razors, toothbrushes)
Laboratory Diagnosis Of Hepatitis C:
-Mild elevation of ALT,AST
-With fluctuation in AST(surrogate Marker of chronic hepatitis C).
1) Serology
.
1-HCV-specific IgG indicates exposure, not infectivity
2) PCR detects viral genome in patient's serum
3) Quantitative PCR to detect viral load response to therapy
Hepatitis D
HDV is a defective single-stranded RNA virus that requires the helper function of HBV to replicate. HDV requires HBV for synthesis of envelope protein composed of HBsAg, which is used to encapsulate the HDV genome.
Hepatitis D - Clinical Features
· Coinfection
o severe acute disease
o low risk of chronic infection
· Superinfection
o usually develop chronic HDV infection high
o risk of severe chronic liver disease
Notes:
HDV infection can be acquired either as a co-infection with HBV or as a superinfection of persons with chronic HBV infection. Persons with HBV-HDV co-infection may have more severe acute disease and a higher risk of fulminant hepatitis (2%-20%) compared with those infected with HBV alone; however, chronic HBV infection appears to occur less frequently in persons with HBV-HDV co-infection. Chronic HBV carriers who acquire HDV superinfection usually develop chronic HDV infection. In long-term studies of chronic HBV carriers with HDV superinfection, 70%-80% have developed evidence of chronic liver diseases with cirrhosis compared with 15%-30% of patients with chronic HBV infection alone.
Hepatitis D Virus Modes of Transmission
· Percutanous exposures
o injecting drug use
· Permucosal
o exposures sex contact
Notes:
The modes of HDV transmission are similar to those for HBV, with percutaneous exposures the most efficient. Sexual transmission of HDV is less efficient than for HBV. Perinatal HDV transmission is rare.
The serologic course of HDV infection varies depending on whether the virus is acquired as a co-infection with HBV or as a superinfection of a person with chronic HBV infection.
In most persons with HBV-HDV co-infection, both IgM antibody to HDV (anti-HDV) and IgG anti-HDV are detectable during the course of infection.
However, in about 15% of patients the only evidence of HDV infection may be the detection of either IgM anti-HDV alone during the early acute period of illness or IgG anti-HDV alone during convalescence.
Anti-HDV generally declines to sub-detectable levels after the infection resolves and there is no serologic marker that persists to indicate that the patient was ever infected with HDV. Hepatitis Delta antigen (HDAg) can be detected in serum in only about 25% of patients with HBV-HDV co-infection. When HDAg is detectable it generally disappears as HBsAg disappears and most patients do not develop chronic infection. Tests for IgG anti-HDV are commercially available in the United States. Tests for IgM anti-HDV, HDAg and HDV RNA by PCR are only available in research laboratories.
In patients with chronic HBV infection who are super-infected with HDV several characteristic serologic features generally occur, including: 1) the titer of HBsAg declines at the time HDAg appears in the serum, 2) HDAg and HDV RNA remain detectable in the serum because chronic HDV infection generally occurs in most patients with HDV superinfection, unlike the case with co-infection, 3) high titers of both IgM and IgG anti-HDV are detectable, which persist indefinitely.
Hepatitis E
Recently identified cause of enterically transmitted non-A, non-B (NANB) hepatitis
ClinicalFeatures
Incubation period 30-40 days
Acute, self limiting hepatitis, no chronic carrier state
Age: predominantly young adults, 15-40 years
Complications
Fulminant hepatitis in pregnant women. Mortality rate is high (up to 40%).
Virus cannot be cultured in vitro.
1) Calicivirus-like particles in the stool, by electron microscopy
2)Specific IgM in serum
3) PCR HEV-specific sequences in stool
Need more
visit
http://www.amazon.com/Lectures-applied-clinical-microbiology-ebook/dp/B004Y0XF54
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