Hepatitis

1. VIRAL HEPATITIS
Dr. Jane Mwongeli
Consultant Paediatrician

2. Introduction
• Hepatitis is a general term used to describe inflammation of the liver.
• Liver inflammation can be caused by
several viruses (viral hepatitis),
chemicals,
drugs,
alcohol,
autoimmune hepatitis.
• Depending on its course, hepatitis can be
acute
Chronic
progressive liver damage.
• Vaccines giving active protective immunity are now available for hepatitis A
and B infection, the most frequently identified causes of hepatitis in
children.

3. Acute Viral Hepatitis
• Acute hepatocellular injury/inflammation
• Reflected by elevated transaminases (AST or SGOT, ALT or SGPT)
• Clinical manifestations often include fever, malaise, jaundice, RUQ
pain, nausea/vomiting
• Typically self-limiting and of short duration
• Causative agents -HAV (50% of cases in U.S.), HEV, CMV, EBV, VZV

4. Fulminant Hepatitis Acute,
• Characterised by massive hepatocellular necrosis
• Impaired synthetic, excretory, and detoxifying functions of the liver
• Cholestasis, ascites, coagulopathy, encephalopathy, multi-system
failure
• Initially very elevated transaminases
• Falling transaminases and rising bilirubin ominous
• Hyperammonemia, hypoalbuminemia, prolonged PT, hypoglycemia
• Caused by Viral agents (50% of cases)
• Most cases of fulminant hepatic failure are caused by unidentified
agent, presumably viral HAV, HBV+/-HDV, HCV, HEV, HSV,
enteroviruses, EBV, CMV, HHV-6, VZV

5. Chronic Hepatitis
• Characterised by Prolonged necro-inflammatory process
• Elevated transaminases for > 4-6 months, Insidious
• clinical manifestations can include cholestasis (jaundice, pruritus),
ascites, hypoalbuminemia, coagulopathy, encephalopathy.
• Can progress to fibrosis and then cirrhosis
• Viral agents: HBV (+/- HDV), HCV
• Other causes include autoimmune, metabolic disorders (Wilson’s, CF,
alpha-1 antitrypsin deficiency), drug/toxin-mediated, idiopathic

6. Causes of viral hepatitis
• This disorder is caused by the 5 pathogenic hepatotropic viruses
recognized to date:
hepatitis A virus (HAV),
Hepatitis B virus (HBV),
Hepatitis C virus (HCV),
Hepatitis D virus (HDV), and
Hepatitis E virus (HEV)

8. Other viral causes of hepatitis
• Many other viruses (and diseases) can cause hepatitis, usually as a
component of a multisystem disease, E.g
herpes simplex virus,
cytomegalovirus,
Epstein-Barr virus,
varicella-zoster virus,
HIV,
rubella,
adenoviruses,
enteroviruses,
parvovirus B19, and
arboviruses

9. Issues Common to All Forms of Viral Hepatitis
a)Common clinical features
Patients present with icterus/jaundice
hepatomegally (usually enlarged liver and tender to palpation and
percussion).
Splenomegaly
Lymphadenopathy may be present.
Extrahepatic symptoms (rashes, arthritis) are more commonly seen in
HBV and HCV infections.
Clinical signs of bleeding, altered sensorium, or hyperreflexia mark
the onset of encephalopathy and ALF.

10. b)The differential diagnosis
(varies with age of presentation).
In the newborn period,
infection is a common cause of conjugated hyperbilirubinemia; Mostly
 bacterial agent (e.g., Escherichia coli , Listeria, syphilis) or
 nonhepatotropic virus (e.g., enteroviruses, cytomegalovirus, and herpes simplex virus, which may also
cause a nonicteric severe hepatitis).
Metabolic diseases (α1 -antitrypsin deficiency, cystic fibrosis, tyrosinemia),
anatomic causes (biliary atresia, choledochal cysts), and
inherited forms of intrahepatic cholestasis.
In later childhood,
extrahepatic obstruction (gallstones, primary sclerosing cholangitis, pancreatic
pathology), inflammatory conditions (autoimmune hepatitis, juvenile inflammatory
arthritis, Kawasaki disease),
immune dysregulation (hemophagocytic lymphohistiocytosis),
infiltrative disorders (malignancies),
toxins and
medications,
metabolic disorders (Wilson disease, cystic fibrosis), and
infection (Epstein-Barr virus, varicella, malaria, leptospirosis, syphilis)

11. C) Pathogenesis
• The acute response of the liver to hepatotropic viruses involves a direct
cytopathic and/or an immune-mediated injury.
The entire liver is involved.
Necrosis is usually most marked in the centrilobular areas.
Acute mixed inflammatory infiltrate predominates in the portal areas
balloon degeneration and necrosis of single or groups of parenchymal cells commonly
occur but lobular architecture remains intact.
Bile duct proliferation occurs.
Diffuse Kupffer cell hyperplasia is noticeable in the sinusoids.
Neonates often respond to hepatic injury by forming giant cells .
In fulminant hepatitis, parenchymal collapse.
• After recovery, the liver morphology returns to normal within 3 months of the
acute infection.
• If chronic hepatitis develops, the inflammatory infiltrate settles in the
periportal areas and often leads to progressive scarring. Both of these
hallmarks of chronic hepatitis are seen in cases of HBV and HCV.

12. d) Common Biochemical Profiles in the Acute Infectious Phase
• Acute liver injury caused by these viruses manifests in 3 main functional liver
biochemical profiles
Cytopathic injury to the hepatocytes, there is a rise in serum levels of alanine
aminotransferase (ALT) and aspartate aminotransferase (AST)
Cholestasis , defined by elevated serum conjugated bilirubin levels, results from abnormal
bile flow at the canalicular and cellular level because of hepatocyte damage and
inflammatory mediators.
 Elevation of serum alkaline phosphatase, 5′-nucleotidase, and γ-glutamyl transpeptidase levels, mark
cholestasis.
Altered synthetic function is the most important marker of liver injury. Synthetic dysfunction
is reflected by a combination of
 abnormal protein synthesis (prolonged PT, high international normalized ratio [INR], low serum albumin
levels),
 metabolic disturbances (hypoglycemia, lactic acidosis, hyperammonemia),
 poor clearance of medications dependent on liver function, and
 altered sensorium with increased deep tendon reflexes (hepatic encephalopathy).
Monitoring of synthetic function should be the main focus in clinical follow-up to define the
severity of the disease.
In the acute phase, the degree of liver synthetic dysfunction guides treatment.
 Abnormal liver synthetic function is a marker of liver failure

13. HEPATITIS A
• Hepatitis A is the most prevalent form.
• Causes acute and benign hepatitis.
• fulminant hepatic failure due to HAV is rare in children but occurs in
adults in hyperendemic areas
• Etiology: cause by HAV which is
an RNA virus
A member of the picornavirus family. I
heat stable and has limited host range (human and other primates).
incubation period for HAV is approximately 3 wks

14. Epidemiology of HAV
• occurs worldwide but is most prevalent in developing countries.
• In the United States:
 30–40% of the adult population has evidence of previous HAV infection.
 Hepatitis A is thought to account for approximately 50% of all clinically apparent acute viral hepatitis
• HAV is highly contagious
• Causes outbreaks in developing countries and in daycare centers
• Transmission is almost always by person-to-person contact through the
fecal–oral route
• Common cause foodborne and waterborne outbreaks
• The mean incubation period for HAV is approximately 3 wk (range of 2-6
weeks)
• Fecal excretion of the virus starts late in the incubation period, peaks just
before the onset of symptoms, and resolves by 2 wk after the onset of
jaundice in older subject. Longer in infants.

15. Pathogenesis
• Causes subacute disease in children and young adults
• HAV invade the human body by faecal-oral route, multiplies in the
intestinal epithelium and reaches the liver by hematologenous spread.
• After one week, HAV reaches the liver cells and replicates within, then
enters intestines with bile and appear in stools
• After HAV replication and discharging, liver cells damage begins
• Animal experiment prove that immune complex play a role in
pathogenesis
• Activated T cells secrete interferon gamma that promote the
representation of HLA on the liver cells, Cytotoxic T lymph may kill
target cells infected with HAV

17. Clinical Manifestations
• Causes acute hepatitis only
• In the young, clinical symptoms are indistinguishable from other forms of viral
gastroenteritis.
• More likely to be symptomatic in older adolescents /adults, patients with
underlying liver disorders, and in immunocompromised.
• An acute febrile illness with an abrupt onset of anorexia, nausea, malaise, vomiting,
and jaundice.
• The typical duration of illness is 7-14 days.
• Regional lymph nodes and the spleen may be enlarged.
• Moderately hypoplastic bone marrow and aplastic anemia.
• Small intestine villous structure changes, and ulceration of the gastrointestinal tract.
• Acute pancreatitis
• Extra-heapatic features: Myocarditis, nephritis, arthritis, leukocytoclastic vasculitis,
and cryoglobulinemia can result from circulating immune complexes.

18. Diagnosis
• Acute HAV infection is
diagnosed by detecting antibodies to HAV, specifically, anti-HAV
(immunoglobulin --IgM)
By identifying viral particles in stool ( via immunoelectrone microscope)
 A viral polymerase chain reaction (PCR) assay is available for research use.
• Anti-HAV (IgM) is detectable when the symptoms are clinically apparent,
and it remains positive for 4-6 mo after the acute infection.
• Anti-HAV (IgG) is usually detected within 8 wk of symptom onset
• Anti -HAV (IgG) confers long-term protection.
• LFTs: raising ALT, AST, bilirubin, alkaline phosphatase, 5′-nucleotidase,
and γ-glutamyl transpeptidase are almost universally found and do not
help to differentiate the cause of hepatitis.

19. Complications
• Most patients achieve full recovery
• Complications;
Acute Liver Failure (especially in adolescents, adults, immunocompromised
patients, pts with underlying liver disorders).
In the United States, HAV represents <0.5% of pediatric-age ALF.
HAV is responsible for up to 3% mortality in the adult population with ALF.
In endemic areas of the world, HAV constitutes up to 40% of all cases of
pediatric ALF.
Prolonged cholestatic syndrome that waxes and wanes over several months.
Pruritus and fat malabsorption

20. Treatment
• No specific treatment for hepatitis A.
• Supportive treatment
intravenous hydration as needed.
antipruritic agents
fat-soluble vitamins for the prolonged cholestatic form of disease (Vit A,D,E,K).
Serial monitoring for signs of ALF.
If ALF is diagnosed, promptly refer to a transplantation center

21. Prevention
Patients infected with HAV are contagious for 2 wk before and approximately 7
days after the onset of jaundice and should be excluded from school, childcare,
or work during this period.
Careful hand-washing.
Immunisation with hepatitis A vaccine: inactivated, highly immunogenic, given
from 1 year of age and a second dose 6 months later (2 doses)
Immunoglobilin prophylaxis in postexposure situations should be used as soon
as possible (it is not effective if administered more than 2 wk after exposure).
Immunoglobulins are recommended for preexposure prophylaxis for
susceptible travelers to countries where HAV is endemic, and it provides
effective protection for up to 2 months
Prognosis
Patient with HAV have excellent prognosis, with no long-term sequelae.
The only feared complication is ALF.

22. HEPATITIS B
• Member of the hapdnavirus grp
• Double stranded DNA virus
• Replication involves a reverse transcriptase enzyme (allows viruses to convert
their RNA genome into DNA so that it can be inserted into the host's genome)
• Endemic in humans in many parts of the world
• The surface of the virus includes particles, designated as the hepatitis B
surface antigen (HBsAg)
• The inner portion of the virion contains the hepatitis B core antigen (HBcAg),
the nucleocapsid that encodes the viral DNA, and a nonstructural antigen
called the hepatitis B e antigen (HBeAg
• HBeAg serves as a marker of active viral replication and usually correlates
with the HBV DNA levels.
• Replication of HBV occurs predominantly in the liver but also occurs in the
lymphocytes, spleen, kidney, and pancreas.

24. Epidemiology
• 400 million persons chronically infected worldwide
• The areas of highest prevalence of HBV infection are sub-Saharan Africa,
China, parts of the Middle East, the Amazon basin, and the Pacific Islands.
• 1.25 million persons in the United States are chronic HBV carriers, with
approximately 300,000 new cases of HBV occurring each year, the highest
incidence being among adults 20-39 yr of age.
• One in 4 chronic HBV carriers will develop serious sequelae in their
lifetime.
• The number of new cases in children reported each year is low( but is
difficult because children are asymptomatic).
• In the United States, since 1982 the overall incidence of HBV infection has
been reduced by more than half after introduction of HB vaccine.

25. Epidemiology
• The risk of developing chronic HBV infection (defined as being positive
for HBsAg for longer than 6 months), is inversely related to age of
acquisition.
90% in children younger than 1 yr
30% for those 1-5 yr of age and
2% for adults.
• Chronic HBV infection is associated with the development of chronic
liver disease and HCC.

26. Replication
• Reverse transcription: one of the mRNAs is replicated with a reverse
transcriptase making the DNA that will eventually be the core of the
progeny virion
• RNA Intermediate: HBV replicates through an RNA intermediate ,
produces and releases antigenic decoy particles
• Intergration: Some DNA intergrates into host genome causing carrier
state

27. Replication
• The replication cycle of HBV begins with attachment of the
virion to the hepatocyte membrane
• The virion is uncoated in the hepatocyte cytoplasm and
the viral genome enters the hepatocyte nucleus.
• In the hepatocyte nucleus, synthesis of the plus strand
HBV DNA is completed and the viral genome is converted
into a covalently closed circular DNA (ccc DNA).
• The pregenomic RNA, nucleocapsid, and polymerase
proteins are encapsidated in the virus core particle inside
which reverse transcription takes place.
• A new minus strand HBV DNA is produced followed by
the synthesis of a new plus strand HBV DNA.
• Nucleocapsids with the partially double stranded
HBV DNA can reenter the hepatocyte nucleus to produce
more ccc DNA or be secreted as complete virions after
coating with envelope proteins.

28. • Serologic markers of HBV infection vary depending on whether the
infection is acute or chronic.
• The first serologic marker to appear following acute infection is
HBsAg, which can be detected as early as 1 or 2 weeks and as late as
11 or 12 weeks (mode 30-60 days) after exposure to HBV.
• In persons who recover, HBsAg is no longer detectable in serum after
an average period of about 3 months.
• HBeAg is generally detectable in patients with acute infection;
• the presence of HBeAg in serum correlates with higher titers of HBV
and greater infectivity.
• A diagnosis of acute HBV infection can be made on the basis of the
detection of IgM class antibody to hepatitis B core antigen (IgM anti-
HBc) in serum; IgM anti-HBc is generally detectable at the time of
clinical onset and declines to sub-detectable levels within 6 months.
• IgG anti-HBc persists indefinitely as a marker of past infection.
• Anti-HBs becomes detectable during convalescence after the
disappearance of HBsAg in patients who do not progress to chronic
infection.
• The presence of anti-HBs following acute infection generally
indicates recovery and immunity from re-infection

29. • In patients with chronic HBV
infection, both HBsAg and IgG anti-
HBc remain persistently detectable,
generally for life.
• HBeAg is variably present in these
patients.
• The presence of HBsAg for 6
months or more is generally
indicative of chronic infection.
• In addition, a negative test for IgM
anti-HBc together with a positive
test for HBsAg in a single serum
specimen usually indicates that an
individual has chronic HBV
infection.

31. Modes of transmission
• Parenteral: Iv drug abusers, health workers are at increased risk
• Sexual; sex workers, homsexuals
• Perinatal( vertical transimission): mother (HBeAg+) to infant
• Concentration of HBV in various body fluids;
High: blood, serum, wound exudates
Moderate: semen, vagina, saliva
Low/not detectable: urine, faeces, sweat, tears, breast milk

32. High risk groups:
• People from endemic areas
• IV drug users
• Sex workers
• People requiring multiple blood transfussions: hemophiliacs, sicklers etc.
• Health workers
• Residents and staff working in institutions of mentally challenged persons
• Risk factors for HBV infection in children and adolescents include intravenous drugs
or blood products, contaminated needles used for acupuncture or tattoos, sexual
contact, institutional care, and intimate contact with carriers.
• Mother to child /vertical transimission; the most important risk factor for acquisition
of HBV remains perinatal exposure to an HBsAg-positive mother (up to 90% of these
infants become chronically infected if untreated)
• Other risk factors include high maternal HBV viral load (HBeAg/HBV DNA titers) and
delivery of a prior infant who developed HBV despite appropriate prophylaxis
• No risk factors are identified in approximately 40% of cases

33. Pathogenesis and immunity
• HBV, unlike the other hepatotropic viruses, is a predominantly non-
cytopathogenic virus that causes injury mostly by immune-mediated
processes.
• Virus enters hepatocytes via blood
• Hepatocyte infection results in expression of viral antigens on the cell surface.
• The most important of these viral antigens may be the nucleocapsid
antigens—HBcAg and HBeAg. These antigens, in combination with class I
major histocompatibility proteins, make the cell a target for cytotoxic T-cell
lysis.
• Immune response(Cytotoxic T cell) to viral antigens is expressed on the
hepatocyte cell surface responsible for clinical syndrome
• 5% become chronic carriers ( positive HBsAg >6 months)
• Hepatocellular carcinomer is common in chronic carriers espe those who are
“e antigen” positive
• Hepatitis B surface antibody likely confers life long immunity (IgG anti-HBs)
• Hepatitis B e antibody indicates low transimissibillity.

34. Pathogenesis and immunity
• Immune-mediated mechanisms are also involved in the extrahepatic
conditions that can be associated with HBV infections.
• Circulating immune complexes containing HBsAg can result in
polyarteritis nodosa,
membranous or membranoproliferative glomerulonephritis,
polymyalgia rheumatica,
leukocytoclastic vasculitis, and
Guillain-Barré syndrome.

35. Clinical features
• Incubation period ranges from 45-160 days, with a mean of 120 days
• Many acute cases of HBV infection in children are asymptomatic ( many
cases of hepatitis B carriage without evidence of acute hepatitis)
• Insidious onset of symptoms
• Tend to cause more severe illness than HAV
• The percentage of children in whom clinical evidence of hepatitis
develops is higher for HBV than for HAV, and the rate of ALF is also
greater.
• symptoms persist for 6-8 wk.

36. Clinical features
• The illness is preceded, in a few children, by a serum sickness–like
prodrome marked by arthralgia or skin lesions, including urticarial,
purpuric, macular, or maculopapular rashes.
• Papular acrodermatitis, the Gianotti-Crosti syndrome, can also occur.
• Other extrahepatic conditions associated with HBV infections in children
include polyarteritis nodosa, glomerulonephritis, and aplastic anemia.
• Jaundice is present in approximately 25% of acutely infected patients and
usually begins 8 wk after exposure and lasts 4 wk.

37. Clinical features
• Most patients do recover.
• chronic carrier state complicates up to 10% of cases acquired in adulthood.
• The rate of development of chronic infection depends largely on the mode and age
of acquisition and occurs in up to 90% of perinatally-infected cases.
• Cirrhosis and HCC are only seen with chronic infection.
• Chronic HBV infection has 3 identified phases:
• immune tolerant, immune active, and inactive.
• Most children fall in the immune-tolerant phase, against which no effective therapy
has been developed. Most treatments target the immune active phase of the
disease, characterized by active inflammation, elevated ALT/AST levels, and
progressive fibrosis.
• Spontaneous HBeAg seroconversion, defined as the development of anti-HBe and
loss of HBeAg, occurs in the immune-tolerant phase. It is more common in
childhood acquired HBV rather than in perinatally transmitted infections.

38. Diagnosis
• The first biochemical evidence of HBV infection is elevation of serum ALT
levels.
• ALT begins to rise just before development of fatigue, anorexia, and
malaise, appro 6-7 wk after exposure.

39. Dignosis
• HBsAg-used as a general marker of infection
• HBsAb; used to document recovery and /or immunity to HBV infection
• Anti-HBc IgM; marker of acute infection
• Anti- HBc IgG; past or chronic infection
• HBeAg- Indicates active replication of virus and therefore infectiveness
• Anti-Hbe- virus no longer replicating, the patient can still be positive for
HBsAg which is made by intergrated HBV
• HB-DNA –indicates active replication of virus, more accurate than HBeAg
especially in cases of escape mutants. Used mainly for monitoring
response to therapy

41. Treatment
• Treatment of acute HBV infection is largely supportive.
• Close monitoring for liver failure and extrahepatic morbidities.
• Treatment of chronic HBV infection is in evolution.
• The goal of treatment is to reduce viral replication defined by having
undetectable HBV DNA in the serum and development of anti-HBe,
termed seroconversion.
• The development of anti-HBe transforms the disease into an inactive
form, thereby decreasing infectivity, active liver injury and inflammation,
fibrosis progression, and the risk of HCC.
• Treatment is only indicated for patients in the immune-active form of
the disease, as evidenced by elevated ALT and/or AST, who have fibrosis
on liver biopsy, putting the child at higher risk for cirrhosis during
childhood.

42. Current treatment options
• Interferon alfa: response rate 30-40%
• Lamivudine; associated with relapses and drug resistance
• Adeforvir dipivoxil (Hepsera); less likely to develop resistance, may be
used to treat lamivudine resistant HBV
• Entecavir
• Tenofovir
• Successful response to treatment will result in the disappearance of
HBsAg, HBV-DNA

43. Complications
• ALF with coagulopathy, encephalopathy, and cerebral edema occurs
more commonly with HBV than the other hepatotropic viruses.
• The risk of ALF is higher if there is coinfection or superinfection with
HDV or in an immunosuppressed host.
• Mortality from ALF is >30%
• Chronic hepatitis, which can lead to cirrhosis, end-stage liver disease
and HCC.
• Membranous glomerulonephritis with deposition of complement and
HBeAg in glomerular capillaries.

44. Prevention
• Vaccination: recombinant HB vaccine is highly effective
• Hepatitis B immunoglobulin (HBIG); Given within 48 hours of exposure/
neonate born to HBsAg and HBeAg positive mothers
• Blood /blood product screening before transfusion.
• Avoid contact with body fluids
• Screening of pregnant mothers and the use of HBIG and hepatitis B
vaccine in infants
• Mothers with an HBV DNA viral load >200,000 IU/mL receive an antiviral
such as telbivudine, lamivudine, or tenofovir during the third trimester
(especially if they had a previous child who developed chronic HBV after
receiving HBIG and the hepatitis B vaccine)
• Health education to Health care workers

45. Prognosis
• The outcome of acute HBV infection
varies substantially depending on the
age at which infection occurs.
• In children less than 5 years of age,
<5% of acute HBV infections are
symptomatic;
however, chronic infection occurs in about
80%-90% of infants infected during the first
year of life and
Chronic infection occurs in about 30%-50%
of children infected between 1-4 years of
age.
• In comparison, 30%-50% of adults with
acute HBV infection are symptomatic,
but only 2%-10% develop chronic
infection.

46. Hepatitis B :conclusion
• anti-HBc exposure (IgM = acute)
• HBsAg  infection (carrier)
• anti-HBs  immunity
• HBeAg  viral replication
• anti-HBe  seroconversion
• HBV-DNA  viral replication

47. HEPATITIS C

48. HEPATITIS C VIRUS
• HCV is a single-stranded RNA virus
• classified as a separate genus within the Flaviviridae family
• It has 6 major genotypes and numerous subtypes and quasi-species,
which permit the virus to escape host immune surveillance.
• Genotype 1b is the most common genotype in the United States and is
the least responsive to the approved pediatric medications.

49. HEPATITIS C

50. Epidemiology
• In the United States, HCV infection,
Is the most common cause of chronic liver disease in adults,
is responsible for 8,000-10,000 deaths per year.
Approximately 4 million people in the United States and 170 million people
worldwide are estimated to be infected with HCV.
• 85% of infected adults remain chronically infected.
• In children, seroprevalence of HCV is
0.2% in those younger than age 11 yr and
0.4% in children age 11 yr or older.
• The incubation period is 7-9 wk (range: 2-24 wk).

51. Pathogenesis of HCV
• The pattern of acute hepatic injury is similar to that of other
hepatotropic viruses.
• In chronic cases, lymphoid aggregates or follicles in portal tracts are
found, either alone or as part of a general inflammatory infiltrate of the
portal areas.
• Steatosis is also seen.
• HCV appears to cause injury primarily by cytopathic mechanisms, but
immune-mediated injury can also occur.
• The cytopathic component appears to be mild because the acute illness
is typically the least severe of all hepatotropic virus infections.

54. Transmission of HCV
• Transfusion or transplant from infected donor
• Injecting drug use
• Hemodialysis
• Accidental injuries with needles/sharps
• Sexual
• Household exposure to anti-HCV positive contact
• Multiple sex partners
• Perinatal ( mother to child )

55. Clinical features
• Acute HCV infection :-
Mild and insidious
Acute liver failure rarely occurs
15 % of infected adults clear the virus while rest develop chronic infection.
In infected children 6-19 % achieved spontaneous sustained clearance of the
virus during a 6-yr follow-up.
• Chronic HCV infection :-
clinically silent until a complication develops.
Serum aminotransferase levels fluctuate and are sometimes normal.
histologic inflammation is universal.
Progression of liver fibrosis is slow over several years,
Approximately 25% of infected patients ultimately progress to cirrhosis, liver
failure, and, occasionally, primary HCC within 20-30 yr of the acute infection.
Progression is rare within the pediatric age range

56. Extrahepatic manifestations
• Most extrahepatic features are seen in adults
• Chronic HCV infection can be associated with
small vessel vasculitis
essential mixed cryoglobulinemia.
cutaneous vasculitis,
porphyria cutanea tarda,
lichen planus,
peripheral neuropathy,
cerebritis,
polyarthritis,
membranoproliferative glomerulonephritis, and
nephrotic syndrome

57. Natural history of HCV

58. Laboratory diagnosis
• HCV antibody- generally used to diagnose HCV infection. Not useful in the
acute phase as it takes at least 4 weeks after infection before antibody
appear.
• HCV-RNA; May be used to diagnose HCV infection in the acute phase.
However, its main use is monitoring the response to antiviral therapy.
• HCV- antigen; used in the same capacity as HCV-RNA test but is much easier
to carry out
• Aminotransferase levels typically fluctuate during HCV infection and do not
correlate with the degree of liver fibrosis.
• ultrasound or magnetic resonance elastography- used to estimate the degree
of fibrosis
• Liver biopsy( decreased use with the advent of ultrasound and magnetic
resonance elastography)

59. Prognostic tests
• Genotyping- genotype 1 and 4 have a worse prognosis overall and
respond poorly to interferon therapy
• Viral load- pts with high viral load are thought to have poorer prognosis
• Viral load is also used for monitoring response to interferon therapy

60. Treatment
• Interferon: may be considered for patients with chronic active hepatitis. Response rate is
around 50%, BUT 50% of responders with relapse upon withdrawal of treatment
• Ribavirin: there is less experience with ribavirin than interferon. Recent studies show that
combination ribavirin and interferon is more effective than interferon alone.
• IFN and ribavirin are approved by the FDA for use in children older than 3 yr of age with
chronic hepatitis C.
• Treatment may be considered for children infected with genotypes 2 and 3, because they
have an 80–90% response rate to therapy with peginterferon and ribavirin
• Pediatric guidelines recommend treatment to:
 eradicate HCV infection,
 prevent progression of liver disease and
 Prevent development of HCC
 to remove the stigma associated with HCV
• Other medication approved by FDA: sofosbuvir alone or in combination with ledipasvir

61. Chronic HCV infection
• The spectrum of chronic HCV infection is like for HBV infection.
• All the manifestations of chronic HBV may be seen in Chronic HCV
though with lower frequency ( i.e Chronic persistent hepatitis, , chronic
active hepatitis, cirrhosis and hepatocellular carcinoma)

62. Prevention
• Screening of blood, organ and tissue donors
• High risk behavior modification
• Blood and body fluid precautions

63. HEPATITIS D VIRUS
• A defective RNA virus ( called defective because it cannot produce infection without
concurrent HBV infection)
• single stranded, codes for 9 proteins.
• Co-infects with and requires the helper function of HBV (or other Hepadnaviruses) for its
replication and expression
• Delta antigens: are expressed in the hepatocyte, facilitating HDV RNA replication by
binding to RNA polymerase 2.
• Intracellular replication of HDV RNA can occur without HBV.
• HDV can either infect a person simultaneously with HBV (co-infection) or super infect a
person already infected with HBV (superinfection);
• The symptoms of hepatitis D are similar to, but usually more severe than, those of the
other hepatotropic viruses
• Duration of HDV infection is determined by the duration of (and cannot outlast) HBV
infection.

64. Diagnosis of HDV
• HDV has not been isolated and no circulating antigen has been
identified.
• The diagnosis is made by detecting IgM antibody to HDV;
• The antibodies to HDV develop approximately 2-4 wk after
coinfection and approximately 10 wk after a superinfection.

65. Treatment of HDV
• Mainly supportive measures once an infection is identified.
• No specific HDV-targeted treatments to date.
• Treatment is mostly based on controlling and treating HBV infection,
without which HDV cannot induce hepatitis.
Prevention:
No vaccine for hepatitis D.
Because HDV replication cannot occur without hepatitis B coinfection,
immunization against HBV also prevents HDV infection.
Hepatitis B vaccines and HBIG are used for the same indications as for
hepatitis B alone.

66. HEPATITIS E VIRUS
• Previously labeled epidemic or enterically transmitted non-A, non-B
hepatitis
• Genome: RNA, single stranded virus.
• Has 3 genes encoding for structural proteins.
• Have a serotype & 5 genotypes
• Has an animal reservior: swine
• In acute infection: Ig M & Ig G
• HEV is the epidemic form of what was formerly called non-A, non-B
hepatitis.
• Transmission is fecal–oral (often waterborne)
• The highest prevalence of HEV infection has been reported in the Indian
subcontinent, the Middle East, Southeast Asia, and Mexico, especially in
areas with poor sanitation.
• The mean incubation period is approximately 40 days (range: 15-60 days).

67. Pathogenesis:
• HEV appears to act as a cytopathic virus. The pathologic findings are similar
to those of the other hepatitis viruses.
Clinical Manifestations :
• The clinical illness is similar to that of HAV but is often more severe.
• As with HAV, chronic illness does not occur ( except in immunosuppressed
patients e.g., post-transplant).
• HEV tends to affect older patients, with a peak age between 15 and 34 yr.
Diagnosis
• Recombinant DNA technology for antibodies to HEV particles.
• IgM and IgG assays are available to distinguish between acute and resolved
infections
• IgM antibody occur after 1 wk of illness.
• Viral RNA can be detected in stool and serum by PCR.

68. Prevention of HEV
• A recombinant hepatitis E vaccine is highly effective in adults.
• Immunoglobulins – not evidence

69. Conclusion

73. References
• Up-to-date
• Nelsons Paediatric text book Volume 21
• Harrison's 17th edition