Causes , Symptoms, Diagnosis Treatment & Prevention . Hepatitis:  Causes , Symptoms, Diagnosis Treatment & Prevention .

Virus causes: Hepatotropic and non - hepatotropic Viral Hepatitis in Children Virus causes: Hepatotropic and non - hepatotropic •Hepatotropic viruses: HAV, HBV, HCV, HDV, HEV, HGV

Transmission Hepatitis A Virus Infection Worldwide infection Fecal-oral route • Close personal contact • Contaminated water and food Parenteral (rare) Incubation: 15-50 days (mean 28)

Pathogenesis HAV infection is biphasic process: • Non-cytopathic stage Hepatocellular damage is immune mediated process and not direct cytopathic effect by hepatitis A virus.

HAV infection is an acute self-limited illness Clinical manifestations HAV infection is an acute self-limited illness • General nonspecific symptoms (fever, malaise, anorexia, vomiting, nausea, abdominal pain and diarrhea) • Jaundice • Choluria (bilirubin in urine) • Mild hepatomegaly Symptomatic hepatitis: 30% of infected children younger than six years. 70 – 80% in older children and adults infected with HAV

Atypical presentations Hepatic manifestations: • Relapsing hepatitis (3-20%) • Acute liver failure (<1%) • Cholestasic hepatitis (30% of adult). • Autoimmune hepatitis. Extra-hepatic manifestations (common) • An evanescent rash (11%) • Arthralgia (14%)

Atypical presentations Extra-hepatic manifestations (rare) • Vasculitis • Arthritis • Optic neuritis • Transverse myelitis • Encephalitis • Bone marrow suppression

Diagnosis Serologic tests: • Anti HAV IgM : indicates an acute infections • Anti HAV IgG : indicates resolved infections or vaccine induced immunity Other techniques: • HAV detection in stool and body fluids by electron microscopy. • HAV RNA detection in stool, body fluids, serum and liver tissues by PCR.(Polymerase chain reaction)

Treatment Self-limited disease, rarely requires hospitalization Only supportive measures in uncomplicated cases: • Bed rest. • Control fever. • Increased fluid intake. • No particular diet is needed. • Limit hepatotoxic medications, ( acetaminophen) Children with HAV infection should be away for 1 wk.

Treatment (cont.) If complicated with acute liver failure: • Hospitalization • Aggressive supportive therapy • Early transfer to liver transplantation center. If HAV triggered secondary disorders • Treat the specific disease

• Adherence to sanitary practices (hand washing). Prevention and Prophylaxis General measures: • Adherence to sanitary practices (hand washing). • Heating food appropriately. • Avoidance of water or food from endemic areas. Active immunization: Two hepatitis A vaccines (inactivated vaccines) • HAVRIX (in1995) • VAQTA (in 1996) Passive immunization: • Polyclonal serum immunoglobulin (IgG)

Hepatitis A Vaccines Pediatric and adult formulations : • Pediatric formulations vaccines approved for 12 months through 18 years • Adult formulations approved for persons 19 years and older

Hepatitis A Vaccines •Adult 1 dose ( >95% seropositive ) booster dose 6-18 months after first dose ( 100% seropositive ) •Children older than 2years of age 1 dose ( >97% seropositive ) in (18 m. ) of age booster dose 6-12 months after first dose ( 100% seropositive )

Polyclonal serum immunoglobulin (IgG) • Passive immunity lasts for up to six months • Effective if administered within 2 weeks post-exposure • Dose is 0.02 ml per kg IM

Hepatitis B Virus

Incubation Period of HBV • Average: 60–90 days • Range: 45–180 days

Clinical manifestations Acute Infection: • Asymptomatic • Symptomatic : Prodromal (serum sickness like syndrome, Constitutional (anorexia, nausea, jaundice, right upper quadrant pain, fatigue) •Occasionally develops acute fulminant hepatitis.

Clinical manifestations Chronic Infection: •Asymptomatic •Vague right upper quadrant pain and fatigue •Occasionally associated with extrahepatic manifestation including polyarteritis nodosa and glomerulonephropathy

Diagnosis of Hepatitis B V

•Tests for HBV replication including HBeAg and HBeAb •Tests for HBV replication including HBeAg and HBeAb. (•Screen for hepatocellular carcinoma with (HCC 1- abdominal ultrasound 2-serum alpha fetoprotein. •Liver biopsy for patients who meet criteria of chronic hepatitis and who are considered for treatment

Serologic responses to hepatitis B Virus infection

Progression to chronic state  90% if perinatal acquisition  20-50% if acquired between 1-5 years of age.  <5% if acquired in adult

Treatment Interferon alfa •First line treatment choice Treatment Interferon alfa •First line treatment choice. •Six month course of interferon alfa-2b, six million units (MU) per m2 (maximum 10MU) SC. three times a week for 24 weeks. •Response rate in 30 – 40% of patients. •Side effects: Flu like symptoms, Bone marrow suppression

Treatment Lamivudine •Second line treatment choice •Dose: 3 mg per kg of body weight (max. 100 mg) •Drug resistance with long term use

Treatment Newer agents •Pegylated interferon therapy approved for ≥ 3 years of age. •Adefovir : licensed for use in patient ≥ 12 years of age. •Tenofovir : licensed for use in patient ≥ 12 years of age. •Entecavir: licensed for use in patient ≥ 16 years of age.

Prevention HBV vaccine •Universally recommended for all infants Prevention HBV vaccine •Universally recommended for all infants. 4 doses in (0,2,4,6 ) months of age . •HBV - exposed family members or closed contacts. HB immune globulin (HBIG )indication for use •Infants born to HBsAg positive mothers. •Post exposure prophylaxis within 24 hours of exposure if no past vaccine.

Prevention Other measures • All pregnant women should antenatal screening for HBsAg. • Investigations for HBV ,HCV and HIV before any surgical intervention • Household contacts: Avoid sharing of tweezers, shavers, toothbrush, nail clippers. •Universal precautions for handling abrasions, bleeding, etc.

Monitoring of patients Disease activity: •ALT every 6-12 months •HBeAg and HBeAb every 12 months •If HBeAg is +ve, measure HBV DNA. hepatocellular carcinoma surveillance: •Ultrasound of liver every 12 months •Alpha fetoprotein every 12 months

Mode of transmission • Vertical • Parenteral • Sexual

Perinatal transmission •Perinatal transmission rates are 5% •Rates are increased up to 15 – 20% if mother is co-infected with HIV. •Risk factors: Use of internal fetal monitoring devices Prolonged rupture of membranes (>6 hours) High viral load HIV co-infection •Breast feeding and vaginal delivery does not increase vertical transmission  Approximately 90% of transfusion-associated hepatitis is caused by HCV

Clinical Features •Incubation period: 30-150 days •Chronic infection will develop in 60-80% of exposed children. Patients with chronic HCV infection are at risk for developing cirrhosis, liver failure, and liver cancer •Majority of patients are asymptomatic in childhood. •End-stage liver disease with decompensated cirrhosis has been described in children. •Acute liver failure from HCV infection has not reported in immunocompetent patients. •Comorbidities: Glomerulonephritis, Cryoglobulinemia Autoimmune hepatitis

Diagnosis •Check liver panel •Screen with HCV IgG antibody after 18 month of age and HCV RNA after 2 month of age. •HCV genotype analysis indicated if treatment is being considered.

Treatment •Subcutaneous weekly pegylated interferon-alpha injections for 48 weeks (genotypes 1 or 4) or 24 weeks (genotypes 2 or 3), plus oral ribavirin. •Treatment response: non detectable HCV RNA by 24 weeks. •Pegylated interferon/ribavirin therapy approved for ≥ 3 years of age.

Prevention •HCV vaccine: none available Prevention •HCV vaccine: none available. •HCV immunoglobulin: none available. •Household contacts: avoid sharing of tweezers, shavers, toothbrush, nail clippers. •Universal precautions for handling abrasions, bleeding, etc. ( Patients with chronic HCV infection can continue to infect others. ) •Screening for hepatocellular carcinoma (HCC)

HEPATITIS D VIRUS •Defective interfering virus, requires HBV co-infection HDV cannot survive on its own because it requires a protein the HBV makes , to enable it to infect liver cells. •Prevalent in Mediterranean basin, North Africa, and South America •10% of HBV infected persons co-infected with HDV Hepatitis D virus (HDV) infections occur only in those who are infected with HBV. 

•Diagnosis: Co-infection with acute HBV showed positive IgM anti-HDV, while super-infection of chronic HBV showed positive IgG & IgA anti-HDV in addition to serological markers of HBV. The dual infection of HDV and HBV can result in a more serious disease and worse outcome. Hepatitis B vaccines provide protection from HDV infection.

HEPATITIS E VIRUS •Incubation period 15-60 days •Enteric transmission via fecal-oral route. •Endemic in Southeast & Central Asia; Middle East, North and West Africa •Acute, self-limited hepatitis

HEPATITIS E VIRUS •Clinical features range from asymptomatic to mild to fulminant picture with high mortality rate in pregnant women in third trimester (20%) •Diagnosis: Anti-HEV IgM positive for 2-3 months, Anti-HEV IgG persists long term in half of patients. •Immunoprophylaxis : none

HEPATITIS G VIRUS • RNA virus HEPATITIS G VIRUS • RNA virus. • Parenterally transmitted agent, can be transmitted perinatally . ● virus (HGV) was recently discovered and resembles HCV. the virus and its effects are under investigation, and its role in causing disease in humans is unclear.

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