أسئلة الـ Hepatitis - حورس

• Acute hepatitis is an acute inflammation of hepatocytes, usually with cell degeneration, necrosis, and dysfunction, resulting in elevated liver function indices and it has a wide range of clinical presentations.

Possible Fates

• Complete resolution
• Chronicity and its sequelae

Causes

• Infectious: Viral and non-viral
• Non-infectious: Autoimmune, drugs, and toxins, parasitic, and bacterial infection

Acute Viral Hepatitis

• It is a systemic infection in which the predominant manifestation is hepatic injury and dysfunction.

Etiology: Hepatotropic viruses and Non-hepatotropic viruses

• Hepatotropic viruses: Hepatitis viruses A, B, C, D, and E.
• Non-hepatotropic viruses: Epstein Barr virus, Herpes virus, CMV, Adenovirus, ECHO virus, and Coxsacki virus

Hepatotropic Viruses Table

Viral Descriptions of Hepatitis A

• Single-stranded RNA genome
• One serotype has been recognized
• Excreted into the stool and bile

Epidemiology of Hepatitis A

• Period of infectivity: 2-3 weeks before clinical symptoms persist in stool for up to 2 weeks after disease onset.
• Maternal neonatal transmission: Not described
• Common source outbreaks: Water and food contamination

Pathogenesis of Hepatitis A

• Immune and non-immune mechanisms are responsible for cell necrosis

Clinical Features of Hepatitis A

• 90% are asymptomatic
• Only 5% of symptomatic cases are icteric
• Acute self-limiting diseases

Symptoms of Hepatitis A

• Prodromal period (1 week): Several days, Fever, headache, malaise
• Symptomatic stage (4 weeks): Non-icteric in 95% of patients, jaundice, abdominal pain, nausea, vomiting, anorexia and pruritus
• Convalescence (4-6 weeks)
• Extrahepatic manifestation

Signs of Hepatitis A

• Liver mild enlargement tender
• Splenomegaly

Atypical Clinical Manifestations of Hepatitis A

• Cholestatic hepatitis: Jaundice persists for more than 12 weeks
• Accompanied by severe pruritis
• Relapsing hepatitis: Multiple courses of acute hepatitis, persistence or recurrence of IgM anti-HAV in serum, recurrence of fecal excretion of HAV
• Immune-complex disorders: Cutaneous vasculitis, arthritis, cryoglobulinemia
• Autoimmune hepatitis: Trigger of autoimmune hepatitis in susceptible individuals
• Fulminant hepatitis

Laboratory findings of Hepatitis A

• Aminotransferases will be 20-30 times the upper limit of normal, within the first 2-3 weeks and minor elevations may persist for months

Diagnosis of Hepatitis A

• HAV-IgM: Peak level acute or early convalescent phase and disappears 3-4 months of the onset of the disease and it can persist for 6-12 months in cases with prolonged cholestasis or relapsing forms of HAV infection
• HAV-IgG: Peak level-convalescent phase and persists for many years

Sequelae of Hepatitis A

• Fulminant hepatitis is rare, chronic hepatitis is absent, and carrier state is absent

Treatment of Hepatitis A

• Supportive treatment, rest, adequate hydration during the acute phase

Viral Descriptions of Hepatitis B

• HBV DNA exhibits 4 open reading frames which correspond to 4 genes that code for specific groups of proteins:
• S gene and pre S region leads to HBsAg.
• C gene: HBcAg and HBeAg
• P gene DNA polymerase
• X gene HBxAg (transcriptional transactivating function)

Viral Markers of Hepatitis B

• HBeAg, HBe antibody, HBsAg - HBsAb, Anti –HBc – IgM & IgG, and HBV DNA.
• The earliest detectable marker HBsAg, which may appear () 1 and 10 weeks
• Subsequently, HBeAg and HBV DNA can be identified
• Clearance of HBsAg with the appearance of anti-HBs occurs within 6–8 months
• Anti-HBc IgM is present before symptomatic infection and is a marker for acute infection

Clinical Features of Hepatitis B

• Prodromal period (prolonged and more sever): Malaise fatigue, nausea, low-grade fever, serum like illness, artralgia, artheritis, urticaria, maculopapular rash, hematuria and proteinuria rare. papular acrodermatitis and lymphadenopathy
• Icteric phase (1-2 weeks from the prodrome): Jaundice, pruritis, nausea, vomiting, hepatomegaly: mild and tender, and splenomegaly mild

Factors that affect the development of HBsAg state in the infant

• Chronic HBV carrier mother, Acute HBV in the 3rd trimester, maternal HBsAg titer, maternal HBeAg positivity, and HBV-DNA or DNA polymerase activity

Implications of Hepatitis B

• 90% of HBsAg-positive infants developed chronic hepatitis or chronic carrier state

Treatment of Hepatitis B

• Purely supportive
• Immunoprophylaxis: Passive (HBIG) and Active (2 types of vaccine, which is plasma derived and recombinant vaccine)

Hepatitis C Viral Descriptions

• Lipid enveloped, single-stranded RNA.
• Single open reading frame.
• Several genotype and subtypes.
• Genus flaviviruses and pestiviruses.

Hepatitis C Epidemiology

• Transmission occurs through transfusion of blood and blood products and IV drug abuses 40%, heterosexual contact 6%, Household contact 3%, occupational exposure 2%, no risk factor 40%

Hepatitis C Perinatal Transmission

• The most important mode of infection in the pediatric population
• Anti-HCV is passively transferred from mother to child

Hepatitis C Pathogenesis

• Immune-mediated hepatocellular damage
• Cytotoxic T-cell responses to various regions of HCV have been demonstrated

Hepatitis C Diagnosis

• Enzyme-linked immunosorbent assay (ELISA)
• ELISA-1
• ELISA-2
• ELISA-3
• PCR polymerase chain reaction
• Detection and quantification of HCV-RNA

Hepatitis C Clinical Features

• IP: 2-26 weeks
• Jaundice: < 25%
• Anorexia, nausea, malaise, fatigue, and infrequent abdominal pain

Hepatitis C Lab Findings

• Aminotransferases: Modest rise.
• Fluctuates for long time
• ELISA-2: positive by 2-4 weeks after infection
• PCR: positive by 2 weeks after infection

Hepatitis C Complications

• Fulminant hepatitis: very rare
• Chronic hepatitis: 50-70% of cases

Hepatitis C Treatment

• No widely accepted recommendation for treatment of acute HCV infection

Hepatitis E Descriptions

• Spherical, non-enveloped RNA virus
• Genus is unknown but is similar to caliciviruses
• Only one serotype

Hepatitis E Epidemiology

• Transmission: Contaminated water + fecal-oral route.

Hepatitis E Pathogenesis

• Immune mechanism has been suggested but NOT confirmed

Hepatitis E Diagnosis

• Stool viral detection by E.M
• Anti-HEV detection: Enzyme-Immunoassay, IgM anti-HEV recent infection, IgG anti HEV past infection, and HEVAg in hepatocytes

Hepatitis E Clinical Features

• IP 2-9 weeks
• Same As in HAV
• Chronic hepatitis: NOT reported

Hepatitis E Treatment

• Therapy: no specific therapy
• Immunoprophylaxis NOT available

Management of Acute Viral Hepatitis

• Early detection
• Monitoring during acute disease
• Recognition of the development of fulminant or chronic liver disease
• Prevention of disease spread to susceptible persons
• Bed rest
• Specific diets
• Hospitalization
• Return to school
• Follow up studied
• Prevention by Elimination of the virus from infected population and Instituting hygienic measures

Passive Immunization

• Standard pooled human serum globulin for Household contacts and acute HAV infection Dose:0.02ml/kg soon after exposure and SIG HBIG (hepatitis B immunoglobulin) for HBV infection as early as possible, post exposure, perinatal exposure, sexual exposure, and household contact

Active Immunization

• Formalin inactivated HA vaccines, 2 doses, 0, 6m interval I.M
• HB vaccine plasma-derive and Recombinant DNA vaccine
• HBIG-HB vaccine given within 12 hrs of birth and HBIG (0.5ml at birth) + HB vaccine (0, 1,6 months schedule), 94% protection of infants born to HBsAg/HBeAg positive mothers

Fulminant hepatitis Definition

• The PALFSG defined ALF as:
• No history of known chronic liver disease
• Biochemical evidence of liver injury,
• Coagulopathy not corrected by parental vitamin K administration
• INR greater than 1.5 if the patient had encephalopathy or greater than 2.0 if the patient does not have encephalopathy.

Fulminant Hepatitis Clinical Picture

• Subtle mental or personality changes.
• Rapid progressing symptoms.
• Decreased liver size.
• Deepening jaundice.

Indices of Poor Outcome in Fulminant Hepatitis

• Increased prothrombin time unresponsive to vit K administration.
• Factor VII levels less than 8% of normal.
• Elevated blood ammonia.

Fulminant Hepatitis Treatment

• Fluid and electrolyte management
• Lactulose
• Decontamination of gut
• Restriction of protein
• Treatment of seizure and brain oedema
• Treatment of coagulopathy
• Treatment of ascites
• Treatment of infection
• Others e.g plasmapheresis, N-acetylcystine
• Liver transplant

Home Message

• Acute viral hepatitis is a common cause of acute liver disease in children
• Fulminant hepatitis occurs in a small proportion of children with HAV & should be managed carefully
• All pregnant women should be screened for HBV for immediate management of children after birth
• Prevention is preferable to treatment as by good oral hygiene & accurate screening of blood products