MANAGEMENT OF

HEPATITS A

Dr Rajdeep SinghDepartment of Gastroenterology

Fortis Hospital Mohali

Human Hepatitis VirusesVirus Genome Genome Envelope Family / genus

size (kb)

HAV RNA 7.5 - Picornaviridae hepatovirus

HBV DNA 3.2 + Hepadnaviridae

HCV RNA 9.6 + Flaviviridae hepacivirus

HDV RNA 1.7 + Unclassified (viroid), delta virus

HEV RNA 7.5 - Unclassified, togavirus and alpha virus-like

Hepatitis A Virus

27 nm· Nucleic Acid: 7.5 kb ssRNA· Classification: Picornaviridae,

Hepatovirus· One serotype and multiple

genotypes· Nonenveloped, acid and heat stable· In vitro model: monkey and

human cell cultures· In vivo replication: in cytoplasm of

hepatocyte; human and other higher primates

Hepatitis A TransmissionFecal-oral route0 Food handlers0 Travel to endemic areas

Close personal contact0 Household or sexual contact0 Daycare centers

Blood-borne (rare)0 Injecting drug users

EPIDEMIOLOGY

Acute hepatitis A is a reportable infectious disease in the USDifferent epidemiological patterns seenIn developing countries where sanitary conditions are poor, most children are affected at an early ageMajority of pre school children in these countries had anti-HAV in serum reflecting previous subclinical infection

In developed countries, there is low prevalence of HAV infection among children and young adultsUniversal HAV vaccination was adopted in 2005 in the US.

Zhou F, Shefer A, Weinbaum C, et al: Impact of hepatitis A vaccination on health care

utilization in the United States, 1996-2004. Vaccine 2007; 25:3581-7.(Ref 34.)

EPIDEMIOLOGICAL SHIFT

Shift in the age of acquiring infection from childhood to older age groupsPeak age of seroprevalence is shifting from 1st decade of life to 2nd and 3rd decadesAn increase in symptomatic cases and severe clinical outcomes including fulminant hepatic failure

Indian J Med Res 128, December 2008, pp 699-704

CASE 37 year male presents with low grade fever for 7 days associated with nausea, vomiting, retching, headache.

H/O passage of deep yellow urine, yellow eyes for 3 days and now fever has subsided. No h/o BT, surgery, jaundice in past.

On examination he is icteric, no stigmata of CLD, mild tender hepatomegaly, no splenomegaly.

Investigated found to have TSB 5mg% with direct 4%, SGOT 3675, SGPT 4698 and ALP 250, INR 1.2.

USG abdomen shows hypoechoic mild hepatomegaly with diffuse thickening of GB wall, no free fluid or spleenomegaly

DIAGNOSTIC APPROACH ACUTE HEPATITIS IgM Anti HEV HbsAg, Anti HCV

Anti HEV + Anti HEV - Anti HEV - HbsAg ,Anti HCV neg HbsAg +, Anti HCV - HbsAg, Anti HCV - IgM Anti HBc + IgM Anti HAV +

Acute hepatitis E Acute hepatitis B Acute hepatitis A

Anti HDV+

Hepatitis D co infection

DIAGNOSTIC APPROACH ACUTE HEPATITIS IgM Anti HAV, HEV - HbsAg, Anti HCV –

IgM Anti HBc

IgM Anti HBc + IgM Anti HBc -

Acute hepatitis B Work up for other causes of hepatitis- drugs, Wilsons, CMV, HSV, EBV

Spectrum of sporadic acute viral hepatitis in India

Saigal Nundy Subrat

Hepatitis E 29% 45% 38%

Hepatitis B 23% 12.5% 7.3%

Hepatitis A 12% 33% 17.5%

Hepatitis C 0 0.8% 2.8%

Saigal et al , Indian Jr of Gastroenterology, 2007

Nundy et al, Medical Jr of armed forces, 2009 Subrat et al, Hepatobiliary Pancreat Dis Int,

2007

Spectrum of acute hepatitis in India

Viral hepatitis 64%Drug induced 10%Ischemic 2%Acute fatty liver pregnancy 0.7%Cryptogenic 23%

Siagal S et al, Indian Journal of Gastroenterology , 2007

Typical Serologic Course of Acute Hepatitis A Virus Infection

FecalHAV

ALT

IgM anti-HAV

Months after exposure

Symptoms

0 1 2 3 4 5 6 12 24

Total anti-HAV

Clinical Variants of Hepatitis A Infection

Asymptomatic (anicteric) disease0 Children under 6 years of age, > 90%0 Children from 6-14 years old, 40-50%

Symptomatic (icteric) disease0 Adults and children over 14, 70-80%

Clinical Patterns of HAV Infection

Cholestatic hepatitis

Relapsing hepatitis

Fulminant hepatic failure

CHOLESTASIS

Can extend upto 8 weeksCorticosteroids have been used No conclusive evidence

EXTRAHEPATIC MANIFESTATIONS

Evanescent rash 14%Arthralgias 11%

Leukocytoclastic vasculitisGlomerulonephritisArthritis

RELAPSING HEPATITS A

10% of patients with acute hepatitis AShedding of HAV in stool documented during the relapse phase BenignInfection ultimately resolvesNo increase in mortality Treatment is symptomatic

SYMPTOMATIC TREATMENT

No specific antiviral drug availableMost patients do not require hospital careRestricted physical activity High calorie diet is desirableAvoid hepatotoxic drugsSimple hygienic precautions

MYTHSStrict bed rest

No fatty foods

No yellow foods

Sugarcane juice

Liv - 52

HEPATITS A VACCINE

Licensed for use after 12 months of ageOnly high risk populations targeted for immunizationHAVRIX by SmithKlineVAQTA by MerckDerived from HAV grown in cell culture

Centers for Disease Control and Prevention: Prevention of hepatitis A thorough active or passive immunization. MMWR 2006; 55(No. RR07):1-23.(Ref 25.)

HEPATITIS A VACCINE

Safe & immunogenic Long lasting immunity ~ 20 years

In age 1-18 yrs0.5 ml ( 720 ELU ) at 0, 6-12 months

In age >18 yrs1ml (1440 ELU ) at 0, 6-12 months

Centers for Disease Control and Prevention: Prevention of hepatitis A thorough active or passive immunization. MMWR 2006; 55(No. RR07):1-23.(Ref 25.)

Post Exposure Prophylaxis

Single dose HAV vaccine within 2 weeks of exposure Long term immunity

Immunoglobulin was preferred earlier Immediate & short term protection

Centers of Disease Control and Prevention: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. MMWR 2007; 56:1080-4.(Ref 54.)

TWINRIXCombined formulation of HAV & HBV vaccinesApproved by FDA for persons 18 yrs or older0,1,6 schedule

At 1 year HAV seroconversion 100% HBV seroconversion 96.4 – 100%

FDA approval for a combined hepatitis A and B vaccine. MMWR 2001; 50:806.(Ref 60.)

IAP RECOMMENDATIONS FOR USE

HAV Vaccine may be offered to all healthy children with special emphasis in risk groups

IAP Guide book on Immunization 2011

RISK GROUPS

Patients with chronic liver diseaseCarriers of Hepatitis B and CCongenital or acquired immunodeficiencyTransplant recipientsAdolescents seronegative for HAV and leaving for boarding schoolsTravelers to high endemic areas for HAVHousehold contacts of patients with acute Hepatitis A within 10 days.

TAKE HOME POINTS

In India, most individuals acquire natural infection in childhoodHAV infection tends to be more symptomatic in adultsHAV infection is a self limiting illnessNo specific antiviral drug is availableHAV vaccine provides long lasting immunity to individuals at risk

THANK YOU