Hepatitis A

Dr. Kailash MakhejaniResident GastroenterologyLiaquat National Hospital Karachi

Introduction

Hepatitis is a general term that means inflammation (irritation and swelling) of the liver

Hepatitis A refers to liver inflammation caused by infection with the hepatitis A virus (HAV)

HAV has been known as “Infectious Jaundice” since 1912

According to WHO1, HAV had many names in the past; • Epidemic hepatitis• Epidemic jaundice • Infectious hepatitis • Catarrhal jaundice • HA and type A hepatitis

1. ANON. “Hepatitis A.” 2000. Available from: http://www.who.int/csr/disease/hepatitis/HepatitisA_whocdscsredc2000_7.pdf. Accessed February 20, 2008

History

HAV is referred to as one of the oldest diseases known to humankind by the WHO1

It was recognized as as separate entity from other types of hepatitis during World war II

It was discovered in 1973 by Steven M. Feinstone as a nonenvoloped, spherical, positive stranded RNA virus

HAV was an unidentified viral disease prior to this discovery

1. ANON. “Hepatitis A.” 2000. Available from: http://www.who.int/csr/disease/hepatitis/HepatitisA_whocdscsredc2000_7.pdf. Accessed February 20, 2008

Virology

Naked RNA virus

Related to enteroviruses, formerly known as Enterovirus 72, now put in its own family: heptoviridae

One stable serotype only

But seven genotypes exist (four human & three simian) most common being 1A in Humans

Difficult to grow in cell culture: primary marmoset cell culture and also in vivo in chimpanzees and marmosets

Human and vertebrates serve as natural hosts

Epidimiology Globally, symptomatic HAV infections are believed to occur in around 1.5 million people a year

In 2010, acute hepatitis A resulted in 102,000 deaths, which is slightly up from 99,000 in 1990*

Hepatitis A is much more common in countries with underdeveloped sanitation systems and, thus, is a risk in most of the world

Developed countries have low circulating levels of hepatovirus A while developing countries have higher levels of circulation.

HAV is a common infection in developing nations of Africa, Asia, and Central and South America.

Most adolescents and adults in developing countries have already had the disease, thus are immune.

*Lozano, R (Dec 15, 2012). “Global and regional mortalityfrom 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010”. Lancet 380 (9859): 2095–128.doi:10.1016/S0140-6736(12)61728-0. PMID 23245604.

Transmision Its communicable (or contagious) disease that spreads from person to person via

“fecal-oral route”

While all other exposure is generally attributable to contaminated food or water

Food-related outbreaks are usually associated with contamination of food during preparation by a HAV-infected food handler

Infected individuals are infectious prior to onset of symptoms, roughly 10 days following infection.

The food handler is generally not ill because the peak time of infectivity—that is, when the most virus is present in the stool of an infected individual—occurs two weeks before illness begins.

Transmission The virus is resistant to detergent, acid (pH 1), solvents (e.g., ether, chloroform), drying, and temperatures up to 60°C

It can survive for months in fresh and salt water.

Infection is common in children in developing countries, reaching 100% incidence, but following infection, lifelong immunity results

Travelers who visit developing countries remain at risk for infection.

Contaminated food, water (e.g., infected food handlers, raw shellfish) Close personal contact (e.g., household contact, sex contact, child day care centers)

Blood exposure (rare) (e.g., injecting drug use, transfusion)

Unknown52%

Intl travel5%

Household/sexual

25%

Outbreak3%

Day care15%

Pathogenesis

Clinical manifestations Apprroximately 70% of hepatitis A infectious children younger than 06 years of age are

asymptomatic

In older children and adults, infection tends to be symptomatic with more than 70% of those infected developing jaundice

Symptoms typically begin about 28 days after contracting HAV, but can begin as early as 15 days or as late as 50 days after exposure

The symptoms include Muscle aches HeadacheAnorexia (loss of appetite) Abdominal discomfortFeverMalaise

Usually manifestations resolve in 6 to 8 weeks but it can also take 6 months

Diagnosis

Acute infection is diagnosed by the detection of HAV-IgM in serum by (enzyme immunoassay)EIA.

Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.

Cell culture – difficult and take up to 4 weeks, not routinely performed

Direct Detection – Electron microscopy, RT-PCR of faeces. Can detect illness earlier than serology but rarely performed.

Events in hepatitis a virus infection

0 1 2 3 4 5 6 7 8 9 10 11 12 13Week

Re

sp

on

se

Clinical illness

ALT

IgM IgG

HAV in stool

Infection

Viremia

CONCENTRATION OF HEPATITIS A VIRUS IN VARIOUS BODY FLUIDS

Source: Viral Hepatitis and Liver Disease 1984;9-22J Infect Dis 1989;160:887-890

Feces

Serum

Saliva

Urine

100 102 104 106 108 1010

Bo

dy

Flu

ids

Infectious Doses per mL

Managemant

No specific treatment is known

Appropriate rest (when nescessary)

In the past, however, strict bed rest until complete resolution of all symptoms was common

An Randomized control trial has shown no difference in the duration of illness with the institution of a deliberate exercise program. So strict bed rest is controversial

Avoid fatty foods and alcohol (these may be poorly tolerated for some additional months during the recovery phase and cause minor relapses)

Eat a well-balanced diet, and stay hydrated.

Managemaent

In fulminant hepatic failure, management is determined by the complications that develop and the availability of transplantation.

Similarly, extrahepatic manifestations such as renal failure and pancreatitis are managed in a routine manner.

The expectation for all patients is for complete recovery without sequelae, which occurs in the vast majority.

Complication

In some individuals, the course of hepatitis A is unusually prolonged.

Since prolonged excretion of virus (i.e., viral nucleic acid detected by RT-PCR) may occur in patients with persistent elevation of alanine aminotransferase , any patient with prolonged course should be regarded as potentially infectious.

The occurrence of “cholangiolytic” or cholestatic variants of acute hepatitis A has been described in 1984 in literature

Severe pruritus, diarrhea, weight loss, and malabsorption may accompany the cholestasis

Complication

Like hepatitis B, delta hepatitis, and hepatitis E, hepatitis A can cause acute hepatic failure

FHF-Less frequent than acetaminophen toxicity and hepatitis B

The spontaneous recovery rate for patients with fulminant acute hepatitis A in retrospective U.S. study, which included all age groupss was 35%, whereas it was 39% in a French pediatric population. Other patients may survive following liver transplantation*

The risk of fulminant hepatitis is increased in patients with underlying chronic liver disease who develop acute viral hepatitis (co-infection or superinfection)

*Debray, D., P. Cullufi, D. Devictor, M. Fabre, and O. Bernard. 1997. Liver failure in children with hepatitis A. Hepatology 26:1018–1022.

Chronic Hepatitis A — Case Report

The

Vaccination

Vaccination

Vaccination

Vaccination

DURATION OF PROTECTION AFTER HEPATITIS A VACCINATION

Persistence of antibody At least 5-8 years among adults and children

Efficacy 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

Need for post exposure prophylaxis uncommon. If needed, administer immune serum globulin within 2 weeks 0.02 ml/Kg IM

PREVENTING HEPATITIS A

Hygiene (e.g., hand washing)

Sanitation (e.g., clean water sources)

Hepatitis A vaccine (pre-exposure)