HEPATITIS Khalid Bzeizi

What Is Hepatitis? The word "hepatitis" means inflammation of the liver. Toxins, certain drugs, some diseases, heavy alcohol use, bacterial and viral infections can all cause hepatitis.

Hepatitis Acute Hepatitis Subacute Hepatitis Chronic Hepatitis

Drug Induced Hepatitis Penicillin Halothane Paracetamol Isoniazid Statins Rifampicin Herbal Medicines

Autoimmune Hepatitis Classical Anti LKM Anti SLA

Viral Hepatitis Common viruses cause hepatitis include A,B,C,D,E Viral Hepatitis: Hepatitis A through E (more than 95% of viral cause). Herpes simplex, Cytomegalovirus, Epstein-Barr, yellow fever virus, adenoviruses.

Hepatitis A An acute liver disease caused by the hepatitis A virus (HAV), Duration: few weeks to several months. It does not lead to chronic infection.

Hepatitis A Virus 6

Transmission of HAV Ingestion of food or water contaminated with faecal matter

Clinical Manifestations Incubation period 2 – 6 weeks May be asymptomatic Overt illness in 5% Present as two stages, 1 Preicteric 2 Icteric

Clinical features Malaise Anorexia Nausea, vomitting liver tenderness Onset of Jaundice Recovery in 4-6 weeks Mortality 0.1 – 1 %

Hepatitis A - Clinical Complications Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae: None 7

Laboratory Diagnosis Acute infection is diagnosed by the detection of HAV-IgM in serum by 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 – EM, RT-PCR of faeces. Can detect illness earlier than serology but rarely performed.

Hepatitis A Infection Typical Serological Course Total anti-HAV Titer Symptoms Titer ALT Fecal HAV IgM anti-HAV 1 2 3 4 5 6 12 24 Months after exposure 9

Treatment No specific antiviral drug is available Treatment is symptomatic Specific passive prophylaxis by pooled normal human immunoglobulin given before exposure or in early incubation period can prevent or attenuate clinical illness.

Vaccination for HAV Hepatitis A vaccination is recommended for all children starting at age 1 year, travellers to certain countries, and others at risk. A full course containing two intramuscular injections of the vaccine Protection starts after 4 weeks after injection and lasts for 10 – 20 years

Hepatitis B Infection

Hepatitis B Causative agent: Double stranded DNA virus. Ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that leads to cirrhosis and/or liver cancer.

Most Important Infectious Disease There are more than 350 million carriers 25% of them will develop chronic active hepatitis. World wide 1 million deaths a year are attributed to HBV related liver disease and Hepatocellular Carcinoma

Transmission of HBV Horizontal Transmission Vertical Transmission Child-to-Child Contaminated Needles Sexual Health Care Worker Transfusion Hemodialysis Perinatal Common in regions with HBsAg prevalence of > 2% CDC Fact Sheet. http://www.cdc.gov/ncidod/diseases/hepatitis/b/. Lee. N Engl J Med. 1997;337(24):1733-1745. Lavanchy. J Viral Hepat. 2004;11(2):97-107.

Hepatitis B - Clinical Features Incubation period: Average 60-90 days Clinical illness (jaundice): <5 yrs, <10% 5 yrs, 30%-50% Acute case-fatality rate: 0.5%-1% Chronic infection: <5 yrs, 30%-90% 5 yrs, 2%-10% 29

Diagnosis A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. 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-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

Typical Serologic Course Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg anti-HBe Total anti-HBc Titre anti-HBs HBsAg IgM anti-HBc 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 30

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc 4 8 12 16 20 24 28 32 36 52 Years Weeks after Exposure 31

Hepatitis B Virus Modes of Transmission Sexual - sex workers and homosexuals are particular at risk. Parenteral - IVDA, Health Workers are at increased risk. Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. 2 2 2

Disease Progression Occurs in 15% to 40% of Chronic HBV Patients

Treatment Interferon Lamivudine . Adefovir Entecavir Tenofovir

Vaccination Genetically Engineered Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries.

Hepatitis B Immunoglobulin Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive

Hepatitis C Infection

What is Hepatitis C Virus Hepatitis C virus was also known as Non A or Non B virus found while doing experiments on Chimpanzees. HCV infections are seen only in humans The epidemiology is like HBV infection.

Hepatitis C Virus capsid envelope protein protease/helicase RNA-dependent RNA polymerase c22 33c c-100 5’ 3’ core E1 E2 NS2 NS3 NS4 NS5 hypervariable region 7 7 7

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Hepatitis C - Clinical Features Incubation period: Average 6-7 wks Range 2-26 wks Clinical illness (jaundice): 30-40% (20-30%) Chronic hepatitis: 70% Persistent infection: 85-100% Immunity: No protective antibody response identified 8 8 8

Hepatitis C virus Six genotypes are identified. In Saudi Arabia, genotype 4 accounts for around 65% of cases and genotype 1 around 25%. Genotypes 1 and 4 are relatively more difficult to treat compared to genotypes 2 & 3.

How HCV transmitted Blood transfusions Transplantation of organs Injectable drug abusers Immunocompromised Sexual transmission ? Less important Vertical transmission is possible

Clinical features Overt Jaundice is seen in 5% of patients About 50 – 80% patients progress to chronic hepatitis May progress to Cirrhosis, or Hepatocellular carcinoma

Laboratory Diagnosis HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. ELISA test results to be confirmed with Immunoblotting assay HCV-RNA

HCV Treatment Pegylated Interferon Ribavirin DAAs No vaccine

Hepatitis D Virus The delta agent is a defective virus which shows similarities with the viroids in plants. The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg. The genome of the virus is very small and consists of a single-stranded RNA

Hepatitis D - Clinical Features Coinfection severe acute disease. low risk of chronic infection. Superinfection usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis. 20 20 20

Hepatitis E Virus Calicivirus-like viruses unenveloped RNA virus, 32-34 nm in diameter +ve stranded RNA genome, 7.6 kb in size. very labile and sensitive Can only be cultured recently

Hepatitis E - Clinical Features Incubation period: Average 40 days Range 15-60 days Case-fatality rate: Overall, 1%-3% Pregnant women, 15%-25% Illness severity: Increased with age Chronic sequelae: None identified 27 27 27

Epidemiologic Features Hepatitis E - Epidemiologic Features Most outbreaks associated with faecally contaminated drinking water. Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico. Minimal person-to-person transmission. 29 29 29