Background

Viral hepatitis A and viral hepatitis E

  • Enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV) are a worldwide problem.
  • Common source epidemics have been related to contaminated water and to contamination via infected food handlers.
  • In general, both HAV and HEV are self-limiting viral infections; case fatality is normally low (0.1 – 0.3%). Women in the third trimester of pregnancy are especially susceptible to fulminant HEV disease.
  • Both HAV and HEV are transmitted via the faecal-oral route.
  • Prevention and control measures for hepatitis A and hepatitis E include adequate supplies of safe-drinking water and improvement of sanitary and hygienic practices to eliminate faecal contamination of food and water.

Viral hepatitis B and viral hepatitis C:

  • Estimates indicate that worldwide, there are 257 million carriers of hepatitis B virus and 71 million carriers of hepatitis C virus.
  • Acute Hepatitis B and C may be anicteric and thus unrecognized, but acute outbreaks are uncommon.
  • Chronic infection and severe sequelae occur with hepatitis B – an estimated 15% to 25% of chronically infected persons will die prematurely of either cirrhosis or hepatocellular carcinoma. Chronic Hepatitis C infection is also common and 5% to 20% of those infected with HCV may develop cirrhosis. The risk of hepatocellular carcinoma in persons with HCV cirrhosis is 2-4% per year.
  • Hepatitis B is transmitted by percutaneous or per mucosal exposure to blood or other infectious body fluids. In most countries where HBV is highly endemic, most acute infections occur during infancy, early childhood or via perinatal transmission from mother to infant. Other important routes of transmission include nosocomial exposure (transfusions, unsafe injection practices), shared needles or syringes among injecting drug users, household contact (e.g., communally used razors and toothbrushes) and sexual contact with an infected person.
  • Hepatitis C is transmitted by parenteral exposure to blood and plasma derivatives. It is found in highest concentrations in blood. The major causes of HCV infection worldwide are use of unscreened blood transfusions and re-use of needles and syringes that have not been adequately sterilised.
  • Prevention and control measures for hepatitis B and C include transfusion safety, safe and appropriate use of injections and vaccination (hepatitis B). Screening and early treatment are efficient modes of secondary prevention.
  • To address the increasing burden of viral hepatitis, in 2016, African member states adopted Prevention, Care and Treatment of viral hepatitis in the African Region: Framework for action 2016-2020

There is no specific treatment for acute viral hepatitis.

Surveillance Goal

Acute viral hepatitis

  • Detect hepatitis outbreaks.
  • Identify areas/populations at high risk to target prevention and control measures.
  • Estimate burden of disease.
  • If countrywide surveillance is not possible, surveillance in sentinel areas or hospitals may provide useful information on potential sources of infection.

Chronic viral hepatitis

  • Estimate burden of chronic viral hepatitis B and C.
  • Measure the impact of control measures/treatment on mortality reduction. To this effect, data is captured on persons diagnosed with hepatocellular carcinoma or cirrhosis

Viral Hepatitis Case Definitions

I) Acute Viral Hepatitis:

Suspected case: Any person with discrete onset of an acute illness with signs/symptoms of;

(i) Acute infectious illness (e.g. fever, malaise, fatigue) and

(ii) Liver damage (e.g. anorexia, nausea, jaundice, dark colored urine, right upper
quadrant tenderness of body),

AND/OR

(iii) Raised alanine aminotransferase (ALT) levels more than ten times the upper
limit of normal.

Confirmed case: A suspected case that is laboratory confirmed by virus specific biomarkers:

  • Acute Hepatitis A: anti-HAV IgM positive or positive for HAV RNA .
  • Acute Hepatitis B: Hepatitis B surface antigen (HBsAg) positive AND anti-hepatitis B core antigen (anti-HBc) IgM positive, HBV DNA positive . Acute Hepatitis C: HCV RNA positive (Viral Load), HCV core antigen positive (where available) and anti-HCV IgM positive. Markers of acute hepatitis A (anti-HAV IgM) and hepatitis E (anti-HEV IgM) are negative.
  • Acute Hepatitis D: HBsAg positive (or anti-HBc IgM positive) plus anti-HDV positive (usually IgM), and HDV RNA (HDV infection ONLY occurs as co-infection or super-infection of hepatitis B).
  • Acute Hepatitis E: anti-HEV IgM positive

I) Chronic Viral Hepatitis Case definition (HBV and HCV):

Chronic Hepatitis B:

  • Persistence of HBsAg for over 6 months after acute infection indicates chronic HBV infection.
  • HBsAg and anti-HBc positive (usually IgG) in asymptomatic persons or patients with chronic liver disease and/or liver tumour indicates chronic HBV infection

Chronic Hepatitis C:

  • Hepatitis C virus RNA positive in a person with anti-HCV positive (usually IgG).
  • HCV RNA positive OR HCV core antigen positive

NB: Antibody detection (i.e. HCV Ab positive) cannot differentiate between acute, chronic infection and past infection.

Surveillance for detecting chronic hepatitis B and C

  • Conduct HBsAg and Anti-HCV antibody sero-prevalence testing of the general population and all patients presenting with chronic liver disease (CLD);
  • These may include:
    • General population testing approaches making use of existing community- or health facility-based testing opportunities or programmes such as at antenatal clinics, HIV or TB clinics
    • General population periodic sero-prevalence surveys using serological markers for viral hepatitis B and C
    • Patients presenting to health facilities with chronic liver disease (CLD) and/or liver tumour.

Respond to alert threshold

If hepatitis cases are suspected:

  • Report case-based information to the appropriate levels (see annexes for case-based reporting form).
  • Collect specimens and send to laboratory to identify the aetiology of the illness .
  • As necessary, treat and manage acute viral hepatitis patient(s) with supportive care.

Respond to action threshold

If hepatitis cases are confirmed:

  • Determine mode of transmission.
  • Identify population exposed to risk of infection.
  • Eliminate common source(s) of infection.
  • Implement appropriate prevention and control interventions.
  • Patients with chronic viral hepatitis should be referred to tertiary or specialist centres; designated treatment centres for treatment, care and follow-up

Analyse and interpret data

Time: Analysis of suspected and confirmed cases by week and month. Graph cases and deaths weekly and monthly.

  • Construct an epidemic curve during outbreaks.

Place: Plot location of case households.

Person: Analyse by age and gender. Assess risk factors to plan and monitor prevention and control measures. Calculate the Incidence Rate for Acute Viral Hepatitis cases and Prevalence Rate for Chronic Viral Hepatitis B and C cases and Case Fatality Rate

Laboratory confirmation: Acute Viral Hepatitis
Diagnostic test

Hepatitis A: anti-HAV IgM positive

Hepatitis B: Hepatitis B surface antigen (HBsAg) positive or anti-HBc IgM positive

Hepatitis C: Anti-HCV Ab positive

Hepatitis D: HBsAg positive (or anti-HBc IgM positive) plus anti-HDV positive (only as co-infection or super-infection of hepatitis B)

Hepatitis E: anti-HEV IgM positive and/or anti-HEV IgG positive

Specimen

Whole blood, Serum or stool (for hepatitis A and E viruses)

When to collect the specimen

Specimens should be collected from suspected patients.

IgM anti-HAV becomes detectable 5-10 days after exposure.

HBsAg can be detected in serum from several weeks before onset of symptoms to days, weeks or months after onset; it persists in chronic infections. IgM anti-HBc positive usually disappears after 6 months.

How to prepare, store and transport the specimen

Use universal precautions to minimize exposure to sharps and body fluids.

Collect 5-10 ml of venous blood.

  • Let clot retract for 30 to 60 minutes at room temperature or centrifuge to separate serum from red blood cells.
  • Aseptically pour off serum into sterile, screw capped tubes.
  • Store serum at 4°C.
  • For storage >5 days, samples are held at -20°C

Transport serum samples using appropriate packaging to prevent breakage or leakage.

Results

Results are usually available within one to 3 days from arrival in the laboratory.

Laboratory Test for Chronic Viral Hepatitis

  1. Chronic Viral Hepatitis B (HBV)

Basic initial laboratory investigations:

The following laboratory tests should be requested after thorough history and physical examination in HBsAg positive individuals;

    1. Establish chronicity: Persistence of HBsAg for over 6 months after acute infection or presence of chronic liver disease/tumour.
    2. Establish HBe antigen (Ag)/Antibody (Ab) status: HBe Ag and Ab
    3. Establish inflammatory activity: liver function tests
    4. Determine the level of viraemia – viral load: HBV DNA
    5. Screen for the presence of chronic liver disease or other complications using clinical examination for stigmata of chronic liver disease, abdominal ultrasound, coagulation profile, full blood count
    6. Screen for other co-infections: HCV Ab, HIV, HDV (in endemic regions)
    7. Supportive investigation: determine blood urea and creatinine
    8. Consider liver biopsy or fibro-scan if indicated
  1. Chronic Viral Hepatitis C (HCV)

Initial Investigations for HCV Patients:

  • Further testing for RNA positive cases include liver function test (LFT),
    abdominal ultrasound, viral genotyping, full blood count (FBC), blood urea
    and electrolytes (BUE) and creatinine
  • Screen for co-infections - HIV, HBV
  • Assess degree of inflammation and fibrosis by conducting the following b
    test:
  1. Aspartate aminotransferase-to-platelet ratio index (APRI) score
  2. Fibrosis-4 (FIB4) score (the score uses a combination of age, platelet
    count, AST, ALT tests to derive the score)
  3. Fibroscan

Liver biopsy is the gold standard.

References

  • WHO Recommended WHO/CDS/CPE/SMT/2001.13 Strategies for Prevention and Control of Communicable Diseases;.
  • WHO Recommended Surveillance Standards WHO/CDS/CSR/ISR/99.2
  • WHO Fact Sheet No 328, Hepatitis A, revised May 2008. 204, Hepatitis B, revised August
  • WHO Fact Sheet No 204, Hepatitis B, revised August
  • WHO Fact Sheet No 2008 164, Hepatitis C.
  • WHO Fact Sheet No 280, Hepatitis E, revised January 2005.
  • World Health Organization http://www.who.int/topics/hepatitis/en/
  • United States, Centers for Disease Control and Prevention http://www.cdc.gov/hepatitis/
  • Control of Communicable Diseases Manual, 18th Edition
  • WHO Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection; March 2015
  • WHO Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection; April 2016
  • WHO Global Hepatitis Report 2017.
  • WHO Guidelines on hepatitis B and C testing February 2017