Viral hepatitis

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    Last updated: October 2021

     

    Several viral infections of the liver are grouped under the heading of viral hepatitis: hepatitis A, B, C, D (delta) and E.

    The different hepatitis viruses are present throughout the world, but their prevalence varies by country. Hepatitis A and B are common in developing countries where the vast majority of infections occur during childhood.

     

    The clinical characteristics of all five diseases are similar enough to make differential diagnosis difficult; however, there are epidemiological, immunological and pathological differences. Patients with hepatitis B, C and D may later develop chronic liver disease.

    The main characteristics of each type of viral hepatitis are summarized in the table below.

    Clinical features

    • Asymptomatic forms
      Mild or anicteric forms are the most common, irrespective of the causal virus. 
    • Icteric forms
      Insidious or sudden onset with symptoms of varying intensity: fever, fatigue, nausea, gastrointestinal disturbance, followed by jaundice, dark coloured urine and more or less claycoloured stool.
    • Fulminant forms
      Hepatocellular failure with severe cytolysis that can be fatal. This form is most frequent in hepatitis B patients with secondary infection with the D virus, and in the event of pregnant women infected with hepatitis E during their third trimester.
    • Chronic hepatitis
      Hepatitis B, C and D may lead to cirrhosis and/or hepatocellular carcinoma (HCC).

     

    The various forms of viral hepatitis

     

    Hepatitis A

    Hepatitis B

    Hepatitis C

    Hepatitis D

    Hepatitis E

    Age group most at risk

    Children

    Children

    Young adults

    Young adults

    Young adults

    Transmission

    Faecal-oral
    Contaminated food and water
    Transfusion (rare)

    Vertical (a) Citation a. Vertical transmission: transmission of the virus from the mother to the child during pregnancy, at the time of delivery, or during the first 28 days after birth.
    Close contact with infected person (especially intra-familial).
    Exposure to blood (transfusion; material contaminated with blood)
    Sexual

    Exposure to blood (transfusion; material contaminated with blood)
    Sexual (low)
    Intranasal (implements shared by intranasal drug users)
    Vertical (a) Citation a. Vertical transmission: transmission of the virus from the mother to the child during pregnancy, at the time of delivery, or during the first 28 days after birth.

    Exposure to blood (transfusion; material contaminated with blood)
    Sexual
    Possibly vertical (a) Citation a. Vertical transmission: transmission of the virus from the mother to the child during pregnancy, at the time of delivery, or during the first 28 days after birth.

    Faecal-oral
    Contaminated food and water

    Incubation period

    2 to 6 weeks

    4 to 30 weeks (average 10 weeks)

    2 to 25 weeks

    Co-infection B/D: as for hepatitis B
    Secondary infection of hepatitis B: approximately 5 weeks

    2 to 8 weeks

    Fulminant forms

    0.2 to 0.4%

    1 to 3%

    More rare than in hepatitis B

    Much more common in patients with secondary infection of hepatitis B than in patients with B/D co-infection

    20% mortality in pregnant women

    Prognosis

    No chronic forms

    Chronicity: 0.2 to 10% (risk is inversely related to age, e.g. up to 90% if infected before the age of 1 year) of which 5 to 15% progress to cirrhosis.
    HCC possible

    Chronicity: up to 50%, of which 10 to 25% progress to cirrhosis.
    HCC possible

    Chronicity: < 5% for patients with B/D co- infection; > 90% if secondary infection of hepatitis B (rapid cirrhosis)

    No chronic forms

    Individual prevention

    Polyvalent immunoglobulin

    Specific anti-HBs immunoglobulin
    Safe sex (condoms)

    Specific anti-HBs immunoglobulin may be effective

    As for hepatitis B (the D virus can only develop with B)

    Cook meat (pork)

    Vaccination

    Anti-hepatitis A

    Anti-hepatitis B

    Does not exist

    Anti-hepatitis B

    Does not exist

    Collective prevention Hygiene, sanitation

    Limit transfusion, screen blood prior to transfusion
    Single use of disposable material

    Hygiene, sanitation

    Laboratory

    Diagnosis

    • HAV, HDV and HEV infection: detection of IgM anti-HAV, anti-HDV and anti-HEV antibodies, respectively.
    • HBV infection: detection of HBsAg; chronic hepatitis B: presence of HBsAG for longer 6 months; chronic active hepatitis B: detection of HBeAg and/or HBV DNA.
    • HCV infection: detection of anti-HCV antibodies and HCV RNA; chronic hepatitis C: viraemia persists for longer than 6 months.

    Other tests

    • ALT (or AST) level, platelet count, creatinine, HCV diagnosis and HBV viral load to decide treatment of chronic active hepatitis B.
    • APRI score (evaluation of liver fibrosis in chronic hepatitis): [(patient's AST level/normal AST level) x 100]/platelet count (109 platelets/litre). An APRI score > 1 indicates probable severe fibrosis.
    • HIV test.

    Other investigations

    Elastography (Fibroscan®): measures the elasticity of the liver to determine stage of liver fibrosis, scored from F0 (absence of fibrosis) to F4 (cirrhosis).

    Treatment

    • Rest, hydration, no special diet.
    • Do not administer drug therapy for symptomatic treatment (analgesics, antipyretics, antidiarrhoeals, antiemetics etc.) during the acute phase as it may aggravate symptoms and the evolution of hepatitis. Corticosteroids are not indicated.
    • Stop or reduce alcohol consumption.

    Treatment of chronic active hepatitis B 

    The goal of treatment is to reduce the risk of cirrhosis and HCC. 

    • Patients with HIV co-infection 
      Lifelong antiretroviral therapy of HIV that includes tenofovir. Do not administer tenofovir monotherapy or tenofovir dual therapy with lamivudine or emtricitabine (risk of developing HIV drug resistance). 
    • Patients without HIV co-infection 
      Treatment is indicated in the event of cirrhosis or advanced hepatic fibrosis (APRI score > 1.5 or Fibroscan F3-F4 > 10 kPa); HBsAg positive with persistently elevated ALT or AST > 2 times the normal values in 2 samples taken 3 or 6 months apart; or persistently elevated ALT or AST with a high viral load (> 20 000 IU/ml).
      tenofovir PO (300 mg tab, equivalent to 245 mg of tenofovir disoproxil), lifelong therapy:
      Children ≥ 12 years and adults, including pregnant women: one tablet once daily taken with a meal

    Treatment of chronic hepatitis C [1] Citation 1. World Health Organization. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. July 2018.
    http://apps.who.int/iris/bitstream/handle/10665/273174/9789241550345-eng.pdf?ua=1 [Accessed 21 December 2018]

    Genotypes 1, 2, 3, 4, 5, 6 without cirrhosis
    or with compensated cirrhosis

    sofosbuvir/velpatasvir PO (400 mg SOF/100 mg VEL tablet)
    1 tablet once daily for 12 weeks

    Genotypes 1, 2, 4, 5, 6 without cirrhosis
    or with compensated cirrhosis
    Genotype 3 without cirrhosis

    sofosbuvir/daclatasvir PO (400 mg SOF/60 mg DCV tablet) 
    1 tablet once daily for 12 weeks

    Genotype 3 with compensated cirrhosis

    sofosbuvir/daclatasvir PO (400 mg SOF/60 mg DCV tablet)
    1 tablet once daily for 24 weeks

     

    In case of decompensated cirrhosis (presence of ascites or jaundice or mental confusion or signs of gastrointestinal haemorrhage): same treatment but for 24 weeks.

     

    Treatment is contra-indicated during pregnancy and breastfeeding.
    For women of childbearing age: provide a contraceptive; do not start treatment in women who do not want contraception.

    Vaccination

    • Routine vaccination of neonates and infants [2] Citation 2. Weekly epidemiological record/Relevé épidémiologique hebdomadaire 7 JULY 2017, 92th YEAR / 7 JUILLET 2017, 92e ANNÉE No 27, 2017, 92, 369–392 
      http://apps.who.int/iris/bitstream/handle/10665/255841/WER9227.pdf?sequence=1 [Accessed 22 November 2018]
       (according to national vaccination schedule): 
      • 3 dose schedule: one dose as soon as possible after birth, preferably within the first 24 hours of life, then one dose at 6 weeks and one dose at 14 weeks a Citation a. At birth, only the monovalent hepatitis B vaccine can be used.
        For the following doses, a monovalent or tetravalent (diphtheria, tetanus, pertussis, hepatitis B) or pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae) vaccine can be used, depending on national recommendations.
        If an infant was not administered the birth dose, this dose can be administered at anytime during the first contact with health-care providers, up to the time of the next dose of the primary schedule.
      • 4 dose schedule: one dose as soon as possible after birth, preferably within the first 24 hours of life, then one dose at 6 weeks, one dose at 10 weeks and one dose at 14 weeks a Citation a. At birth, only the monovalent hepatitis B vaccine can be used.
        For the following doses, a monovalent or tetravalent (diphtheria, tetanus, pertussis, hepatitis B) or pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae) vaccine can be used, depending on national recommendations.
        If an infant was not administered the birth dose, this dose can be administered at anytime during the first contact with health-care providers, up to the time of the next dose of the primary schedule.

     

    • Catch-up vaccination (unvaccinated individuals):
      3 dose schedule (0-1-6): 2 doses 4 weeks apart, then a third dose 6 months after the first dose

    ​​​​​​​

    • Post-exposure prophylaxis:
      One dose on D0, one dose on D7 and one dose between D21 and D30 then a booster dose 12 months after the first dose​​​​​​​

     

    Footnotes
    • (a) At birth, only the monovalent hepatitis B vaccine can be used.
      For the following doses, a monovalent or tetravalent (diphtheria, tetanus, pertussis, hepatitis B) or pentavalent (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae) vaccine can be used, depending on national recommendations.
      If an infant was not administered the birth dose, this dose can be administered at anytime during the first contact with health-care providers, up to the time of the next dose of the primary schedule.
    • (a) Vertical transmission: transmission of the virus from the mother to the child during pregnancy, at the time of delivery, or during the first 28 days after birth.
    References