Viral hepatitis


– 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)

Vertical1
Close contact with infected person
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

Exposure to blood (transfusion; material contaminated with blood)
Sexual
Possibly vertical

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% 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 determination to decide treatment of chronic active hepatitis B.
– APRI score (evaluation of liver fibrosis in chronic hepatitis): [(patient's ASAT level/normal ASAT level) x 100]/platelet count (109 platelets/litre). An APRI score > 1 indicates probable fibrosis.

Other investigations

– Elastrography (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. 

– Patients without HIV co-infection 
Treatment is indicated in the event of cirrhosis or advanced hepatic fibrosis (APRI score or Fibroscan) or hepatic cytolysis (persistently elevated ALT > 2 times the normal values in 2 to 3 samples taken 3 months apart).
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 C1

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 PO: 400 mg once daily for 12 weeks
+
daclatasvir PO: 60 mg once daily for 12 weeks

Genotype 3 with compensated cirrhosis

sofosbuvir PO: 400 mg once daily for 24 weeks
+
daclatasvir PO: 60 mg once daily for 24 weeks

Genotypes 1 and 4 without cirrhosis
or with compensated cirrhosis
sofosbuvir/ledipasvir PO (400 mg SOF/90 mg LED tablet)
1 tablet once daily for 12 weeks

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

Vaccination

 Routine vaccination of neonates and infants2 (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
2
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 weeks2

– 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
Ref Notes
1 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.
2 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 b ]


References

  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]

  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]