Defective, dependent on biological help from the HBV

Pathogenic, causes severe liver diseases

Virion: 36 nm particle, enveloped in the HBsAg

Genome: 1.7 Kb RNA, 8 genotypes , subtypes (Karimzadeh H ,2019)

1980Hepatitis D (delta) Virus

• HDV transmitted by two modalities :coinfection with HBV or superinfection on the HBsAg

EPIDEMIOLOGY OF HDV

Superinfection

Coinfection

HDV Chimps Experiments

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

HDAg

HEPATITIS

CHIMP n° 39

0

1

2

3

4

5

6

7

0 8 9 10 11 12 13 14 15 16 17 18

HbsAg

HDAg positive cells

CHIMP n° 32HEPATITIS

(Weeks)

HDAg

L.M.Undil

Infectivity: 10-6

(1:1.000.000)serum dilutions

Infectivity: 10-

11

(: ( 1:100.000.000.000)serum dilutions

Virologic and sierologic markers in coinfection (HDV/HBV) and superinfection (HBsAg/HDV)

= HBsAg

= HDV

HDV-RNA - - + + - -Weeks

Virologic and sierologic markers in coinfection (HDV/HBV) and superinfection (HBsAg/HDV)

= HBsAg

= HDV

HDV-RNA - - + + - -Weeks

HDV-RNA - + + + + +Years

Virologic and sierologic markers in coinfection (HDV/HBV) and superinfection (HBsAg/HDV)

= HBsAg

= HDV

HDV-RNA - - + + - -Weeks

HDV-RNA - + + + + +Years

• HDV transmitted by two modalities :coinfection with HBV or superinfection on the HBsAg

• chronic carriers of the HBsAg are the only reliable source of information on the prevalence of the HDV but not all chronic carriers of HBsAg are equally suitable for epidemiologic screening

EPIDEMIOLOGY OF HDV

Chronic HBV,natural history= HBV

= HDV

Inactive (Healthy Carrier)Asymptomatic HBsAg carriers

Clinical impact of HDV on HBV= HDV

Inactive (Healthy Carrier)

s

Asymptomatic HBsAg carriers

HDV MORE PATHOGENIC THAN HBV .

Chronic hepatitis D drives to cirrhosis within 5 to 10 years in 70% of cases ,with a risk three times higher in HBsAg/HDV than in HBV

Anti-HD increases significantly along the severity of the chronic HBsAg/HDV hepatitis .The antibody is lowest in asymptomatic patients/minor disease ,highest in advanced cirrhotic disease

Prevalence of anti-HD in different clinicalcategories of HBsAg carriers

Italy1

1983

Iran2013/2014

Uzbekistan4

2018

Blood donors 5% 2%2 8%

Chronic hep. 18% 16,3%3

Cirrhosis 51% 65,9%3 >80%

1 Smedile A, 1983; 2 Keshvari M 2014; 3 Bakshipour A, 2013: 4 Musabaev E ,2018

HDV superinfection converts healthy HBsAg carriers into HBsAg

carriers with chronic hepatitis D

the epidemiology of HDV (anti-HD) is best evaluated in HBsAg

carriers with advanced liver disease,

not in “healthy” or asymptomatic HBsAg carriers

(at bloodbanks, pregnancy clinics , general populations ,

general HBsAg populations,professional screening ..)

INAPPROPRIATE TESTING

HBV PREVALENCE IN AFRICAJefferies M,2018

DISTRIBUTION OF HDV GENOTYPES IN SUB-SHARAN AFRICA

47%

28%

43%

13%52%

19%

20%

33%

2,1%

2,5%

43,6%

0

0

0

5%

4,3%

2,7%

3%

4%

4%

General population of Cameroon and Gabon

Patients with chronic liver disease

Patients collected at blood banks, pregnancy clinics, in the general population, in outpatients clinics

Prevalence rate of antibody to HDV by six commercial assays, reported in HBsAg carriers in Africa from 2009

8%

HDV prevalence in the HBsAg population in Africa

North Africa:5,1% = 7.000.000 individuals4.000.000 in Egypt alone--- Genotype 1 In liver disease patients 3 x 4 times higher than in the general population

Daw MA, 2018

Sub-Saharan Africa :8,39%=7.000.000 peoplehighest in Central Africa, lowest in east and southern

Stockdale A , 2018

HDV prevalence in the HBsAg population in Sub Saharan Africa

• Epidemiological scenario widely heterogeneous ,evenacross similar populations from close geographical areas

• Prevalence highest in Central Africa, lowest in East and South Asia

• Increased seropositivity among HBsAg carriers with liverdisease.

HDV IN AFRICA –CONCLUSIONS

• Important cause of liver disease but data are limited , sparse and heterogeneous

• Need for systematically collected data, particularly for east and south Africa

• Genotypes 5-8 unique to Africa : clinicalcharacterization needed.

HOW TO ASSESS THE MEDICAL IMPACT OF HDV

• Anti-HD is by itself a diagnostic marker of pathogenic HDV infection. Confirmatory HDV RNA is out of reach for most laboratories in developing Africa ; however, in field diagnostics the further testing for HDV-RNA appears superfluous because in liver disease anti-HD correlates with HDV-RNA in serum with an almost 100 % consistency.

• Surveys for anti-HD are most reliable on a denominator of HBsAgcirrhosis and in multiple clinical centers throughout a country.

• Convenience screening in asymptomatic HBsAg carriers at blood banks , in pregnancy clinics , in the general population ,etcunderestimates the medical impact of HDV