HEV Virus

 
The hepatitis E Virus is single-stranded, RNA virus, with a genome of approx. 7.2 KBp possessing positive polarity. 

 

Hepatitis E (HEV)

Unmet Medical Need

20 millions infections annually

3,4 millions symptomatic cases / annum
(chronic & acute)

70.000 deaths

3.000 stillbirths / annum

up to 25% mortality rate in pregnant women, and poor fetal outcomes

 

Backround

Hepatitis E was not recognized as a significant human disease until 1980, when specific tests for antibody against hepatitis A were first applied to the study of epidemic waterborne hepatitis in India.

The results showed that the epidemics were not due to hepatitis A; indeed, very few epidemics of waterborne disease in developing countries of Asia and Africa have been linked to hepatitis A.

The first experimental evidence for the existence of an additional waterborne hepatitis agent was reported in 1983. [Balayan MS, et al.]

 

Hepatitis E - The Disease

Hepatitis E virus is a leading cause of acute viral hepatitis in the developing world; the clinical features are similar to those caused by other hepatic viruses, hepatitis B and hepatitis C virus. The WHO is estimating an annual infection burden with HEV 1 and 2 with around 20 million cases, where 3.4 million symptomatic cases giving rise to 70,000 deaths and 3,000 still births per year[1].
However, although the WHO and many others are still referring to above numbers even in 2016, they arise from a global survey on the global distribution of HEV genotypes 1 & 2 in the year 2005, published only in 2012[2]; therefore this does not take into account the global annual infections of genotype 3 & 4, which are now known to be of zoonotic nature.
 
No recent updated global data on HEV infection globally are available, however, due to the rapidly rising figures in countries where developed health infrastructure enables accurate and specific diagnosis of disease, a much higher infection- and death rate thus must be assumed.
 
Today, HEV has reached worldwide distribution, as illustrated by the US Centre for Disease Control and Prevention (see Figure 1: Global distribution of hepatitis E in 2012). Besides highly endemic regions in Asia and Africa, with an infection rate well above ≥ 25% of sporadic non-A non-B hepatitis, virtually all other regions worldwide are regarded as endemic (infection rate ≤ 25% of sporadic non-A non-B hepatitis).
 
Figure 1: Global distribution of hepatitis E in 2012[3]
HEV is usually regarded as a self-limiting disease, has an incubation period ranging from 30-60 days, and in most cases is symptomatically indistinguishable from infection with hepatitis A (HAV). Where an HEV infection in immunocompetent people in most cases is self-limiting[4], with a mild to moderate disease with a mortality rate of 0.4-4%, this contrasts starkly with infection during pregnancy, where approx. 25% of patients suffer fatal disease, typically within their third trimester[5].
 
Further high-risk groups include post-transplant patients, immunocompromised patients (e.g. HIV infection) and liver disease patients. Liver disease, specifically non-alcoholic steatosis, remains one of the fastest growing disorders in developed countries, and is most probably linked to dietary factors and lifestyles, and is poised to increase further over the coming decades, highlighting the requirement of prophylaxis and treatment of a viral disease which results in exacerbated and worsening outcomes in those patients.
All of these risk groups of patients show a history of chronicity developing from infection, which leads to unfavourable outcomes and highlights the absence of specific therapeutics for treatment.
 
Although HEV infection is commonly through the faecal-oral route through consumption of undercooked meats such as pork and venison, much of the infection burden is attributed to poor hygiene and underdeveloped infrastructure such as water sanitation in developing countries.  HEV infection has become a global major threat, and the burden of disease, incidence of mortality and morbidity, and importance of the public health challenge posed by HEV infection is now recognised in the developed world, including Europe and USA.

World Hepatitis Alliance - Elimination of viral Hepatitis

Is there a cure or preventation available?

  Vaccine Therapeutic
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis E

&

China & World

 

Viral hepatitis landscape – a comparison

 

HAV

HBV

HCV

HEV

 

Classification

Picornavirus

Hepadnavirus

Flavivirus

Hepevirus

 

Genome

ssRNA

dsDNA

ssRNA

ssRNA

 

Infections

1,4 mio1

240 mio

175 mio

20 mio1

 

globally

globally

 

Deaths1

<110k2

750 k

350-500 k

70.000

 

Chronic

No

Yes

Yes

No/Yes

 

Directly acting antivirals

No

Off-label Rx with nucleosides


No specific treatment

Yes (Ribavirin/Interferon/Sofosbuvir3)

Off-label Rx with Ribavirin/IFN

 
 

Vaccine

Yes

Yes

No

No(4)

 

Table 1: Comparison of different hepatitis viruses

(1 annual cases; 2 in 2010; 3= Sovaldi – €65k for treatment/patient in Austria; 4 apart from Hecolin® licensed in China)

[1] WHO (2015); Hepatitis E vaccine: WHO position paper, May 2015, 90(18), 185–200
[2] Rein, D. B., et al.; (2012); The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology, 55(4), 988–997
[3] Source: US Centre for Disease Control and Prevention (CDC); http://wwwnc.cdc.gov/travel/pdf/yellowbook-2012-map-03-06-distribution-hepatitis-e-infection.pdf
[4] Wedemeyer, H, et al.; (2012); Pathogenesis and treatment of hepatitis E virus infection. Gastroenterology; 142:1388 – 97
[5] Kumar, S., et al.; (2013); Hepatitis E virus: the current scenario. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases, 17(4), e228–33