CHAPTER 4 HEPATITIS E---Hepatitis A,B,C,D, and E.

 

Hepatitis E is caused by a positive-stranded RNA virus and is the most common cause of acute viral hepatitis world-wide. An estimated 20 million infections occur annually with approximately 3.3 million acute HEV cases, resulting in about 56,600 deaths per year (Lozano et al. 2012; Rein et al. 2012).  Four genotypes of HEV are endemic in different regions in the world.  (HEV-1 and HEV-2) infect humans only or both humans and animal species.

In developed countries the virus is a zoonosis—HEV3 and HEV4, mainly transmitted to humans through consumption of contaminated, not-properly-cooked pork or game meat or other meat products, but also through shellfish or contaminated vegetables.  In developing countries the fecal-oral route predominates (HEV-1).

Over the last 10 years, human hepatitis E cases have been increasingly reported in Europe where genotype 3 (HEV-3) is common and mostly responsible for human hepatitis E virus infections. The main reservoir of HEV in Europe are pigs and wild boar. The majority of the infections are asymptomatic or mild. In acute cases the disease is a self-limiting hepatitis affecting mostly male adults above 60 years of age; on rare occasions the infection can result in a severe, fulminant hepatitis with acute liver failure.

Immunosuppressed people e.g. organ transplant recipients under immunosuppressive therapy, are at risk of developing chronic hepatitis E infection. Recently, extrahepatic manifestations have also been described in patients with acute and chronic HEV-3 infection causing a number of significant neurologic problems.. HEV-7 has been recently detected in a dromedary camels and transmitted to an immunosuppressed patient in the Middle East.  

HEV infection in humans is mostly asymptomatic.  The majority of cases do not develop any symptoms but seroconvert. The incubation period is estimated to be between two and six weeks. In symptomatic individuals the infection can cause fatigue, asthenia, nausea, fever and jaundice. Other signs can be elevated liver enzyme levels and abnormal liver function tests, abdominal pain and hepatosplenomegaly. Most people with an acute infection recover completely within one to five weeks. Patients with pre-existing chronic liver disease are at risk of severe disease progression with liver failure

In December 2011, the first HEV recombinant subunit vaccine (Hecolin®) was registered in China for the prevention of HEV infection and HEV-related diseases in humans. So far, it has not been licensed and approved in any other country.

Although randomized controlled trials have shown a high efficiency and very low number of serious adverse events following hepatitis E vaccination, it is not recommended by WHO for routine use in children aged under 16 years, pregnant women, people with chronic liver disease, people on organ transplant waiting lists, and travelers.  The current WHO position concerning routine vaccination programs should not preclude the use of the vaccine in specific situations such as outbreaks where the risk of hepatitis E or of its complications or mortality is particularly high.

https://www.ecdc.europa.eu/en/hepatitis-e/facts

https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/hepatitis-e-vaccines

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890447/#:~:text=While%20HEV%20genotypes%201%20and,mainly%20through%20fecal%2Doral%20transmission.

The recombinant hepatitis E vaccine (Hecolin), also designated HEV 239, encompasses amino acids 368-606 of the HEV open reading frame 2 (ORF2) capsid protein from HEV genotype 1 and is expressed as a non-fusion protein in Escherichia coli. The purified HEV 239 assembles as homodimers resulting in virus-like particles. The vaccine is manufactured by Xiamen Innovax Biotech, Xiamen China. It was approved by the Chinese Food and Drug Administration in 2011 and has been available in China but not elsewhere in the world since October 2012.

https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/hepatitis-e-vaccines

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