#17 – Hepatitis E: Why Undercooked Pork Can Be Risky

00:00:06: Again, a lot of these virus infections happen in Asia but also in Africa.

00:00:10: But that doesn't mean the virus is not present in North America or Europe.

00:00:15: There's for example recent outbreak from twenty-twenty four where a cluster is described in Finland.

00:00:46: Hello and welcome to this episode of VAROLOGICAL.

00:00:49: This was recorded on June first, Twenty-twenties six in New York And I thought after all this excitement about Anders virus and Ebola virus in the last few weeks, i'm going to record a relatively boring episode.

00:01:04: About a virus that is not very well known but can be problematic... ...and it's actually relatively prevalent globally.

00:01:14: So today we're gonna talk about the Hepatitis E Virus.

00:01:18: There are different hepatitis viruses.

00:01:20: We talked some of them already.

00:01:22: there's hepatitis A, hepatitis B which is associated with hepatitis D and then there's Hepatitis C. And hepatitis E the last one that was discovered in.

00:01:32: that's why it's e. so this virus belongs to their hepiviridae.

00:01:39: I think initially was classified as a Calici virus but then turned out genome is closer to rubella distantly related to rubella virus.

00:01:56: So we're going to talk about hepatitis E-virus, but there is actually a bunch of similar related viruses in this family.

00:02:04: There's viruses that Hepatitis E like viruses that infect fish Bats rodents birds so they really punch off them.

00:02:13: What type of virus?

00:02:14: Is this?

00:02:14: the genome is positively polarized or plus sense.

00:02:19: It's a single stranded RNA genome and it has approximately seven thousand two hundred base pairs.

00:02:26: The genome codes for three open reading frames, so basically protein coding regions are called Open Reading Frames.

00:02:35: we have Open Reading Frame One which encodes the replication machinery So that's basically a polymerase.

00:02:42: in then number of other proteins.

00:02:44: We have the Open Reading frame Two Which encodes a capsid.

00:02:48: that capsid has three domains.

00:02:50: One is the shell and then we have a protruding domain one, and a protruting domain two but it's basically just one capsid protein.

00:02:58: And then we open reading frame Three which encodes for small proteins in addition to Open Reading Frame One and Open Reading Frames Two.

00:03:07: The virus is super simple structure.

00:03:10: The regular virus version is about thirty-two nanometers in diameter.

00:03:16: It has an RNA genome and then it has a capsid.

00:03:20: And that's it, there is nothing else!

00:03:23: That's actually the version you find in Thickly Matter for example basically what we found on the GI tract.

00:03:31: But the virus also circulates in blood during infection.

00:03:35: There does something very weird.

00:03:37: It acquires quasi-envelopes so a lipid envelope.

00:03:42: Many viruses have lipid envelopes but those are proper.

00:03:47: In this case, it's not a proper lipid envelope.

00:03:51: So cells also produce little lipid particles that are called exosomes.

00:03:56: and basically these virus, these hepatitis E-virus can wrap itself in basically an exosome And then its'a bit bigger.

00:04:05: It is about forty nanometers.

00:04:07: so the viral proteins aren't in their lipid envelopes They're covered by it.

00:04:12: Its hiding on inside prevent recognition by antibodies, for example.

00:04:19: And so it uses this mechanism to escape the immune response at a certain degree.

00:04:25: So again in thesis we have version without lipid envelope and then in blood circulation We have version with quasi-envelope.

00:04:37: Interestingly, we don't know too much about the life cycle of this virus or its receptor usage.

00:04:43: So there's a lot of unknown questions about hepatitis E-virus.

00:04:47: so there are lots of unknowns on Hepatitis E virus.

00:04:51: What you do now is that it relatively stable.

00:04:54: This non-enveloped version can basically survive relatively high temperatures compared to other viruses.

00:05:03: It needs more than seventy degrees Celsius for five minutes in order to get inactivated.

00:05:11: The other interesting aspect here is that this virus is both circulating humans, but it's also so knowledge and we'll get through how that's possible In terms of getting infected.

00:05:23: typically the infections are... the infections happen through the fecal oral route So basically via the GI tract often also via contaminated water and you can acquire the infection from eating meat, from infected animals usually meat that hasn't been cooked long enough.

00:05:45: Once your infected.

00:05:46: the inoculation time is around forty days on average but it can be as short two weeks or ten weeks.

00:05:54: most of these infections are actually asymptomatic.

00:05:58: if people become symptomatic its usually a very acute but self-limiting disease, meaning that there's not really treatment needed in most cases.

00:06:07: and you know the disease basically disappears within a relatively short period of time.

00:06:14: But if people become symptomatic it is characterized by fatigue, by nausea elevated liver enzymes.

00:06:20: so the liver is getting attacked by the virus and damaged.

00:06:25: And If their damage is extensive enough People can also get jaundice.

00:06:31: The recovery is usually relatively fast and first you see viral clearance from the blood.

00:06:38: And it takes quite some time for the virus to disappear from stool, and the persistence there in the GI tract actually helps the virus spread easier.

00:06:50: so For regular healthy adults this doesn't seem to be a big problem.

00:06:56: But the virus infection can be very problematic on pregnant women.

00:07:00: they can progress to fulminant level failure.

00:07:03: And if that happens, the case fidelity rate or mortality rate is twenty-to thirty percent.

00:07:09: so thats substantial and biggest risk for this in the third trimester.

00:07:14: it's not just a model affected often leads to preterm deliveries.

00:07:20: still birth problem here is that virus seems to replicate into placenta might be the mechanism behind damage to the fetus.

00:07:33: Another group that is often affected by hepatitis E in terms of more severe disease are solid organ transplant patients, they can get chronic liver infection and then often leads to cirrhosis.

00:07:49: Cirrhosis basically means that their liver's damaged of the liver and then it doesn't function very well anymore.

00:08:00: When you have hepatitis B and hepatitis C infections that happens too, and there they can lead to liver cancer.

00:08:07: but cirrhosis is seen with hepatitis E infection in transplant patients aswell And other organs also be involved.

00:08:17: The pancreas can be infected or inflamed.

00:08:20: You get acute pancreatitis.

00:08:24: The infection can lead to kidney damage.

00:08:27: Goyepare syndrome has been described with hepatitis E infections, so basically what that is is the immune system triggered by the infection attacks the nervous system.

00:08:38: This something thats known for a lot of infections A lot viral infections but also bacterial infections and Hepatitis E can do this too.

00:08:46: And people could get Drombocytopenia meaning they They have a low platelet count and that can lead to bleeding.

00:08:56: In severe cases, people get treated with riboburin.

00:09:00: how well it really works is not known but seems to be an effect.

00:09:06: And vaccines were also developed against hepatitis E virus.

00:09:10: I believe one of the first vaccines was developed by GSK, GlaxoSmithKline.

00:09:16: they moved into phase-one then into phase two trials.

00:09:19: actually could show in Phase Two trials the vaccine worked really well, but due to financial considerations they decided not move forward with it.

00:09:28: So there was no commercial case of getting this vaccine on market.

00:09:35: and another vaccine development by Xiamen University in China and their vaccine was actually licensed in China, that vaccine is called AGV-II-III-IX.

00:09:49: And so Chinese the only country currently where hepatitis E vaccines are available.

00:09:54: Just a little bit about technology used here by GSK but also by Xiamen University.

00:10:01: Basically what they did?

00:10:02: it to express the capsid protein recombinantly and then forms virus like particles.

00:10:08: the shell is there, so it looks like a virus particle and that can be used as vaccine.

00:10:15: And that's actually also something that has been used for hepatitis B. GSK did that in insect cells on the baccalae virus expression system That same system that was used for the Novavex SARS-CoV-II vaccine.

00:10:29: I believe Shemen University use an expression in E. coli bacteria.

00:10:34: But again, the vaccine licensed in China seems to work really well and it might be, you know a vaccine that is needed in other areas globally too.

00:10:45: We'll get to the epidemiology little bit later but I think it would useful we have this vaccine wider available.

00:10:52: so A Little Bit about history of the virus.

00:10:56: i Think there were first hints About new hepatitis virus In nineteen seventy eight when There was an outbreak in Kashmir with non-A Non B Hepatitis Virus.

00:11:08: There were hepatitis cases and there are severe cases in pregnant women.

00:11:12: So that might have been a first outbreak with Hepatitis E virus, which was detected And then in three years it was discovered.

00:11:22: the virus was discovered in Afghanistan.

00:11:24: so Afghanistan is not that far away from Kashmir.

00:11:27: It's very close but its at same region Back than.

00:11:32: this virus caused infections of Russian soldiers.

00:11:36: I believe they had consumed contaminated kefir and Russian virologist figured out that they were infected with a new virus.

00:11:45: I read he also did self-experimentation and inoculated himself, so basically swallowed contaminated feces from one of these cases and then got sick himself.

00:11:55: So yeah very heroic effort to discover and confirm virus infections And then retrospectively The virus was also shown to have caused an outbreak in nineteen fifty-five.

00:12:08: In ten thousands of people in New Delhi, so there were stored samples from that outbreak and the people went back and did a retrospective analysis.

00:12:18: In nineteen eighty nine the viral genome was sequenced And once you had the genome sequence Of many isolates You can start looking into phylogenetic relationships and phylogenetic clock analyses.

00:12:32: And now the hypothesis is that this virus emerged and started to infect humans, potentially about six thousand years ago when pigs were domesticated.

00:12:43: And pigs play a really big role with these virus infections... ...and their ideas are that current genotypes – we'll get to them in a minute – likely separated between five hundred two thousand three hundred years ago.

00:12:59: So I mentioned genotypes.

00:13:00: There are eight genotypes of hepatitis E virus that are known, the Genotype one and Genotype two are human viruses.

00:13:10: so basically they only circulate in humans And they're spread from human to human.

00:13:15: Genotype One is prevalent in Asia, Genotype Two is prevalent In Africa and Mexico.

00:13:22: At the same time The virus is zoonotic.

00:13:24: Genotypes three and Genotape four circulate mostly in swine, but also in deer and some types of rodents including the Asian house shrew.

00:13:38: Genotype three is found Europe or North America And genotype four is found Asia The virus at same time a human virus But also zoonotic depending on the genotype.

00:13:52: Then we have also genotype five & six.

00:13:54: they are associated with asian wild boar and genotype seven, eight.

00:14:00: And they're associated with camels but there also sometimes cause human cases due to consumption of camel meat.

00:14:08: I think Genotype Eight was the one that was shown do some times infect humans But it might be mistaken.

00:14:13: It may have been Genotype Seven.

00:14:17: So these viruses are relatively prevalent.

00:14:20: The estimate is about twenty million infections in humans occur every year.

00:14:26: people most at risk or four infections are males between fifteen and thirty-five years of age.

00:14:34: And there're numbers for two thousand fifteen in terms of deaths, I think for twenty fifteen.

00:14:40: the estimate was that they were forty-four thousand deaths due to hepatitis E virus globally.

00:14:46: so you know looking at many infections the virus is not very dangerous.

00:14:50: probably a lot of infections are missed because also lots of asymptomatic infection but some cases as mentioned in Bregan women, but also in people with underlying conditions.

00:15:02: This can lead to a severe infection that can also lead to hospitalizations and deaths.

00:15:08: I mentioned already that people get infected through the fecal oral route.

00:15:14: this can happen through direct contact But much more commonly this happens through contaminated water that's contaminated with sewage, and this often happens in endemic areas due to heavy rainfall.

00:15:30: Often in the monsoon season but then specifically... And these can happen both for human hepatitis e-viruses with sewages of course But also with the zoonotic hepatitis E viruses because you know feces from animals Can also end up contaminating drinking water.

00:15:47: But then another way of getting infected is, of course the consumption of undercooked meat.

00:15:52: And here specifically pork is an issue because as I mentioned earlier a lot of these virus genotypes actually circulate in swine and domesticated pigs but also wild boar that might be hunted again.

00:16:08: A lot of this virus infections happen in Asia or those in Africa But that doesn't mean, the virus is not present in North America or Europe.

00:16:17: There's for example a recent outbreak from twenty-twenty four where cluster is described in Finland with ninety two infected individuals and forty two of them were hospitalized.

00:16:29: Of course there are probably many more infected asymptomatic cases here but you know it was ninety two Infected and forty to hospitalised.

00:16:39: That doesn't seem like it's a harmless disease, right?

00:16:42: There is another way to look at infection rates and that's basically by doing serology.

00:16:47: So you can do zero-service where we measure antibodies in the population... ...and see how many people have antibodies against hepatitis E virus.

00:16:56: And if you take one of those countries with highest prevalence is South Sudan With about seventy five percent prevalence meaning that seventy five per cent of the population had this infection Other countries that are relatively high between forty and fifty percent of India, China Vietnam Central African Countries.

00:17:18: Typically in Europe the prevalence to zero prevalence.

00:17:22: That's what we call this is lower.

00:17:24: Germany found a number that indicates about seventeen percent of individuals have antibodies to hepatitis E virus.

00:17:33: for Austria where I come from it's about thirteen to fourteen percent And in the US it varies.

00:17:39: There are areas where its as low as six percent, but they can go up to twenty one percent.

00:17:45: In France for example and Europe there are regional hotspots were people have upto fifty per cent zero prevalence.

00:17:53: That probably has do with pork consumption Where you have infected pigs and then probably a lot of consumption Of raw pork products potentially something like panchetta lard, so I think lard is the french version of uncured bacon that could also lead to exposure.

00:18:16: All right what i wanted to mention more recently related virus was discovered in rats called rat hepatitis e-virus found back then.

00:18:31: since its discovery it became clear that this virus can also be zoonotic.

00:18:36: So, that's related to hepatitis E-virus but doesn't fit into the agenotapes further away... ...but is now described as a zoonic agent and infections with red Hepatitis E virus have been demonstrated in a number of countries.

00:18:54: That's all for today again compared to last few weeks with Hunter virus and Ebola virus This episode is not very spectacular, but I think it's also important to know about hepatitis E virus.

00:19:07: even though doesn't seem to be super dangerous.

00:19:10: It certainly a virus that can cause trouble specifically if you belong one of the high risk groups like pregnant women or people with underlying conditions and if your traveling in endemic areas.

00:19:25: so as always If you have any suggestions, questions or comments feel free to write an email to virological at podcastjagstatt.com And if you like this podcast You can always support us on steady.

00:19:41: Thanks for listening in and until next week Bye!

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