A new Swiss study is a useful reminder that we are not counting a pork-borne virus that is almost certainly circulating here.
On October 26, the journal IJID One Health published the first epidemiological investigation of a nationwide hepatitis E outbreak in Switzerland. It is worth reading, not because Switzerland is exotic, but because the Swiss did something we do not do. They counted.
What the Swiss found
Between January and early May 2021, Swiss health officials watched hepatitis E notifications more than double. Twenty hepatitis E–positive blood donations turned up in February and again in March, more than twice the previous monthly record. Combining infected blood donors with symptomatic patients, 105 cases were reported to the Federal Office of Public Health through May 4 — a projected annual rate of 1.19 per 100,000, against an incidence below 0.2 in prior years.
The investigators ran a nationwide case-control study: questionnaires to all 105 cases and 370 matched controls, with an 85 percent response rate among cases. That is a response rate American investigators can only dream about. And it still did not identify a food.
The questionnaires pointed weakly at producer-cooked pork products — lyonnaise, mortadella, cervelat, pâté containing pork. The association was significant on univariable analysis and faded in the multivariable models, with wide confidence intervals. The classic suspects — blood sausage, liver sausage, raw game — were no more common among cases than controls.
The sequencing did the real work. Of 59 samples successfully subtyped, 52 were subtype 3h3 — a strain reported only in Switzerland, found there in people, in pigs, in wild boars and in pork products. Two tight clusters of identical sequences accounted for a large share of the cases. The authors concluded that no specific food was identified, but that the molecular evidence supports a local, zoonotic origin in the Swiss swine herd.
One detail should stop anyone who works on traceback. A blood donor sequence from August 2022 fell into the 2021 cluster, and was linked to a frozen product stored from the year before. Hepatitis E has an incubation period of two to six weeks, infects most people without symptoms, and hides in the freezer. Good luck with a food history.
Two of the Swiss cases died. One relative confirmed the cause of death as neurological complications of the infection. A third of responding cases were hospitalized.
The American history, briefly
For most of my career, the official American line on hepatitis E was that it is a travel disease — a problem of contaminated water in places with poor sanitation. CDC still describes it as uncommon here, with most cases in people who have recently traveled.
That line started coming apart in 1997. That year, Dr. Xiang-Jin Meng and colleagues at NIH and Iowa State identified a novel virus in pigs on an Illinois farm, closely related to human hepatitis E virus, and reported that most swine over three months of age in Midwestern herds were seropositive. The same year, Kwo and colleagues described a hepatitis E case in an Indiana man who had not left the country. The virus from the American patients turned out to be a near-match to the American pig virus. That is the whole story in a sentence: our pigs have it, and so do some of our patients.
It got less comfortable from there. In 2007, Dr. Meng’s group bought 127 packages of commercial pig liver off U.S. grocery store shelves. Fourteen were positive for hepatitis E RNA, all genotype 3, and pigs inoculated with the liver homogenates became infected — the virus in retail pork liver was alive. A follow-up study found that stir-frying or boiling inactivated it, but that holding it at 56°C for an hour did not.
In 2020, the same laboratory tested 5,033 serum samples from market-weight pigs at 25 slaughterhouses in ten states, collected 2017 through 2019. About 6.3 percent were viremic at slaughter — the entry point to the food chain — and roughly 40 percent had antibodies. Plant-to-plant rates ran from zero to 17 percent.
On the human side, NHANES III found antibodies to hepatitis E virus in 21 percent of Americans sampled between 1988 and 1994. Later surveys using different assays put it at about 6 percent in 2009–2010. Argue about the assays all you like; nobody is arguing the number is zero. Exposure here is common and recognized illness is rare — which is exactly what you would expect from a virus that is mostly silent and that nobody is testing for.
CDC’s own laboratory study of samples referred for testing from 2005 to 2012 found hepatitis E in 26 of 154 people, and 15 of them had not traveled anywhere. The non-travelers were older and more likely to be transplant recipients — the patients who get chronic infection and cirrhosis.
Four things that are missing
Here is what the United States does not have, and Switzerland does.
No national surveillance. Hepatitis E is not nationally notifiable. A handful of states require reporting — California logged 43 cases in 2021 — but there is no standard national case definition. CDC’s own travel guidance says plainly that because systematic surveillance is lacking, the incidence and characteristics of hepatitis E in this country are unknown. You cannot investigate an outbreak you are not counting.
No approved test. Serologic and nucleic acid tests for hepatitis E are commercially available, but none is FDA-approved for use here. A physician confronting unexplained liver injury in a patient who has not traveled has to think of hepatitis E, send specimens to CDC or use an unapproved assay, and most do neither.
No blood screening. Switzerland has screened every whole blood and apheresis donation for hepatitis E RNA since October 2018. Ireland and the United Kingdom screen; the Netherlands started in 2017; parts of Japan have screened for years. We do not, and there is no FDA-licensed donor screening test to do it with. American Red Cross researchers found hepatitis E RNA in about 1 in 9,500 donations and antibodies in 7.7 percent, and concluded the question of whether to screen remained open. The Swiss paper makes a point we have missed for a decade: their donor screening program is what detected the outbreak. The blood supply turned out to be the surveillance system.
No vaccine. A recombinant hepatitis E vaccine has been licensed in China since 2012. Nothing is approved here.
What we should do
I am not asking for a crisis. I am asking for the ordinary machinery we apply to every other foodborne pathogen.
First, make hepatitis E nationally notifiable with a standard CSTE case definition. Switzerland made it notifiable in 2018 and had an outbreak signal three years later. We have had neither for thirty years.
Second, get an FDA-cleared diagnostic. Clinicians cannot report what they cannot test for, and nobody will test for a disease the textbook says Americans do not get.
Third, build the baseline in pork. USDA already knows how to run national microbiological baselines. Add hepatitis E to a market hog and retail pork baseline — including liver and offal, which carry the highest loads — and publish it. The industry should want this number before someone else generates it in litigation. Pork Checkoff funded the slaughterhouse study; that was the right instinct, and it should be finished rather than filed.
Fourth, fix the cooking advice for liver. FSIS tells consumers to cook whole pork cuts to 145°F with a three-minute rest, and organ and variety meats to 160°F. The inactivation work the Swiss investigators cite is less forgiving: liver at 71°C — 160°F — for five minutes, and liver pâté at that temperature for twenty. For ready-to-eat pork liver products, the gap between a label instruction and a validated viral kill step is a gap somebody will fall through.
Fifth, resolve the blood question. FDA’s Blood Products Advisory Committee voted unanimously in 2012 that the transfusion risk needed to be characterized. Fourteen years later it still has not been, while most of Western Europe moved on without us. Transplant recipients and immunosuppressed patients — the people who get chronic hepatitis E — are the ones receiving the most blood.
Why industry should care first
Every pathogen I have litigated for thirty years followed the same arc. First the industry says the organism is not in the product. Then the science says it is. Then someone gets sick, a lawyer finds the science, and the rules get written in a courtroom instead of a rulemaking. E. coli O157:H7 in hamburger went that way. Listeria in deli meat went that way.
Hepatitis E is sitting at the start of that arc. The peer-reviewed literature already says the virus is in American market hogs at slaughter, in American retail pork liver, and alive. A validated kill step, honest labeling on liver products, and a surveillance system that can tell us whether anyone is getting sick are cheap compared with what the alternative costs — and far cheaper than finding out, as the Swiss did, by sequencing blood donations after two people have died.
We are not counting. That is the whole problem. The Swiss counted, and even with an 85 percent response rate they could not name the food. We would not even know to ask.
Recent Comments