Hepatitis in children, cause still unknown (but some hypotheses are beginning to be ruled out)

Hepatitis in children

The most honest answer that the scientific community can give about hepatitis in children at the moment is simply not known. As to who or what is actually responsible for the anomalous number of serious hepatitis in children that were recorded in many European countries during the month of April, there remains a gigantic question mark. Certainly there is no lack of hypotheses and conjectures, indeed with the passing of the days we have witnessed an overlapping of suppositions, proposals, theses and much more.

For now, however, all the proposals have one element in common : "None of the theories formulated on the origin (of pediatric hepatitis, ed) has had a confirmation through scientific evidence", wrote the Higher Institute of Health (ISS) in taking stock of the situation on Tuesday 26 April. In short, on the front of the answers we are point and head, if not for the fact that some theories have been excluded due to scientific implausibility. But let's go in order.

Vaccines and adenoviruses, hypotheses that do not hold In the first days after the international alarm spread - starting from the United Kingdom - one of the hypotheses that immediately found a foothold was that of a phantom correlation between the Covid-19 vaccination and the development of hepatitis. "At the moment there are no elements that suggest a connection between the disease and vaccination", wrote the ISS, "and indeed various considerations would lead to exclude it". The first element among many is the fact that not all the children affected by the disease were vaccinated, and that indeed in the vast majority of cases the disease concerned children without vaccination coverage.

Even in the specific case of viral vector vaccines (i.e. the AstraZeneca and Janssen formulations), scientists exclude any possible correlation with hepatitis, first of all because the adenovirus contained in vaccines has been modified at the genetic level and not it can replicate within the human body, so much so that the hypothesis that these vaccines are the origin of the problem is considered "implausible". And even the idea of ​​a genetic remixing between the viral vector of vaccines and other adenoviruses "is not possible", wrote the Higher Institute of Health. More generally, finally, the hypothesis that it is an adenovirus of any kind to cause hepatitis in children is considered in itself not impossible but at least "unlikely" (despite the fact that in several cases an adenovirus has been identified in patients), given that the associations between viruses of this type and liver diseases are not known in the scientific literature.

Sars-Cov-2, transmissibility and statistical anomaly: where to look As anticipated, at the moment the only scientific news is that there is no news on the origin of hepatitis. This does not mean, however, that scientists are without ideas on what to look for. A first attempt was to understand if there were common exposures to toxic substances contained in foods, drinks or drugs, or with which one could have come into contact through specific personal or family habits as well as through travel to specific places: given the enormous variability of the recorded cases and the great geographical distribution, at the moment this road seems to be a dead end.

A further road taken by researchers, which in a certain sense is the premise for all the others, is to establish whether actually there is an excess of hepatitis of unknown origin compared to the norm of what happens every year. In the case of the United Kingdom, where registered cases have already exceeded one hundred, it is clear that the number is clearly in excess of the expected value. But in several other countries, where the number of cases is at least an order of magnitude lower (for example 12 in Israel, 9 in Alabama and 4 ascertained in Italy - out of a dozen recent reports and 17 overall since January, including adults) , at the moment it seems to be still to be understood whether we are at the beginning of a more extensive phenomenon or if instead the numbers of hepatitis with unknown cause are all in line with the standard values, or at most corresponding to a small statistical anomaly but which, however, is part of the fluctuations that can occur from one year to the next. Unfortunately, however, at least for the United Kingdom, it is now clear that the problem is real, given that the country has currently registered the absolute majority of the 190 cases that have emerged so far.

To date, the main element on which the scientists seem ready to pronounce on the hypothesis that the infection is somehow transmissible: "On the basis of the epidemiological and clinical picture, an infectious etiology seems to be more probable", they write from the ISS. As to which specific pathogen is responsible, however, the darkness remains. The investigations excluded for all recorded cases the hepatitis viruses of types A, B, C, D and E, and the correlation with Sars-Cov-2 (in the hypothesis that these hepatitis could be a side effect of Covid -19) seems rather weak. At the moment, the statistics are still too modest to say, but in the only group of small patients taken into consideration (consisting of 13 Scottish children) about half never appears to have come into contact with Sars-Cov-2, about a quarter had contracted Covid-19 in the previous months and 3 out of 13 tested positive during the acute phase of hepatitis.

Whether it is Sars-Cov-2 or not, the hypothesis of transmissibility still seems reasonable : of the aforementioned 13 pediatric cases identified throughout Scotland, epidemiological links have been found in at least two (pairs of) cases which could correspond to as many links in the chain of transmission.

What do we do then? In this scenario of uncertainty, there are several lines of action. First of all, in the coming weeks it will be important to continue to monitor the situation, not only for the counting of the cases itself, but above all to strengthen the statistical basis and therefore to be able to draw more solid conclusions than the few data available at the moment. In parallel, a sequencing effort is already underway for the Sars-Cov-2 viruses identified in some of the children, to understand if there may be any variant of the virus associated with hepatitis, and even more generally to establish whether there really is a connection between Sars-Cov-2 and these cases (or if instead it is simply a confounding effect, given the wide circulation of the virus in Europe and beyond).

Finally, in Italy we have been active since 1985 the Seieva network (Integrated epidemiological system of acute viral hepatitis) and also the Italian epidemic intelligence network - set up last October to respond to emerging diseases - was put on alert as early as 5 April. In practice, however, no correlations have been identified even with individual characteristics at the level of predisposition or fragility, except for the fact that the age group up to 7 seems to be the most affected. According to the scientists, it is urgent to definitively establish whether or not it is a pathology that can be transmitted from person to person, so as to eventually activate the containment procedures.