Hepatitis E : A newcomer to the hepatitis alphabet – Case report and review of the literature

A YEAROLD CAU CA SIAN MALE PRE SENTED TO THE travel clinic of the authors’ hos pi tal (Clin ique des mala dies tropi cales, Hôpi tal MaisonneuveRosemont, Mon tréal) in June 1993, com plain ing of’ ab domi nal pain, di ar rhea and jaun dice. He was re turn ing from a sixmonth va ca tion in Asia, hav ing spent most of his time in In dia. The pa ti ent’s symp toms started 10 days af ter his re turn. While in In dia, the pa tient was tat tooed on his thighs, and he lived in subop ti mal con di tions. He drank non bot tled wa ter, ate a va ri ety of un cooked foods and was re peat edly sub jected to po ten tially con tami nated wa ter (river wa ter) in his daily hy giene. The pa tient was a nurse, had no par ticu lar medi cal his tory, was an oc ca sional smoker and did not drink al co hol. When ques CASE RE PORT

tioned, the pa tient was am biva lent re gard ing his sex ual ori enta tion and de nied any drug use.Be fore leav ing for Asia, the pa tient went to a dif fer ent travel clinic where he re ceived all the ap pro pri ate im mu ni za tions (hu man gamma globu lins, typhoid vac cine, diphtheria-tetanus:d2T5).Dur ing his trip, the pa tient did not take any medi ca tion.He was pre vi ously im munized against hepa ti tis B due to his oc cu pa tion and had no his tory of liver dis ease.Physi cal ex ami na tion was nor mal except for jaun dice and mild right up per quad rant ten der ness.Blood tests re vealed ab nor mal liver func tions (Ta ble 1), and a mod er ate amount of bili ru bin was de tected in the uri naly sis.Ab domi nal ul tra sound was nor mal ex cept for a mod er ately thick ened gallblad der.No he pa tomegaly was seen.Se rologies for hepa ti tis A (im mu no globu lin [Ig]M an ti he pa ti tis A vi rus [HAV]), hepa ti tis B (hepa ti tis B sur face an ti gen, IgM an ti he pa titis B core an ti gen), hepa ti tis C (HCV) (anti-HCV), an ti hu man im mu no de fi ciency vi rus and IgM anticy tomega lovi rus were nega tive.Se rum was col lected in June 1993 for hepa ti tis E an ti body de tec tion.The test was per formed at the Cen ters for Dis ease Con trol and Pre ven tion in At lanta, Geor gia by a micro plate ELISA method us ing a re com bi nant an ti gen made on the prem ises (per sonal com mu ni ca tion).The test was positive.At a follow-up visit in July, the pa tient was no longer expe ri enc ing his origi nal dis com fort and liver func tion was back to nor mal.This is, to our knowl edge, the first con firmed case of hepa ti tis E di ag nosed in Can ada.

RE VIEW OF THE LIT ERA TURE
Hepa ti tis E is a rarely en coun tered type of hepa ti tis in the west ern world.The first docu mented out break of hepa ti tis E (di ag nosed ret ro spec tively) oc curred in In dia in 1955 (1); it was sup pos edly re lated to the in ges tion of con tami nated water and re sulted in over 50,000 cases.Since then, more in cidences were docu mented of what was pre vi ously called 'e nter ically ac quired non-A non-B hepa ti tis'.The vi rus as so ciated with hepa ti tis E was iso lated in 1989 by Krawczyn ski and Brad ley (2,3).It is a nonen vel oped vi rus of 27 to 34 nm (3) con sist ing of a single-stranded, positive-sense RNA mole cule (4).Mor pho logi cally, hepa ti tis E vi rus (HEV) has some simi larities with cali civi ruses ( 5), but mo lecu lar char ac teri za tion shows sig nifi cant dif fer ences; the fi nal taxo nomic clas si fi cation of' HEV is still un clear.Dur ing the past two dec ades, many out breaks have been de scribed in sev eral coun tries, but In dia re mains a re gion where this type of hepa ti tis seems to be highly preva lent (6)(7)(8)(9), proba bly largely due to wa ter con tamina tion.Other coun tries where cases have been de scribed include: Tur key (10), Ethio pia (11), Su dan (12), Egypt (13), Mo rocco (14), Al ge ria, Tu ni sia and Bang la desh (15), Burma, Paki stan and China (16), the former USSR (17), Mex ico (18), Sene gal (19) and Ivory Coast (19) (Fig ure 1).As more in forma tion on the dis ease in ci dence and dis tri bu tion be comes avail able, it ap pears that hepa ti tis E is a ma jor cause of hepati tis in de vel op ing coun tries, if not the most com mon cause in adults (5).
In the west ern world, the dis ease has al ways been re lated to trav el ling to en demic ar eas.In the United States, four cases were con firmed by se rol ogy be tween 1989 and 1992 (20): one pa tient ac quired hepa ti tis in Mex ico and the other three on the In dian sub con ti nent.Im ported cases have also been re ported in Europe, no ta bly in the United King dom (21), the Neth er lands (22) and Spain (23).The trans mis sion of' HEV is very simi lar to that of HAV.The in cu ba tion pe riod ranges from two to nine weeks, with a mean of 45 days (20).A fecaloral route has been im pli cated and proved by the vi rus be ing trans mit ted to a vol un teer (24).HEV is not trans mit ted ver tically (25), and there are no chronic car ri ers.Per son to per son trans mis sion by cas ual con tact is still con tro ver sial (7,26).Hepa ti tis E symp toms are simi lar to those of hepa ti tis A, but a few dif fer ences can be ob served.First, the mor tal ity rate seems to be higher -1 to 2% over all -10-fold greater than that for HAV.The at tack rate is high est among young adults 15 to 40 years old, who for the most part are al ready anti-HAV-pos itive.Aside from a few out breaks (7,27), it is a rela tively un com mon con di tion in chil dren.An other par ticu lar find ing is that HEV causes se vere dis ease in preg nant women, with a fa tal ity rate reach ing 25% in cer tain stud ies (11,16), the peak oc cur ring in the third tri mes ter.Why hepa ti tis E is respon si ble for such mor tal ity dur ing preg nancy re mains unknown.Since vi ral hepa ti tis is the most com mon cause of jaun dice in preg nant women in North Amer ica, it is im por tant to re mem ber that hepa ti tis E has a sig nifi cantly dif fer ent clinical course in preg nant pa tients (28).
Di ag nos tic tests have re cently been de vel oped but are still not eas ily avail able for rou tine test ing in North Amer ica.Krawczyn ski and Brad ley (2) were the first to use a fluo rescent an ti body block ing as say for HEV an ti bod ies in se rum.How ever, an im por tant draw back of the test was in abil ity to dif fer en ti ate be tween past and pres ent in fec tion.An HEV ELISA has since been de vel oped at Ge nelabs Tech nolo gies Inc (Cali for nia) (27), us ing an ti gens de rived from ORF2 and ORF3 of the Burma and Mex ico strains.Acute phase sera were collected dur ing out breaks in In dia, Paki stan and Mex ico and tested posi tive with the HEV ELISA.The test was used to document cases in the United King dom and in an epi de mi ol ogi cal sur vey of hepa ti tis E in Hong Kong (29).Fi nally, a West ern blot as say for hepa ti tis E an ti bod ies served as a labo ra tory tool in a Su da nese out break (12).All these tests per formed fairly well and were able in some in stances to dif fer en ti ate between IgM and IgG an ti bod ies.While more data are ac cu mulated on their sen si tivi ties and speci fici ties (27) Treat ment of hepa ti tis E is mainly sup por tive, and, as with other types of hepa ti tis, pro longed prothrom bin time, hy po glyce mia and al tered men tal status at ad mis sion are omi nous signs.There is no vac cine avail able, and an In dian study failed to prove any pro tec tive ef fect of im mune se rum globu lin from an In dian source as pro phy laxis (26).Hepa ti tis E is rarely en coun tered in Can ada; nev er the less, it should be suspected in any trav el ler re turn ing from a de vel op ing coun try or in a re cently landed im mi grant from an en demic area pre senting with symp toms of acute hepa ti tis.As Ca na di ans are more and more of ten trav el ling to ex otic des ti na tions, phy si cians in this coun try should be aware of the ex is tence of hepa ti tis E, which is likely un der re ported.It is worth not ing that, since March 1994, hepa ti tis E se rol ogy has been avail able for selected cases at the Labo ra tory Cen tre for Dis ease Con trol in Ot tawa.

AC KNOW LEDGE MENTS:
We thank Dr Steve Lam bert at the Centers for Dis ease Con trol and Pre ven tion for his col labo ra tion.
Fig ure 1) Re gions where cases of hepa ti tis E have been con firmed (shaded ar eas) , these tests could CAN J INFECT DIS VOL 6 NO 1 JANU ARY/FEB RU ARY 1995 be avail able in the near fu ture for rou tine se rol ogy.