Hepatitis E in a Canadian traveller

H EPA TI TIS E, PRE VI OUSLY KNOWN AS EN TERI CALLY TRANSMIT ted non-A, non-B hepa ti tis, is clini cally in dis tin guish able from hepa ti tis A. It is etio logi cally as so ci ated with a re cently iden ti fied singlestranded lin ear RNA vi rus struc tur ally simi lar to a cali civi rus (1). Epi demic and spo radic dis ease have been rec og nized in tropi cal and sub tropi cal de vel op ing coun tries of Asia, Af rica, the Mid dle East and North Amer ica (Mex ico), and in fec tion is highly as so ci ated with con tami nated wa ter sources (1,2). Most cases iden ti fied in de vel oped coun tries in volve trav el lers re turn ing from en demic ar eas (2). The av er age in cu ba tion pe riod has been es ti mated to be six weeks, with a range from two to nine weeks (1). CASE RE PORT

The dis ease is usu ally self-limited with no chronic sequelae, ex cept dur ing the third tri mes ter of preg nancy when ful mi nant hepa ti tis is more com mon, with a high case fa tal ity rate of ap proxi mately 20% (1,2).In a large se ries of 583 cases from Turk meni stan dur ing a 1985 out break (4), a pro drome of mal aise and ano rexia char ac ter is ti cally oc curred a mean of 3.5 days be fore the on set of jaun dice, along with right up per quad rant or epi gas tric pain (in 70.5% of pa tients), nau sea (50%), vom it ing (25%), fe ver greater than 37.7°C (15%) and fe ver greater than 38°C (3.1%).Jaun dice, which was ac compa nied by pru ri tis in 10% of pa tients, lasted a mean of 14.2 days, and 3% of pa tients de vel oped cho lesta sis with jaun dice and pru ri tis last ing for al most a month.In four re cently described cases among Ameri can trav el lers (2), to tal bili ru bin lev els be tween 43 and 129 µmol/L (nor mal 0 to 17 µmol/L), as par tate ami no trans fe rase (AST) lev els be tween 1262 and 2256 U/L, and al ka line phos phatase (ALP) lev els be tween 172 and 516 U/L, were re ported.
Un til re cently, no se ro logi cal test was avail able to iden tify hepa ti tis E, and di ag no sis de pended on ap pro pri ate his tory of ex po sure, clini cal pres en ta tion and ex clu sion of other causes of hepa ti tis (2,3).This re port de scribes one of the first cases of hepa ti tis E re ported in Can ada, and was con firmed by West ern blot and ELISA at the Cen ters for Dis ease Con trol and Pre ven tion (CDC), At lanta, Geor gia (4).

CASE PRES EN TA TION
A 27-year-old male pre sented to the In ter na tional Travel and Im mu ni za tion Clinic (ITIC) at the Uni ver sity of Cal gary on Sep tem ber 3, 1993, three weeks fol low ing his re turn from a year-long trip to Ne pal, Thai land and In dia.He gave a oneweek his tory of dark urine, light-coloured stools and jaun dice for less than 24 h.He dated his ill ness to a bout of non bloody di ar rhea (ini tially as so ci ated with fe ver and ab domi nal cramps), fa tigue, ano rexia and weight loss of 4.5 to 6.8 kg start ing six weeks pre vi ously when he was in In dia.
The pa tient was pre vi ously healthy and had re ceived tetanus, po lio, mea sles, mumps, ru bella, ty phoid and men in gococ cal vac cines as well as im mu no globu lin (Ig) be fore travel.Dur ing his trav els he oc ca sion ally drank wa ter that was not dis in fected or boiled.He had had one un pro tected het ero sexual en coun ter with a Euro pean trav el ler more than seven months be fore pres en ta tion.To ob tain a driv er's li cense in India, he also had a fin ger prick six months be fore pres en ta tion, for a blood group ing test.
On physi cal ex ami na tion, he was afeb rile but ill look ing and had scleral icterus.He had mild right up per quad rant abdomi nal ten der ness but no he pa tosple no megaly.
Two days be fore pres en ta tion, a fam ily phy si cian had ordered the in ves ti ga tions with the fol low ing re sults.Uri naly sis showed oc ca sional white blood cells and in creased bili ru bin.Com plete blood count was nor mal with no evi dence of anemia, and eryth ro cyte sedi men ta tion rate was 0 mm/h.Se rum elec tro lytes were nor mal but se rum al anine ami no trans fe rase (ALT) was 3110 U/L (nor mal range 7 to 56 U/L) and ALP 261 U/L (nor mal range 39 to 117 U/L).En ta moeba his to lytica tropho zoi tes and cysts, Cam py lo bac ter je juni and Sal mo nella ty -phimurium were iden ti fied in stool (along with En do li max nana, Escheri chia coli and En ta moeba hart mani).Se rum an tihe pa ti tis A vi rus (HAV) IgM and hepa ti tis B sur face an ti gen assays were nega tive.Ad di tional in ves ti ga tions at the ITIC showed that chest x-ray was nor mal and se rum an ti he pa ti tis B core an ti gen and an ti he pa ti tis C vi rus an ti body as says were nega tive, as were se rum an ti cy tomega lovi rus, anti-Epstein-Barr vi ral cap sid an ti gen, an ti toxo plasma IgM and an ti lep to spira ti tres.Se rum was also sent to the CDC for hepati tis E se rol ogy.For amoe bia sis, the pa tient was pre scribed oral met roni da zole 750 mg three times daily for 10 days.
The pa tient was ad mit ted to hos pi tal Sep tem ber 7, 1993 be cause of in creas ing jaun dice and weak ness.At this time, se rum ALT was 3230 U/L, ALP 325 U/L, gammaglutamyltransferase 65 U/L (nor mal range 11 to 50 U/L), to tal bili ru bin 390 µmol/L (nor mal range 3 to 20 µmol/L), con jugated bili ru bin 337 µmol/L, al bu min 34 g/L (nor mal range 3 to 20 g/L), prothrom bin time 17.1 s (con trol 11.6 s), par tial throm bo plas tin time 38.2 s (con trol 28.7 s) and glu cose 4.7 µmol/L.Ab domi nal ul tra sonogra phy showed no evi dence of bili ary ob struc tion or he patic mass or ab scess.The pa tient improved symp tomati cally and was dis charged Sep tem ber 10.To eradi cate E his to lytica cysts, he was sub se quently given oral io do qui nol 650 mg three times daily for 20 days.Re peat anti-HAV IgM meas ure ment on the day of dis charge was negative.Elec tron mi cros copy on stool col lected at dis charge showed no vi ral par ti cles, but se rum col lected on Sep tem ber 3 was posi tive for an ti he pa ti tis E vi rus (HEV) IgG and anti-HEV IgM by West ern blot and ELISA.
The pa tient sub se quently made an un event ful re cov ery and his liver en zymes and liver func tion tests re turned to normal by Sep tem ber 30.At this time stool cul tures were negative for en teric bac te rial patho gens and para sites.

DIS CUS SION
This pa tient most likely ac quired hepa ti tis E through contami nated drink ing wa ter while in In dia.As this case il lustrates, trav el lers to de vel op ing coun tries are at risk of ac quir ing hepa ti tis E, a dis ease that may be par ticu larly severe and even fa tal in preg nant women (1,2).In en demic areas sub clini cal in fec tion may ex ist, and clini cally overt dis ease oc curs most of ten in the 15 to 40 year age group, includ ing in di vidu als who are al ready anti-HAV posi tive and presuma bly im mune to HAV.
Apart from rig or ous at tempts to avoid con tami nated drinking wa ter and food, there are no pro phy lac tic meas ures against this dis ease.Im mu no globu lin ob tained from nonendemic popu la tions in de vel oped coun tries is in ef fec tive in prophy laxis (2).How ever, as with hepa ti tis A, pro tec tive im mu nity is thought to de velop fol low ing in fec tion but its du ration is un known (3).
Al though vi ral an ti gen or ge nomic se quences in sera, stool, bile or liver bi opsy tis sue can be de tected by a va ri ety of tech niques in clud ing im mune elec tron microscopy, polymerase chain re ac tion and di rect fluor escent an ti body tests (1), such tech niques are not gen er ally used for di ag nosis.HEV is a la bile vi rus, and stool shed ding de creases and may be un de tect able by the time pa tients pres ent with symptoms (1,5).Hepa ti tis E is best di ag nosed by de tec tion of serum anti-HEV IgM, which in di cates re cent (less than four to five months) in fec tion.Anti-HEV IgG re mains per sis tently ele vated fol low ing in fec tion and is less use ful in dif fer en ti at ing acute from pre vi ous in fec tion.Anti-HEV an ti body can be de tected by fluo res cent antibody-blocking as says us ing na tive HEV an tigens, and by im munoblot ting and en zyme im mu no as say using re com bi nant HEV pro teins (1,4).How ever, given that these tests are not yet widely avail able, and that hepa ti tis E clini cally re sem bles hepa ti tis A, many cases of HEV in fec tion in re turning trav el lers may be missed.This di ag no sis should be consid ered in any per son re turn ing from abroad with acute hepa ti tis and in whom other causes of vi ral hepa ti tis (in clud ing hepa ti tis A, which re mains, by far, the more com mon en terically ac quired hepa ti tis in trav el lers re turn ing from de vel op ing coun tries [2]), sys temic in fec tions such as lep to spi ro sis and Q fe ver, and non in fec tious causes such as gall stone ob struc tion and drug-related hepa ti tis (eg, from sul pha drugs) have been ruled out.