Pitfalls of hepatitis E

Transcription

1 Pitfalls of hepatitis E Antwerp, October 18th 2016 prof.dr. Hans L. Zaaijer MD PhD, medical microbiologist Sanquin Blood Supply Foundation & Academic Medical Centre, Amsterdam NL Disclosure of interests of Hans Zaaijer - No conflicts of interests. - Links to commercial partners: Hans Zaaijer is or was paid by ACTA, Abbott, Gilead, Griffols, ISBT, Janssen-Cilag, Roche, Virology Education for unrestricted lectures and teaching. - No consultancy, no shares or other interests in companies. 1

2 pitfall #1 'hepatitis E' does not exist: 2 separate disease entities, caused by different pathogens R.H. Purcell, aangepast Zaaijer 2

3 R.H. Purcell #1 hepatitis E = 2 disease entities HEV genotype 1 human to human HEV genotype 3 pig to human pregnant women 20% fatality no disease children acute hepatitis no disease adults acute hepatitis #1 no disease #2? sporadic: neuralgic amyotrophy middle aged, elderly acute hepatitis acute hepatitis (mild) #3 organ/sc Tx patients? chronic hepatitis, cirrhosis #4 GBS? GBS? 3

4 #1 21x acute hep E in NL ( ) among returning travellers: m 38 Pakistan m 28 Bangladesh m 30 Bangladesh m 34 Bangladesh m 38 India v 35 India m 36 India m 26 India v 23 India v 29 India m 32 India m 34 India v 24 India (fulminant, recovered) v 34 India (fulminant, 2x liver-tx) m 59 China (fulminant, liver-tx, ) m 28 Soedan m 40 Somalie m 32 Midden Oosten m 48 Aruba m 20 NL: Breezand v 45 NL: Amsterdam #2: silent HEV gt3 infection in Dutch donors Monthly HEV PCR screening of Dutch plasmapools of 96: Overall ( ) : 79/101,793 = 1/1289 HEV RNA+ Incidence: 1% / yr 4

5 : 4067 samples submitted for 'hep.serology' : 144 HEV-IgM and PCR pos. > questionnaire > 81 responses: #3: 52 Dutch hep E patients, no travel or immune sup./def. Koot ea, J.Clin.Virol #4: hepatitis E in solid organ and in allogeneic stem cell transplant patients, caused by HEV gt3 5

6 pitfall #2 chronic hepatitis E in: - solid organ transplant patients and - allogeneic stem cell transplant patients often mistaken for: - drug induced liver injury ('dili') - graft versus host disease of the liver rapidly causing liver cirrhosis case 1: mr. A, 51 yrs diagnosis de Niet ea. Neth. J. Med. 2012; 70:

7 case 2: boy B, now 10 yrs of age 2006: severe pneumococcal infection HUS kidney Tx 2011: chronic hepatitis eci, 'drug induced liver injury' (dili)? diagnosis Bouts ea. Pediatrics 2015 step 1 = mycophenolate mofetil: 800 to 600 mg/m2/day step 2 = tacrolimus: 0.1 to 0.05 mg/kg/day (prednisolone remained unmodified at 2 mg/m2/day) case 3: mrs. C, 55 yrs 7

8 pitfall #3 patients with immuno suppression or immuno deficiency: diagnosis of acute and chronic hep E must be based on HEV RNA PCR, do not use serology serology often is negative during infection (including improved, modern HEV Ab EIAs) case 4: mr. D, 67 yrs - CLL, anti-cd20 chronic hep E without antibody response: IgG and IgM anti-hev negative (Wantai EIA) 8

9 pitfall #4 avoid relapse after ribavirin treatment of chronic hep E: continue ribavirin 2 or 3 months after plasma HEV PCR became negative (or 1 month after feces HEV PCR = neg?) case 5: mr.e, 60 yrs. 2006: CLL: allo-sct, 2014 relapse, chemo 9

10 sources and transmission of HEV genotype 3 adapted from: WHM vd Poel - Current Opinion in Virology 2014, 4:

11 Sanquin project L1965: transmission of HEV After fruitless testing of raw sausages, vegetables, etc, by HEV PCR: Leverworst: Paté s: 43 / 55 (78%) PCR+ 12 / 15 (80%) PCR+ confirmed by NVWA (Dutch Food Safety Authority) dietary advice for organ- and allo-sc Tx patients. mmm: Mettbrötchen! 11

12 pitfall #5 phylogeny of HEV gt3: sequencing of ORF1 and ORF2 does not provide sufficient genetic resolution to study HEV genotype 3c dynamics in EU patients, pigs, blood donors and food. > sequencing of hyper variable region? (dendogram not yet available for public domain) Summary of HEV pitfalls - 'Hepatitis E' refers to 2 distinct diseases: tropical human-to-human hepatitis by HEV genotypes 1/2, and endemic-zoonotic hepatitis by HEV genotypes 3/4. - Beware of chronic HEV gt3 infection in organ transplant patients and hematological patients, - which may remain seronegative during years. In these patients test for hep E using HEV PCR, not IgG/IgM serology. (in immuno competent persons, modern IgG/IgM HEV serology is okay for diagnosis of acute tropical or acute endemic hep E). - Response to ribavirin treatment of hep E: do not stop ribavirin too early. - Phylogeny of EU strains of HEV subgenotype 3c : insufficient resolution of common HEV RNA sequencing. 12

13 HEV team at Sanquin: Boris Hogema Michel Molier Hans Zaaijer Anneke de Vos Mart Janssen H.L.Zaaijer, 2016, Amsterdam, NL not to be copied or distributed without written consent of H.L.Zaaijer. 13