Kalliopi Azariadi, Pinelopi Arvaniti, Nikolaos Gatselis, George N. Dalekos, Kalliopi Zachou

Transcription

1 Severe acute non-a, non-b, non-c hepatitis with autoimmune features: Consider acute hepatitis E virus (HEV) infection not just autoimmune hepatitis (AIH) Kalliopi Azariadi, Pinelopi Arvaniti, Nikolaos Gatselis, George N. Dalekos, Kalliopi Zachou Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece

2 World-Wide Burden of Hepatitis E

3 World-Wide Burden of Hepatitis E 2 million new cases per year 3.4 million symptomatic cases 17% 7. deaths 3. stillbirths

4 Molecular virology small icosahedral, nonenveloped, single-stranded, positivesense RNA virus nm genome 7.2 kb 3 non overlapping reading frames (ORF1, ORF2, ORF3) Sayer, Hepatology 215. Wedemeyer, Gastroenterology 212.

5 Geographical Distribution & Genotypes Genotype 1 and 2: common cause of epidemic hepatitis E Genotype 3 and 4: zoonoses found mostly in swine Wedemeyer, Gastroenterology 212

6 Routes of HEV transmission autochthonous cases proven modes (solid arrows) potential modes (dashed arrows) Sayed, Hepatology 215

7 Hepatitis E Seroprevalence in Europe: A meta-analysis Anti-HEV IgG prevalence 29% 17% 16% 16% 18% Anti HEV Assays Hartl, Viruses 216.

8 Clinical course of HEV infection Wedemeyer, Gastroenterology 212.

9 Fulminant Hepatitis E cases in Europe Lappa D., Int. J. Mol. Sci. 215

10 Acute Hepatitis E with autoimmune features 13 acute non-a, non-b, non-c hepatitis cases during 2 years period 4 HEV cases (3.7%) 3/4 diagnosed as acute AIH 1/4 diagnosed as AIH relapse in an AIH patient under immunosuppression Zachou, Gatselis, Azariadi, Dalekos (submitted)

11 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

12 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

13 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

14 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

15 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

16 Patient A Interface hepatitis Emperipolesis Rosette formation

17 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

18 IU/L AST ALT BIL Clinical course under prednisolone 1mg/kg A mg/dl IU/L B mg/dl day IU/L C mg/dl IU/L day Prednisolone increase D mg/dl 1,6 1, ,8 day day 7.5mg 3 25mg,4

19 A B C D age sex medical Hx none alcohol NHL AIH, ITP AST/ALT (U/L) 1231/ /96 455/ /475 bilirubin (mg/dl) INR Hepatitis A, B, C negative negative negative negative IgG (mg/dl) SMA >1/32 >1/32 >1/32 >1/32 animal contact travel no no no no liver biopsy AH compatible n.a. n.a n.a. simplified score AIH definite probable probable n.a. anti-hev IgG/IgM pos pos pos pos HEV RNA pos pos pos pos

20 16 12 AST ALT BIL Prompt prednisolone withdrawal IU/L mg/dl IU/L mg/dl A B IU/L month C mg/dl 6 4 IU/L month Prednizolone tapering D mg/dl 1,6 1, ,8 month month 2mg 7.5mg 25mg 1 4,4

21 HEV infection & Autoimmune Hepatitis Hypotheses: a) triggering factor? b) cross reactivity? c) risk factors for acquiring HEV d) false AIH diagnosis? CD4 proliferation 3.5% 1.8% 1.8% CD8 proliferation 7.7% n=19 n=537 n=114 anti-hev IgG n=28 Pischke, PLos ONE 214

22 HEV infection & Autoimmune Hepatitis P>.5 van Gerven, J Gastrointestin Liver Dis 216.

23 Conclusion common in the developing world but also may occur in the West as autochthonous infection (a zoonosis) causes: acute self-limited disease, acute liver failure, acute-on-chronic liver injury

24 Conclusion The diagnosis of Autoimmune hepatitis is not safe without the exclusion of acute HEV testing for hepatitis E should be part of the diagnostic work-up of all patients with acute hepatitis

25 Thank you for you attention!