Hepatitis Delta Revival

Heiner Wedemeyer

HEPATITIS VIRUSES HEPATITIS VIRUSES

Hepatitis A Hepatitis B p Hepatitis C Hepatitis D Hepatitis D Hepatitis E

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Feinstone Blumbergg Houghton Rizzetto Balayan    

1973 1965 1988 1977 1980

RNA DNA RNA RNA RNA

EASL Monothematic EASL Monothematic Conference: Delta Hepatitis September 24‐26, 2010 Istanbul, Turkey M Manns, M Rizzetto, C Yurdaydin

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

% anti-H HDV-posittive / HBs sAg+

Declining Prevalence of Hepatitis D Virus Infection  Declining Prevalence of Hepatitis D Virus Infection in Italy 30

1987

25 20

1992

15

1997 10 5 0 0-29

30-49

>50

Age of Patients

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Gaeta, Rizzetto et al., Hepatology 2000

HDV‐Infection in Germany

% anti HDV+ / H HBsAg+

Anti-HDV-Prevalence in HBsAg+ patients Hannover Medical School (1-1992 (1 1992 bis 4-2006; 4 2006; n=2354) n 2354)

15

10

5

* 0 1992 H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

1994

1996

1998

2000

2002

2004

2006

Wedemeyer et al., Hepatology 2007

HDV‐Infection in Germany

% anti HDV+ / H HBsAg+

Anti-HDV-Prevalence in HBsAg+ patients Hannover Medical School (1-1992 (1 1992 bis 4-2006; 4 2006; n=2354) n 2354)

15

10

5

* 0 1992 H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

1994

1996

1998

2000

2002

2004

2006

Wedemeyer et al., Hepatology 2007

Emerging HDV Epidemiology: Migration

Taiwan Pacific Islands

HDV Prevalence High Intermediate Low Very Low No Data H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Long‐term outcome of hepatitis D in Italy Developing cirrhosis

Hepatocellular Carcinoma

Cli i l Decompensation Clinical D ti Main Cause of Death: Liver Failure (38%) Only independent Factor of mortality: HDV replication

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Romeo et al. Gastroenterology 2009

Hepatic Decompensation but not HCC development  is the primary cause of mortality HCC

Hepatic Decomp.

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Calle-Serrano et al. AASLD 2009

Diagnostic Steps in Delta Hepatitis g p p HDV-RNA-neg HBsAg+ HBsAg

Anti-HDV+ Anti HDV HDV-RNA-pos

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

HDV-RNA quantitative

Quantitative HDV‐PCR: Cobas‐TaqMan Assay

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Mederacke et al. J Clin Microbiol 2010

Diagnostic Steps in Delta Hepatitis g p p HDV-RNA-neg HBsAg+ HBsAg

Anti-HDV+ Anti HDV HDV-RNA-pos

HDV-RNA quantitative

Does HDV viremia D i i correlate l t with ith the th stage/grade of liver disease?

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

HDV‐RNA does NOT correlate with liver fibrosis HDV RNA< 105 HDV-RNA< copies/ml (n=20) 3 4 ± 0.9 3.4 09

HDV RNA> 105 HDV-RNA> copies/ml (n=47) 3 2 ± 1.4 3.2 14

p value

Cirrhosis Ci h i (Ishak 5-6) (%)

2 (10)

11 (23 (23.4) 4)

NS§§

Significant Si ifi t fibrosis fib i (Ishak 3-6) (%)

16 (80)

31 (66)

NS§

Ishak fibrosis score

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

NS*

Zachou et al. Liver International 2009

Diagnostic Steps in Delta Hepatitis g p p HDV-RNA-neg HBsAg+ HBsAg

Repeat PCR ALT levels, Histology?

Anti-HDV+ Anti HDV HDV-RNA-pos

HDV-RNA quantitative

HDV Genotype yp

D Does the th course off Delta D lt Hepatitis H titi differ diff b between t different genotypes?

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Different HDV genotypes in different regions

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Wedemeyer et al., Nat Rev Gastroenterol 2010

Different HDV genotypes are associated with different  Different HDV genotypes are associated with different clinical outcomes Su et al, Gastroenterology 2006

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

Diagnostic Steps in Delta Hepatitis g p p HDV-RNA-neg HBsAg+ HBsAg

Repeat PCR ALT levels, Histology?

Anti-HDV+ Anti HDV HDV-RNA-pos

HDV-RNA quantitative

HDV Genotype yp

HBeAg HBV-DNA

H. Wedemeyer –Delta Hepatitis – Paris Jan 2011

HBeAg and HBV‐DNA  are suppressed in Delta Hepatitis d i D lt H titi aHDV positive aHDV positive

HBsAg+ / aHDV negative

2 p‐level

HBeAg positive 

44/ 257 (17%)

610/ 2024 (30%)