Update of hepa++s E in Hong Kong Dr Chow Chi Wing Department of Medicine Tseung Kwan O Hospital
HEV: The History Probably causing human disease for centuries Iden+fied on EM by Dr Balayan in 1983 Viral genome sequenced in year 1990, and the virus renamed as HEV
HEV: Virology Genus Hepevirus of Hepeviridae Incuba+on: average 40 days, range 15-64 days Diagnosis: presence of an+- HEV IgM in serum OR HEV RNA in serum or faeces (Xing L. J Biol Chem. 2010)
Geographic distribu+on of 4 hepa++s E virus genotypes. Hong Kong Genotype 1 Asia (e.g. India, Pakistan, Myanmar, China, Kyrgyzstan and North Africa) Genotype 2 Mexico, Africa Genotype 3 North and South America, Europe and Asia (e.g. Japan) Genotype 4 Asia (e.g. Japan, China, Taiwan, Vietnam) (Purcell RH. J Hepatol. 2008)
Zoono+c hepa++s E virus: sources and routes of infec+on (Dalton HR. Curr Opin Infect Dis 2013)
Zoono+c hepa++s E virus: sources and routes of infec+on (Dalton HR. Curr Opin Infect Dis 2013)
Course of acute HEV infec+on (Hoofnagle JH. N Engl J Med. 2012)
Clinical features by genotype Characteris*c Geographic distribu+on Padern of spread Species specificity Major mode of spread Genotypes 1 & 2 Developing countries Epidemic and sporadic Human Waterborne Genotypes 3 & 4 Both developing and developed countries Sporadic Swine, human (accidental host) Foodborne
Clinical features by genotype Characteris*c Genotypes 1 & 2 Genotypes 3 & 4 Rate of icteric illness Age distribu+on Sex distribu+on Mortality High Highest among aldolescents and young adults Similar between & High among pregnant women Low Highest among older adults : ~ 3 : 1 High among older adults
Clinical features by genotype Characteris*c Genotypes 1 & 2 Genotypes 3 & 4 Extrahepa+c features Few Neurologic complica+ons Chronic infec+on None Common in the immunosuppressed Therapy None known Ribavirin, peginterferon (experimental) Preven+on Vaccine Vaccine
HEV vaccines GSK Innovax / XMU Protein 56kDa 26kDa Expressed type HEV1ORF2 HEV1ORF2 Exp Syst. Insect cells E. Coli Stage Completed Phase II study Completed Phase III study Licensed by Chinese SFDA Commercially available in China
HEV vaccine: Innovax
HEV vaccine: Innovax (Zhu. Lancet. 2010)
HEV in HK: Epidemiology
HEV in HK: Epidemiology HAV incidence trend
HEV in HK: Epidemiology 90 73 118 119 HEV incidence trend
HEV in HK: Epidemiology Sex distribu+on of HEV no+fied from 1996 to 2011 Male 474 cases (68.3%) Male Female Female 220 cases (31.7%) (Source: DH)
HEV in HK: Epidemiology Age distribu+on of HEV infec+on (2001 to 2010) (Source: DH)
120 HEV in HK: Epidemiology Seroprevalence of HAV & HEV by age in different years 100 80 % 60 40 20 Age 18-20 Age>40 Age>40 Age>50 Age > 60 Age>50 Age>50 an+- HEV (1989-91) an+- HAV (1987-89) an+- HAV (1978-79) an+- HEV (2001) an+- HAV (2001) an+- HEV (2008-09) an+- HAV (2010) 0 0-10 0 to 10 Age 18-20 11 to 21 to 31 to 41 to 51 to 61 to 71 to 20 30 40 50 60 70 80 11-20 21-30 31-40 41-50 51-60 Age (years) 61-70 71-80 >81 71-80 >81 (Wong KH. J Med Virol. 2004.) (Chiu DM. J Med Virol. 2013.) (DH)
HEV in HK: Epidemiology (Source: DH)
HEV in HK: Epidemiology Mortality From 2001-2010, there were 524 cases 78.4% pa+ents needed hospitaliza+on 12 pa+ents died, they are older, none were pregnant Case fatality rate was 2.3%
HEV in HK: Genotypes HEV Genotypes (2001-07), n=171 (%) 8 (5) 1(<1) Genotype 1 Genotype 3 Genotype 4 162 (95) (Tai AL. J Med Virol. 2009)
HEV in HK: vs HAV (Chau TN. Am J Gastroenterol. 2006)
HEV in HK: vs HAV (Chau TN. Am J Gastroenterol. 2006)
HEV vs HAV with HBV in China (Zhang X. Hepatol Int. 2010)
HAV in HBV carriers Is HBV carrier + HAV having more severe disease than HAV alone? Some studies did not show any difference, e.g. Zachoval R, et al. Hepa++s A Infec+on in Chronic Carriers of Hepa++s B Virus. Hepatology. 1983 Jul- Aug;3(4):528-31. (Germany) Tassopoulos N, et al. Double infec+ons with hepa++s A and B viruses. Liver. 1985 Dec;5(6):348-53. (Greece) Chu CM. The incidence of fulminant hepa+c failure in acute viral hepa++s in Taiwan: increased risk in pa+ents with pre- exis+ng HBsAg carrier state. Infec+on. 1990 Jul- Aug;18(4):200-3. (Taiwan) Some studies showed HBV carrier + HAV may be more severe
HAV in HBV carriers (Pramoolsinsap C. Ann Trop Med Parasitol. 1999)
HAV in HBV carriers (Kim JI. Korean J Hepatol. 2010)
HEV in HBV carriers HEV can cause acute hepa++s in unrecognized HBV carriers (Kumar M. J Gastroenterol Hepatol. 2008)
HEV in HBV carriers 161 HEV pa+ents from year 2000-2011 in 3 regional hospitals in HK were retrospec+vely studied 31 cases were HEV + HBV carrier, 130 isolated HEV Baseline characteris+cs: Mostly similar, but HEV+HBV has more cases with underlying cirrhosis (4/31 vs 3/130, p=0.03) (Submided for publica+on)
HEV in HBV carriers HEV (n=130) HEV+HBV (n=31) p value Liver Failure 4 (3.1) 3 (9.7) 0.13 All- cause mortality 4 (3.1) 2 (6.5) 0.33 Liver- related mortality 2 (1.5) 2 (6.5) 0.17 median (range) median (range) Day 1 bilirubin (umol/l) 102 (3-601) 59 (6-371) 0.13 Day 28 bilirubin (umol/l) 21 (3-634) 25 (6-869) 0.40 Day 1 ALT (U/L) 1519 (45-9064) 730 (101-6282) 0.03 Day 28 ALT (U/L) 48 (8-478) 60 (15-784) <0.01 Admission dura+on (days) 6 (0-177) 6 (0-90) 0.78 (Submided for publica+on)
HEV in HBV carriers Demographic and clinical characteris+cs of the HEV+HBV and HEV group (Cheng SH. World J Gastroenterol.
Conclusion: HEV incidence is running a rising trend in HK HEV mortality occur in older pa+ents, while pregnant HEV pa+ents in HK did not show a significant higher mortality HEV+HBV carrier may have a longer disease course +/- worse prognosis, but studies for more evidence will be needed
Possible direc+ons for future research: Vaccine efficacy in special group of pa+ents Condi+on of chronic hepa++s E in HK Effects of acute or chronic HEV treatment by ribavirin or peg- interferon in HK
The End Q&A