Presentation on theme: "Case finding for HBV in the UK"— Presentation transcript:
1 Case finding for HBV in the UK Stuart McPhersonConsultant HepatologistLiver Unit, Freeman Hospital, Newcastle upon Tyne andInstitute of Cellular Medicine, Newcastle University.1
2 Background 350 million HBV-infected individuals worldwide 15-40% will develop serious complications related to cHBVWorldwide there are an estimated 620,000 deaths HBV-related deaths/year50-55% of all liver HCCs in Europe are due to HBVPrevalence varies significantly across the worldOverall the UK is a low prevalence area (~0.3% of population HBsAg pos)Cooke, BMJ 2010; Lok, Hepatology 2009; DOH 2002
3 Geographic Distribution of Chronic HBV Infection UK 0.3%HBsAg Prevalence (%) 8: High2-7: Intermediate<2: LowCenters for Disease Control. Dec /Vol 54/No RR-16. Web site: Available atCHMP Guidelines on the Clinical Evaluation of Medicinal Products Intended for Treatment of Chronic Hepatitis B. Feb 2006.3
4 HBV can be treated and prevented Several effective treatment for HBVTenofovirEntecavirPEG-IFNTreatment have been shown to:Reduce hepatic inflammation and reverse fibrosisprevent progression to cirrhosisreduce risk of HCCReduce liver related mortality in those with advanced diseaseThere is a highly effective vaccine for HBVLok Hepatology 2009; Liaw NEJM 2004; Zhang Virol J 2011
5 Effective treatment of HBV in the “real world” - Tenofovir 302 NA-naive patients with median baseline viraemia of 5.9 log IU/mL (1.6–>9).Median age: 55 (19–80) yearsCirrhosis: 35%Concomitant diseases: 43%HBeAg(-)ve: 80%Baseline characteristics(n=302 naïve patients)HBeAg(-)veHBeAg(+)ve10010089%92%93%92%85%8075%69%70%71%71%806057%60Patients %40Patients %4026%202069121518216912151821MonthsMonthsPatients on f-upPatients on f-up535151433428211205194166143116Lampertico P, et al. EASL Poster 731.
6 Effective treatment of HBV in the “real world” - Entecavir HBeAg(+)veHBeAg(-)ve100%10095%96%86%100Median age (range): 58 (18–82)Cirrhosis: 49%Concomitant diseases: 56%HBeAg(–)ve: 83.1%Baseline characteristics (n=418):90%93%82%8073%8065%6060Patients %Patients %37%40402020Primary Non Response at week 12 : < 1%Partial Virological response at week 48: 14%Virological breakthrough: < 1%0%0%Baseline612182430Baseline612182430MonthsMonthsPatients on f-up716762513521Patients on f-up347332315283220137Adapted from Lampertico P, et al. AASLD Abstract 391.
7 HBsAg-seroconversion in HBeAg neg sAg seroconversion with treatmentHBsAg-seroconversion in HBeAg neg2518%2015Percentage of patients (%)103%2%50%An=11Bn=43Cn=63Dn=55Hadziyannis, 2005
8 Rationale for the promotion of case-finding for viral hepatitis Surveys by the ELPA suggest that up to 90% of HBV infected individuals in the EU are unaware of their conditionIn the UK the majority of HBV is imported from endemic areas, so at risk groups could be targetedThere is no universal screening or vaccination program for HBV in the UKThe ELPA has called for targeted screening or case finding in risk groups for viral hepatitis to facilitate early diagnosis and if appropriate treatmentIn the US the CDC and AASLD recommend screening for all subjects born in Countries with HBsAg prevalence of >2%Piorkowsky N. J Hepatol 2009: 51;
9 High risk groups for Hepatitis B • Persons with elevated liver enzymes and/or clinical sign of hepatitis• Patients with liver cirrhosis or fibrosis• Patients with hepatocellular carcinoma• People who share or have ever shared needles (injecting drug users)• People with long-term imprisonment history• People who are undergoing or have undertaken hemodialysis• Men who have sex with men or heterosexual persons with multiple sex partners• People with HIV or HCV infection• Families and household members or sexual partners of persons infected with HBV• Pregnant women and newborns of HBV-infected mothers• Patients before or during immunosuppressive treatment or chemotherapy• Migrants from countries with high prevalence of Hepatitis B• Unvaccinated healthcare workers and public safety workers who undertake exposure-prone procedures.Piorkowsky N. J Hepatol 2009: 51;
10 NICE Hepatitis B and C: ways to promote and offer testing Key Questions Which interventions are effective and cost effective in encouraging people from high-risk groups to use services that currently (or potentially could) offer hepatitis B or C testing?What prevents people in high-risk groups from seeking and accepting a hepatitis B or hepatitis C test? How do these factors differ for each group – and what factors increase the likelihood that they will seek and accept a test?Which interventions are effective and cost effective at overcoming the barriers to hepatitis B or C testing faced by high-risk groups and professionals?What type of services and activities need to be commissioned to encourage people who have tested positive to continue to seek support?
11 Geographic Distribution of Chronic HBV Infection HBsAgPositive, %TaiwanVietnamChinaAfricaPhilippinesJapanIndonesia4.0Pakistan1.5-3IndiaRussiaUSHBsAg Prevalence (%) 8: High2-7: Intermediate<2: LowCenters for Disease Control. Dec /Vol 54/No RR-16. Web site: Available atCHMP Guidelines on the Clinical Evaluation of Medicinal Products Intended for Treatment of Chronic Hepatitis B. Feb 2006.11
12 Chinese Hepatitis Awareness, Surveillance and Education – B The British-Chinese community is the largest in Europe and the fastest growing non-European ethnic group in the UK.It is estimated that in 2007 there were 430,000 British-Chinese people in the UK.Case finding was undertaken in collaboration with the Newcastle Chinese Healthy Living Centre (NCHLC) based in Newcastle’s Chinatown.hase BSupported by Gilead Fellowship 2010
13 CHASE-B - “Awareness-raising among at-risk groups” Supported by Gilead Fellowship 2010
14 CHASE-B- “Education among at-risk groups” Supported by Gilead Fellowship 2010
15 CHASE-B – testing for HBV Dried blood spot testinghase BSupported by Gilead Fellowship 2010
16 CHASE-B – “reducing the barriers to hepatitis B testing” Supported by Gilead Fellowship 2010
17 CHASE-B – “reducing the barriers to hepatitis B testing” Supported by Gilead Fellowship 2010
18 CHASE-B methodsCase finding undertaken at 4 sites in the NE of EnglandNewcastle Chinese healthy living centreTrue Jesus Church in NewcastleTrue Jesus Church in SunderlandTees Valley Chinese centre in MiddlesbroughTesting session advertised in the local Chinese press and at testing locationsA presentation in English and Chinese at each sessionAll attendees were given written information in English and Chinese and those wanting to be tested had dry blood spot testing for HBVResult of the test was communicated to the subjects in English and ChineseGPs were advised of subjects with positive HBsAg tests and repeat testing was recommendedSpecialist referral was recommended for all confirmed HBsAg pos testsSupported by Gilead Fellowship 2010
19 CHASE-B – results of case finding 606 subjects were screened in 11 sessions at the 4 sites.Mean age was 49 ± 17 years (range 16-94)61% were female.53 subjects (8.7%) were HBsAg positive (48% female) indicating chronic HBV10 reported being previously diagnosed with HBV, but were not under follow up.When previously diagnosed individuals were excluded the prevalence of HBsAg positivity was 7.2%.Country of birth of screened subjectsSupported by Gilead Fellowship 2010
20 CHASE-B – results of case finding Prevalence of HBVinfection by country of birthPrevalence of past HBV infection by country of birth80 (14%) subjects were HBsAg –ve & HBcAb +ve indicating past HBV infection.Supported by Gilead Fellowship 2010
21 CHASE-B – results of case finding Only 12% of subjects reported previous vaccination against HBV.31 HBsAg pos subjects have been reviewed in the NUTH viral hepatitis clinic1 eAg pos and 30 eAg neg CHB3 (10%) had active eAg neg CHB (bloods +biopsy)1 immunotolerant eAg pos20 inactive CHB (ALT<40 and HBV DNA <2000 and LSM <8KPa)7 currently indeterminate activity (ALT > 40 and DNA <2000 or ALT<40 and DNA >2000)No cases of HCV, HIV or delta co-infectionOne incidental RCC on ultrasound – had nephrectomy
22 CHASE-B conclusionsUndiagnosed chronic HBV is highly prevalent in British-Chinese in NE England, including subjects born in the UK.If the our results were applied to the entire UK British-Chinese population targeted case finding should lead to approximately 32,250 newly diagnosed cases of chronic HBVThe frequency of previous HBV vaccination was low in this high risk group.Supported by Gilead Fellowship 2010
23 Case finding in migrants from countries with intermediate prevalence of HBVThe UK’s South Asian population is the largest minority ethnic group at approximately 4% of the total population (2.3 million). The term ‘south Asian’ refers to anyone of Indian, Bangladeshi, Pakistani or Sri Lankan origin.Within the British Asian community, the largest ethnic minority is people of Indian descent (1.8%), followed by those of Pakistani origin (1.3%).It is estimated that there are approximately 50 million people affected with chronic HBV in India and 7-9 million in Pakistan, whilst the prevalence of HBsAg in Bangladesh has been reported to be 5.5%.Datta S. Virology journal. 2008;5:156.Ali M et al. Virology journal. 2011;8:102.Mahtab MA et al. Hepatobiliary Pancreat Dis Int. 2008;7:595.
24 SHADE-B – case finding in the British South Asian community Conducted Case finding in South Asian Community of the NE of England7 sessions at Mosques in Newcastle, Sunderland and Middlesbrough and Bangladeshi community centre in SunderlandDry blood spot testing for HBsAg, anti-HBcAb and HCV AbOtherwise methods similar to CHASE-B studySupported by Gilead Fellowship 2010
25 SHADE-B results520 subjects screened in 7 sessions to date at 4 locations in NE of EnglandMean age 43 ± 16 years (range 6-83)76% males9 subjects (1.7%) were HBsAg pos9 subjects had evidence of past HBV (HBcAb pos and HBsAg neg)4 subjects (0.8%) were HCV Ab pos
26 SHADE-B results Serological evidence of past infection by country of birthHBsAg prevalence by country of birth
27 All 4 HCV Ab pos subjects were from Pakistan SHADE-B Other resultsAll 4 HCV Ab pos subjects were from Pakistan1.8% prevalence in the Pakistani community1 Patient previous HCV with SVR following treatment3 HCV G3 – undergoing workup for treatmentOnly 5% reported vaccination against HBV
28 SHADE-B conclusionsUndiagnosed cHBV is prevalent in the Pakistani community of NE England, although the prevalence was lower than in the local British-Chinese community.The prevalence of cHBV in subjects born in Pakistan was above the 2% threshold for screening suggested by the AASLD and ELPA, which provides evidence for targeted case finding in this population.
29 Other studies from the UK in South Asian population Country of birthNo.HBV%HCVUK4520.2%0.4India11970.1%0.2Bangladesh7261.5%0.6Pakistan -Punjab10493.7Pakistan - Kashmir5702.5%0.5Pakistan - Other2392.9%0.8Pakistan – unknown6001.2%3.8A total of 4998 people attending community centres were screened for viral hepatitis using oral fluid testing.London, Birmingham and BradfordFor chronic HBV infection, the prevalence was similar in migrants from Pakistan and Bangladesh, where the prevalence was in line with WHO estimates, but the prevalence was lower in people from India.J Viral Hep. 2010;17:327
30 Cost effectiveness of case finding or screening No clinical trials of screening for HBV or HCVOne recent study that used Markov modelling showed thatScreening and treatment with Lamivudine or PEG-IFN is cost effective at HBV prevalence of only 0.3%If high cost low resistance drugs are used screening is cost effective at recommended level of screening of >2% ($43000 per QALY)NICE economic evaluationA ‘one-off’ HCV case finding intervention in prevalence areas of 2% or more, that achieves levels of testing of at least 17.5%, is likely to be cost effective at a willingness to pay for an additional QALY of £20,000 if it costs between £50-75 per person invited for a test.The base case ICER for HBV case finding was estimated to be approximately £21,000 when similar assumptions were made (intervention effect of 17.5%, £20 per person invited for a test and a 2% prevalence level).Uptake of “screening” in populationsA study in New Zealand found uptake of 27% to targeted Radio advertisements and opportunistic letters and phone calls from primary careUK colorectal cancer screening uptake is 50-55% (only 20-30% in South Asian Ethnic minorities)Robinson NZ Med J 2005, Whynes D Public Health 2003; Miners NICE 2012
31 Vaccination No universal vaccination program in the UK Taiwan started a Nationwide universal vaccination program in 1984All infants given vaccinations at birth and those born to HBeAg pos mothers also had HBIGThere coverage >96% to 3 dose programReduction of HBsAg prevalence from 10% pre-vaccination to 0.9% post vaccinationThe majority (86%) of subjects who were HBsAg pos despite vaccination are believed to have acquired it in uteroReduction in incidence of paediatric HCCYen-Hsuan N el al. J Hepatol 2012
32 ConclusionsFinger prick dry blood spot testing in community settings is an effective method for targeted case finding for blood borne viruses.Undiagnosed cHBV was prevalent in the British Chinese and Pakistani communities of the NE of EnglandThese results provide evidence for a targeted case finding or screening program in those populationsThe optimum method of screening or case finding remains to be determined
33 Acknowledgments Gilead LIVErNORTH NCHLC HPA Dr Manoj Valappil Dr Samuel MosesGary EltringhamFreeman HospitalDr Mark HudsonProf Maggie BassendineCarolyn MillerKerry BaxterSunderlandDr Kamran ShafiqGatesheadDr Athar SaaedNCHLCAmanda ChanAnnie HoGileadLIVErNORTHNCHLC