Hepatitis B and C diagnosis and treatment guidelines

Philippa Easterbrook Global Hepatitis Programme

.

UNICEF-UNFPA-WHO MEETING WITH MANAFACTURERS AND SUPPLIERS

30 November 2020

Sources – WHO Global Health Estimates

0

0.5

1

1.5

2

2000 2005 2010 2015

Mill

ion

s o

f d

eath

s

Year

Hepatitis Tuberculosis HIV Malaria

1.34 milliondeaths in 2015

96% of the global hepatitis burdenfrom hepatitis B (66%) and C (30%)

Hepatitis silent epidemic, rising mortality

.

due to cirrhosis and hepatocellular carcinoma

Impact of hepatitis B vaccine on prevalence of HBsAg in children under 5 years

Before 2000: 4.7% In 2017:0.8%

257million

900 000deaths

People living with hepatitis B

Global burden of HBV infection

.

Incidence: 1.75 million new infections/yr(Unsafe health care and injection drug use)

Prevalence: 71 million infected, all regions64% burden in 14 countries

Global burden of HCV infection

Sources – WHO (Center for Disease Analysis )Source: WHO Global hepatitis report, 2017

Hepatitis C in Children/Adolescents : 3.5 (3.1-3.9) million infected 19 Countries account for 80% of infections

-

100

200

300

400

500

600

700

800

900

1,000

To

tal

Vir

em

ic In

fecti

on

s (

000)

5

Cascade of care for HCV and HBV infection, WHO region 2016 Major testing and treatment gap

❖Majority of 71 m infected persons remain undiagnosed (80% testing gap)

❖1.76 million started HCV treatment in 2016 and 1.1 million in 2015. (75% treatment gap)

Source – WHO (Center for Disease Analysis )

❖Majority of 257 m infected persons remain undiagnosed (90% testing gap)

❖4.5 million persons were on HBV treatment in 2016 and 1.7 million in 2015. (80% treatment gap)

HBVHCV

6

Progress to date

1. More national strategic plans (93 countries + 43 developing)

2. Achieved price reductions in drugs/ diagnostics (<$100 for HCV cure in 62% countries; Tenofovir<$30/yr)

3. WHO delivered on key global guidance, and Global Reporting process initiated

6. Champion countries moving towards elimination- Egypt: 60m tested and 3.1m treated DAAs: <US$50/cure. Also Georgia,

Mongolia- Pakistan: Launch of Prime Ministers national initiative and micro-elimination

project in Punjab- Australia: “universal ‘treatment access; prisoners and PWID are priority

populations; Nurse prescribing

5. Around 5 m HCV treated and same for HBV

4. On track to achieve 2020 target of >90% HepB3 vaccine. Development of criteria for validation of HBV EMTCT

.

TOPIC RECOMMENDATION

Staging/ non-invasive test (NIT)

▪ APRI preferred NIT to assess for the presence of cirrhosis

Who to treat

▪ Decompensated cirrhosis or cirrhosis (clinical criteria or APRI score >2), regardless of ALT levels, HBeAg, or HBV DNA.

▪ No cirrhosis but persistently abnormal ALT levels +/- ongoing HBV replication, (HBV DNA >20,000 IU/mL or HBeAg +ve).

First line treatment ▪ Drugs with a high barrier to resistance (TDF or ETV ?TAF)

▪ ETV in children aged 2-11 years.

Treatment failure ▪ Switch to TDF if evidence of resistance to 3TC, ETV, ADF, TBV.

Treatment discontinuation

▪ Never discontinue in persons with cirrhosis.

▪ If no cirrhosis, discontinuation on case-by-case basis (persistent HBeAgand/or HBsAg loss or undetectable HBV DNA)

Monitoring (treatment response/toxicity)

▪ On or pre-treatment: ALT + HBV DNA (HBsAg, HBeAg + APRI pre-treatment) annually. More frequent monitoring with cirrhosis.

▪ Assessment of baseline renal function prior to treatment initiation.

Monitoring for HCC ▪ Ultrasound + AFP every 6 months in persons with cirrhosis and/or family history of HCC.

HBV Guideline Recommendations (2015) and planned topics for revisions (2021)

End 2021 CONSOLIDATED HEPATITIS GUIDELINES

Part 4 – HBV –

expanding

eligibility for

treatment and use

of ? TAF

• https://www.who.int/publications/i/item/978-92-4-000270-8

New WHO recommendations on prevention of mother-to child HBV transmissionGuidelines on antiviral prophylaxis in pregnancy (July 2020)

8

.

Triple Elimination of HIV, syphilis and Hepatitis BOpportunity to advance the HBV EMTCT agenda

▪ Triple elimination of HIV, syphilis and HBV

in PAHO and WPRO and now globally

▪Multiple countries developing triple

elimination framework and guidelines

(WPRO/SEARO and PAHO regions)

▪Development of validation criteria for

elimination of viral hepatitis (June and Nov

2020)

.

Updated WHO HCV guidelines (2018)

• Simplified criteria (Who to treat?): HCV treatment for all infected people above 12 years of age (pregnant women excepted)

• Simplified preferred regimens (What to use?): Pan-genotypic regimens (avoid genotyping). Treatment in children and adolescents:

>18 yearsWithout cirrhosis

•Sofosbuvir/Velpatasvir for 12 weeks or•Sofosbuvir/Daclatasvir for 12 weeks or

•Glecaprevir/Pibrentasvir for 8 weeks²

With compensated cirrhosis

•Sofosbuvir/Velpatasvir for 12 weeks or•Glecaprevir/Pibrentasvir for 12 weeks² or

•Sofosbuvir/Daclatasvir for 24 weeks

In adolescents 12-17 years/≥ 35kg⚫ Sofosbuvir/Ledipasvir for 12 weeks in GT 1, 4, 5, 6⚫ Sofosbuvir/Ribavirin for 12 weeks in GT 2⚫ Sofosbuvir/Ribavirin for 24 weeks in GT 3

In children <12 years⚫ Deferring treatment until age 12 years ⚫ Avoiding interferon-based regimens

FOR UPDATE in 2021

• Reconciling DAA

regimens in adult,

adolescents and

children (3-12 years)

treatment

recommendations

• Re-treatment

strategies

.

Topic Recommendation

Who to test? ▪ Focused testing for most affected populations*, those with a clinical suspicion of chronic viral hepatitis, family members/children, and sexual partners (HBV), healthcare workers.

▪ General population testing: In settings with ≥2% or ≥5% (intermediate/high) HBsAg or HCV Ab prevalence.

▪ Birth Cohort testing (HCV): where specific identified birth cohorts of older persons at higher risk of HCV infection

▪ Routine antenatal clinic testing (HBV)

How to test? ▪ A single serological assay (EIA or RDT) that meets minimum performance standardswith prompt NAT testing + linkage to care

Confirmation of HCV viraemia

▪ Nucleic acid testing (NAT) (quantitative or qualitative RNA) or core HCV antigen assay, with comparable clinical sensitivity

Promoting uptake and linkage

▪ Use of DBS specimens for virology ± serology ▪ On-site or immediate RDT testing with same day results▪ Trained peer and lay health workers▪ Clinician reminders to prompt provider initiated, facility-based testing ▪ Testing as part of integrated services at a single facility

Hepatitis testing guideline recommendations 2017

* PWID, people in prisons, MSM, sex workers, HIV-infected, tattoos, transfusions, some migrant pops from endemic

countries, some indigenous populations, children of HBV/HCV +ve mothers

FOR UPDATE in 2021⚫ How to test - serologic

– HCV self-testing -

useablity, acceptability

studies in 5 countries)

– Dried blood spots (HCV

serology and virology)-

Manafacturers protocols

⚫ Confirmation HCV VL

– Use of point of care VL

(5 projects)

– LoD for test of cure

⚫ Linkage to care (completed WHO

systematic review)

– Decentralised HCV test

and treat

– Integrated HCV testing

and treatment at harm

reduction site

– Task-shifting for HCV care

Implement Good Practice Principles for Simplified Service Delivery

1. Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis, WHO 2018

1. Simple and standard algorithms across the continuum of care.

2. Strengthening the linkage from testing to care.

3. Integration of hepatitis testing, care and treatment with other

services.

4. Decentralized testing and treatment.

5. Task-shifting to support decentralized care.

6. Engagement with community.

7. Efficient procurement and supply management of quality

medicines and diagnostics.

8. Data systems to monitor the quality of care and coverage

Service delivery in specific populations

• Persons who inject drugs

• People in prisons and other closed settings

• MSM and sex workers

• Adolescents and Children

• Migrant/indigenous populations

• Pregnant women

Moving HCV treatment out of speciality clinics De-centralised testing and treatment “one-stop shops”

PWID

140 studies; 33 countries. High Income countries- 120 (86%), LMIC- 20 (14%)

New WHO Evidence: Full decentralization of testing and treatment increased uptake of testing, linkage and treatment, and achieved comparable SVR12

Lancet Global Health (in press)

Role of Point-of-care viral load in improving linkage

Finger-prick

Minivette capillary tube

Single-use test cartridge

LaptopGeneXpert machine

GeneXpertcartridge

.

Role of HCV self-testing in expanding access to testing

15

HCV self-testing (FIND –WHO -UNITAID)

• Several countries in different geographic regions:• China: Guangdong Center for Skin Disease & STI

Control – MSM population

• Egypt: Egyptian Liver Research Institute and Hospital – General population

• Kenya: UW-Kenya – PWID population

• Georgia: NCDC – general population, MSM, PWID

• Vietnam – community clinic, high risk population

• District hospitals and harm reduction sites

• 100-150 participants per site

• OraQuick HCV rapid diagnostic test modified for self-testing

Integration with other

testing settings or

opportunities eg. HIV,

antenatal or TB

Integrated combo

serology (HIV/HBV/HCV

RDTs), including self-

testing

Build on and integrate

existing multi-disease

platforms (HIV, HCV

RNA and HBV DNA)

HCV care at harm reduction

sites

HIV, HCV and HBV care in

prisons

HCV and HBV care at HIV,

and TB clinics

Opportunities for IntegrationCase Example: Integration of harm reduction with treatment

Through the Medicins du Monde program in Kenya, PWID are able to receive HCV testing and treatment at a drop-in center, promoting a client-centered approach.High retention and adherence are bolstered by• Pre-treatment counselling• Treatment navigation by peer-educators• Psycho-social support

.

• Innovations: Use of PoC viral load, Combo testing, HCV Self-testing, low cost PoC HCV core antigen test, Need WHO PQ for HBeAg RDT for HBV PMTCT, and HBV DNA VL

• Guiding countries on integration with other disease areas and sharing of multidisease platforms

• Gaps in country support for forecasting, drug registration, procurement, price negotiation

• New pricing models (bundled procurement) for diagnostic platforms offer an alternative to traditional procurement contracts

• HCV: Rapid introduction of simplified care model is key

• HBV: Gaps in partner activity

• Treatment indications less clear - expand criteria for treatment (lower APRI score and HBV DNA threshold)

• Simplified care models are needed - integration opportunities with HIV

• No global funder - primarily domestic funding, plus out of pocket costs

Future directions and plans for updated guidelines

End 2021 CONSOLIDATED HEPATITIS GUIDELINES

• Part 1- Service Delivery

and PoC viral load

• Part 2 – HCV DAA

regimens in children and

Re-treatment

• Part 3- HCV self-testing

• Part 4 – HBV – expanding

eligibility for treatment and

use of ? TAF

18

Acknowledgements

WHO Regional office (Antons Mozalevskis, Leandro Sereno, Polin Chan, Fumni Lesi, Joumana Hermez, BB Rewari,)

WHO HQ (Ena Oru, Mark Bulterys, Yvan Hutin, Niklas Luhman, Fuqiang Cui)