Web Annex C. Estimates of the coverage of diagnosis and ... · Centre for Disease Analysis. Web Annex C. Estimates of the coverage of diagnosis and treatment for hepatitis B and C

Web Annex C. Estimates of the coverage of diagnosis

and treatment for hepatitis B and C virus infection, by

WHO region and income group, 2015

Centre for Disease Analysis

In: Global hepatitis report 2017

WHO/CDS/HIV/18.47

© World Health Organization 2018

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CONTENTS

1. Background

2. Methods

2.1 Country-level estimates

2.2 Extrapolations to generate regional estimates

2.3 Stratifications

2.4 Sensitivity analysis

3. Results

3.1 Cascade of care for HBV infection

3.2 Cascade of care for HCV infection

4. Discussion

5. Acknowledgements

6. Cascades

7. Tables

8. Figures

References

Page 1 of 21

ESTIMATES OF THE COVERAGE OF DIAGNOSIS AND TREATMENT FOR HBV

AND HCV INFECTION, BY WHO REGION AND INCOME GROUP, 2015

Online annex # 3 to the 2017 WHO Global Hepatitis Report on the cascade of care – Version: 20 April 2017

Report prepared by the Center for Disease Analysis for the World Health Organization

BACKGROUND

The global health sector strategy (GHSS) on viral hepatitis calls for elimination of viral hepatitis as a public

health threat by 2030 (reduction of 90% in incidence and of 65% in mortality). Chronic sequelae of HBV and

HCV infection account for 95% of the mortality from viral hepatitis [1]. The monitoring and evaluation

framework of the GHSS includes indicators for the five core interventions [2]. The four prevention

interventions are already implemented and data are available to monitor coverage. For testing and treatment,

data systems to generate information are not yet in place and estimates are not available to determine how

far the world is from the 2030 target. By 2030, the proportion of persons living with HBV or HCV who have

been diagnosed should reach 90% (30% in 2020), and among those diagnosed, 80% of eligible persons should

be treated (5 million for HBV and 3 million for HCV in 2020) [3].

The cascade of care concept originates from HIV and quantifies the series of steps that occur between testing

and the achievement of viral suppression or sustained virological response (SVR) [4]. The cascade of care for

HBV and HCV infection [5, 6] addresses diagnosis, treatment and viral suppression (for HBV) and eventual cure

(for HCV) [5, 7, 8]. Reports that address the cascade for HCV [9, 10 , 11, 12 , 13, 14] are mostly from high-

income countries. Monitoring the cascade facilitates the identification of gaps in access to and engagement in

care and treatment [15]. New direct-acting antivirals for HCV have already improved adherence and SVR rates.

Reports quantifying the cascade of care for HBV are also mostly from high-income countries [16–22]. Among

antinucleos(t)ides with a high barrier to resistance recommended by WHO for the treatment of chronic

hepatitis B, tenofovir has been the most widely used. With full adherence to antinucleos(t)ides with a high

barrier to resistance, viral suppression occurs at 48 weeks in 83–97% of patients. Disease progression stops in

patients who respond to treatment [23–26]. However, older therapies such as lamivudine are still in use, even

though they are not recommended by WHO as they induce resistances.

Before implementing the GHSS on viral hepatitis, a baseline quantification of the cascade of care for HBV and

HCV was necessary to (a) identify priorities for action, and (b) compare regions in terms of access to diagnosis

and treatment. We therefore abstracted the available data to estimate the number of patients infected with

HBV and HCV who were (a) diagnosed, (b) treated and (c) virologically suppressed or cured at the regional and

global levels, using 2015 as the reference year. WHO regions included the African Region, Region of the

Americas, Eastern Mediterranean Region, European Region, South-East Asia Region and Western Pacific

Region.

Page 2 of 21

METHODS

General approach

To estimate the indicators that reflect the cascade of care regionally and globally, we proceeded through four

steps (Fig. 1). First, we reviewed the data to estimate the indicators along the cascade by country. Second, we

compiled data from countries that had data available and extrapolated these results to generate regional and

global estimates. Third, we stratified results by WHO region and income level. Fourth, we calculated

uncertainty intervals around the estimates.

Operational definitions

We estimated the indicators selected by WHO to quantify the various steps of the cascade of care [2].

Proportion of infected persons diagnosed (WHO core indicator C6)

We defined persons diagnosed (C.6) as persons living with chronic HBV (C.6.a) or HCV (C.6.b) infection who

had been diagnosed through in vitro diagnostic methods. The proportion of diagnosed individuals was

calculated as the number of persons with chronic infection diagnosed out of the total number of persons with

chronic infection.

Treatment coverage (HBV) or initiation (HCV, WHO core indicator C7)

For HBV, we defined persons on treatment (C.7.a) as persons living with chronic HBV infection who were on

treatment in 2015. For HCV, we defined persons initiating treatment (C.7.b) as persons living with chronic HCV

infection who started any HCV antiviral treatment (including direct-acting antiviral regimens and non-direct-

acting antiviral regimens) in the past 12 months. We calculated the treatment initiation rate for 2015 as the

number of persons initiating treatment during that year out of the total number diagnosed.

Viral suppression (HBV) or sustained virological response (HCV, WHO core indicator C8)

For HBV, we defined the proportion of persons virally suppressed (for C.8.a) as the number of persons with

undetectable HBV DNA in the past 12 months out of the number of persons on HBV treatment in the past 12

months who were tested. For HCV, we defined the proportion of cure (for C.8.b.) as the number of persons

with documented SVR out of the number of persons initiating treatment (within the past 12 months).

Time period

We estimated cascade indicators for the year 2015. Our literature search considered available published

studies and ministry of health reports between January 1990 and November 2016 (HBV), and published studies

and national databases between January 1950 and March 2016 (HCV).

Geographical scope

We considered all countries for the development of our global and regional cascade of care estimates. We

included countries with prevalence data, as well as those without prevalence data but with a population of 1

million or more (HBV) and 1.5 million or more (HCV).

Page 3 of 21

1. Country-level estimates

Number of infected persons

We used the 2015 WHO estimates of the total number of persons infected with HBV and HCV. The estimates

for HBV were generated by the London School of Hygiene &Tropical Medicine for the WHO department of

Immunization, Vaccines and Biologicals. The estimates for HCV were generated by the Center for Disease

Analysis for the WHO Global Hepatitis Programme.

Proportion of infected persons diagnosed (WHO core indicator C6)

HBV

Methods to estimate the size of the population diagnosed included (in order of priority): (a) national

notification or registry data; (b) studies that included estimates or data on the number of persons known to be

living with HBV in a country and published in the peer-reviewed literature; (c) the number of people found to

be infected through blood donation screening programmes; (d) extrapolations from other countries in the

same region.

HCV

In countries where notifications led to a reliable number of newly diagnosed infections, we added all

notifications by year and subtracted mortality. In countries without surveillance data, we used national reports

or expert panel input (in that order). We also considered blood donor data (when available), under the

assumption that the total number of diagnosed patients would at a minimum include those testing positive at

a blood transfusion centre. We assumed that the proportion of anti-HCV-positive persons with viraemia was

identical among persons diagnosed and in the total infected population, and that the newly diagnosed cases

remained constant after the last reporting.

Treatment coverage (HBV) or initiation (HCV) (WHO core indicator C7)

HBV

We estimated the number of individuals treated annually for HBV through (in order of priority): (a) national

databases or government reports; (b) sales audit data of generic tenofovir; (c) published data on the number

of treated patients in the country; or (d) estimates provided by national experts. To use medicine sales audit

data, we converted the annual number of units of treatment sold into the number of treated patients using

the average number of units per patient.

HCV

We estimated the number of individuals initiating treatment for HCV each year through (in order of priority):

(a) national databases or government reports; (b) medicine sales audit data; (c) publications or reports from

major treatment centres; or (d) estimates provided by experts. We considered all therapies available in 2015,

including older regimens containing interferon as well as newer direct-acting antiviral combinations (with or

without ribavirin). To use medicine sales audit data, we converted the annual number of units of each

Page 4 of 21

treatment sold into the number of treated patients using the average number of units per patient. To estimate

the average number of units per patient, we considered several factors that affect the speed and probability of

achieving an SVR, particularly when patients are treated with pegylated interferon. As the average SVR varies

by genotype, we considered the genotype distribution and the duration of treatment by genotype. We also

included the number of treatment units used per week and the proportion of treatment effectively completed.

We further adjusted the annual number of units to account for uses other than for treatment of HCV and for

any underreporting, using inputs from the expert panel in each country when possible. When reports from

individual treatment centres were used, experts provided input on the number and size of other treatment

centres in the country so that the numbers could be extrapolated to determine a countrywide estimate. We

assumed the annual number of patients initiating treatment was constant after the last year of reported data.

Projected treatment effectiveness (WHO core indicator C8)

HBV

We assumed that with full adherence to treatment, viral suppression would occur in 90% of individuals with

chronic hepatitis B [23, 27]. Assuming that 80% of those undergoing treatment were adherent, we assumed

that globally, 72% had effective viral suppression [16, 28–32].

HCV

We used the proportion of treated patients with SVR by genotype to estimate the number of patients with SVR

per year. In the absence of better information, we assumed that the genotype distribution of the treated

population was the same as the one of the total infected population. We interviewed national experts to

estimate the actual proportion of SVR for the different treatment regimens (with or without direct-acting

antivirals). Experts took into consideration the proportion of patients with prior treatment experience, disease

stage and reduced compliance.

2. Extrapolations to generate regional and global estimates

We estimated the proportion of patients diagnosed and treated for the Global Burden of Disease (GBD)

regions, weighted by the sizes of the populations infected and diagnosed, respectively. We used GBD regional

diagnosis and treatment estimates for countries without estimates. If a GBD region did not have any countries

with data, we used the weighted average of neighbouring GBD regions as a surrogate. All GBD regions were

then added to generate a global estimate.

3. Stratifications

We stratified our outputs based on the six WHO-defined regions and four World Bank income groups.

4. Uncertainty analysis

We conducted a sensitivity analysis and developed 95% uncertainty intervals (UI) for our regional and global

outcomes. To this effect, we ran a Monte Carlo analysis that turned off and on the inclusion of each country in

the regional and global estimates. After completing the Monte Carlo analysis, we used the resulting

uncertainty ranges by country to calculate the regional and global levels. This allowed us to determine the

Page 5 of 21

impact of including each country’s forecast in the regional cascade of care estimate, which in turn estimated

the numbers diagnosed, treated and suppressed/cured for all countries with missing data in the same region.

We conducted these analyses using Crystal Ball®, an Excel® add-in by Oracle® with a binomial distribution to

include or exclude countries [33].

RESULTS

Cascade of care for HBV infection (see Cascade 1)

Data availability

Data on diagnosis were available for 163 countries (94% of the population) with 46% coming from blood donor

data, 31% from registries or published data, 10% from WHO registries (particularly in the European Region and

Western Pacific Region), and 7% utilizing a combination of registry and blood donor data (Fig. 2). Data on

diagnosis accounted for >99% of the population in the Western Pacific, European and American regions. The

South-East Asia Region (94% of the population with data on diagnosis, 98% of which was from blood donations)

and African Region (85% of the population with data on diagnosis, 91% from blood donor donations) had

intermediate data availability. The Eastern Mediterranean Region had the lowest proportion of the population

with data on diagnosis (69%, with 71% of the information coming from blood donations).

Treatment data were available for 59 countries, representing 43% of the global population, ranging from 90%

in the South-East Asia Region to 10% in the European Region. In all but six countries, we used sales data of

generic tenofovir to estimate the number of treated patients. In New Zealand, Poland, Slovakia and Viet Nam,

experts estimated the total number of those treated. These estimates include non-tenofovir treatments. For

Greece and China, previously published estimates were utilized and also include non-tenofovir treatments [19,

34].

No data were available regarding treatment in the Andean Latin America, Southern Latin America and tropical

Latin America; nor were they available for the high-income Asia Pacific subregions. The weighted average of

the proportion treated in a neighbouring region was extrapolated and applied. Sufficient diagnosis and

treatment data for inclusion were available for countries in all the other subregions.

Diagnosis of chronic HBV infection

Overall, in 2015, of the 257 million persons with HBV infection, we estimated that 21 million persons (95% UI:

20–22 million, 9% of the infected population) had been diagnosed (Table 1). The proportion of those infected

who were diagnosed was highest in the Western Pacific Region (25%, 17 million diagnosed) and lowest in the

African Region (0.3%, 153 000 diagnosed). The highest number of diagnosed individuals was in the upper–

middle-income group (2 million, with the lowest in the low-income group, with 312 000 diagnosed. Upper–

middle-income countries also had the highest proportion diagnosed (18.7%), while low-income countries had

the lowest (0.8%).

Page 6 of 21

Treatment coverage for chronic HBV infection

Overall, in 2015, 1.7 million (95% UI: 1.5–1.7 million) persons (8% of those diagnosed) were on treatment for

chronic hepatitis B (Table 1). This proportion varied from 0.5% to 18% by region. Treatment coverage was the

highest in high-income countries (14%) and the lowest in lower–middle-income countries (3%).

Projected viral suppression for chronic HBV infection

Of the 1.7 million on treatment in 2015, an estimated 1.2 million individuals (95% UI: 1.2–1.6 million) achieved

viral suppression globally.

Sensitivity analysis

Globally, 97% of the variation in the total number diagnosed was due to the Western Pacific, South-East Asia

and European regions, with 75% being due to the Western Pacific Region alone. With respect to treatment, 76%

of the variation in the total number treated was due to the Western Pacific Region, followed by the European

and South-East Asia regions, which together account for 94% of the variation (Fig. 4).

Cascade of care for HCV (see Cascade 2)

Data availability

Expert panels approved estimates of the HCV cascade in 59 countries. Published and unpublished data were

available for another 41 countries. For 74 countries (79% of the world population), we estimated the number

of patients diagnosed through expert consensus (39 countries, 36% of the population), published studies (10

countries, 8% of the population) and surveillance (25 countries, 35% of the population, Fig. 3). Surveillance

accounted for >50% of the population in the Region of the Americas and Western Pacific Region (Fig. 3).

We were able to estimate the number of patients with hepatitis C treated in 76 countries (81% of the global

population) through the use of expert consensus (29 countries, 16% of the population), published studies (6

countries, 3% of the population), medicine sales audit data (34 countries, 41% of the population) and

surveillance (7 countries, 22% of the population, Fig. 3). In two regions (Eastern Mediterranean and European),

more than 50% of estimates came from medicine sales audit data or national treatment databases (5% of the

population). National treatment databases were available in the European and the Western Pacific regions (Fig.

3).

Three GBD regions (Latin America, Andean; Oceania; sub-Saharan Africa, central) lacked country data for

diagnosis and two (Oceania; sub-Saharan Africa, central) lacked country data for treatment and SVR. We

estimated the data for the Andean Latin America region using the population-weighted averages from Latin

America, central/southern/tropical; sub-Saharan Africa, central was estimated using the population-weighted

average from sub-Saharan Africa, east/south/west; and Oceania was assumed to have the same proportion

diagnosed and treated as Australasia.

Page 7 of 21

Diagnosis of chronic HCV infection

Of the 71 million persons with chronic HCV infection in 2015, 20% (95% UI: 19–21%) had been diagnosed (14

million, 95% UI: 13–15, Table 2). The European Region had the largest total diagnosed population (4.3 million)

and the African Region had the smallest (582 000). The Region of the Americas had the highest proportion of

infected persons diagnosed (36%). The high-income group had the largest number of persons diagnosed (6

million, 43% of all). In the high-income group, 46% of infections were diagnosed, compared with 17% in the

upper–middle-income and 14% in the lower–middle-income groups.

Treatment initiation rate for chronic HCV infection

In 2015, of 14 million diagnosed with HCV infection, an estimated 7% (95% UI: 7–8%) initiated treatment in

2015 (1 million, 95% UI: 1.0–1.1, Table 2). The Eastern Mediterranean Region had the largest number of

persons initiating treatment (326 000) and the highest treatment initiation rate (12%), followed by the Region

of the Americas (11%). The high-income group accounted for the largest number of patients initiating

treatment (483 000), followed by the lower–middle-income group (398 000). Globally, a cumulative 5 million

persons (95% UI: 5.4–5.6) have initiated treatment since 2004.

Projected sustained virological response for HCV infection

The SVR among patients treated in 2015 was 80% overall (95%UI: 76–82%), highest in the Region of the

Americas (88%) and lowest in the Western Pacific Region (63%, Table 2). The high-income group had the

highest SVR (88%) and the upper–middle-income group the lowest (62%).

Sensitivity analysis

For the proportion diagnosed, the European, South-East Asia and African regions accounted for 95% of

variation (Fig. 5). The Western Pacific and Eastern Mediterranean regions accounted for less than 1% of

individuals diagnosed globally. By income, the lower–middle-income and lower-income groups accounted for

approximately 95% of uncertainty. For treatment initiation rate, the European, Eastern Mediterranean and

South-East Asia regions accounted for more than 98% of variation (Fig. 5). The Region of the Americas and

Western Pacific Region accounted for less than 1% of treatment initiation globally. By income, the lower–

middle-income and upper–middle-income groups accounted for 99% of uncertainty. Lower–middle-income

countries alone accounted for about 94% of the uncertainty. For SVR, the European, Eastern Mediterranean

and South-East Asia regions accounted for 95% of variation (Fig. 5). The American and Western Pacific regions

accounted for less than 1% of variation. By income, the lower–middle-income and upper–middle-income

groups accounted for 99% of uncertainty.

DISCUSSION

Globally, we estimated that in 2015, 9% of the 257 million infected with HBV had been diagnosed, a 21% gap

from the GHSS 2020 target of 30%. With widespread diagnosis campaigns documented with registries, the

Region of the Americas, European and Western Pacific regions could meet the 2020 target for diagnosis.

However, given the difficulties in documentation in the African, Eastern Mediterranean and South-East Asia

Page 8 of 21

regions, meeting the 2020 and 2030 targets would be difficult, even with a massive increase in the number of

individuals diagnosed. Registries often suffer from limitations. They do not operate at the national level, do

not differentiate between acute and chronic cases, and exclude the private sector. In addition, a registry would

need to link diagnosis to treatment and continue follow up for patients not yet eligible for treatment until they

are suppressed. With regard to treatment, in 2015, we estimated that 1.7 million individuals (8% of those

diagnosed) were being treated (34% of the 5 million targeted to be on treatment by 2020). However, given the

absence of population-based estimates of the proportion of infected individuals eligible for treatment [35, 36],

it is difficult to determine how far the world is from the 2020 target [16]. As treatment is limited by the

number of individuals diagnosed, the regions that will require the largest scale up of diagnosis will also require

large scale up of treatment. Thus, the African, Eastern Mediterranean and South-East Asia regions have the

greatest need for focused strategies to diagnose and treat chronic HBV. The Western Pacific Region has made

progress in diagnosis, but needs to follow up diagnosis with treatment.

Globally, we estimated that in 2015, 20% of the 71 million infected with HCV had been diagnosed. This

presents a 10% gap from the 30% targeted for 2020. However, the degree of effort necessary to achieve these

targets varies by region. In the African Region, only 6% of HCV infections are diagnosed. Laboratory facilities

equipped to test for HCV are sparse in the Region, and many countries send specimens abroad for testing. This

is both expensive and inefficient for large-scale screening programmes. Although the proportion diagnosed

varies by WHO region, it varies even more by income group. The high-income group has already achieved or

exceeded the 2020 targets. Lack of quality data in low-income and lower–middle-income groups may explain

the variation by income group. While the low-income group had the smallest number of data sources for those

diagnosed, the lower–middle-income group accounted for the largest variation in diagnosis estimates due to

the limited sources available for a large number of included countries. With respect to treatment, worldwide in

2015, 7.4% of diagnosed patients initiated any kind of treatment. Given the 2020 GHSS target for treatment (3

million people have received treatment) [3], these results suggest that at a global level, diagnosis and

treatment must be scaled up. Cumulatively, an estimated 5.5 million patients initiated treatment between

2004 and 2015, which means that 20% of these patients were treated in 2015 alone. In the low-income group,

this proportion was much higher at 88% due to emerging treatment efforts in the African Region where 81% of

patients who cumulatively initiated treatment since 2004 did so in 2015. Overall, 80% of those who started

treatment in 2015 were cured. This proportion of those cured is expected to continue to rise as countries

switch to direct-acting antiviral therapies. Although we are unable to provide quantifiable estimates of

patients treated by therapy type at a regional level, approximately 50% of patients treated globally in 2015 and

approximately 10–15% of the cumulative number of patients treated globally from 2004 to 2015 were treated

with direct-acting antivirals. The annual proportion of cure reflects the uptake of direct-acting antiviral

therapies across regions, as well as the change in treatment over time. More than 80% of treated patients

were cured in the Region of the Americas, African, Eastern Mediterranean and South-East Asia regions, while

less than 80% were cured among those treated in the Western Pacific and European regions. The high

proportion of cure in the Region of the Americas (88%) is largely due to access to direct-acting antivirals in the

Page 9 of 21

USA and Brazil, which account for a majority of treatment in the Region. The scarcity of data and small number

of treated patients in the African Region may indicate that prior to the launch of direct-acting antivirals, there

was very little treatment available in that Region. Variations in treatment onset rates and cure rates by income

group highlighted the need for expanded treatment and improved access to direct-acting antivirals in middle-

income and low-income countries.

These estimates suffer from a number of limitations. First, the number of individuals diagnosed may have been

underestimated. Underreporting may occur in public health-care facilities. Some countries do not include data

from the private sector. Second, the number of patients treated could be overestimates. For HBV, in 53

countries with available data, we estimated the number of individuals on treatment based on generic

tenofovir sales. In low-income countries that account for the largest proportion of infected persons and where

most of the tenofovir used is from generic manufacturers, this may have led to an overestimation of treatment

coverage, as some tenofovir could have been used for the prevention or treatment of HIV infection. In contrast,

in upper–middle-income and high-income countries, data on the sales of generic tenofovir may not represent

all the sales of tenofovir, which could have led to an underestimation of the number on treatment. In addition,

we were not able to capture the use of other types of treatment that are not recommended by WHO, such as

lamivudine. Use of these treatments can lead to resistance and wastage of resources. As a consequence of

these limitations of the treatment data for HBV, WHO decided not to consider the regional breakdown in the

indicator reflecting treatment coverage for HBV (Core indicator C.7.a) but only the global aggregated data. For

HCV, we were unable to provide specific estimates of breakdown according to the type of treatment, such as

the use of interferon-based regimens versus direct-acting antivirals. Where the exact proportion of patients

treated with direct-acting antivirals was available in a country, it was reflected in the average SVR by genotype,

as described above. Third, our data on viral suppression for HBV and SVR for HCV were not based on national

systems to monitor patients from diagnosis through evaluation of treatment effectiveness. Instead, we used

multiple sources to project an estimate of the viral suppression or SVR indirectly, through published studies of

the efficacy and observance that can be expected (HBV) or in-country expert opinions based on their own case

series (HCV). Finally, as the situation is developing fast, 2015 estimates reflected a situation that has evolved

substantially since. Unfortunately, as of March 2017, 2016 estimates were not yet available for all countries,

even though preliminary data suggest that there is increasing availability of direct-acting antivirals in many

countries, and that the number of patients treated is increasing [37]. For example, Egypt started 500 000

patients on treatment in the first nine months of 2016 (an increase from October 2014 to December 2015

when 170 000 patients were treated) [37]. These patients are not reflected in these 2015 estimates. The

recent WHO report on access to hepatitis C treatment suggests that 1 million patients have been treated with

direct-acting antivirals since these drugs were first released in 2014 [37]. This is generally compatible with our

estimate that half a million patients were treated in 2015, with between 550 000 and 825 000 patients treated

with direct-acting antivirals in 2014 and 2015 combined. However, once we include data from 2016, our

estimates are likely to exceed 1.1 million treated with direct-acting antivirals between 2014 and 2016.

Page 10 of 21

In conclusion, in 2015, some information is available to provide initial baseline estimates of the cascade of care.

Only 9% and 20% of those with chronic HBV and HCV infection, respectively, have been diagnosed. Of those

infected with HBV, 8% are on treatment. Of those infected with HCV, 7% initiated treatment in 2015. Based on

what is known of the effectiveness of these treatments, we estimate that the majority of those treated are

virally supressed (in the case of HBV) or cured (in the case of HCV). However, most countries do not monitor

the effectiveness of treatment. To achieve the GHSS impact targets of reduced mortality and incidence, scaling

up testing and treatment will be necessary in all regions. In some cases, a switch is needed from older and less

safe therapies such as lamivudine for HBV and pegylated interferon for HCV, and further research required to

develop therapies for chronic HBV infection that would lead to a functional cure. A test-and-treat policy may

avoid post-diagnosis attrition in the future as it is estimated that up to 30% of people who are not eligible

when they are first diagnosed will become treatment eligible within three years [38]. Despite the availability of

surveillance systems and registries in many countries, more work is needed to identify best practices that lead

to improved accuracy and reliability of data systems to monitor the cascade of care. The implementation of

patient registries, especially in the African and South-East Asia regions, will be a necessary consideration in the

development of national strategies as countries move toward eliminating HBV and HCV. In the absence of such

registries, countries may want to consider other mechanisms that will provide preliminary estimates of the

indicators that reflect the cascade of care. Finally, to document SVR or viral suppression, effective systems of

follow up to assess and document the effectiveness of treatment are needed in order to replace estimates

with empirical data collected in-country.

ACKNOWLEDGEMENTS

We would like to acknowledge the 400+ country collaborators who provided and analysed data, participated in

meetings, provided guidance on methodology, and/or critically reviewed the model.

Country-level analyses were funded by industry research grants, the John C. Martin Foundation, and/or the

World Health Organization regional offices through the Center for Disease Analysis and the Polaris Observatory.

The development of WHO regional estimates, and the analysis to ensure adherence to the Guidelines for

Accurate and Transparent Health Estimates Reporting (GATHER) process were funded by the World Health

Organization through the Polaris Observatory.

The unit data for medicine sales audit data were reported by QuintilesIMS, which is a vendor of de-identified

prescription sales data.

Page 11 of 21

CASCADES

Cascade 1. HBV cascade of care estimates by WHO region, 2015

Page 12 of 21

Cascade 2. HCV cascade of care estimates by WHO region, 2015

Page 13 of 21

TABLES

Table 1. HBV cascade of care estimates by WHO region and income categories, 2015

Region

Chronic HBV infections

Total number (000) Diagnosed (000) Treated (000) Viral suppression (000)

Best estimate Range Best estimate Range

C.6.

Proportion

of infection

diagnosed Best

estimate * Range *

C.7.

Proportion

of

diagnosed

treated *

Best

estimate Range

WH

O r

egi

on

African 60 000 45 000–84 000 153 110–200 0.3% (28) (19–30) (18.4%) 20 20–27

The Americas 7 000 4 000–16 000 669 589–743 9.6% (110) (94–125) (16.4%) 79 79–107

Eastern Mediterranean 21 000 17 000–28 000 351 173–486 1.7% (2) (0.6–2) (0.5%) 1 1–2

European 15 000 11 000–23 000 1 965 1 728–2 218 13.1% (98) (52–98) (5.0%) 71 70–95

South-East Asia 39 000 29 000–77 000 888 848–1 552 2.6% (55) (48–78) (6.2%) 40 39–53

Western Pacific 115 000 93 000–160 000 17 484 15 975–17 621 2.3% (1 382) (1 290–1 395) (7.9%) 995 986–1 340

Wo

rld

Ban

k

inco

me

gro

up

High 10 000 8 000–15 000 1 874 1 664–2 375 18.7% (255) (189–256) (13.6%) 184 182-249

Upper–middle 119 000 95 000–153 000 16 132 15 452–16 295 13.5% (1 334) (1 269–1 333) (8.3%) 961 948-1 295

Lower–middle 87 000 67 000–133 000 3 195 2 265–3 920 3.7% (85) (52–118) (2.7%) 61 61-83

Low 40 000 30 000–66 000 312 273–333 0.8% (28) (27–29) (8.9%) 20 20-27

Global 257 000 199 000–367 000 21 513 19 887–22 285 8.4% (1 702) (1 537–1 703) (7.9%) 1,226 1 196–1 624

* Given the limitations of the estimates of HBV treatment, WHO decided not to use the estimates at the regional level but to only use the worldwide, aggregated estimates

Page 14 of 21

Table 2. HCV cascade of care estimates by WHO region and income categories, 2015

Region

Total

cases

(000)

Diagnosed Treatment initiation (annual) Cumulative number of

persons started on

treatment (000)

Sustained virological response (annual)

Total number (000) Proportion (%) Number (000) Rate (%) Number (000) SVR (%)

Best

estimate Range

Best

estimate Range

Best

estimate Range

Best

estimate Range

Best

estimate Range

Best

estimate Range

Best

estimate Range

WH

O r

egi

on

African 10 284 582 399–718 5.7 3.9–7.0 13 315 2.2 0.6–3.0 16 6–17 11 2–13 84.6 48.3–87.6

The Americas 7 237 2 625 2 446–2 707 36.3 33.8–37.4 290 286–290 11.1 10.7–11.8 1 252 1 248–1 251 255 253–255 87.9 87.7–88.2

Eastern Mediterranean 15 190 2 686 2 644–2 732 17.7 17.4–18.0 326 302–331 12.1 11.2 –12.4 1 576 1 553–1 581 264 242–269 81.1 79.5–81.5

European 13 641 4 250 3 443–4 735 31.2 25.2–34.7 208 186–302 4.9 4.2–7.2 1 157 1 136–1 251 162 156–207 77.9 62.1–85.0

South-East Asia 10 391 906 627–1 016 8.7 6.0–9.8 64 45–69 7.1 4.9–8.4 235 216–240 54 41–55 84.0 79.8–90.5

Western Pacific 13 898 2 985 2 815–2 998 21.5 20.3–21.6 144 141–145 4.8 4.7–5.0 1 169 1 166–1 171 91 88–92 63.1 62.6–63.4

Non-WHO 506 221 221–223 43.8 43.7–44.0 8 8–8 3.8 3.7–3.8 90 90–90 6 6–6 69.9 69.0–70.1

Wo

rld

Ban

k

inco

me

gro

up

High 13 499 6 242 6 169–6 257 46.2 45.7–46.4 483 479–483 7.7 7.7–7.8 2 650 2 647–2 650 423 420–423 87.6 87.6–87.7

Upper–middle 18 439 3 053 2 885–3 139 16.6 15.6–17.0 164 148–176 5.4 4.9–5.9 1 060 1 044–1 072 101 88–109 61.7 55.7–63.9

Lower–middle 33 341 4 599 3 792–4 913 13.8 11.4–14.7 398 354–461 8.7 7.7–10.6 1 776 1 732–1 839 313 284–350 78.7 69.8–82.0

Low 5 846 357 182–445 6.1 3.1–7.6 7 1–9 2.1 0.2–3.2 8 1–9 4.7 0.3–5.7 64.7 41.6–85.9

Other 20 4.4 1.8–5.0 21.5 8.6–24.5 0.3 0.0–0.4 7.7 2.1–17.2 0.3 0.0–0.4 0.3 0.0–0.3 86.0 55.1–89.9

Global 71 146 14 255 13 166–14 638 20.0 18.5–20.6 1 053 987–1 116 7.4 7.0–8.1 5 495 5 429–5 558 843 795–886 80.0 75.6 - 81.6

Page 15 of 21

FIGURES

Fig. 1. Conceptual framework to extrapolate country-level estimates to regions for the cascade of care for HBV and HCV infection

Estimated Disease Burden ModelsStrong input data that have not yet

been approved by countries(N=41)

Compilation of country modelsModels underwent a second

independent review and were compiled for analysis

(N=100)

Cascade of Care Database2015 diagnosed, treated and cured

were extracted from models and analyzed to generate regional

estimates

Cascade of Care DatabaseGBD regional cascade of care

estimates were used as surrogates for countries without models

Approved Disease Burden ModelsModels that have been approved by

local expert panels(N=59)

PubMed + EmbasePrevalenceGenotype

Age distributionRisk factors

Grey LiteratureMOH, UN databasesTreatment databasesTransplant databases

Diagnosed

HCV Disease Burden ModelCountry models were developed

using input from the literature

Global EstimatesCascade indicators for all countries were compiled and divided by the global population to estimate the

global cascade of care

Stratification by WHO and WB region Data were stratified by WHO region

and World Bank Income Group

Syst

emat

ic

Sear

chN

atio

nal

m

od

els

Ext

rap

ola

tio

ns

to g

ener

ate

reg

ion

al e

stim

ate

s

In c

oun

try

revi

ew

Co

un

try-

leve

l E

stim

ates

GB

D re

gio

nal

est

imat

es fo

r co

un

trie

s w

ith

dat

a

Str

ati

fica

tio

ns

GB

D e

xtra

po

lati

on

s to

co

un

trie

s w

itho

ut

dat

a an

d d

evel

op

men

t o

f gl

ob

al e

stim

ates

Sensitivity and Uncertainty AnalysisSensitivity and uncertainty analysis were conducted to generate 95%

uncertainty intervalsUn

cert

ain

ty

Page 16 of 21

Fig. 2. Data available on diagnosis and treatment of HBV infection, by region, adjusted for population size, 2015

AFR: African Region; AMR: Region of the Americas; EMR: Eastern Mediterranean Region; EUR: European Region; SEAR: South-East Asia Region; and WPR: Western Pacific

Region.

Page 17 of 21

Fig. 3. Data available on diagnosis and treatment of HCV infection, by region, adjusted for population sizes

AFR: African Region; AMR: Region of the Americas; EMR: Eastern Mediterranean Region; EUR: European Region; SEAR: South-East Asia Region; and WPR: Western Pacific

Region.

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

AMR (989 million)

AFR (1,000 million)

EMR (654 million)

EUR (914 million)

SEAR (1,945 million)

WPR (1,867 million)

Non-WHO (25 million)

High (1,408 million)

Upper middle (2,393 million)

Lower middle (2,946 million)

Low (644 million)

Other (3 million)

Global (7,394 million)

WH

O R

eg

ion

WB

Inco

me

Gro

up

Diagnosis data distribution, by region (Regional population)

No Data Expert Consensus Published Study National Surveillance

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

AMR (989 million)

AFR (1,000 million)

EMR (654 million)

EUR (914 million)

SEAR (1,945 million)

WPR (1,867 million)

Non-WHO (25 million)

High (1,408 million)

Upper middle (2,393 million)

Lower middle (2,946 million)

Low (644 million)

Other (3 million)

Global (7,394 million)

WH

O R

eg

ion

WB

Inco

me

Gro

up

Treatment data distribution, by region (Regional population)

No Data Expert Consensus Published Study IMS data National Surveillance

Page 18 of 21

Fig. 4. Sensitivity analysis to estimate the impact of regional uncertainties on the global cascade of care for HBV infection, by region, 2015

AFRO: Regional office for the African Region; AMRO: Regional office for the Region of the Americas; EMRO: Regional office for the Eastern Mediterranean Region; EURO:

Regional office for the European Region; SEARO: Regional office for the South-East Asia Region; and WPRO: Regional office for the Western Pacific Region.

Page 19 of 21

Fig. 5. Sensitivity analysis to estimate the impact of regional uncertainties on the global cascade of care for HCV infection, 2015

AFR: African Region; AMR: Region of the Americas; EMR: Eastern Mediterranean Region; EUR: European Region; SEAR: South-East Asia Region; and WPR: Western Pacific

Region.

WH

O R

eg

ion

WB

Inc

om

e G

rou

p

Total Diagnosed Patients Cured, 2015Initiating Treatment, 2015

102%

101%

101%

100%

100%

100%

97%

99%

99%

99%

99%

100%

95% 100% 105%

EUR

SEAR

AFR

AMR

WPR

EMR

102%

100%

100%

100%

97%

99%

99%

100%

95% 100% 105%

Lower middle income

Low income

Upper middle income

High income

104%

100%

100%

100%

100%

100%

98%

99%

99%

99%

100%

100%

95% 100% 105%

EUR

EMR

SEAR

AFR

AMR

WPR

103%

101%

100%

100%

97%

99%

100%

100%

95% 100% 105%

Lower middle income

Upper middle income

Low income

High income

103%

100%

100%

100%

100%

100%

100%

99%

99%

99%

100%

100%

95% 100% 105%

EUR

EMR

SEAR

AFR

AMR

WPR

103%

101%

100%

100%

98%

99%

100%

100%

95% 100% 105%

Lower middle income

Upper middle income

Low income

High income

Page 20 of 21

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