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BARRIERS AND STRATEGIES FOR HEPATITIS B AND C ELIMINATION IN PAKISTAN

Huma Qureshi,
Huma Qureshi
Gastroenterologist and National Focal Point Hepatitis, Hepatitis Control,
Ministry of National Health Services
,
Regulations and Coordination, Islamabad
,
Pakistan
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Hassan Mahmood,
Hassan Mahmood
In-Charge Hepatitis Planning, Development and Monitoring Unit, USAID Funded GHSC
PSM Project seconded at Ministry of Health, Hepatitis Control, Ministry of
National Health Services
,
Regulations and Coordination, Islamabad
,
Pakistan
Correspondence: Dr. Hassan Mahmood MBBS (PAK), MPH (UK), FRSPH (UK); House 86,
Street 44, Sector F-10/4, Islamabad, Pakistan (hassanmahmood1@hotmail.com).
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Ahmed Sabry,
Ahmed Sabry
Universal Health Coverage/Department of Communicable Disease Prevention and
Control, World Health Organization Regional Office for the Eastern Mediterranean
,
Cairo
,
Egypt
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Joumana Hermez
Joumana Hermez
Universal Health Coverage/Department of Communicable Disease Prevention and
Control, World Health Organization Regional Office for the Eastern Mediterranean
,
Cairo
,
Egypt
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The Journal of Infectious Diseases, Volume 228, Issue Supplement_3, 15 September
2023, Pages S204–S210, https://doi.org/10.1093/infdis/jiad022
Published:
13 September 2023
Article history
Received:
01 December 2022
Editorial decision:
21 January 2023
Accepted:
21 January 2023
Published:
13 September 2023

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CITE

Huma Qureshi, Hassan Mahmood, Ahmed Sabry, Joumana Hermez, Barriers and
Strategies for Hepatitis B and C Elimination in Pakistan, The Journal of
Infectious Diseases, Volume 228, Issue Supplement_3, 15 September 2023, Pages
S204–S210, https://doi.org/10.1093/infdis/jiad022

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ABSTRACT

Background

Pakistan has a high hepatitis burden for both hepatitis C virus (HCV) and
hepatitis B virus (HBV). To achieve World Health Organization (WHO) 2030 targets
for hepatitis elimination, there is a need to constitute progress in the
country, find the barriers and strategies for HCV elimination, and take actions
to address the gaps.

Methods

We collected data from (1) WHO estimates in 2020, (2) midterm review
questionnaire of the WHO regional action plan, and (3) WHO estimates on
immunization. We analyzed these data to inform (1) the burden defined as
prevalence and mortality and (2) response in 3 thematic areas: governance,
policy, and finance; strategic information; and service delivery.

Results

The prevalence of hepatitis B in the general population is 1.6% with 12 000
deaths/year. The prevalence of hepatitis C in the general population is 7.5%
with 19 000 deaths and 545 000 new cases (incidence)/year. The selected
indicators to monitor progress on viral hepatitis in Pakistan were governance
and financing, policies and guidelines, and strategic information. The overall
governance indicators are good with a focal point, a national hepatitis
strategy, an operational plan, strategy for price reduction, and involvement of
civil society but the costed action plan and the advocacy strategy are missing.
The indicators on policies and guidelines are also adequately addressed. The
hepatitis B and C testing and treatment guidelines are available, there is a
policy to screen all blood donations, and there is an injection safety policy,
but the policy for timely hepatitis B vaccine birth dose and hepatitis B
vaccination for the vulnerable is missing. Both indicators regarding strategic
information, that is measures of key hepatitis indicators and regular data
review, are missing. The status of 5 key interventions in Pakistan show that the
hepatitis B vaccination coverage is 74% and only 3% of newborn children are
given the hepatitis B vaccine birth dose. Only 22% of HCV cases have been
diagnosed and 2% have received treatment. Treatment response is 96%. Same-day
testing and treatment of hepatitis C reduced the overall dropout rate and
improved the cascade of care. Decentralization and task shifting are important
tools to improve service delivery and reach communities. Finances to implement
hepatitis elimination is a major barrier.

Conclusions

Pakistan has the highest hepatitis disease burden. With the current pace,
hepatitis elimination appears impossible. Introduction of the birth dose of
hepatitis B vaccine and improving access and affordability of testing can
improve the testing and treatment numbers. Finances need to be mobilized from
within the country and outside to support disease elimination.

hepatitis elimination, Pakistan, eastern Mediterranean region (EMR), global
health sector strategy (GHSS), regional action plan (RAP), testing, treatment,
viral hepatitis
Topic:
* hepatitis
* hepatitis b
* hepatitis c
* child
* pakistan
* safety
* world health organization
* viral hepatitis
* hepatitis b vaccines
* hepatitis c virus

Issue Section:
Supplement Article

The World Health Organization (WHO) emphasized hepatitis as a global public
health problem and launched the global health sector strategy (GHSS) on human
immunodeficiency virus (HIV), viral hepatitis, and sexually transmitted
infections 2022–2030 [1]. The GHSS has a vision and goals set towards
elimination of viral hepatitis as a public health threat by 2030 along with a
regional action plan (RAP) for the implementation of the GHSS [2, 3]. Pakistan
developed its National Strategic Framework 2017–2022 [4], followed by its action
plan for 2 larger provinces [5].

By the end of 2020, the eastern Mediterranean region (EMR) had almost 12 million
people living with hepatitis C virus (HCV). The disease prevalence in the region
is 1.6% with 31 000 yearly deaths. The HCV incidence is 470 000 new
infections/year, which is the highest in the EMR [6]. Pakistan is contributing
to the largest hepatitis C burden [2]. For HBV, over 85% of the burden lies with
Egypt, Pakistan, Somalia, Yemen, and Sudan [2, 7, 8]. Facing this burden, the
region has shown a modest progress in the response to viral hepatitis in most
countries while excellent progress was noted in Egypt [6].

Pakistan is the largest and the most populous country in the EMR. The hepatitis
B virus (HBV) prevalence in Pakistan is 1.1% and that for anti-HCV is 7.5%,
which translates to 2 million people living with hepatitis B surface antigen
(HBsAg), 16 million who are anti-HCV positive [9, 10], and 9.8 million are
viremic [11]. Currently, Pakistan has the second highest HCV burden in the world
[12]. WHO recommends 5 key intervention targets for achieving the elimination of
hepatitis B and C [13]. These are (1) vaccination against hepatitis B, (2)
prevention of mother to child transmission of hepatitis B, (3) safe injections
and blood transfusion, (4) harm reduction, and (5) hepatitis B and C testing and
treatment. There is a need to evaluate the response to viral hepatitis in
Pakistan in view of the elimination agenda and WHO recommendations. Given the
share of disease burden that is borne by Pakistan, the country's progress in the
elimination of viral hepatitis may impact the regional and global progress
indicators towards achieving the goal of hepatitis elimination. Findings from
this review should help the government of Pakistan to constitute progress as of
2022, as well as identify its opportunities and challenges towards global
targets. This should also inform the country’s directions towards the
implementation of the new WHO Global Strategy 2022–2030 and the new RAP
2022–2030.

METHODS

We conducted a desk review of different sources of data. We structured the input
from all the data sources to describe the context of viral hepatitis in Pakistan
along 2 dimensions: (1) burden, defined as prevalence and mortality attributed
to viral hepatitis B and C; and (2) response along key strategic areas, namely
governance and finance, policies and guidelines, and strategic information. The
main data sources reviewed were the midterm review from EMR RAP [6], WHO and
UNICEF estimates 2020 [7, 8], national hepatitis testing and treatment
guidelines [14, 15], Center for Disease Analysis (CDA) final assumptions for
Pakistan [11], national hepatitis strategic framework and national action plans
[4, 5], provincial data from hepatitis control programs [16], data from local
microelimination projects [17–19], as well as from related published
international literature. In this analysis, data collected in 2019 and published
by WHO in the midterm review of the EMR are presented.

DATA ANALYSIS

We compared the Pakistan-specific data extracted from different sources to the
global targets set by WHO in the GHSS to assess progress. We developed the
cascade of care to determine key bottlenecks in access to hepatitis diagnosis,
treatment, and care.

RESULTS

BURDEN OF DISEASE

The burden of hepatitis B and C in Pakistan as of 2019 is shown in Table 1. The
prevalence of hepatitis B in the general population was 1.6%, while it was 0.3%
for children younger than 5 years. The number of deaths caused by HBV and its
complications was 12 100 per year. The prevalence of hepatitis C in the general
population was 7.5% with an incidence of 454 000/year. Yearly, about 19 000
people died of HCV and its complications.

Table 1.
Open in new tab

Burden of Viral Hepatitis B and C in Pakistan in 2019

Measure . Value . Hepatitis B Prevalence of hepatitis B infection among the
general population1.6% Prevalence of hepatitis B infection among children
younger than 5 y0.3% Hepatitis B incidence, No. of new cases30 400 No. of deaths
caused by HBV infection12 100Hepatitis C Prevalence of hepatitis C infection
among the general population at start of 20197.5% Hepatitis C incidence, No. of
new HCV cases454 000 No. of deaths caused by HCV infection19 000

Table 1.
Open in new tab

Burden of Viral Hepatitis B and C in Pakistan in 2019

In 2020, the hepatitis C testing and treatment data collected from all provinces
was shared with the CDA and they undertook modeling of the HCV situation in
Pakistan. As of 2020, 9.8 million people had viremic infection nationally, with
a viremic prevalence of 4.3% and viremic rate of 60% (Table 2).

Table 2.
Open in new tab

Results of the National Analysis Done by the Center for Disease Analysis in 2020

Epidemiological Data . Year of Data . National Analysis . Province-Combined
Analysis . Viremic infections20207 582 0009 807 000Viremic
prevalence20203.4%4.3%Viremic rate202057%60%Treated2020No data209 500Newly
diagnosed2020No data159 200Previously diagnosedThrough 20191 930 0001 870 000New
infections2020411 000454 000

Table 2.
Open in new tab

Results of the National Analysis Done by the Center for Disease Analysis in 2020

GOVERNANCE

The status of some selected indicators for governance and financing, policies
and guidelines, and strategic information for viral hepatitis in Pakistan for
2022 are shown in Table 3. At the national level, the governance is strong with
a focal point, a national hepatitis strategy, an operational plan, strategy for
drug price reduction, and involvement of civil society, but the costed action
plan and the advocacy strategy are missing. However, launch of the national
hepatitis C program was delayed due to the coronavirus disease 2019 (COVID-19)
pandemic, therefore provinces continued with their provincial hepatitis testing
and treatment program. Similar arrangements are present at the provincial level
where provincial programs are established and provincial action plans for the
implementation of the national strategies have been developed in 2 out of the 4
provinces. Policies and guidelines for most areas of the hepatitis response are
also in place. The hepatitis B and C testing and treatment guidelines are
available; a policy to screen all blood donations and a policy on injection
safety have been developed. However, policies for timely hepatitis B vaccine
birth dose and hepatitis B vaccination for the vulnerable are missing.

Table 3.
Open in new tab

Status of Selected Indicators for Governance and Financing, Availability of
Policies and Guidelines, and Strategic Information for Viral Hepatitis in
Pakistan 2022

Indicator . Status . Governance and finance Presence of a focal unit, or a
personYes Availability of a national strategy, or an operational
planYes Availability of a costed action planYes Availability of fund to
implement the costed action planNo Availability of a strategy for price
reductionYes Civil society involvementYesAvailability of policies and
guidelines Availability of an advocacy strategyNo Availability of guidelines for
diagnosis and testing of HBV and HCVYes Availability of guidelines for hepatitis
B and C case management and treatmentYes Presence of a policy for screening of
blood donationsYes A policy for timely hepatitis B vaccine birth doseNo A policy
to integrate hepatitis B vaccination for the vulnerableNo A policy for injection
safetyYesStrategic information Measures of key hepatitis indicatorsNo Data
reviewed regularlyNo

Table 3.
Open in new tab

Status of Selected Indicators for Governance and Financing, Availability of
Policies and Guidelines, and Strategic Information for Viral Hepatitis in
Pakistan 2022

PROGRESS IN 5 KEY INDICATORS

Progress in the 5 key interventions compared to the global targets is shown in
Table 4. Pakistan has missed all the global targets for 2020, and stands too far
from achieving the 2030 targets in all indicators of the viral hepatitis
response.

Table 4.
Open in new tab

Progress in 5 Key Interventions for Viral Hepatitis in Pakistan 2022 Compared to
the Global Targets

Interventions . Indicators . Pakistan 2022 [Reference] . Global Targets
2020 . Global Targets
2030 . Hepatitis B vaccinationCoverage of third dose of hepatitis B vaccine
among infants, %74 [8]9090Mother to child transmission of HBVCoverage of timely
hepatitis B vaccine birth dose within 24 h, %3 [22]5090Blood safetyBlood
screening coverage, donations screened with quality assurance, %…95100Injection
safetyProportion of unsafe injections, %…00Harm reductionNo. (%) of sterile
needles and syringes per person who injects drugs per year46 [23]200 (50)300
(75)HBV testing% HBV-infected diagnosed…3090HCV testing% HCV-infected
diagnosed22 [11]3090HBV treatment% Diagnosed with HBV on treatment…5Million80HCV
treatment% Diagnosed with HCV started on treatment2 [11]3Million80

Table 4.
Open in new tab

Progress in 5 Key Interventions for Viral Hepatitis in Pakistan 2022 Compared to
the Global Targets

HEPATITIS B VACCINATION AND PREVENTION OF MOTHER TO CHILD TRANSMISSION

Hepatitis B 3-dose vaccination coverage is 74% and only 3% of newborn children
are given the hepatitis B vaccine birth dose. Only 22% of HCV cases have been
diagnosed and 2% have received treatment.

BLOOD SAFETY

In blood safety, Pakistan is struggling in ensuring 100% safe blood. Although no
figure exists on the percentage of blood donations screened in a quality assured
manner, there are proxy measures that reflect unsafe transfusion. Waheed et al
[20], published a review of HBV and HCV prevalence among a multitransfused
group, namely beta thalassemia major patients. In this study, the overall pooled
prevalences of HBV and HCV in this population group were 4.13% and 29.79%,
respectively.

INJECTION SAFETY

No recent data are available on the proportion of unsafe injections in Pakistan.
However, repeated outbreaks of HIV have been associated with unsafe injections,
indicating challenges in injection safety [21, 22, 23].

HARM REDUCTION

Pakistan has had a harm reduction program comprising needle and syringe exchange
since the year 2000, implemented by the nongovernmental organization Nai Zindagi
[24]. Supported by the Global Fund to fight AIDS, Tuberculosis, and Malaria, Nai
Zindagi's needle and syringe program has reached 45.3% of persons who inject
drugs in the country [25]. As a result, UNAIDS estimates that Pakistan provides
46 syringes per person who injects drugs per year.

TESTING AND TREATMENT

According to the CDA modelling in 2020 (Table 2), only 2.16 million (22%) have
been diagnosed with hepatitis C and only 215 000 (2%) have been treated.
Treatment response is 96%. There is lack of data on hepatitis B testing and
treatment coverage in Pakistan. Figure 1 presents the cascade of hepatitis C
care in Pakistan.

Figure 1.

Cascade of care for hepatitis C in Pakistan prepared in 2020 by the Center for
Disease Analysis (CDA).

Open in new tabDownload slide

SUCCESS STORIES

In one Union Council of Nankana Sahib, Punjab, 29 500 people (96% of the total
population of this Union Council) were screened for hepatitis B and C, those
negative in hepatitis B testing were vaccinated, those positive for hepatitis B
were referred to care, and those HCV positive were treated for HCV. In the
project an awareness campaign was conducted using mobile vans where
announcements were made using loud speakers on free screening, testing, and
treatment services at the designated health facility. This campaign resulted in
a massive turn out of patients to the health facility.

An HCV microelimination project was implemented in 17 slums of Islamabad
(federal capital of Pakistan) where 50 000 people from the underserved
population were screened, tested, and treated for HCV infection using a
public-private partnership. The community outreach services were used where
people were tested at their doorsteps and positive cases were referred to a
public sector primary health care dispensary for HCV RNA testing and dispensed
treatment the same day. For posttreatment sustained virologic response (SVR)
testing, those who did not come were followed up by the community workers and
referred to the testing site. The same-day testing and treatment led to high
treatment initiation (98.5%) with low loss to follow-up (10%).

In another microelimination project in the general population, although 93.7%
cases were initiated treatment but 41% were lost to follow-up for SVR because we
could not find them at their homes. The cascade for care for the 2 studies are
shown in Figure 2 and Figure 3, with 98% cure rates using locally produced
direct-acting antivirals (DAAs).

Figure 2.

Cascade of hepatitis C microelimination pilot project in urban slums of
Islamabad, 2 March 2019 to 13 April 2022.

Open in new tabDownload slide
Figure 3.

Cascade of care for hepatitis C in the general population of Pakistan.

Open in new tabDownload slide

DISCUSSION

Pakistan can be considered to be a country with intermediate endemicity for
hepatitis B and high endemicity for hepatitis C, with prevalence of HBsAg and
anti-HCV of 1.3% and 7.5%, respectively. The HBV prevalence is showing a
reduction in adults, from 2.5% in 2008 [26] to currently 1.3% [10]. This
prevalence remains above the regional prevalence, which is 0.8%. In children
younger than 5 years, HBV prevalence in Pakistan was 1.3%, which has dropped to
0.3% [9, 10, 26]. Better coverage of childhood vaccination is the main reason
for this drop. Coverage of a timely birth dose of hepatitis B vaccine remains
very low in Pakistan. Notably, low coverage of a timely birth dose is low in the
EMR as a whole (34%), with variation between countries. Pakistan has to improve
its childhood vaccination coverage and introduce universal hepatitis B vaccine
birth dose to achieve the global target of less than 0.1%, which, being the
largest EMR country, would eventually impact the regional-level targets.

The HCV prevalence increased from 5% in 2008 to 7.5% in 2019 [9, 10, 20]. Almost
454 000 new infections occur yearly [11]. The main factors behind the HCV spread
are improperly screened blood, unsafe therapeutic injections, and poor infection
control in health settings [9, 10, 26]. EMR has the highest rate of unsafe
injections [27], mainly driven by the rate of unsafe injections in Pakistan.
Although Pakistan has policies for safe blood, safe injections, and infection
control, their implementation is weak. In Pakistan, an average of 5 injections
per person per year are given, which is the highest in the region [28]. These
issues are being addressed through establishment of blood transfusion
authorities in each province, hepatitis prevention act in the provinces, and a
ban on multiple-use syringes in health care settings and replacing them with
auto-disable syringes. The behavior changes and communication strategies to
change the population's demand for injections, as well as health care worker's
offer of therapeutic injections, are being developed in parallel to address
these issues. The repeated outbreaks related to unsafe injections in Pakistan,
the latest of which was an outbreak of HIV in the general population including
children in Larkana, which strongly demonstrates the need for enforcing the
implementation of those strategies [29, 30].

The WHO Eastern Mediterranean Regional Office conducted a midterm review of the
implementation of its RAP for the GHSS 2016–2021. Data from this review show
that only Egypt, Pakistan, and Morocco have undertaken hepatitis serosurveys. To
monitor the progress on the testing and treatment of hepatitis cases, electronic
data collection is clearly needed. In Pakistan, only the Punjab hepatitis
program is using an electronic data system to provide real-time data, while
other provinces are using paper-based data. It is time for other provinces to
move from paper entry to electronic to monitor real-time data.

In governance and financing, Pakistan, like most EMR countries, has developed
its national strategies and action plans. They have established good governance
mechanisms, policies, and strategies towards hepatitis elimination but finances
remain a major barrier to the implementation of HCV elimination in the region
[6]. Modeling by the US Center of Data Analysis has shown that Pakistan needs to
enhance its testing and treatment by 5 times and reduce infections by 10% each
year to achieve the HCV elimination targets for 2030 [11]. Many modelers have
also used Pakistan to build a case for investing in hepatitis elimination and
all have reported that Pakistan needs to invest a lot to achieve HCV elimination
[31–34]. The Prime Minster of Pakistan had also decided to launch an HCV
elimination program from 2020 to 2030 and its total budget was calculated as
Pakistani rupee (PKR) 7 billion per year or PKR 74 billion in 10 years [35].
This program could not be launched due to COVID-19 and changes in the
leadership, and the national plan for hepatitis elimination in Pakistan remains
largely unfunded. Provinces invest relatively small amounts in hepatitis control
and their investment remains too modest to make an impact on the epidemic. Egypt
has been the first country to allocate US$ 260 million from domestic funding
from 2017 to 2020 [36]. Currently it is screening, testing, and treating HCV in
children and adolescents and high-risk populations, including renal dialysis
patients and persons who inject drugs [37]. Furthermore, involving civil society
and patients’ groups has also been found to be a an effective way to achieve
allocation of funding [38].

As shown in the cascade of care, only a small proportion (22%) of people living
with hepatitis C have been diagnosed and a very small number have received
treatment. In contrast, there is a lack of data on access to diagnosis and
treatment for hepatitis B. Although Pakistan is producing DAAs and the
nucelos(t)ide analogues [39], in Pakistan many patients are unable to start
treatment because of the high cost of viral testing and the expertise required
for polymerase chain reaction (PCR) testing. To get a larger number of the
population screened at their doorstep, there is a need to introduce self-testing
in the population, along with enhanced testing and treatment of hepatitis C in
Pakistan. Efforts should be made to set up a system for transporting blood
samples to the laboratory for PCR testing, so that patients do not have to
travel for testing. Similarly, dispensing of medicines should also be done from
the health facility in the community. The situation is similar in other EMR
countries, apart from Egypt, which by the end of 2019 had tested around 60
million people and treated over 2.3 million people [36]. With this effort, Egypt
has brought the HCV prevalence down from 13% to less than 2% [40].

CONCLUSIONS

The elimination of hepatitis B and C hepatitis by 2030 will be difficult to
achieve if Pakistan and other EMR countries continue to move at the current
pace. The success stories presented in this review provide promising models for
rapidly scaling up hepatitis testing and treatment, towards elimination.
Self-testing at the community level and reflex testing for PCR can play a major
part in improving the cascade of care. Oru et al conducted a meta-analysis that
illustrated the importance of task shifting, decentralization, and integration
in improving access to hepatitis C testing and treatment [41]. Similarly, 2
studies in Pakistan found that same-day testing and treatment under one roof can
improve the linkage to care in HCV-positive cases, as seen in some
microelimination projects [17, 18]. Both these studies demonstrated task
shifting and decentralization as a successful model in accessing larger
population in Pakistan. Furthermore, low-priced but efficient and sensitive
point-of-care tests and self-testing can be game changers, and these should be
introduced in EMR, especially in Pakistan, to accelerate the HCV elimination
plan.

NOTES

Supplement sponsorship. This article appears as part of the supplement “Current
Barriers and Strategies Toward HCV Elimination Globally,” sponsored by Gilead
Sciences Hong Kong Ltd.

Potential conflicts of interest. All authors: No reported conflicts of interest.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts
of Interest. Conflicts that the editors consider relevant to the content of the
manuscript have been disclosed.

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