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Hepatitis C prevalence and elimination planning in Pakistan JVH Feb 2023

February 2023
Journal of Viral Hepatitis 2023;00:1–10(J Viral Hepat. 2023;00:1–10.):1-10

Authors:

Muhammad Tariq

University of Washington Seattle

Predictive modeling on HCV Elimination from Pakistan.

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J Viral Hepat. 2023;00:1–10. wileyonlinelibrary.com/journal/jvh

Received: 20 October 2022

Revised: 23 December 2022

Accepted: 30 December 2022

DOI: 10.1111/jvh.13802

ORIGINAL ARTICLE

Hepatitis C prevalence and elimination planning in Pakistan, a

bottom- up approach accounting for provincial variation

Ellen Mooneyhan1 | Huma Qureshi2 | Hassan Mahmood2 | Muhammad Tariq3 |

Nabeel Ahmed Maqbool3 | Masood Anwar3 | Mujahid Aslam4 | Farooq Azam3,5 |

Sarah Blach1 | Aamir Ghafoor Khan4 | Saeed Hamid6 | Tanweer Hussain3 |

Mohammad Khalil Akhter7 | Ambreen Khan3 | Uzma Khan8,9 | Saira Khowaja10 |

Khalid Mahmood11 | Samra Mazhar2 | Ahmad Nawaz4 | Ayub Rose3,5 |

Gul Sabeen Azam Ghorezai12 | Sabeen Shah10 | Syeda Zahida Sarwar3 | Homie Razavi1

Abbreviations: CDAF, Center for D isease Analys is Foundation; DA As, direc t- actin g antivirals; H CC, hepatocel lular carcino ma; HCPs, provi ncial Hepatit is Control Progr ams; HCV,

hepati tis C virus; MoNH SRC, Ministr y of National He alth Servic es, Regulatio ns and Co ordina tion; RN A, ribonucl eic acid; UI, unc ertainty in tervals; WHO, Wo rld Health Org anization.

1Center for Disease A nalysis Foundation

(CDAF), Lafayette, Colorado, USA

2Ministry of National He alth Services,

Regulations and Coordination, Islamabad,

Pakistan

3Chemonics Inte rnational, Lahore,

Pakistan

4Lady Reading Hospital, Peshawar,

Pakistan

5United St ates Agency for International

Develop ment (USAID), Karachi, P akist an

6Aga Khan University a nd Hospitals,

Karachi, Pakistan

7Health D epar tment K hyber

Pakhtunkhwa, Peshawar, Pakistan

8Interactive Research and Devel opment

(IRD) Pakistan , Karachi, Pakistan

9IRD Global, Singapore City, Sing apore

10Indus Hospit al and Health Network ,

Karachi, Pakistan

11Punjab Hepatitis Control Progr amme,

Lahore, Pakistan

12Balochistan H epatitis Control

Programme, Quetta, Pakistan

Correspondence

Ellen Mooneyhan, Center for Disease

Analysis Foundation, 1120 W. South

Boulder Rd, Suite 102, Lafayette, CO

80026 , USA.

Email: ellenjenndugan@gmail.com

Funding information

John C. Martin Foundation; ZeShan

Foundation

Abstract

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treat-

ment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-

HCV prevalence. In the absence of an updated national study, this analysis uses

provincial data to estimate a national prevalence and the interventions needed to

achieve elimination. Using a Delphi process, epidemiologic HCV data for the four

provinces of Pakistan (accounting for 97% of the population) were reviewed with

21 subject- matter experts in Pakistan. Province- level estimates were inputted into a

mathematical model to estimate the national HCV disease burden in the absence of

intervention (Base), and if the World Health Organization (WHO) elimination targets

are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80%

treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated

9,746,000 (7,573,000– 10,006,000) Pakistanis were living with viraemic HCV as of

January 1, 2021; a viraemic prevalence of 4.3% (3.3– 4.4). WHO Elimination would

require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700

new infections prevented anually between 2022 and 2030. Elimination would reduce

total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases

of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data,

and expert panel input uncovered more HCV infections and lower treatment numbers

in the provinces than estim ated using nationa l ext rap olati ons, de monstr ating the ben-

efits of a bottom- up approach. Screening and treatment must increase 20 times and

5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination

by 2030.

KEYWORDS

cascade of care, elimination, hepatitis C, Pakistan, prevalence

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MOONEYHAN e t al.

1 | BACKGROUND AND AIMS

Persons with chronic hepatitis C virus (HCV) are at high risk of de-

veloping advanced- stage liver disease and cancer, however, high

treatment success rates and increased access to direct- acting anti-

virals (DAAs) in recent years have inspired a global movement to-

wards HCV elimination by 2030.1,2 Pakistan has a substantial HCV

disease burden, demonstrated in a 2008 national serosurvey (4.8%

anti- HCV prevalence), and access to care for viral hepatitis has since

been evolving.3 The Prime Minis ter's Programme for Prevention and

Control of Hepatitis was launched in 2005, contributing 13.9 million

PKR (79,089 USD) to support patients unable to afford treatment.4

In 20 09, the first sentinel sur veillance system for viral hepati-

tis in Pakistan was established, and in 2010, provincial Hepatitis

Prevention and Control Programmes (HCPs) in Punjab, Sindh,

Balochistan and Khyber Pakhtunkhwa (KP) became responsible for

program implementation and tracking. By 2011, the Government of

Pakistan began providing free screening, diagnosis and treatment

through the provincial HCPs and introduced a nationwide plan to

reduce the HCV disease burden.4,5 Cure rates in Pakistan have dou-

bled from the early 2000s to 2013, and Pakistan reports one of the

lowest treatment prices globally; generic DAAs are available for $15

USD per month.5

In 2020, the Ministry of National Health Services, Regulations

and Coordination (MoNHSRC) developed the Prime Minister's

Programme for Elimination of Hepatitis C: Annexures to Programme PC- I

(PC- I), with a national goal to screen 50% of the Pakistani popula-

tion from 2020 to 2025 and treat all eligible patients.4 The PC- I pro-

vides screening targets for the initial years of the national program,

outlines the resources needed and demonstrates the political will

to improve care for HCV- infected persons. Recent publications6,7

forecast the interventions needed to achieve the 2030 elimination

targets, defined by the World Health Organization's (WHO) Global

He alth Se c to r Strat egy on vi r al he p ati tis .2 Thes e publ icat ions use th e

seroprevalence survey conducted over a decade ago,3 despite sub-

stantial changes in access to viral hepatitis care and programming

over the past 15 years, and before the global COVID- 19 pandemic

that altered the landscape of HCV prevention, care and treatment.

This analysis builds on the PC- I and models the interventions

needed to achieve the 2030 elimination targets. Center for Disease

Analysis Foundation (CDAF) has been conducting analytics on hepa-

titis for over a decade; prevalence estimates are used as the baseline

for the 2017 WHO's Global Hepatitis Report and serve as the basis

for many countries’ hepatitis elimination efforts.8 As a crucial start-

ing point, we obtained estimates of HCV prevalence and cascade of

care from recent serosurveys and programmatic data from an exper t

panel of provincial leaders. Like many nations, access to viral hepati-

tis care in Pakistan in 2020 and 2021 was impacted by the COVID- 19

pandemic; the effects of which were also considered in this analysis.

The primary aims of this study were to estimate the prevalence of

HCV in Pakistan using a bottoms- up approach (based on data from

the fou r ma jor provinces) and to ev aluate scen ar ios for HC V elimina-

tion at the national level by 2030.

2 | METHODS

2.1 | The analytic approach and model features

2.1.1 | Study design

This anal ys is comb ine s a liter ature review, De lphi pr oce ss, and math -

ematical modelling to estimate the current and future burden of

HCV in Pakistan. We estimated the cascade of care for HCV (viremic

infections, diagnosed, treated) in 2021 and forecasted the HCV

disease burden (new infections, hepatocellular carcinoma [HCC],

decompensated cirrhosis, and liver- related deaths [LRDs]) and inter-

ventions (screens, treatments) by 2030, under both the current care

paradigm and WHO elimination protocol. CDAF has leveraged this

combination of consensus- finding and modelling to develop HCV

disease burden predictions with leaders in 83 countries, publishing

results in over 100 manuscript s.9,10

2.1.2 | Literature review and Delphi process

To begin, a review of published data on the epidemiology of HCV

was completed for the four provinces of Pakistan (Punjab, Sindh, KP,

and Balochistan). A literature search conducted in PubMed with the

terms (‘hepatitis C’ AND ‘prevalence’ AND ‘province’) identified arti-

cles and grey literature published between 1 January 2000, and 31

September 2021 (all languages). A modified Delphi process was then

utilized to access unpublished data from 21 subject- matter experts

(expert panel) recruited from provinces. The expert panel included

representatives from the provincial HCPs, district health depart-

ments, universities, hospitals, the Pakistan Technical Advisory Group

on hepatitis (TAG), the MoNHSRC, and private industry (Section 1 in

Appendix S1). Ten virtual meetings (between two and four meetings

per province) were held from January– September 2021 to review

epidemiologic data inputs and outputs for the model, identify data

gaps, and gain consensus on results.

2.2 | The HCV disease burden model

Th e Mar ko v dis eas e pro gre ssion mo del used in thi s ana lysis was co n-

structed in Microsoft Excel® (Microsoft Corp.) to quantify the size

of the HCV- infected population using country- specific epidemio-

logic data inputs. It underwent an independent review, with meth-

od olo gic al up d at es pu b li she d in 20 22.10,11 In br ief, th e mod e l tra cke d

HCV progression from acute infection to chronic infection (account-

ing for spontaneous clearance) and through end- stage liver disease

and liver- related mortality or cure. Age and sex- specific progression

rates are reported in Section 2 in Appendix S1. The annual number

of new (incident) infections at each stage of the disease was cal-

culated by multiplying annual progression rates times the prevalent

population (stratified by 1- year age cohort and sex) in the previous

disease stage. The model also accounted for all- cause mortality and

MOONEYHAN et al.

was inputted with Pakistan- specific population data and mortalit y

data from 1950 to 2050, and Pakistan- specific HCV epidemiologic

data by year of data availability. The model also calculated the an-

nual number of screens associated with diagnosing a given number

of HCV infections. Starting with the undiagnosed, antibody- positive

population, the model used Pakistan- specific epidemiologic data,

number of screens per person and screening eligibility criteria from

Pakistan (i.e. risk category, age, fibrosis stage, and histor y of screen-

ing, diagnosis, sustained virologic response [SVR]) to calculate the

size of th e pop ulati on in Pakista n eligi ble for scre eni ng, and th e num -

ber needed to screen to diagnose one antibody positive infection.

Available data on viraemic proportion were used to adjust anti- HCV

diagnosed cases and estimate HCV RNA- positive diagnosed cases

for Pakistan. The primary epidemiologic inputs used to customize

the mathematical model for Pakistan are described below in detail.

2.3 | Epidemiologic data inputs

Epidemiologic data for the HCV- infected population in Pakistan

were gathered and inputted into the model, including; background

population, total viremic prevalence, incidence, newly diagnosed,

treated, total diagnosed, and prevalence among high- risk popu-

lations. Data were first collected for each of the four provinces,

Punjab (53%), Sindh (23%), KP (15%), and Balochistan (6%), rep-

resenting 97% of the country, and then combined. The remaining

3% of Pakistan's population resides in the autonomous territories

Gilgit- Baltistan (GB) and Azad Jammu and Kashmir (AJK) and the

federally administered Islamabad Capital Territory (ICT ). Due to in-

sufficient epidemiological data to conduct independent analyses for

these locales, population- weighted estimates were first calculated.

Data were then combined with estimates from the four provinces

to create a national model. In the absence of available data, group

consensus from the expert panel was required to include estimates

in the model.

2.3.1 | Background population

The annual population of Pakistan was available from the United

Nations Database by sex and 5- year age cohort for 1950 to 2030.12

Population estimates by province were available from the Pakistan

census database for 1951, 1961, 1972, 1981, 1998, and 2017, and

da ta wer e trend ed line arly bet ween gap ye ars (i.e . 1952– 196 0 , etc.) .13

Provincial population estimates for the remaining years (2017– 2030)

and the population distribution by 5- year age cohort and sex were

extrapolated from national data.12

2.3.2 | Viraemic prevalence

Anti- HCV prevalence estimates in Punjab (8.9%), Sindh (6.2%),

Balochistan (5.2%), and KP (6.5%) were adjusted for province- specific

viremia (Table 1), weighted by the population, and combined to cal-

culate a prevalence estimate and case count for 97% of the Pakistan

population.4,14– 16 This prevalence estimate was then applied to the

remaining 3% of the country's population to calculate the remaining

cases. Finally, both case counts were summed to compute a national

prevalence (Section 3 in Appendix S1). Ranges were applied to cap-

ture the uncertainty in this estimate.

Viremic prevalence by age and sex was calculated in 2020

using a population- weighted distribution of HCV- RNA (ribonucleic

acid) cases reported from two studies in Sindh and one study in

Punjab,14,15,17 detailed in Section 4 in Appendix S1. When all three

studies’ results were combined, the viraemic prevalence was margin-

ally higher in females, resulting in a national male- to- female preva-

lence ratio of 0.94, with a peak HCV prevalence in ages 35– 39 years.

No HCV serosur veys have been conducted for Balochistan and KP

provinces or other municipalities.

2.3.3 | Incidence

For Balochistan and KP provinces, historical incidence (anti- HCV posi-

tive or HCV- RNA positive infections before spontaneous cure) were

back- calculated using known prevalence and historical risk factors. The

nationwide survey in 20083 and the two prevalence studies available

for Punjab14 and Sindh15 (2018 and 2020, respectively) were used to

calculate the average number of incident cases between these two

time points by province (historical incidence). The four province- level

incidence estimates and population- weighted estimates for the re-

maining 3% of the population were combined to estimate national his-

torical incidence, detailed in Section 5 in Appendix S1. Future incident

cases were assumed to increase/decrease at the same annual rate as

prevalent HCV cases, relative to the last year of incidence data.

2.3.4 | Newly diagnosed and treated

For the public sector, the number of patients diagnosed with viraemic

HCV (adjusted for province- specific viremia) and treated for HCV

was available from the provincial HCPs. Private sector data (N) were

estimated using a proportion diagnosed in the private sector (y%),

given the known number diagnosed in the public sector (x) (treat-

ment data were assumed to follow the same trends) (Equation 1).

The estimated proportion diagnosed (and treated) in the private

sector was supplied by private facilities or clinics involved in HCV

management and from unpublished literature. Punjab was the only

province to report private- sector treatment data (Table 1).

Equation 1: Number of people newly diagnosed (or initiated on

treatment) with viraemic HCV

Based on similarities in access to care, treatment and diagnosis

trends from Punjab were used to calculate population- weighted

(1)

N=x∕(1−y%).

MOONEYHAN e t al.

estimates for ICT, and treatment and diagnosis from KP were used

to compute population- weighted estimates for A JK and GB. When

combined, national newly diagnosed and treated estimates were

164,000 and 215,000, in 2020, respectively.

2.3.5 | Total diagnosed

An estimated 20% of the infected population in Pakistan was diag-

nosed with HCV- RNA by the end of 2019 (n = 1,962,000), calcu-

lat ed usi ng provi nce- level tot al dia gn osis rates (Table 1), weighted by

prevalence in each province.

2.3.6 | High- risk populations

At the end of 2019, 11% of infections in Pakistan were estimated due

to blood transfusion, and 1.2% were estimated to be among people

who injected drugs. This estimate was derived using province- level

estimates (exper ts reported similar risk factors for HCV among all

provinces).

2.4 | Disease burden scenarios

Two scenarios were developed to forecast the course of the HCV

epidemic and quantify the hepatitis disease burden in Pakistan.

The burden of HCV was described using end- stage outcomes in-

cluding HCV- liver related deaths, incident cases of hepatocellular

carcinoma, and incident cases of decompensated cirrhosis. Both

scenarios assumed no treatment restrictions by fibrosis stage and

a 96% SVR (proportion of patients treated who achieve sustained

SVR, or no detectable HCV- RNA, 12 weeks post- treatment) (Section

6 in Appendix S1).

Standard of Care; the absence of targeted interventions for HCV

care and treatment.

Starting with 2018 baseline treatment levels, treatment was pro-

jected to decline 50% between 2019 and 2023 and remain level

thereafter. This scenario assumed adult patients (aged 18 and

older) were eligible for treatment (Section 6 in Appendix S1).

WHO Elimination; achieve the screening goals of the PC- I and the

WHO Elimination Targets for HCV.

Under the assumptions of the PC- I, 50% of the eligible population

aged 12 years and older were screened for anti- HCV, all anti-

positive cases were tested for RNA, and all HCV- RNA positive

cases were treated (patients aged 12 and older were treatment-

eligible) between 2022 and 2025 (Section 7 in Appendix S1). From

2026 to 2030, the remaining eligible population aged 12 years

and older were screened, tested and treated.4 Interventions were

augmented to also achieve the WHO elimination targets by 2030,

TAB LE 1 Hepatitis C epidemiological data inputs by province, Pakistan.

Punjab Sindh Balochistan Khyber Pakhtunkhwa

Value (year of

estimate) Source (s)

Value (year of

estimate) Source (s)

Value (year of

estimate) Source (s)

Value (year of

estimate) Source (s)

Anti- HCV prevalence 8.9% (2018) [14]6.2% (2020) [15]5.2% (2020) [16]6.5% (2018) [4]

Prevalence by age and sex NA [14]NA [15]NA [14,15,17]NA [14,15,17]

Viraemic proportion 59% (2018) [14]62% (2020) [15] 61% (2019) [14,15] 61% (2019) [14,15]

Initiated on treatment 118,700 72,100 660 18,000

Public sector 57,043 (2020) DS, SS 14,432 (2020) SS 230 (2020) SS 11,704 (2020) SS

Private sector 61,658 (2020) DS 80% (2020) EC 65% (2020) EC 35% (2020) EC

Newly viraemic diagnoseda97,9 0 0 4 4,900 1,70 0 14,700

Public sector 39,200 (2020) SS 8,980 (2020) SS 600 (2020) SS 9,560 (2020) SS

Private sector 60% (2020) EC 80% (2020) EC 65% (2020) EC 35% (2020) EC

Total diagnosed 23% (2019) [14] 14% (2019) EC 12% (2020) EC 20% (2019) EC

Abbreviations: DS, drug sales data; EC, expert consensus; NA, not applic able; SS, surveillance system.

aThe estimated proportion of diagnoses occurring in the private sector are drawn from observations in private facilities or clinics involved in HCV management and from unpublished literature.

MOONEYHAN et al.

defined as an 80% reduction in new infections, 90% diagnosis

coverage, and a 65% reduction in mor tality from 2015 to 2030. 2

3 | RESULTS

3.1 | The HCV disease burden

An estimated 9,746,000 (7,573,000– 10,006,000) Pakistanis were

living with viraemic HCV as of January 1, 2021, corresponding to

a viraemic prevalence of 4.3% (3.3– 4.4) (Figure 1). An estimated

462,000 incident infections occurred in 2021, an incidence rate of

20 5 per 10 0,000. By th e end of 2021, 21% (2 ,010 , 0 0 0) of th e 9.7 mi l-

lion viraemic infections had been diagnosed (Figure 1). An estimated

2% (215,000) of the infected population received treatment in 2021,

of which approximately 96% (207,000) achieved SVR (Figure 1).

An estimated 2,865,000 cumulative patients had been treated in

Pakistan historically (through the end of 2021). Each year, approxi-

mately 27,000 Pakistanis die due to HCV- related complications and

20,80 0 Pakistanis develop incident HCC. Provincial experts inde-

pendently reported a decline in HCV diagnosis and treatment from

2019 to 2020, indicating the reduced capacity in hepatitis program-

ming resulting from the COVID- 19 pandemic.

3.2 | Standard of Care projections

Under the Standard of Care, prevalence was estimated to increase

to 10,390,000 infections by 2030, with new incident infections in-

creasing by about 5% (from 463,0 00 infections in 2015 to 490,000

inf ect io ns in 203 0) . Be twe en 2015 an d 20 30, inc id ent HCC was pro-

jected to increase by about 1% (from 25,500 to 25,700 cases), LRDs

were expected to decline nearly 15% (from 36,000 to 31,000 cases)

and incident decompensated cirrhosis was projected to remain

relatively stable (at 19,900 cases) (Figure 1). An average of 807,000

anti- HCV screens were expected annually from 2022 to 2030,

with 180,000 patients treated and 476,00 0 new HCV infections

occurring annually, on average (Table 2). Elimination targets2 would

not be reached under this scenario.

3.3 | WHO Elimination projections

WHO Elimination could be achieved by screening an average of

18,755,000 people annually, treating 1,064,00 0 annually, and re-

ducing new infections by 10% annually (a mean annual reduction

of 46,700 incident infections) (Table 2). Compared to the Standard

of Care, achieving these interventions would result in the following

outcomes from 2015 to 2030; total infections would decline 70%

(reduced by 7,045,000), with 152,000 lives saved and 104,000 inci-

de nt case s of HC C preve nt ed (Figure 2). Between 2022 and 2030, an

additional 9,576,000 patients would need to be treated to achieve

elimination, a mean average of 1,064,000 treated annually (Figure 3).

4 | DISCUSSION

Our analysis found a viraemic prevalence of 4.3% (3.3– 4.4) in

Pakistan in 2021. Converting this statistic for comparison, we es-

timate 7.2% (5.5– 7.3) anti- HCV prevalence in 2021, which captures

the 6.5% prevalence estimated by the MoNHSRC4 within its un-

certainty interval.3 The difference between estimates is likely due

to increased data availability at the province level for this analysis.

Recent blood sur veys conduc ted in Punjab and Sindh14,15,17 and pro-

grammatic data from Balochistan16 found that more people are in-

fected with HCV than previousl y estimated.4 The expert panel in KP

also reported a higher prevalence.4 As well, 124,545 samples were

collected in the three seroprevalence studies in this analysis14 – 16 ;

over 2.5 times larger than the original seroprevalence survey in

which 47,043 samples were collected.3 Unlike the 2008 serosurvey,

however, no prevalence data were available from KP for this study.

An estimated 9.7 million Pakistanis are living with HCV and nearly

27,000 die annually from HCV- related causes. Eliminating HCV in

Pakistan by 2030 could save 152,00 0 lives and prevent 104,00 0

FIGURE 1 HCV cascade of care for

2021 in Pakistan. Includes the total

number of viraemic infections, the

number of viraemic diagnosed patients,

and the number of patients treated and

cured for HCV.

9,746,000

2,010,000

215,000 207,000

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

12,000,000

Viraemic

Infections

Diagnosed Treate

ured

Start of 2021 Through 2021During 2021

21%

96%

MOONEYHAN e t al.

new cases of liver cancer through a scale- up in screening, treatment,

and infection prevention. To begin, Pakistan must screen nearly

18.8 million patients for HCV annually, on average, which is 20 times

the current estimate of 807,000 annual screens. Ensuring provincial

HCPs are coordinated and unified would enable leaders to track and

monitor cases and reduce duplicative screening.18 Integrated test-

ing across multiple disease domains (tuberculosis, HIV, STIs, etc.)

has proven successful to increase outreach, optimize resources and

improve case- finding.19 Routine healthcare evaluations could also

include hepatitis screening. As well, patients previously diagnosed

through hospitals and blood banks could be identified and evalu-

ated retrospectively, and a review of protocols could ensure proper

patient referral.

Access to HCV treatment in Pakistan has increased in recent

years. Treatment expansion is evident in the data; an annual aver-

age of 60,70 0 patients were treated through the Prime Minister's

Programme from 2005 to 2010, and after the launch of the provin-

cial programmes in 2011, annual treatment increased to 230,00 0 in

2015 and again to 35 4,000 in 2018. Dur in g th is time, inte rferon and

combination therapies were replaced with DAA oral drugs which

are short (12 weeks or less), have few side effects, and are effective

in preventing advanced liver disease, cancer, and death. Branded

DAA's were first introduced in Pakistan in 2014, followed by ge-

neric DAAs in 2015, resulting in large- scale local generic production

and a substantial price drop.5 Cure rates improved in- kind; Pakistan

reported a 64% average SVR before 2014 (accounting for the vari-

ation in treatment efficacy by genotype), increasing to a 96% SVR

in 2 0 1 7. 5 Despite making significant strides in treatment access,

additional efforts are needed to eliminate HCV. 215,000 patients

were treated in 2020, suggesting annual treatment must increase

five times to reach the target of >1 million patients treated annu-

ally to achieve elimination. One bottleneck to elimination program-

ming is the availability of specialists to administer treatment. Care

for patients with cirrhosis and decompensation currently must be

managed by gastroenterologists or infectious disease specialists,

however, general practitioners could initiate treatment for most

non- cirrhotic patients since medication dosage and combinations

are fixed. This approach has been successful during several national

program rollouts.2 0,21

To achieve WHO targets, the elimination program must also re-

duce new HC V infections by an average of 46,700 cases each year

(a 10% reduction annually), however, new infections are increasing

(Section 8 in Appendix S1). New infections in Pakistan are mainly

healthcare- associated, spread via improper screening of blood

transfusions (only 50% of blood donations are screened for HCV),22

poor infection control in healthcare settings,23 unsafe community

practices including unnecessary therapeutic injections for common

ailments such as fever and fatigue,24 and sharing shaving razors at

the barber; a major risk factor for males.3 Optimizing a safe and

clean blood supply with the Pakistan Blood Transfusion Authority,

ensuring healthcare providers have access to auto- disable syringes,

and instituting infection control committees in hospitals to track and

reduce new infections, could curb this trend.25

This analysis is subject to limitations, many of which are inherent

to mathematical modelling and forecasting.10,11 The greatest limita-

tion is the availability and quality of data, which affects the accuracy

of forecasts. Uncer tainty intervals address some of these unknowns

but may not capture all sources of bias, including selection bias due

to missing data, sampling bias and measurement bias. In this analysis,

the greatest uncertainty in prevalence was for KP province due to the

lack of data. Applying the lowest estimated prevalence for KP (1.5%

anti- HCV positivity, agreed upon by the expert panel to be the low-

est probable)4 to the model would estimate a 4.1% national viraemic

prevalence, which is within the uncertainty interval. Additionally,

one of the three studies used to estimate HCV prevalence by age

and sex was likely sampled in a high- prevalence district. However,

since the sampling technique of this study was of high quality, and

since age- specific prevalence estimates were combined with two

other sources and weighted for the total population of Pakistan,

the national prevalence was not af fected. Another study limitation

is the lack of private- sector data. In combination with high- quality

programmatic data for the public sector combined with expert panel

discussions with practising healthcare practitioners, we believe the

best possible estimates for the private sector were utilized. Expert

panel discussions also strengthened the analysis results. As practis-

ing healthcare workers in their respective regions, experts helped

to conserve the heterogeneity of epidemiologic data by province

within the national estimate. In the absence of an updated national

serosur vey and with the existence of robust, provincial programmes,

conducting local- level analyses was a crucial step to assess the cur-

rent state of HCV in Pakistan.

CDAF facilitators are trained to identify and challenge assump-

tions and cognitive biases, gather balanced feedback from multiple

sources and engage local representatives through the Delphi pro-

cess. This was particularly evident when discussing the distribu-

tion of HCV care by sector. In previous MoNHSRC analyses, 60%

of national treatments and 60% of diagnoses in Pakistan were es-

timated to occur in the private sector. This analysis found varying

proportions for the private sector by province, ranging from 35% to

80% ( Table 1). While the average of this range remains 60%, apply-

ing 60% of treatments in the private sector to each province would

increase the total number of patients treated in Pakistan in 2020 by

15% (from 215,00 0 to 248,000). Local input ensured that the differ-

ences in health infrastructure and access to care by province were

incorporated.

Provincial expert panels independently reported a decline in

HCV diagnosis and treatment from 2019 to 2020, demonstrating

attrition of hepatitis programming due to the COVID- 19 pandemic.

The report was unable to address the duration of recovery from

the COVID- 19 pandemic (after 2020) or the effects of destabiliza-

tion due to conflict in and around the region, as these are global

unknowns. However, the base scenario was designed to be less op-

timistic, by simulating reduced interventions into the future. To ac-

count for programmatic delays, the elimination plan was also offset

by 1 year. One benefit of modelling analytics is that, after a baseline

is established, forecasts can be revised readily as new data become

MOONEYHAN et al.

TAB LE 2 Screening, treatment and reduction in new infections by scenario, Pakistan, 2022– 2030

2022 2023 2024 2025a2 026 2027 2028 ≥2029

Annual

average

Anti- HCV screens

Standard of Care 807,000 807,000 807,000 821,000 814,000 810,000 804,000 798,000 807,000

WHO Elimination 9,410,000 22,595,000 19,753,000 11,619,000 22,619,000 22,365,000 21,994,000 21,474,000 18,755,000

HCV RNA PCR screens

Standard of Care 188,000 188,000 189,000 193,000 192,000 192,000 192,000 191,000 191,000

WHO Elimination 595,000 1,441,000 1,289,000 776,000 1,517,000 1,528,000 1,543,000 1,569,000 1,292,000

Initiated on HCV treatment

Standard of Care 180,000 180,000 180,000 180,000 180,000 180,000 180,000 180,000 180,000

WHO Elimination 491,000 1,189,000 1,060,000 636,000 1,240,000 1,240,000 1,240,000 1,240,000 1,064,000

New HCV infections

Standard of Care 463,000 467,000 470,000 472,000 475,000 479,000 483,000 487,000 476,000

WHO Elimination 463,000 431,000 353,000 288,000 245,000 209,000 157,000 123,000 262,000

WHO Elimination – New

infections to prevent

(from previous year)

– 32,000 78,000 65,000 43,000 36,000 52,000 34,000 46,700

Abbreviations: HCV, hepatitis C virus; PCR, polymerase chain reaction; RNA, ribonucleic acid; WHO, World Health Organization.

aThe decline in screening and treatment projected for 2025 in the WHO Elimination scenario was extracted from the Prime Minister's Programme Annexures (PC- I), Section 7 in Appendix S1.

MOONEYHAN e t al.

available. The disease projection and forecasting component s of the

model also allowed us to leverage data from various years and loca-

tions across Pakistan to create a standardized cascade of care and

elimination plan.

Implementing a national hepatitis elimination program requires

engagement from governmental authorities, healthcare provider

associations, patients, and patient representatives at the national

and subnational levels early on in strategic planning. This analysis

FIGURE 2 Hepatitis disease burden outcomes by scenario in Pakistan, 2015– 2030. (A) Total viraemic HCV infections. (B) Incident cases

of HCV- liver related deaths. (C) Incident cases of hepatocellular carcinoma. (D) Incident cases of decompensated cirrhosis

6,000

12,000

18,000

24,000

30,000

Standard of Care WHO Elimination

5,000

10,000

15,000

20,000

25,000

Standard of Care WHO Elimination

3,000,000

6,000,000

9,000,000

12,000,000

Standard of Care WHO Elimination

8,000

16,000

24,000

32,000

40,000

Standard of Care WHO Elimination

(B)(A)

(D)(C)

FIGURE 3 Cumulative number of patients treated for hepatitis C by scenario, 2004– 2030. For 2004– 2020, the annual number of

patients treated for HCV was compiled from provincial Hepatitis Control Program data for the public sector and, for the private sector,

estimates were gathered from exper t obser vations in private facilities/clinics involved in HCV management and/or unpublished literature.

For 2021– 2030, treatment estimates were based on the current treatment trends (Standard of Care) and number of treatments needed to

achieve the WHO Targets for HCV elimination (WHO Elimination).

2,800,000

5,600,000

8,400,000

11,200,000

14,000,000

WHO Eliminaon Standard of Care

MOONEYHAN et al.

allowed key hepatitis stakeholders in Pakistan to examine the

needs of each region, and gain consensus on the current state of

care and steps forward. Results can be leveraged to update the

national elimination plan and inform public health decision- making

as the country recovers from the pandemic and refocuses effor ts

on HCV elimination.

FUNDING INFORMATION

This analysis was funded by a grant from the John C. Martin

Foundation and ZeShan Foundation. The funders had no role in

the study design, data collection, data analysis, interpretation of

data, decision to publish or preparation of the manuscript. E.M.,

S.B. and H.R. had access to the raw data. The corresponding author

had full access to all data and the final responsibility to submit for

publication.

CONFLICT OF INTEREST

E.M., S.B. and H.R. are employees of CDAF. CDAF has received re-

search funding from Gilead, AbbVie and Vaccine Impact Modelling

Consortium in past years. CDAF has also received grants from CDC

Foundation, John Martin Foundation, ASTHO, Zeshan Foundation

and private donors.

DATA AVAILAB ILITY STATE MEN T

For a period of 1 year after publication, the authors will share the

data used in the figures in an Excel format after a writ ten request

to the corresponding author. Data sharing will be limited to gov-

ernment agencies, academic institutions and non- profit organiza-

tions, and will not apply to for- profit or consulting organizations.

Additionally, select data from the manuscript will be available pub-

licly on the Polaris Observatory Website https://cdafo und.org/polar

i s - c o u n t r i e s - d a s h b o a r d /

ETHICAL APPROVAL

Ethics approval was not required for this study as it does not involve

human participation or personally identifiable data/information.

PATIENT CONSENT STATEMENT

Patient consent was not required for this study as it does not involve

human participation.

PERMISSION TO REPRODUCE MATERIAL FROM

OTHER SOURCES

This analysis does not include any previously published material.

ORCID

Ellen Mooneyhan https://orcid.org/0000-0003-2281-8105

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SUPPORTING INFORMATION

Additional supporting information can be found online in the

Suppor ting Information section at the end of this article.

How to cite this article: Mooneyhan E, Qureshi H, Mahmood

H, et al. Hepatitis C prevalence and elimination planning in

Pakistan, a bottom- up approach accounting for provincial

variation. J Viral Hepat. 2023;00:1-10. doi:10.1111/jvh.13802

ResearchGate has not been able to resolve any citations for this publication.

Increased integrated testing for HIV, hepatitis C and sexually transmitted infections in health care facilities: results from the INTEGRATE Joint Action pilots in Lithuania, Romania and Spain

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Initial success from a public health approach to hepatitis C testing, treatment and cure in seven countries: The road to elimination

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With political will, modest financial investment and effective technical assistance, public sector hepatitis C virus (HCV) programmes can be established in low- and middle-income countries as a first step towards elimination. Seven countries, with support from the Clinton Health Access Initiative (CHAI) and partners, have expanded access to HCV treatment by combining programme simplification with market shaping to reduce commodity prices. CHAI has supported a multipronged approach to HCV programme launch in Cambodia, India, Indonesia, Myanmar, Nigeria, Rwanda and Vietnam including pricing negotiations with suppliers, policy development, fast-track registrations of quality-assured generics, financing advocacy and strengthened service delivery. Governments are leading programme implementation, leveraging HIV programme infrastructure/financing and focusing on higher-HCV prevalence populations like people living with HIV, people who inject drugs and prisoners. This manuscript aims to describe programme structure and strategies, highlight current commodity costs and outline testing and treatment volumes across these countries. Across countries, commodity costs have fallen from >US

100 per diagnostic test and US

750–US

900 per 12-week pan-genotypic direct-acting antiviral regimen to as low as US

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8·1 billion, reducing to

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Full-text available

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Abstract Blood transfusions are contributing to a higher rate of hepatitis C virus (HCV) in Pakistan. Half of all blood transfusions in Pakistan are not screened for hepatitis C, hepatitis B or HIV. Family members donate blood that is likely not tested due to social stigma attached to HCV. Paid donations are also quite common in the country, especially by people who inject drugs (PWID), which increases the population’s exposure to HCV. Most of the population utilizes the private sector for their health needs; this sector has lax regulation due to the lack of oversight by the government or any other regulatory body. In addition, groups who are at most need for blood transfusions, such as hemophiliacs and those with thalassemia, have a higher rate of hepatitis C. This fact reinforces the need for blood transfusion reform in Pakistan, which includes improving oversight, upgrading infrastructure and promoting health literacy through cultural norms, according to the World Health Organization (WHO) recommendations. The lessons learned in Pakistan can be adapted to countries facing similar issues. Keywords: Pakistan,

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Content available: Audio Recording

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Auto-disable (AD) syringes are specifically designed to prevent syringe reuse. However, the notion that specific AD syringe designs may be unsafe due to reuse concerns related to the syringe’s activation point has surfaced. We conducted a systematic review for evidence on the association between AD syringe design and syringe reuse, adverse events following immunization (AEFI), or blood borne virus (BBV) transmission. We found no evidence of an association between AD syringe design and unsafe injection practices including syringe reuse, AEFIs, or BBVs. Authors of three records speculated about the possibility of AD syringe reuse through intentionally defeating the disabling mechanism, and one hinted at the possibility of reuse of larger-than-required syringes, but none reported any actual reuse instance. In contrast to AD syringes, standard disposable syringes continue to be reused; therefore, the global health community should expand the use of AD syringes in both immunization and therapeutic context as an essential strategy for curbing BBV transmission.

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The Lancet Gastroenterology & Hepatology Commission Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission

Article

Feb 2019

Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.