Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination

Abstract

Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide.

Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets.

Results: With no further treatment (currently ∼150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually.

Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan's HCV burden will increase markedly.

Figure 1

A schematic illustration showing the structure of the full mathematical model, which incorporates (a) demographic characteristics of the population, including stratification by gender and age, (b) medical and community risk factors that contribute to HCV transmission, and (c) the infection dynamics of the HCV epidemic with disease progression stages. High medical risk is defined as having either over 5 therapeutic injections in the last year, history of blood transfusions, surgery, or haemodialysis, whereas high community risk is defined as ever barbering (males), ear/nose piercings (females), tattoo/acupuncture, or sharing smoking equipment. HCV: hepatitis C virus; PWID: people who inject drugs; DC: decompensated cirrhosis; HCC: hepatocellular carcinoma; CR: community risks; MR: medical risks; SVR: sustained virologic response.

Figure 2

Model projections for (a) total population size, (b) chronic HCV prevalence in Pakistan from 1960 to 2030. The solid black line and shaded grey areas show the median and 95% credible intervals (95% CrI) for the model projections. For comparison, asterisks indicate available demographic or HCV prevalence data and the wedge-shaped region in Figure 2b indicates the permitted trend in HCV prevalence. Population data for Figure 2a come from the UN Department of Economic and Social Affairs, Population Division, whereas HCV prevalence data for Figure 2b come from the 2007 national survey while reflecting the increasing HCV prevalence trend observed in studies from blood donors for 1994 to 2014.

Figure 3

Projections of the 15-year impact from 2016-2030 of interventions reducing either high or all transmission risks and/or treating a percentage of chronically infected individuals annually. Intervention scenarios are described in Table 1. The solid black line and shaded grey areas show the median and 95% credible intervals for the epidemic projections at baseline without treatment interventions from 2016. Median curves for the various interventions are as indicated.

Figure 4

Estimated number of annual treatments required to achieve the WHO HCV-elimination target for reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030, for different treatment targeting and prevention interventions. The intervention scenarios consider three treatment intervention scenarios without (Intervention Scenarios A to C) or with HCV risk reduction interventions (Intervention Scenarios D to F). The treatment intervention scenarios considered were: (A) Non-targeted treatment; (B) Targeted treatment towards 80% of chronically infected people with cirrhosis each year; (C to F) Targeted treatment towards 80% of cirrhosis cases and treating PWID at twice the rate of non-PWID. Three HCV risk reduction interventions were considered: (D) Halve HCV transmission risk due to injecting drug use; (E) Halve HCV transmission risk due to injecting drug use and high medical and community risk factors and, lastly, (F) Halve transmission risk amongst PWID as well as amongst those with low and high community and medical risk. Whiskers denote the 95% credibility intervals around all projections.