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Impact of COVID-19 on global HCV elimination efforts
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The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so. The '1-year delay' scenario resulted in 44,800 (95% uncertainty interval [UI]: 43,800-49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths, relative to the 'no-delay' scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries.
• As of June 8, 2020, >400,000 deaths due to COVID-19 had been registered globally.
• For comparison, there were an estimated 400,000 deaths attributable to HCV in 2015 (1.34 million deaths were attributed to viral hepatitis in the same year).
• The full impact of COVID-19 is yet to be seen; however, in addition to the substantial morbidity and mortality directly attributed to infection, there are expected to be downstream consequences from delayed programming and care in other disease areas. This analysis suggests that a 1-year hiatus in HCV elimination programs could result in 72,300 (95% UI: 70,600-79,400) excess LRDs and 44,800 (95% UI: 43,800-49,300) excess liver cancers globally over the next 10 years.
• Currently, it is impossible to know how long treatment and programming delays will last, or if intermittent disruptions will become a 'new normal'. Even after programs formally resume, patients might be reluctant to access healthcare services due to fear of contracting COVID-19 in those settings.
• This analysis suggests that, if a delay in programming and treatment occurs globally, most missed treatments would be in LMIC.
• Additionally, most excess incident HCV infections would occur in LMIC. This poses a significant challenge, because incident infections are unlikely to be diagnosed for decades, meaning that elimination efforts beyond 2030 might be necessary. One interesting finding was that the American Region is not expected to see a large number of incremental incident infections as a result of delayed treatment. These estimates are largely driven by treatment restrictions in the USA, which prevent access to treatment for people who inject drugs in many states.13 As a result, the disruption in diagnosis and treatment modelled here does not result in an increase in incident cases for the USA.
The '1-year delay' scenario would result in 623,000 (95% UI: 609,000-685,000) more prevalent infections in 2030, relative to the 'no-delay' scenario, with 121,000 (95% UI: 118,000-133,000) excess incident infections, globally, from 2020 to 2030 (Table 2). Similarly, end-stage outcomes would increase, with 44,800 (95% UI: 43,800-49,300) excess HCC cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths predicted over 2020-2030.
At the WHO regional level, the largest increase in incident HCV infections would be expected in the Eastern Mediterranean Region (47,900 excess incident cases from 2020 to 2030), with the most excess HCC and LRDs in the Western Pacific Region (11,700 excess incident HCC and 18,200 excess LRDs from 2020 to 2030) (Table 2). Considering World Bank Income Groups, most excess incident HCV infections would be in the LMIC group (66,200 excess incident HCV, 55% of all excess incident HCV infections). However, most excess HCC and LRDs would be among the HIC group (45% of excess HCC and 41% of excess LRDs) (Figs. 1 and 2).
Impact of COVID-19 on global HCV elimination efforts
Sarah Blach1,*, Loreta A. Kondili2, Alessio Aghemo3,4, Zongzhen Cai1, Ellen Dugan1, Chris Estes1, Ivane Gamkrelidze1, Siya Ma1, Jean-Michel Pawlotsky5,6, Devin Razavi-Shearer1, Homie Razavi1, Imam Waked7, Stefan Zeuzem8, Antonio Craxi9
1Center for Disease Analysis Foundation, Lafayette, CO, USA; 2National Center for Global Health-Istituto Superiore di Sanita, Rome, Italy; 3Internal Medicine and Hepatology Division, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy; 4Humanitas University, Department of Biomedical Sciences, Milan, Italy; 5National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Hopital Henri Mondor, Creteil, France; 6INSERM U955, Creteil, France; 7National Liver Institute, Menoufia University, Al Minufya, Egypt; 8Internal Medicine Department, Goethe University Hospital, Frankfurt, Germany; 9Gastroenterology and Hepatology Unit, Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
Highlights
• With only 10 years left to meet the WHO's hepatitis elimination targets, COVID-19 is impacting progress.
• A 1-year delay in HCV programs could cause excess HCV morbidity and mortality.
• A 1-year delay could cause 72,000 excess deaths from HCV.
• Most excess deaths would be in the lower middle income and high-income groups.
Background & Aims
Coronavirus disease 2019 (COVID-19) has placed a significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs.
Methods
Previously developed models were adapted for 110 countries to include a status quo or 'no delay' scenario and a '1-year delay' scenario assuming significant disruption in interventions (screening, diagnosis, and treatment) in the year 2020. Annual country-level model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the 'no-delay' estimates from the '1-year delay' estimates.
Results
The '1-year delay' scenario resulted in 44,800 (95% uncertainty interval [UI]: 43,800-49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths, relative to the 'no-delay' scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries.
Conclusions
The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so.
Lay Summary
COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate to do so.
Discussion
As of June 8, 2020, >400,000 deaths due to COVID-19 had been registered globally. For comparison, there were an estimated 400,000 deaths attributable to HCV in 2015 (1.34 million deaths were attributed to viral hepatitis in the same year).
The full impact of COVID-19 is yet to be seen; however, in addition to the substantial morbidity and mortality directly attributed to infection, there are expected to be downstream consequences from delayed programming and care in other disease areas. This analysis suggests that a 1-year hiatus in HCV elimination programs could result in 72,300 (95% UI: 70,600-79,400) excess LRDs and 44,800 (95% UI: 43,800-49,300) excess liver cancers globally over the next 10 years.
For the past few years, HCV treatment starts have been declining, even in HIC (e.g. the USA was estimated to have treated 60% fewer patients in 2019 than in 2015).
By 2020, 1 million patients were expected to initiate treatment globally, but recent estimates suggest that only 5 countries would be considered 'on-track' for HCV elimination (defined as a 65% reduction in LRDs, a 90% reduction in incident infections, and 80% diagnosed and 90% of diagnosed initiated on treatment).
This means that even before COVID-19, many countries were playing 'catch-up' to reach the elimination targets. One example of a country that was previously on track for elimination but lost progress before the pandemic is Italy, where a 35% reduction in the annual number of patients initiated on treatment occurred in 2019, relative to 2018.
Although the Government responded by enacting into law a screening program to begin in 2020 (see Section 2 in the supplemental information online), screening efforts have now been delayed due to COVID-19; and average weekly treatment starts have been reduced by >88% compared with 2018 (>80% reduction compared with 2019) (see Section 2 in the supplemental information online). This illustrates that further delays in elimination programming are likely to exacerbate already strained national and regional plans for hepatitis elimination. Most regions were not projected to reach any of the WHO targets under a '1-year delay' scenario, with only the HIC group projected to achieve the mortality targets.
Currently, it is impossible to know how long treatment and programming delays will last, or if intermittent disruptions will become a 'new normal'. Even after programs formally resume, patients might be reluctant to access healthcare services due to fear of contracting COVID-19 in those settings. To allow for even comparisons across regions, delays were assumed to occur uniformly within a scenario (i.e. in the 1-year delay scenario, we assumed that every country in the world simultaneously experienced a 1-year hiatus in programming). This analysis suggests that, if a delay in programming and treatment occurs globally, most missed treatments would be in LMIC. Although not all LMIC are experiencing or responding to the COVID-19 pandemic in the same way, access to treatment and care have still been impacted. For example, although Egypt has not imposed a strict lockdown, Ministry of Health-sponsored HCV management centres have experienced a 50% reduction in new patients and monthly visits, in addition to temporarily suspended screening programs (unpublished data provided by Professor Imam Waked). To account for differences in COVID-19 response and duration of response, data are presented by delay intervals (3-month, 6-month, and 1-year) and separately by the regional level (1-year delay) where outbreak responses are more likely to be similar. These provide decision makers with an array of options when considering how best to recover from delayed treatment.
Additionally, most excess incident HCV infections would occur in LMIC. This poses a significant challenge, because incident infections are unlikely to be diagnosed for decades, meaning that elimination efforts beyond 2030 might be necessary. One interesting finding was that the American Region is not expected to see a large number of incremental incident infections as a result of delayed treatment. These estimates are largely driven by treatment restrictions in the USA, which prevent access to treatment for people who inject drugs in many states.
As a result, the disruption in diagnosis and treatment modelled here does not result in an increase in incident cases for the USA.
Limitations
A few limitations exist in our analysis and are described here. First, the number of excess incident HCV infections was calculated on the basis of delayed diagnosis and treatment programs and did not include the impact of increased risk behaviors (e.g. the impact of the economic crisis on drug or alcohol use) or delayed access to harm reduction. Including disruptions to harm reduction programs and changing patterns of substance use would likely increase the number of incremental incident infections seen in HIC. Additional studies are warranted to better understand the long-term impact of COVID-19 on HCV incidence.
A second limitation is that calculations for 3- and 6-month delays assumed that outcomes were evenly distributed across all calendar months. In reality, country-level treatment programs have shown that monthly distributions of treated patients vary based on local customs and holidays, as well as program rollouts. It is possible that countries experiencing only a 3-month delay in treatment programs might make up progress in the remaining months of the year, resulting in fewer excess incident cases and end-stage outcomes. However, it is also possible that countries experiencing a 3-month delay in formal programming might continue to experience decreased patient volume because of patient concerns over health and safety in healthcare settings.
The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so.
Introduction
The emergence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, which causes coronavirus disease 2019 (COVID-19) and was declared a global emergency by the World Health Organization (WHO), has resulted in an unprecedented global response and placed a significant strain on national healthcare systems.
National responses to the COVID-19 pandemic vary, but disruptions in the supply chain and the necessary reallocation of healthcare resources and public health personnel are likely to have broad-reaching consequences for other disease areas. This event occurs at a critical moment in the context of hepatitis elimination, with only 10 years remaining to reach the Global Health Sector Strategy targets by 2030.
Disruptions to hepatitis programming across the cascade of care have already been documented in Egypt and Italy, 2 countries with very different COVID-19 experiences, and are expected in many other countries. In February 2020, the Italian government enacted a law to conduct graduated birth cohort screening for hepatitis; however, as of May 2020, the implementation of these programs is still delayed. Meanwhile, in Egypt, all ongoing screening programs (including screening of children, pregnant women, foreigners living in Egypt, and prisoners) were halted in March 2020, and the number of Ministry of Health-affiliated HCV treatment and cirrhosis follow-up units operating regularly was reduced by >75% (unpublished data provided by Professor Imam Waked, Menoufia University, Egypt).
Although the full impact of delaying hepatitis elimination programs is yet to be seen, mathematical models can be used to evaluate the possible impact on hepatitis disease burden and mortality resulting from programmatic delays. The objective of this analysis was to evaluate the incremental change in hepatitis C virus (HCV) liver-related deaths and liver cancer at a regional and global level, following a 1-year hiatus in hepatitis elimination program progress. Secondary objectives for the analysis included evaluating the incremental change in HCV diagnosis, treatment, and new infections (indicators for hepatitis elimination) and to evaluate the impact of shorter delays (3 month or 6 month) on morbidity and mortality. This analysis can assist decision makers with the reprioritization of hepatitis programming and resources, once the pandemic has subsided.
Results
Missed diagnoses
Under the 'no-delay' scenario, globally, ~1.1 million patients were expected to be newly diagnosed in 2020, with 10.5 million expected to be newly diagnosed from 2020 to 2030. Only the high-income group (HIC) was expected to meet the WHO target for diagnosis under the 'no-delay' scenario (a projected 91% of the 2015 population would be diagnosed by 2030). Under the '1-year delay' scenario, no patients were modelled to be newly diagnosed in 2020, with 9.6 million expected to be newly diagnosed from 2020 to 2030 (a difference of 906,000 diagnosed from 2020 to 2030). Approximately 45% of missed diagnoses would be in the World Bank Income-designated upper-middle income group, followed by 35% of missed diagnoses in the lower-middle income (LMIC) group (Table 2). No regions were expected to meet the WHO target for diagnosis under the '1-year delay' scenario (HIC projections would result in only 89% of the 2015 population diagnosed by 2030).
Missed treatments
Under the 'no-delay' scenario, globally, approximately 1 million patients were expected to initiate treatment in 2020, with 9.1 million expected to initiate treatment from 2020 to 2030. Under the '1-year delay' scenario, no patients were modelled to initiate treatment in 2020, with 8.4 million expected to initiate treatment from 2020 to 2030 (a difference of 746,000 treatment starts from 2020 to 2030). Approximately 43% of missed treatments would be the World Bank Income-designated LMIC group, with <3% of missed treatments in the low income group (Figure 1). No regions were projected to meet the WHO targets for treatment (80% of eligible patients initiated on treatment by 2030).
1-year delay scenario
The '1-year delay' scenario would result in 623,000 (95% UI: 609,000-685,000) more prevalent infections in 2030, relative to the 'no-delay' scenario, with 121,000 (95% UI: 118,000-133,000) excess incident infections, globally, from 2020 to 2030 (Table 2). Similarly, end-stage outcomes would increase, with 44,800 (95% UI: 43,800-49,300) excess HCC cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths predicted over 2020-2030.
At the WHO regional level, the largest increase in incident HCV infections would be expected in the Eastern Mediterranean Region (47,900 excess incident cases from 2020 to 2030), with the most excess HCC and LRDs in the Western Pacific Region (11,700 excess incident HCC and 18,200 excess LRDs from 2020 to 2030) (Table 2). Considering World Bank Income Groups, most excess incident HCV infections would be in the LMIC group (66,200 excess incident HCV, 55% of all excess incident HCV infections). However, most excess HCC and LRDs would be among the HIC group (45% of excess HCC and 41% of excess LRDs) (Figs. 1 and 2).
No regions were projected to meet the targets for incidence (90% reduction in new infections by 2030); and only the HIC group was projected to meet the target for mortality (65% reduction in liver-related deaths).
3- and 6-month delay scenarios
A shorter delay in hepatitis elimination programming would result in fewer LRDs, with only 50,600 excess deaths expected in the 6-month delay scenario and 25,300 excess deaths expected in the 3-month delay scenario.
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