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The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm
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Journal of Viral Hepatology Dec 2014
"In conclusion, while the total number of HCV infections is expected to decline in many countries, HCV related mortality and morbidity is expected to increase as the infected population ages and progresses to more advanced liver diseases. In all countries but the Netherlands, the HCV disease burden will not be controlled by the current treatment paradigm. Increased treatment and/or higher efficacy therapies are needed to keep the number of HCV individuals with advanced liver diseases and liver related deaths from increasing. This suggests that strategies are required to manage the expected increase in HCV disease burden."
ABSTRACT
Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013-2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.
DISCUSSION
A modeling approach was used to forecast HCV mortality and morbidity. Since HCV disease burden changes over time, this approach allowed us to compare data across countries reported in different years (15) by estimating the disease burden in 2013 (Table 1). As shown in Figure 3, the total number of viremic infections is expected to decline or remain flat in nearly all countries except for Russia, where the high incidence of new infections is anticipated to continue to grow the infected population. The total number of HCV infections reported here will be lower than those reported elsewhere, since this study focused on estimating the number of viremic cases in the population. Those who spontaneously cured the virus or were treated and cured were not considered. Figure 4 shows the change in disease burden over time, while Figure 5 shows that the number of individuals with late-stage liver disease is expected to continue to grow in all countries except for the Netherlands and South Africa.
The Netherlands stands out as the only country where the future morbidity and mortality is projected to decrease from 2013-2030. The Netherlands already has a high treatment rate where 4.5% of the infected population is treated annually with current high SVR therapies (Table 1). This combination results in a reduction in HCV disease burden. If treatment rate is lowered to 1.5%, where 310 patients are treated annually between 2013-2030, liver related deaths, HCC, decompensated cirrhosis and cirrhotic HCV infections will actually increase by 45%, 60%, 21% and 21% respectively in 2013-2030. Thus, HCV disease burden can be managed through increased treatment rate if combined with high SVR therapies.
The number of individuals with advanced liver disease in South Africa is projected to drop after 2026 due to all-cause mortality. As shown in Figure 2, South Africa has the oldest infected population among the countries studied. By 2026, the all-cause mortality is anticipated to result in a reduction in the total number of infections. This projection, however, is highly dependent on the accuracy of the age distribution estimate and the rate of new infections. As stated earlier, it was difficult to estimate the number of new HCV infections entering the country through illegal immigration. If the true number of new infections is higher than our estimates, the disease burden will continue to grow beyond 2030.
As shown in Table 1, viremic HCV prevalence ranged from 0.12% in the Netherlands to 3.17% in Russia, with the highest diagnosis rate represented by countries with a centralized registry (Finland, Ireland, Norway and Poland). India, Slovak Republic, South Africa and Poland were estimated to have the lowest diagnosis rate (range: 5-15%), while Luxembourg, Finland, the Netherlands and Norway all had more than 55% of their infected population diagnosed. In addition, it was estimated that 0.6-5% of the infected population is newly diagnosed each year, with the lower end of the range represented by India and the upper end of the range represented by Norway. The Netherlands has the highest treatment rate, with 4.5% of the infected population treated annually. This was followed by Luxembourg at 3.2% and Norway at 2.8%. Of the countries studied, South Africa, Russia, Argentina and India all had treatment rates less than 0.5% (range: 0.03-0.17%).
Mortality (all cause and liver related) was driven by the age of the infected population (Figure 2) as well as risk factors such as IDU and transfusion (Table 1). Older populations had a higher all cause mortality rate (24) and in addition, disease progression rates increased with age. Thus, older individuals were more likely to have more advanced liver disease and associated liver related deaths. As stated in the methodology section, active IDU cases also had a higher mortality rate due to the high-risk behavior associated with drug use. Table 1 presents the percentage of the infected population who were actively injecting drugs. The all-cause mortality was adjusted accordingly for this portion of the population.
In each country, details of the current treatment protocols were gathered. For the purpose of the model, it was assumed that all treatment assumptions (including the number of treated patients, treatment eligibility, the number of newly diagnosed cases, SVR and treated patient segments) would remain constant between now and 2030. This was not meant to be a realistic scenario, but was rather a baseline that could be used to compare the impact of new strategies to manage the future disease burden (59). Thus, this work does not imply that the current treatment paradigm will remain as it is today. Instead, the scenarios shown here represent what would be the outcome if the current paradigm stayed the same.
Numerous limitations could influence the outcomes from this study. The model used the annual number of new cases and tracked their progression over time. As described earlier, distribution of new cases from 1950 to the year of available data was back-calculated using relative incidence and allocation of the new cases by age and gender. However, it was more difficult to estimate the number of new infections after the year of known prevalence. An analysis of the key risk factors was used to estimate the more recent number of new infections. Factors considered were new HCV infection among IDU, continued nosocomial infection and impact of immigration on the new cases of HCV. A key limitation of this study is the assumption that the number of new cases will remain constant after 2013. Higher numbers of new infections in 2013 could thus result in higher total numbers of infections in 2030.
A further limitation of this analysis is the assumption that sufficient numbers of diagnosed patients will be available for treatment. In reality, as the diagnosis rate increases, it will become more difficult to find undiagnosed patients. In addition, diagnosed patients may not have easy access to care. Thus, the ability of a country to treat its HCV population may be limited by the number of available diagnosed eligible patients.
In addition, the model does not consider the progression of cured HCV patients. Studies have shown that more advanced patients may continue their disease progression after achieving SVR, although at a slower rate (16). The data presented here may overestimate the reduction in HCC and decompensated cirrhosis cases, since the scope of the analysis was limited to HCV viremic individuals. Another element not addressed by this model is the potential contribution of extrahepatic manifestations of HCV infection on all-cause mortality.
In conclusion, while the total number of HCV infections is expected to decline in many countries, HCV related mortality and morbidity is expected to increase as the infected population ages and progresses to more advanced liver diseases. In all countries but the Netherlands, the HCV disease burden will not be controlled by the current treatment paradigm. Increased treatment and/or higher efficacy therapies are needed to keep the number of HCV individuals with advanced liver diseases and liver related deaths from increasing. This suggests that strategies are required to manage the expected increase in HCV disease burden.
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