A modeling approach to describe the burden of chronic HCV infection in Brazil was used based in a previously described model.9 Briefly, a disease progression model was constructed in Microsoft Excel (Microsoft Corp., Redmond, WA) to quantify the size of the HCV-infected population by liver disease stages, from 1950 to 2030. Frontline Systems’ Solver, was used to calculate the number, age and gender distribution of annual acute infections. The model started with the annual number of acute infections that progressed to chronic HCV infection after accounting for spontaneous clearance of the virus. The progression of these new cases was followed along with all chronic infections from prior years.

Then two strategies for addressing chronic HCV infection in Brazil and their effect on HCV-related morbidity and mortality were considered. In strategy 1, SVR rate increases in 2014 to 80% for genotypes 1, 2 and 4, and to 70% for genotype 3. Eligibility to treatment increases to 85% in individuals infected with genotypes 2 or 3. In 2016, medical eligibility was increased to 85% for all genotypes, and SVR to 85% for genotypes 1, 3 and 4, and 90% for genotype 2. In 2018, medical eligibility and SVR rates were increased to 95% for all genotypes.

In strategy 2, the same treatment eligibility and SVR rates as strategy 1 were used. However, the annual number of diagnosed patients increases, in 2014, to 30,000 as compared to 10,000 in 2013, and the number of treated patients increases to 15,260 in 2014, as compared to 11,740 in 2013. In 2016, the annual number of newly diagnosed patients increased to 90,000, and the annual number of treated patients to 30,520. In addition, this model considers treating patients with any HCV genotype with a Metavir fibrosis score ≥F2. In 2018, the annual diagnosed population was set at 270,000, and annual treated population was set at 91,570. At this point all patients with a Metavir fibrosis score ≥F1 would be treated. In 2020, the parameters includes a total of 109,880 patients up to age 74 and any fibrosis stage (Metavir ≥F0) been treated annually.

Brazilian population data were organized by gender and five-year age cohorts according to United Nations population database.10

Total HCV seroprevalence was estimated from a national study at 1.38% in 2007, the midpoint of the data collection period (2005–2009).3 Age and gender specific HCV incidence by five-year age group reported by the Brazilian Ministry of Health was used to calculate age and gender specific prevalence rates.4 HCV genotype distribution was based upon a study of blood samples collected between 1995 and 2000 from all Brazilian states. This study found a distribution of 64.9, 4.6, 30.2, and 0.3% for genotypes 1, 2, 3 and 4, respectively.11 (Fig. 1)

Fig. 1.

Anti-HCV prevalence according to age and gender, Brazil, 2007.

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Age and gender specific disease progression probabilities were simulated by multiplying the total number of cases at a particular stage of the disease by a progression rate to the next stage. A more detailed description is provided in a previously published paper.9

To estimate changes in annual incidence over time, we used estimates based on United States data.12 The magnitude of incidence, when not available for a specific year, gender or age group, was back-calculated based on the prevalence in 2007.3

In 2010, it is estimated that 11,750 patients were treated in Brazil. We used IMS Health data for standard units of peguilated interferon (Peg-IFN) sold in Brazil, with a multiplier to account for under-reporting.5 The Brazilian genotype distribution was used to estimate the average number of weeks of treatment per patient. After accounting for underreporting, we estimate that in 2010, over 372,000 units of Peg-IFN sold in Brazil. With 85% compliance/persistence, we estimate an average of 31.7 units and 39.6 weeks per patient.

In 2011, there were 1494 liver transplants in Brazil. Based on expert consensus, it is estimated that 50% of transplants were related to HCV in 1997, declining to 30% by 2011. This was validated using a regional estimate for the proportion of transplants related to HCV.2

Based on expert consensus, the number of people living with a diagnosis of HCV chronic infection in 2013 in Brazil was estimated to be 300,000. Each year, it was estimated that 10,000 viremic individuals are newly diagnosed.

Background mortality rates by age group and gender were calculated using United Nations mortality data.13 To account for excess mortality in the IDU population, we estimated that 5.1% of the prevalent population are active IDU, based on data from a national study.3 Increased mortality among active IDU was estimated using standardized mortality ratio of 10.0 for individuals between 15 and 44 years of age.14–19 In addition, we considered excess mortality among blood transfusion recipients. In Brazil, a national study estimated that 14.8% of the HCV population was infected through blood transfusion.3 For this population, a standardized mortality ratio of 1.5 was applied for all age groups.20

For the base case, the current Brazilian Ministry of Health recommendation for HCV treatment was considered. Thus, patients between 18 and 69 years of age have been treated. For HCV genotype 1 (G1) infected individuals, treatment with protease inhibitors (telaprevir or boceprevir) is supposed to be prescribed for individuals with Metavir fibrosis score ≥F3. Individuals with G1 and lower fibrosis (Metavir21 while an SVR of 70% was assumed for HCV genotypes 2 and 3 treated patients.22

Based on these inputs, the prevalence of HCV viremic individuals peaked in 1996 at 2,255,000, and a total of 1,938,700 were viremic in 2013. By 2030, it was estimated that will be over 1,255,000 viremic HCV infected individuals in Brazil, and over 16,600 HCV-related annual liver deaths. We estimate 45,000 cases of decompensated cirrhosis and 18,900 HCC cases by 2030. Approximately 35% of the infected population will be cirrhotic or have advanced liver disease (Fig. 2).

Fig. 2.

Base case model outputs. (A) Total viremic cases, by age, 2013; (B) Annual mortality due to liver related and background cause, 2013–2030; (C) Number of viremic cases, in total, and by disease stage, 1950–2030; (D) Expanded graph of viremic cases by disease stage for cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma, 1950–2030.

As a result of strategy 1 (increase in SVR only), the total number of infected individuals would decline by 46,000 in 2030 as compared to the base case, a 3.7% reduction. In addition, cumulative HCV-related mortality would decrease by 7570 deaths (2.5%) during 2013–2030 as compared to the base case. Cases of HCV-related HCC and decompensated cirrhosis would decrease by 2290 cases (5.1%) and 6030 cases (3.2%) in 2030, respectively, as compared to the base case.

Strategy 2: HCV elimination as a result of this strategy (increase in SVR associated with an increase in HCV diagnosed and treated individuals), the HCV infected population declines to 190,600 individuals by 2030, an 85% decrease as compared to the base case. Prevalent cases of decompensated cirrhosis and liver cancer in 2030 decrease, respectively, by 36,350 (81% decrease), and 13,810 (73% decrease) cases as compared to the base case. Finally, cumulative HCV-related mortality from 2013 to 2030 declines by 84,880 deaths, a 28% reduction as compared to the base case (Figs. 3 and 4).

Fig. 3.

Background and liver related mortality projections under the base case and three strategies, 2013–2030.

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Fig. 4.

Total viremic cases and viremic cases by disease stage. Projections under the base case (A), and strategies 1 (B) and 2 (C) with estimates for cirrhosis, decompensated cirrhosis and HCC, 1950–2030.

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