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Abstract

Hepatitis C is considered one of the most neglected diseases in world. Worldwide about 150 million people are chronically infected by hepatitis C virus (HCV), and 60% to 70% of them will develop severe liver disease. This article describes Brazil’s response to hepatitis C, from the first steps in 1993 to a national program in 2002. We reviewed the available literature, most of it in Brazilian Portuguese, and compiled them in order to share this experience with those seeking some pragmatic solutions. After 12 years, the national program has achieved universal coverage of treatment, resulting in saved lives and resources for the health system. There is abundant evidence that the HCV epidemic deserves attention. The overall consequence of long-term HCV infection is a negative impact on the health care economy. The Brazilian experience can be adapted to many countries in the world, in compliance with the 2010 World Health Organization World Health Assembly Resolution.

Keywords

hepatitis C viral hepatitis HCV Brazil public health

Introduction

By 1977, after the discovery of hepatitis A, hepatitis B (HBV), and Delta viruses, it became clear that unknown but distinct agents were responsible for a considerable proportion of hepatitis cases worldwide. Initially termed non-A hepatitis and non-B hepatitis, the hepatitis C virus (HCV) was identified in 1989 as advances in molecular biology took place.¹

This single-stranded RNA virus of the Flaviridae family is considered one of the most common blood-borne infections and is less frequently transmitted by sexual intercourse than the HBV or HIV.² At present, HCV mostly affects people who inject drugs (PWIDs) and those who receive blood transfusion,^1,3

-6 which contribute to chronic hepatitis, liver cirrhosis (LC), cancer, and liver transplantation numbers^7,8 in both developed and developing countries.^8,9

About 150 million people worldwide are chronically infected with HCV,¹⁰ and 60% to 70% of them will develop chronic liver disease, which requires expensive and specialized medical care. The cost of hepatitis C infection is thus high.

Despite public acknowledgment that hepatitis C is a worldwide health problem with substantial morbidity and mortality, the lack of clinical signs and low awareness among the general public and medical professionals¹¹ result in health complications, and the patient doesn’t permit to break the transmission chain of the virus. Compounding this is the poor response by governments and lack of optimum infection control measures in health care settings.¹² The reduction in global mortality and morbidity related to chronic hepatitis C should be of public health concern, and preventive and therapeutic measures must be provided to those in need.

The discovery of HCV happened in a moment of social mobilization in Brazil. Such civil society movements, patients, and health care professional representatives pushed forward the elaboration of better health care politics.

In 1996, as a measure to depict the Brazilian scenario of hepatitis C infection, diagnostic tests were made progressively available and disease suveilance was enforced. By 1997, the World Health Organization announced that Brazil was estimated to have a hepatitis C prevalence of 2.6% among the general population.^13
-15 Simultaneous detection rates of hepatitis C in all 5 regions of Brazil became available in the following year, accounting for 186 new cases notified in 1999. By 2004, 5 years later, as much as 7029 new cases were reported per year¹⁷ (Table 1).

Table 1.

New Cases of Hepatitis C in Brazil, 1999 to 2012.^a

Region	Year
Region	1999	2000	2001	2002	2003	2004	2005	2006	2007	2008	2009	2010	2011	2012	Total, 1999-2012
Brazil	186	306	626	1987	3954	7029	8524	9306	9317	9757	10 490	10 504	11 755	10 568	94 309
North	2	31	20	33	66	66	127	100	219	261	270	237	232	284	1948
Northeast	1	0	6	37	102	197	384	416	370	546	664	641	832	805	5001
Southeast	108	163	356	1389	2758	5069	6051	6611	6302	6449	7058	6631	7524	6894	63 363
South	72	110	223	398	896	1511	1742	1946	2065	2213	2154	2626	2773	2228	20 957
Central-West	3	2	21	130	132	186	220	233	361	288	344	369	394	357	3040

^aAdapted from MS/SVS—Sistema de Informação de Agravos de Notificação—SINAN.¹⁶

During these years, comprehensive response to HIV took place, and after the introduction of highly active antiretroviral therapy (HAART), hepatitis C has also been understood as a risk factor for mortality among people living with HIV/AIDS (PLWHA).^18,19

Considering the importance of viral hepatitis and the demand of structure for prevention and control of this disease at every level of health care, the Ministry of Health instituted Ordinance No. 263/GM dated February 5, 2002, and later substituted by No. 2080 dated October 31, 2003, creating the National Program for Prevention and Control of Viral Hepatitis. This program covered not only hepatitis C but all viral hepatitis.^20,21 We report 12 years of Brazil’s experience in confronting hepatitis C infection and its consequences through a public health approach, with universal access as the baseline.

Objectives

This article aims to describe the Brazilian response to hepatitis C in the last 12 years, compiling information mostly available only in Brazilian Portuguese, to help countries around the world to consider a likewise comprehensive approach to the hepatitis C infection.

Methods

We extensively reviewed the scientific literature on viral hepatitis, with emphasis on hepatitis C, especially from Brazil. Studies regarding the epidemiology on hepatitis C and multiple consensus statements from national and international medical associations were included and were then carefully studied with the Brazilian consensus on viral hepatitis as the baseline. We also considered conference abstracts, government documents, reports by nongovernmental organizations (NGOs), the gray literature, and online resources as sources of information on hepatitis C epidemiology and economic burden, the government response, and the efficacy of the public health measures. Many of the documents and publications reviewed were available only in Brazilian Portuguese, and this is an extra contribution of this article; information found only in Brazil’s official language can now be accessed internationally.

Current Information Available on the Epidemiology of Hepatitis C in Brazil

Hepatitis C is a major cause of chronic liver disease worldwide. Significant variations in the epidemiology of hepatitis C infection can be found around the world, including distinct geographical regions.⁶ Brazil is a continental country with large demographic, social, and cultural variations among its different regions. The official incidence and prevalence rates are obtained by passive surveillance of compulsory notification of viral hepatitis cases.²² Alongside this current system, the epidemiological patterns of the viral hepatitis have been assessed from surveys conducted in restricted geographical areas and special groups of people such as blood donors, volunteers, PLWHA, PWIDs, and indigenous populations.^22

-27

Data from compulsory notification indicate an increase in hepatitis C incidence from 1999 to 2011, respectively, from 0.1 to 6.1 per 100 000 people. From 2006 until 2012, HCV detection remained stable at between 5.0 and 6.0 per 100 000 people. In 2010, 10.3% of cases with hepatitis C were reported in Information System for Notifiable Diseases (SINAN) as associated with HIV/AIDS. With respect to age, the highest rate of detection of HCV and HIV coinfection per 100 000 people was observed in the age-group between 40 and 44 years (1.86) followed by age group 45 to 49 years (1.65) and 35 to 39 years (1.56).^16,28
-30 In 2012, the HCV incidence changed across the country, with 1.7 in the North, 1.5 in the Northeast, 2.5 in the Central-West, 8.5 in the Southeast, and 8.0 (per 100 000 people) in the South regions.^16,28
-30

Despite the increase in the number of confirmed cases, there is still undernotification, the number of people on treatment is increasing in Brazil, which strengthens the necessity of discussing and implementing strategies to increase qualification and notification of the states and municipalities.

Surveys during the 90s decade found an HCV prevalence of 1.7% among the Native Americans,³¹ and prevalence rate of between 1.25% to 1.42% among the general urban population.^32,33 Among the blood donors, the prevalence ranged from 0.65% in the South region to 2.12% in the North.^34,35 The highest prevalence was found among PWIDs, with 75% of tested people infected by HCV.³⁶

Recently a nationwide household survey was conducted among residents of Brazilian state capitals and the Federal District (FD), and the nationwide anti-HCV seroprevalence was estimated at 1.38%. Extreme poverty, higher ages, and injection drug use (IDU) were the most related risk factors.²³ Seroprevalence varies according to the macro region of Brazil, being as low as 0.7% in Northeast region and 0.9% in the FD, increasing to 1.2% in the South and 1.3% in Southeast and Central-West regions, and reaching the highest rates in North region, with a seroprevalence of 2.1%.²³

The northern part of the country is known for the Amazon rainforest, nonurbanized areas, traditional indigenous populations, and general low population density.³⁷ The difficulties to provide and access proper medical care in this region increase the risk for viral hepatitis infection. Moreover, there is a significant aggravation by traditional practices and low acceptance of prevention measures. Despite having the lowest population density, the northern Brazil has been reported to have the third highest prevalence of viral hepatitis and the highest prevalence of hepatitis C and hepatitis D infection in Brazil.^23,38,39

The smaller South and Southeast regions are more urbanized and have better access to health care and prevention programs, but they account for the highest prevalence of viral hepatitis in the country for the past 20 years, which is a direct and long-lasting consequence of IDU.^37,40

-43

According to this survey, it is estimated that about 2 million people in Brazil are living with chronic hepatitis C.²³ Most of them are unaware of their serological status, and data from the SINAN identify 82 041 new patients with hepatitis C diagnosed between 1999 and 2011, 67.3% of them from the southeast region.^16,44

Moreover, since the 80s, an increase in the mortality rate was observed due to hepatitis B. After 1996, with the notification of HCV, it was possible to identify progressive mortality rates due to hepatitis C.⁴⁵ The mortality rate due to hepatitis C increased from 0.14 deaths per 100 000 people in 1996 to 0.73 in 2003. An increase was observed in all of the 5 regions, and the most affected were people between 60 and 80 years. By 2005, the mortality rate reached 1.01 per 100 000 people, which became stable by 2010.⁴⁵

Furthermore, patients with viral hepatitis B and C are at higher risk of developing LC and hepatocellular carcinoma (HCC). In Brazil, 31% of LC and 64% of HCC are attributable to viral hepatitis. Hepatitis C virus is the cause of 23% of LC and 21% of HCC.^45

-48 Between 1980 and 2010, there were 139 530 deaths related to liver and intrahepatic biliary tract cancer, of which 21% specifically related to HCC.⁴⁵ By 2010, it represented 4.3% of the deaths among all malignant neoplasms¹⁷ and the seventh cause of death by cancer among women and the sixth among men.⁴⁹

Given the estimation of 2 million HCV-infected people, of whom 80% are not aware of their serological status, it is evident that the future burden of hepatitis C in Brazil will be very heavy for any of the health systems. Additionally to the diverse regional epidemiology of HCV infection, the response in Brazil demands complete and integrated policies.

Treatment

Hepatitis C is treatable and can be cured, as the virus can be totally eliminated along with its consequences. Hepatitis C virus has a large genetic heterogeneity. There are several genotypes and subtypes of HCV, which differ from each other by 20% to 23% in their nucleotide sequences with differences in treatment response. At least 6 major HCV genotypes have been identified.

Hepatitis C virus genotypes 1, 2, and 3 are commonly found around the world, while genotypes 4, 5, and 6 are restricted only to certain areas.⁵⁰ In Brazil, genotypes 1, 2, and 3 are commonly found, although genotypes 4 and 5 have also been found.⁵¹

Treatment of HCV infection requires planning. Treatment should be initiated by considering the stage of liver injury, the risk of disease progression, probability of good therapeutic response and adverse events, and the presence of comorbidities.^1,52
-54

The most common treatment regimen for hepatitis C is interferon and ribavirin, an oral antiviral drug. The type of interferon as well as the length of treatment of hepatitis C depends on the HCV genotype.³⁸ The introduction of the direct-acting antiviral agents (DAAs) has improved treatment prospects, but these are expensive and most countries find it difficult to offer these drugs to their people.

Despite its treatment cost, the HCV epidemic deserves attention and competent public health approach. The overall consequence of long-term HCV infection involves a negative impact on health care economy, which is much more than the costs of oriented prevention and therapy,^4,6,55,56 even with the newly approved and expensive drugs.³⁹

Neglecting access to prevention and treatment of hepatitis C due to a temporary lack of funds maybe an important public health omission and a repetition of the mistakes made in the first decade of the HIV epidemic.^57
-59

The Brazilian Response

Law and Right to Treatment

“A saúde é direito de todos e dever do Estado”—Health care is a right of all and an obligation of the State.⁶⁰ This excerpt of the Brazilian Constitution of 1988 not only defined health care as a fundamental right of human beings but also paved the way for the most important revolution in the publicly funded health care policy in Brazil so far.

By 1990, through the “8080” law, the Brazilian Government had officially created Sistema Único de Saúde—Unified Health System (SUS), the current decentralized health system of Brazil designed to provide medical care, improve well-being, and prevent diseases. It is based on the following 4 principles: integrity, equity, universal nature, and recognized social participation. These principal elements are essential elements for policy and executive decisions.^61,62

Following the World Health Organization report that estimated that 2.5% of Brazilians were infected by HCV, it became clear that some action needed to be taken.^13
-15 The diverse features of HCV, such as pattern of transmission, clinical progression, diagnosis, and treatment, require an adequate governmental health care policy. Inattention to the problem has been shown to result in grave consequences such as liver failure and cancer.⁶

Hepatitis C infection in Brazil has been understood not only as a disease but also as a human rights issue. The concrete application of SUS principles and oversight by a strong civil society movement lead the government to designing policies to confront viral hepatitis. The constant evolution of the measures over the years led to the creation of the National Program for Prevention and Control of Viral Hepatitis, a free-of-charge program ranging from the diagnosis to liver transplantation. Through the many legal channels made available for HIV treatment, HCV-infected patients and health care professionals requested the Brazilian Government to regularly improve treatment options in keeping with the latest scientific evidence.

Daring Beginning

Observational evidence suggests that, in Brazil, the main route of transmission is parenteral. People who inject drugs are at highest risk of hepatitis C infection,³⁶ followed closely by blood transfusion recipients. The Brazilian Government’s response to hepatitis C infection commenced by banning paid blood donation in the 1988 Brazilian Constitution.⁶³ Screening of blood donors was started in 1992 and fully implemented by 1993.^64,65 Notification of hepatitis C infection became obligatory in 1996.³⁸

Partial credit for the quick response to hepatitis C is possibly attributable to the HIV epidemic. World prevalence of HCV infection among PLWHA is estimated as being greater than 30%, and it can reach 90% depending on the transmission route,⁶⁶ thus granting hepatitis C the status of a biological marker for higher risk of HIV infection.¹

In 2002, 6 years after the advent of universal, free, HAART in Brazil, a decrease in mortality rate of HIV cases was reported, thereby indicating that HCV is one of the main causes of death in this group. People living with HIV/AIDS were now dying of hepatitis C infection.⁶⁷

Harm reduction has been proven to be effective in controlling the spread of viral hepatitis among PWIDs. A harm reduction strategy was adopted publicly for first time in Brazil in 1989 in the city of Santos (located in Sao Paulo state).⁴¹ This led to disagreements between the city and the state governments and an embargo on implementation, due to the incorrect conclusion that harm reduction would further stimulate drug use. Although the efficacy of needle and syringe programs (NSPs) had been proved in the Netherlands since 1984,⁶⁸ it was accepted only in 1995 in Salvador (Bahia), in Brazil, ⁶⁹ which was influenced by organized society groups, health care workers, harm reduction specialists, and by foreign experiences.

In 1998, the law was modified to allow NSPs specifically in the state of Sao Paulo. Later other cities and states created their NSPs, and by 2004, there were 134 NSPs across the country.⁶⁹

Although NSPs were not originally meant for interrupting HCV transmission, and despite the obstacles imposed by law enforcement authorities, the surprising success of NSPs in other countries and in the Brazilian city created a demand for a more functional and integrated national plan for prevention and control of blood-borne pathogens.⁷⁰

Twelve Years of National Policy

In February 2002, the Ministry of Health formulated the National Program for Prevention and Control of Viral Hepatitis, with the intention of connecting the Ministry of Health, State, City, and District Health Departments, with representation of Brazilian patients. Funding, testing, epidemiological profiling, and treatment responsibility were divided among the different levels of governance according to the levels of complexity and preexisting health care structure. Medication with ribavirin and regular interferon was also made available.^38,42

By the end of its first year, the National Program had extended the services of existing HIV testing and counseling centers to diagnosing viral hepatitis and supplying diagnostic kits. Funding transfer protocols for laboratory technology and medication budgets were reviewed, and pegylated interferon was included for treatment.⁴² The Clinical Protocol and Therapeutic Directives of Viral Hepatitis C was published in 2002,⁴⁰ and possible flaws and deficiencies present in the system at the time were reviewed.⁷¹ Structuring the hepatitis C response using the preexisting structure of the HIV services proved to be a rational and cost-effective decision, as it saved costs by optimizing the use of existing health infrastructure.

During the following years, the first Manual of Viral Hepatitis Counselling was released in 2005. This led to a better understanding of viral hepatitis by health care providers and improved education by testing centers.⁷² Other publications followed, such as updated editions of the Clinical Protocol and Therapeutic Directives for Viral Hepatitis C (2011 and 2013) and the first nongovernmental hepatitis C treatment consensus edited by the national infectious diseases medical association.^38,73,74

Currently, the estimated cost for dual therapy with pegylated interferon α and ribavirin for the public health system is US$6270 per HCV-infected person and US$28 000 for triple therapy with protease inhibitors (PIs), which is approximately US$200 million/year.⁷⁵

Current data reveal that, 13 000 people are treated with conventional treatment in Brazil, and from September 2013 until March 2014, approximately 3400 people started treatment with PIs—boceprevir and telaprevir.⁷⁶

Dealing with Coinfection

Coinfection of HBV and HCV increases the chances of developing fulminant hepatitis as well as cirrhosis and HCC, thus increasing morbidity and mortality due to HCV infection. In view of this, the Brazilian Government provides hepatitis B immunization coverage to hepatitis C-infected patients, and by 2011, the government initiated the production of tenofovir (TDF), a drug originally designed for HIV but also effective in treating HBV infection.³⁹

Health Care Levels and Attributes

Currently, the Brazilian Government’s hepatitis C health care program is divided into basic, intermediate, and high-complexity units. This decentralized 3-level health care network at the first level is composed of voluntary counseling and testing units, basic health care units, and family health units, which are responsible for diagnosis and referral. At the second level are the outpatient clinics, and at the third level, hospitals of high complexity, which act as treatment providers. The distribution and tasks attributed to each of these elements can be adjusted according to the regional demand, geography, and availability,³⁷ with optimum results.

Ongoing Refinement

Constant reviews are essential for health policy makers to keep up with the ever-changing dynamics of diseases and scientific advances. Some of the later improvements in the Brazilian health care system in the area of hepatitis C are discussed subsequently.

Harm reduction services are also provided to crack and cocaine users, apart from PWIDs. Scientific evidence shows that this hard-to-reach population is at a higher risk of being infected with HCV than the general population⁷⁷ because of hazardous practices (shared smoking devices, usually improvised pipes, unsafe sex, and commercial sex). Counseling and protective lipstick are offered at government facilities, while heat-resistant pipes are distributed by NGOs and universities.⁴²

The supply of medical and laboratory equipment has increased (eg, the number of biopsy needles needed and supplied in 2010 alone was more than 21 000).⁴³ A readily available supply and greater coverage result in faster and more efficient diagnosis of HCV infection.

Reaching Indigenous and Traditional Populations

Health care and disease prevention activities have been offered in conjunction with the Brazilian Armed Forces through hospital ships and routine visits of medical staff in thickly forested areas located in the northern areas of the country.⁷⁸ Those actions are not specifically for HCV; however, they clearly contribute to prevent and control viral hepatitis in that region.

Hepatitis C Virus Screening during Prenatal Care

Optional HCV testing is offered free of charge to pregnant women, especially those from large urban districts or with a history of high-risk activities.⁷⁹

Innovation

Projects have been developed in places where transmission is likely and infection may go undetected, such as prisons and hard-to-reach populations. Development of such projects requires creative and careful planning, along with decisive action.^80,81

Inclusion of New Medication and Technology

Inclusion of the first DAAs, boceprevir and telaprevir, for the treatment of chronic HCV genotype 1 has already been assessed for inclusion and formally recommended by the Governmental Healthcare Technology Innovations Commission (CONITEC).⁸² Both drugs are classified as PIs. This new class of drugs was incorporated in the national guidelines in 2013 as an extra tool.⁷³ Currently 50 drugs for the treatment of hepatitis C are in the pipeline, and the Ministry of Health monitors the results of these studies for possible incorporation in Brazil.

Conclusion

Consequently, through the execution of all these measures, an increase in the incidence of hepatitis C due to better counseling and testing was observed in the first years of the National Program for Prevention and Control of Viral Hepatitis. Despite its higher prevalence among people in the North region, most of the cases are identified in the Southeast and South regions. Probably this difference is related to the urban and more developed characteristics of southern Brazil, compared to northern.

The increase in the counseling and testing over the year creates an awareness among people of their HCV infection, giving them the opportunity to take treatment for the disease in earlier stages. Thus, the number of people receiving treatment is increasing, and from 2010 to 2012, the number increased from 10 507 to 13 000.^30,83 Therefore, the mortality rates due to hepatitis C followed an increasing rate pattern from 1996 to 2006, and stabilized to around 1 per 100 000 people in the following years.

Additionally, the results achieved by Brazil so far in preventing and controlling hepatitis C are outstanding, especially in the short time since the changes in public health care were mandated by the 1988 Constitution. Despite the rapid deceleration of the incidence and mortality rates, the most important reduction in the burden will be notable over the next years, with the decrease in the incidence of viral hepatitis infection, LC, and HCC.

Finally, the country, despite its geographical and economic diversity, provides an example for other countries to emulate. With its expertise in the prevention and control of viral hepatitis, Brazil together with Indonesia and Colombia cosponsored the resolutions on viral hepatitis adopted by the 63rd World Health Assembly held in 2010. The resolutions have the objective of drawing attention to the viral hepatitis epidemic and state the need for global coordinated actions to improve prevention and control of viral hepatitis.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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12 Years of Universal Access to Hepatitis C Treatment

Abstract

Keywords

Introduction

Objectives

Methods

Current Information Available on the Epidemiology of Hepatitis C in Brazil

Treatment

The Brazilian Response

Law and Right to Treatment

Daring Beginning

Twelve Years of National Policy

Dealing with Coinfection

Health Care Levels and Attributes

Ongoing Refinement

Reaching Indigenous and Traditional Populations

Hepatitis C Virus Screening during Prenatal Care

Innovation

Inclusion of New Medication and Technology

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

References