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Disease burden in Brazil: an investigation into alcohol and non-viral cirrhosis/Carga de doenca no Brasil: um olhar sobre o alcool e a cirrose nao viral.

Introduction

The abuse of, or dependence on, alcohol ("alcohol use/dependency") is an important risk factor for many diseases and disabilities that can threaten a person's health. It is responsible for approximately 2.5 million deaths per year. Between 20% and 50% of the incidence of liver cirrhosis, epilepsy, poisoning, traffic accidents, violence, and several types of cancer was caused by alcohol consumption (1).

Globally, it has been estimated that approximately 11.5% of those who drink are in the category heavy episodic drinking (consumption of 60 grams or more of pure alcohol in the last seven days); for the American continent, this prevalence is 12%, of which 17.9% is for men and 4.5% for women (1). In the study entitled Global Burden of Disease (GBD) 19 902 the value for Disability Adjusted Life Years (DALY) attributed to alcohol use/ dependence was 248/100,000 which corresponded to 0.5% of the total world DALY value. In the same study for 2010, the figure increased by 3.4%, to 256/100,000 (0.7% of the total world DALY value). In Brazil, the situation is also a cause for concern. In 2003, the World Health Organization estimated that 19.1% of men and 4.1% of women in Brazil were in the category heavy episodic drinking. When analyzing only those who drank, these values rose to 32.4% for men and 10.1% for women (3). In relation to the DALY value for Brazil, the alcohol abuse rate was 938/100,000 (2.5% of DALY) in 1998, of which 740/100,000 for men and 198/100,000 for women (4).

Among the disabilities attributable to alcohol use/dependence, liver cirrhosis was singled out as a major cause of fatalities from chronic morbidity (5). At a global level, in 2010, an average of 2% (1.4% for women and 2.4% for men) of all deaths and 1.2% of DALY were attributed to cirrhosis (2,6). It was estimated that 48% of fatalities and 47% of DALY for cirrhosis was attributed to alcohol consumption (6). In addition there was a relationship between the amount of alcohol consumed and the risk of developing the disease. Men who consumed more than 60 grams of alcohol per day, had a relative risk of 5.0, while those who consumed from 48 to 60 g/day had a risk of 2.3 (7).

In the study of the disease burden in Brazil for 1998 (ECDB-98), liver cirrhosis accounted for 2.6% of deaths; 2.8% of years of life lost due to premature death (YLL) and 1.5% of DALY (4). In this study, however, the different etiologies of the disease were not evaluated separately, and so it did not establish the percentages of mortality and morbidity attributed to alcohol. The burden of disease study for the year 2008 (ECDB-2008), in turn, incorporated methodological changes that permitted the calculation of estimates for cirrhosis by etiological categories.

The purpose of this article is to describe and comparatively analyze the value of DALY in terms of its components, YLL and YLD, for alcohol use/ dependence and the non-viral etiology of cirrhosis, a category that includes alcoholic cirrhosis, in the Brazilian study of the disease burden for 2008, broken down by gender and age range.

Data sources and methodology

The ECDB 2008 evaluated about 100 types of disabilities, which were classified into the three broad groups defined by the GBD: infectious and parasitic diseases, maternal causes, perinatal causes and nutritional deficiencies (Group I); chronic non-communicable diseases (Group II); and external causes (Group III). Alcohol use/dependence and liver cirrhosis were included in the study and classified in Group II.

The analysis in this study was conducted using the DALY indicator, a summary measure that aims to capture the effect of morbidity and mortality in the health condition of populations. The DALY is the sum of two other indicators: the YLL and YLD (8).

The estimates for YLL, fatalities from cirrhosis and alcohol/use dependence (according to the classification described below), in the period from 2007 to 2009, were obtained from the Mortality Information System [Sistema de Informacao de Mortalidade (SIM)], using the average number of fatalities during the period. They were adjusted for the under-reporting of fatalities for each Brazilian state, for gender and age range, and also a national adjustment of 28% for those less than 1 year old and 13% for those more than 1 year old. In accordance with the traditional methodology used in the GBD study (9), fatalities with inadequately defined causes (7.4% of deaths in Brazil in 2008), and those defined as being incorrectly coded (10.5% of deaths) were redistributed proportionally by gender, age range and cause of death in each Brazilian state (10).

The ICD-10 codes used to identify deaths for alcohol use/dependence were F10.1 and F10.2. In relation to fatalities from cirrhosis, a meeting among Brazilian hepatologists (11) defined the ICD-10 codes that corresponded to deaths from the disease and distributed them into four etiologic categories: "hepatitis C", "hepatitis B", "alcohol" and "other causes of cirrhosis." Specifically for the etiologies studied in this article, and based on the above-mentioned expert consensus (11), the ICD-10 code descriptions were as follows: "alcohol" (K70) and "other non-viral causes of cirrhosis" (K71.1, K71.7, K74.3, K74.4, K74.5, K75.4, K76.0). Additionally, the codes K72.1, K73.9, K74.0, K74.1, K74.2, K74.6 and K76.7 were redistributed proportionally among the four etiological categories. And, for the codes K72.9 and K76.9 it was decided that 70% of the fatalities for adults over 40 years old would be attributed to liver cirrhosis (11,12).

The YLD component was calculated from estimates of the frequency of occurrence, the duration and the severity of the disability, the latter being defined according to a standardized table in the GBD (8) study. Given the lack of parameters for the frequency of alcohol use/dependence and liver cirrhosis in Brazil, estimates were made of the prevalence of such disabilities. These estimates, together with the data on remission and mortality, were input into the Dismod II program, which has been made available publicly by the World Health Organization (WHO). The use of this program enabled a model to be built that facilitated the obtaining of estimates of the frequency and duration of both disabilities.

For the disability from alcohol use/dependence, the data on such prevalence adopted for Brazil was that presented in the GBD-2000 study (13). It was assumed that such prevalence rates would correspond to those found in the Southeast region of Brazil. Adjustment factors for the other regions were calculated, based on the data of Naranjo et al. (14). The prevalence parameters for the Southeast region were then modeled in the Dismod II program, together with the data on remission and relative risk of death from the GBD-2000 study already cited (13). The frequency rate for people below five years of age was considered to be zero. Adjustment factors were applied to the frequency rates generated to determine the parameters to be used in the model for the other regions. The durations generated in the modeling process were adjusted in order to maintain a longer time period for the disabilities for men (15).

In order to estimate the viral etiology of cirrhosis we used the prevalence rates for hepatitis B and C reported in the "Study of Population-based Prevalence of infections by hepatitis viruses A, B and C in the Brazilian state capitals ", conducted in 2008, the only national population-based study on viral hepatitis (16).

The consensus meeting of hepatologists mentioned above established that of all the HBsAg positive cases in this study, 6% referred to cirrhosis cases. Furthermore, for those patients who tested positive for anti-HCV, the percentage with cirrhosis patients would be 14% (11). In the ECDB study, in 2008, such frequencies were applied to the Brazilian population at that time to estimate the prevalence of cirrhosis derived from hepatitis B and C. A survey conducted by the Brazilian Society of Hepatology of the etiology of cirrhosis in Brazil in 200117 found that approximately 37 % of the cases of cirrhosis in Brazil were derived from hepatitis C and 11% from hepatitis B.

Thus, it was considered that the viral etiology of cirrhosis represented 48% of all cirrhosis cases, with the remainder (52%) being due to the etiologies of alcohol and other causes of cirrhosis. The distribution by gender and age range of the category "cirrhosis due to alcohol and other causes of cirrhosis" was based on the distribution of fatalities from alcoholic cirrhosis from the SIM, in 2008, since no other data could be found in the Brazilian literature. The remission of the disability was considered to be zero and the frequency rates generated after shaping the Dismod II for the age range of 80 years and above were eliminated (12).

Regarding the ethical aspects of this study, the data in SIM was obtained from the internet site of DATASUL/MS, and the data on the hepatitis survey was made available by the Secretariat of Health Surveillance. The ECDB-2008 study was approved by the Committee on Ethics in Research of the Sergio Arouca National School of Public Health (ENSP).

In the present article we have presented our estimates for DALY, YLL and YLD for alcohol use/dependence and for the non-viral etiology of cirrhosis, that is, cirrhosis attributed to alcohol and other causes. A discount rate of 3%, as proposed in the GBD methodology, was incorporated in the calculations for mortality (YLL) and morbidity (YLD) for these two disabilities.

Results

Table 1 shows the DALY for each large group of disabilities (I, II and III) for the various regions of Brazil for 2008. It can be observed that over 70% of disease burden in Brazil was attributed to Group II effects, which was also the situation in all regions. The table also presents the DALY for "alcohol use/dependence" and "cirrhosis due to alcohol and other causes", with the respective percentages of the total. Alcohol use/dependence was responsible for a DALY value of 1.1 million for Brazil, representing 3% of the country's total disease burden. The same proportion was observed in all the regions except the Center-west, where the DALY due to alcohol was 4%. The DALY value for cirrhosis due to alcohol and other causes was approximately 536 thousand for Brazil, representing 1% of the country's total disease burden for 2008. The Southern region was the region with the highest absolute DALY value, followed by the Northeast.

Considering the first ten most frequent causes of DALY for men, alcohol was ranked second, third and sixth in the age ranges of 15-29, 30-44 and 45-59, respectively (Figure 1). Cirrhosis due to alcohol and other causes, in turn, is one of the top ten causes of DALY in men in the age ranges 30-44; 45-59 and 60-69 years (ranked eighth, fifth and eighth, respectively). The ranking for women was not presented since the disabilities in question were not among the top ten causes of DALY in females in any of the age ranges.

Figure 2 shows the YLD, YLL and DALY per 100,000 of population by age for the two disabilities. For the YLD, higher rates were observed for alcohol use/dependence, especially in the age range 15 to 29 years. For cirrhosis derived from alcohol, higher values of YLD were found in the age range of 45-59 years, decreasing thereafter. With respect to the YLL, higher rates were observed for cirrhosis due to alcohol. In both situations, the age range with the highest rates of YLL was that for 45-59 years. By analyzing the DALY figures, one can see that the higher rates relate to alcohol use/dependence in the younger age ranges, mainly from 15 to 29 years, being overtaken by cirrhosis in the age range of 45-59 years. Thus, from the age of 45 onwards, the highest DALY rates were attributed to alcoholic cirrhosis.

Figure 3 shows that the major contribution of the disease burden from alcohol use/dependence is from the YLD component (83%), which occurred for all age ranges. It was observed, however, an increase in the participation of the YLL component with increasing age. In relation to age range, the DALY for alcohol had a greater impact on the age range of 15-29 years (47.5%), followed by 30-44 years (27.4%) and 44-59 years (19.4%) of the DALY value. With regard to distribution by gender, we observed that men have higher values of DALY, with little variation by age range (male: female ratio of 2.3).

Cirrhosis derived from alcohol and other causes has the largest percentage of DALY represented by the YLL component (75%), which was also the case for all age ranges (Figure 4). The impact of cirrhosis on the age range of 15-29 years was small (4.4%), while the group of 44-59 years had the highest impact (40.2%), followed by the age ranges 30-44 years and 60 years or older (27.4% and 20.4%, respectively). For cirrhosis, as for alcohol dependence, higher percentages of DALY were observed among men (male: female ratio of 4.6).

Discussion

In the ECDB-2008 study, the non-communicable diseases (Group II) accounted for the largest share of DALY in Brazil (77%). In recent years, the phenomenon of the epidemiological transition has resulted in a change in the pattern of morbidity and mortality in the Brazilian population (18). One can see, for the population, a reduction in infectious and parasitic diseases and an increase in non-communicable diseases. Neuropsychiatric diseases, for example, accounted for 18.6% of the DALY for Brazil in 199818, and rose to 27.8% by 2008 (10). This group includes the incidence of alcohol use/dependence, which in this study was responsible for 3% of the national DALY value, with regional variations of 3-4%; compared to the 0.7% observed in the GBD-2010 (2) study. For the global ranking of DALY in 2010, alcohol use/dependence was ranked 35th overall and 17th for the category Tropical Latin America, which included Brazil and Paraguay (2). In Brazil, in 1998, alcohol was ranked 11th (4), then in 2008, for men it was ranked 3rd, and for women 13th.

In relation to liver cirrhosis, the ECDB-2008 study introduced an important methodological change, by evaluating the disabilities in etiological categories. This made it difficult to compare the ranking in this study to that of the previous study for 1998, which had been prepared using the traditional GBD methodology (4) and which ranked liver cirrhosis in 17th for both genders. The current article deals only with the category "cirrhosis derived from and other causes of cirrhosis". It does not cover viral etiologies of cirrhosis. The etiological category in question was responsible for 1% of the Brazilian DALY value and is one of the top 20 causes for men only, being ranked 11th. On the other hand in the GBD20102 study, cirrhosis derived from alcohol was responsible for 0.6% of the total DALY.

It is noteworthy that in the ECDB-2008 study there was no separation between cirrhosis attributed to alcohol or to other causes. Such other causes include, for example, metabolic, genetic and auto-immune diseases, many of which have epidemiological behaviors different from the hepatopathy derived from alcohol. It was not possible to use an approach to separate them into categories due to the lack of national data on the prevalence of alcoholic cirrhosis. One of the few data sources available was the survey made by the Brazilian Society for Hepatology in 2001, in which alcohol accounted for approximately 60% of the non-viral causes of cirrhosis (17). Thus, for the category investigated in this study, alcoholic cirrhosis probably represented the largest percentage of the cases. In this context, the percentage of the DALY value attributed to alcoholic cirrhosis in Brazil could be close to the global percentage (0.6%) (6), unlike that for alcohol use/ dependence, which indicated highest percentages for Brazil compared to the global average, as shown earlier.

Both alcohol use/dependence to alcohol and liver cirrhosis are known to be more frequent disorders in males (2,7,14). According to WHO, 6.2% of fatalities for men was attributed to alcohol, while for women this percentage was 1.1% (1). In 2010, fatalities from cirrhosis derived from alcohol accounted for 0.9% of all deaths worldwide, of which 0.7% for women and 1.2% for men (19). Furthermore, in 2010, alcoholic cirrhosis accounted for 0.8% of the total DALY value for men and 0.4% of the total DALY for women (6). The data from the present study reinforced this male prevalence, since both harmful effects were among the top ten causes of DALY in men but not in women. For this reason, the data was presented only for men, thus it represents the higher risk group for both disabilities.

Moreover, the analysis of the DALY distribution curves by age range in the present study revealed that the disease burden of alcohol has a greater impact on the younger age ranges, while the greatest impact of cirrhosis comes later, in the age range of 45 to 59 years. In the GBD-2010 study, the disorders related to alcohol use had a higher disease burden between the ages of 25-50 years, declining gradually thereafter (20). As for cirrhosis, the global curve also showed a greater impact of the disease for the age range of 45-59 years, with a more marked decline thereafter (2). The similarity of the curves for Brazil and the global study is probably related to the underlying reasons for the disabilities: alcohol is considered an important risk factor for cirrhosis, with a relationship between its consumption and the development of liver damage (7). Thus, the higher incidence of alcohol usage in the younger age ranges would be reflected by more cases of alcoholic cirrhosis in older age ranges.

For alcohol, the YLD was the component with the highest percentage impact on the DALY value while for cirrhosis, YLL was the principal factor. This distribution was also observed in the GBD-2010 study (20). Samokhvalov et al. (21) conducted a systematic review of the literature on disabilities related to alcohol abuse. Although they found a degree of heterogeneity in the studies, they observed that changes in emotional state, social relationships and memory were significant disability attributes. When assessing alcohol as a risk factor for cirrhosis, Rehm et al. (7) found that its consumption was associated with a higher impact on mortality from liver disease than on morbidity.

There are few published epidemiological studies on alcohol use/dependence and liver cirrhosis in Brazil. By producing estimates of YLL, YLD and DALY for Brazil and its regions, this study helped to characterize the morbidity and mortality profiles and, therefore, the impacts of these disabilities on the population. Furthermore, they also facilitate comparative analysis, due to the distribution by gender and age range, of alcohol use/dependence and cirrhosis, typifying this disease process in Brazil, as well as providing information for government actions.

On the other hand, certain limitations should be highlighted. Firstly, there was a lack of population studies on the subject, requiring the use of parameters from various studies for the construction of indicators. Besides this, the studies used for the estimation of parameters such as the hepatitis survey (16), were conducted in the Brazilian state capitals and then extrapolated to the rest of the country, which could mean that they do not adequately portray the other cities.

Another point to note was the absence of data on the age range distribution for the prevalent cases of cirrhosis in the population, which led to the use of the distribution of this disease from the SIM system. Finally, the absence of specific data for alcoholic cirrhosis did not permit the breakdown of the data for the category of "alcohol and others". Thus, despite the greater proportion of this category being due to alcohol, one should emphasize that there was also the influence of other liver diseases that could have a epidemiological behavior different from that of alcoholic cirrhosis.

Alcohol use/dependence is a major concern of the health service, since today its use at increasingly earlier age ranges has been observed and which is often associated with risk situations, such as driving under the influence of alcohol (14). Thus, the present study provides information to enable preventive actions against alcohol abuse, by demonstrating the higher values for DALY in the age range of 15-29 year, and indicating the importance of adopting specific actions for this age range. Generally, in this age range there are constant changes in people's lives, such as going to university, more socializing with friends (compared to before when the social circle was based on the family environment) and entry into the labor market. These situations can generate sources of stress which may be associated with the increased use of alcohol (22,23). Thus, preventive actions in these age ranges, such as limiting the sale of alcoholic beverages, higher taxation and restrictions on the places/hours could help reduce the alcohol use/dependence (24).

On the other hand, cirrhosis due to alcohol and other causes presented higher rates in the age range of 45-59 years. This data suggested that actions to reduce alcohol consumption in the earlier age ranges could minimize the impact of this disease in the older age ranges, given the underlying reason for these diseases. Also, it should be emphasized that there is the need to equip the health service system to allow the early diagnosis and appropriate treatment of alcohol dependence in order to prevent the subsequent effect of cirrhosis on patients' lives.

Finally, this study pointed to some developments. Given that alcohol use is an important risk factor for liver disease (25), it is necessary to calculate the total percentage of cirrhosis attributable to alcohol, aiming at understanding its influence on the population disease burden and proposing preventive actions. Another point to note is the lack of population-based studies, as well as those of a longitudinal nature in order to obtain a better understanding of the disease profile from these causes among the population. We also suggest that investments be made in cost-effectiveness studies, in which the impact of different interventions in these diseases is assessed.

Collaborations

FB Portugal, MR Campos, JR Carvalho, LS Flor, JMA Schramm and MFS Costa participated equally in all stages of preparation of the article.

DOI: 10.1590/1413-81232015202.01142014

Acknowledgments

We would like to thank the Department of Science and Technology of MS for funding this study; the entire team at the Center for Applied Research Methods for Global Disease Burden Studies, especially Roberta Benitez Freitas Passos, Iuri Costa Leite and Joaquim Valente. We would also like to thank the participants in the expert's consensus discussions, for their contribution to this study: Angelo Alves de Mattos (RS), Cristiane Alves Villela-Nogueira (RJ), Francisco Jose Dutra Souto (MT), Henrique Sergio Moraes Coelho (RJ), Jorge Andre de Segadas-Soares (RJ) and Renata de Mello Perez (RJ); as well as the team that prepared the national survey on hepatitis coordinated by Leila Maria Moreira Beltrao Pereira for the clarifications and details of the survey data.

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Article submitted 09/03/2014

Approved 03/08/2014

Final version submitted 05/08/2014

Flavia Batista Portugal [1]

Monica Rodrigues Campos [1]

Juliana Ribeiro de Carvalho [2]

Luisa Sorio Flor [1]

Joyce Mendes de Andrade Schramm [1]

Maria de Fatima dos Santos Costa [3]

[1] Escola Nacional de Saude Publica, Fiocruz. R. Leopoldo Bulhoes 1480, Manguinhos. 21041-210 Rio de Janeiro RJ Brasil. flaviabportugal@gmail.com

[2] Servico de Pronto Atendimento, Hospital do Cancer, Instituto Nacional do Cancer.

[3] Departamento de Informacao e Documentacao, Instituto Fernandes Figueira, Fiocruz.

Table 1. DALY (a)--Absolute number and percentage by Brazilian region
and disease group, 2008.

Region            DALY         DALY            DALY             DALY
                  Total       Group I        Group II         Group III

                                                         %

North          2,728,319.97     18%      1,949,395.08   71%      10%
Northeast     11,142,080.51     16%      8,391,663.22   75%       9%
Southeast     15,487,347.64     11%     12,310,421.98   79%       9%
South          5,177,988.94     11%      4,071,152.11   79%      10%
Center-West    2,421,925.03     12%      1,825,057.22   75%      12%
Brazil        36,957,662.09     13%     28,547,689.61   77%      10%

                   Alcohol abuse and alcohol
                          dependence

Regiao             DALY       % DALY/   % DALY/
                               total    Group II

Norte             87,224.66     3%         4%
Nordeste         360,111.59     3%         4%
Sudeste          461,870.49     3%         4%
Sul              145,499.22     3%         4%
Centro Oeste      87,420.79     4%         5%
Brasil         1,142,126.75     3%         4%

                 Cirrhosis due to alcohol and
                         other causes

Regiao             DALY       % DALY/   % DALY/
                               total    Group II

Norte            29,895.16      1%         2%
Nordeste        173,533.59      2%         2%
Sudeste         227,041.53      1%         2%
Sul              75,639,89      1%         2%
Centro Oeste     30,058.35      1%         2%
Brasil          536,168.52      1%         2%

(a) DALY (Disability Adjusted Life Years).


Introducao

O uso nocivo e a dependencia de alcool ("uso/dependencia do alcool") sao um importante fator de risco para diversas doencas e lesoes que ameacam a saude. E responsavel, aproximadamente, por 2,5 milhoes de mortes por ano, sendo que de 20% a 50% da ocorrencia de cirrose hepatica, de epilepsia, dos envenenamentos, dos acidentes de transito, da violencia e dos varios tipos de cancer sao causados pelo seu consumo (1).

No mundo, estima-se que aproximadamente 11,5% entre aqueles que bebem apresentam o padrao heavy episodic drinking (consumo de 60 gramas ou mais de alcool puro nos ultimos sete dias); no continente americano, esta prevalencia e de 12%, sendo 17,9% para os homens e 4,5% para as mulheres (1). Ja no estudo Global Burden of Disease (GBD) de 19902, os Disability Adjusted Life Years (DALY)--anos de vida perdidos ajustados por incapacidade--atribuidos ao uso/ dependencia de alcool eram de 248/100.000, correspondendo a 0,5% do DALY total no mundo. No estudo de 2010, este numero aumenta em 3,4%, assumindo valor de 256/100.000 (0,7% do DALY). No Brasil, a situacao tambem e preocupante. Em 2003, a Organizacao Mundial de Saude estimou que 19,1% dos homens e 4,1% das mulheres no pais apresentavam o padrao heavy episodic drinking e ao analisar somente aqueles que bebem, estes valores subiam para 32,4% nos homens e 10,1% nas mulheres (3). Sobre o DALY no Brasil, ao abuso de alcool foi atribuida uma taxa de 938/100.000 (2,5% do DALY) em 1998, sendo de 740/100.000 para homens e de 198/100.000 para mulheres (4).

Dentre os agravos atribuidos ao uso/dependencia de alcool, a cirrose hepatica merece destaque como uma importante morbidade cronica fatal causada pelo seu consumo (5). Mundialmente, em 2010, 2% (1,4% para mulheres e 2,4% para homens) das mortes e 1,2% do DALY foram atribuidos a cirrose (2,6). Estima-se que 48% das mortes e 47% do DALY por cirrose sao atribuidos ao consumo de alcool (6). Ha ainda uma relacao entre quantidade de alcool consumida e risco de desenvolvimento da doenca, onde os homens que consomem mais que 60 gramas de alcool por dia, apresentam risco relativo de 5.0, enquanto que aqueles que consomem de 48 a 60g/dia tem risco de 2,3 (7).

No estudo de carga de doenca no Brasil, relativo a 1998 (ECDB-98), a cirrose hepatica foi responsavel por 2,6% das mortes; 2,8% dos anos de vida perdidos por morte prematura (Years of Life Lost--YLL) e 1,5% do DALY (4). Nesse estudo, porem, nao foram avaliadas separadamente as diferentes etiologias da doenca, de forma que nao se determinou as parcelas de mortalidade e morbidade atribuidas ao alcool. O estudo de carga de doenca relativo ao ano de 2008 (ECDB-2008), por sua vez, apresentou alteracoes metodologicas que permitiram estimativas de cirrose em categorias etiologicas.

O objetivo do presente artigo e descrever e analisar comparativamente o DALY em seus componentes, YLL e YLD--Years Lived with Disability, para o uso/dependencia de alcool e para a cirrose de etiologia nao viral, categoria que inclui a cirrose alcoolica, no estudo brasileiro de carga de doenca em 2008, segundo sexo e faixa etaria.

Material e metodos

O ECDB-2008 avaliou cerca de 100 agravos, classificados em tres grandes grupos segundo o GBD: doencas infecciosas e parasitarias, causas maternas, causas perinatais e deficiencias nutricionais (Grupo I); doencas cronicas nao transmissiveis (Grupo II); e causas externas (Grupo III). O uso/ dependencia de alcool e a cirrose hepatica foram incluidos no estudo e classificados no grupo II.

As analises nesse estudo foram realizadas por meio do indicador DALY, uma medida sumaria que visa apreender o efeito da morbidade e da mortalidade no estado de saude de populacoes. O indicador e composto pela soma de duas parcelas: o YLL e o YLD (8).

Para as estimativas de YLL, os obitos por cirrose e uso/dependencia de alcool (segundo classificacao a ser descrita abaixo), no periodo de 2007 a 2009, foram obtidos do Sistema de Informacao de Mortalidade (SIM), utilizandose a media dos obitos no periodo. Realizou-se correcao para o sub-registro de obitos em cada estado do pais, segundo sexo e faixa etaria, sendo a correcao nacional de 28% para menores de 1 ano e de 13% para maiores de 1 ano. Conforme a metodologia tradicional do estudo GBD (9), os casos de obitos oriundos das causas mal definidas (7,4% dos obitos no Brasil em 2008), bem como os casos definidos como codigos-lixo (10,5% dos obitos), foram redistribuidos proporcionalmente por sexo, faixa etaria e causa do obito em cada estado do pais (10).

Os codigos da CID-10 utilizados para identificar os obitos por uso/dependencia de alcool foram F10.1 e F10.2. Em relacao aos obitos por cirrose, uma reuniao de consenso entre hepatologistas brasileiros (11) definiu os codigos da CID-10 que corresponderiam aos obitos pela doenca e distribuiu os mesmos em quatro categorias etiologicas: "hepatite C", "hepatite B", "alcool" e "outras causas de cirrose". Especificamente para as etiologias trabalhadas neste artigo, com base no consenso de especialistas (11), segue a descricao dos codigos da CID-10: "alcool" (K70) e "outras causas de cirrose nao virais" (K71.1, K71.7, K74.3, K74.4, K74.5, K75.4, K76.0). Alem disso, os codigos K72.1, K73.9, K74.0, K74.1, K74.2,K74.6 e K76.7 foram redistribuidos proporcionalmente entre as quatro categorias etiologicas. E, para os codigos K72.9 e K76.9, decidiu-se que 70% dos obitos em maiores de 40 anos seriam atribuidos a cirrose hepatica (11,12).

O componente YLD e calculado a partir de estimativas de casos incidentes, da duracao e do peso da incapacidade, este ultimo definido em tabela padronizada no estudo GBD (8). Diante da ausencia de parametros de incidencia para uso/ dependencia de alcool e cirrose hepatica no Brasil, foram realizadas estimativas de prevalencia para esses agravos. Tais estimativas, juntamente com dados de remissao e de mortalidade, foram inseridas no programa Dismod II, disponibilizado para dominio publico pela Organizacao Mundial da Saude (OMS). Atraves deste programa foi entao realizada a modelagem, processo que permitiu a obtencao de estimativas de incidencia e duracao de ambos os agravos.

Para o agravo uso/dependencia de alcool, os dados de prevalencia adotados para o Brasil foram aqueles apresentados no estudo de GBD-2000 (13). Assumiu-se que tais prevalencias corresponderiam aquelas encontradas na regiao Sudeste, sendo calculada uma razao de correcao para as demais regioes, com base nos dados de Laranjeira et al. (14). Os parametros de prevalencia para a regiao Sudeste foram, entao, modelados no programa Dismod II, juntamente com os dados de remissao e risco relativo de morte do estudo GBD-2000 ja citado (13). As incidencias abaixo de 5 anos de idade foram consideradas zero, sendo aplicados os fatores de correcao nas incidencias geradas para determinacao dos parametros utilizados na modelagem das demais regioes. As duracoes encontradas no processo de modelagem foram ajustadas a fim de manter uma maior duracao do agravo entre homens (15).

Para as estimativas da cirrose de etiologia viral foram utilizadas as prevalencias das hepatites B e C obtidas no "Estudo de Prevalencia de Base Populacional das infeccoes pelos virus das hepatites A, B e C nas capitais do Brasil", realizado em 2008, unico estudo de base populacional de abrangencia nacional sobre hepatites virais (16).

Apos o consenso de hepatologistas ja citado, foi estabelecido que, dentre os casos HBsAg positivos nesse estudo, 6% representariam casos de cirrose. Ja entre os pacientes anti-HCV positivos, a porcentagem de cirroticos seria de 14% (11). No ECDB-2008, tais frequencias foram aplicadas a populacao brasileira do periodo para estimar as prevalencias de cirrose por hepatites B e C. Um inquerito realizado pela Sociedade Brasileira de Hepatologia sobre a etiologia da cirrose no Brasil em 2001 (17) observou que aproximadamente 37% dos casos de cirrose no pais eram decorrentes da hepatite C e 11%, da hepatite B.

Assim, considerou-se que a cirrose de etiologia viral corresponderia a 48% do total de casos de cirrose, sendo o complemento (52%) destinado as etiologias alcool e outras causas. A distribuicao por sexo e faixa etaria da categoria "cirrose por alcool e outras causas de cirrose" seguiu a distribuicao dos obitos por cirrose alcoolica do SIM, no ano de 2008, uma vez que nao se encontrou dados a respeito na literatura nacional. A remissao do agravo foi considerada zero e as incidencias geradas apos a modelagem no Dismod II para as faixas etarias superiores a 80 anos foram zeradas (12).

Quantos aos aspectos eticos para a realizacao deste estudo, o SIM foi obtido no site do Datasus/MS e as informacoes do inquerito de hepatite foram disponibilizadas pela Secretaria de Vigilancia em Saude. O ECDB-2008 foi aprovado no Comite de Etica em Pesquisa da Escola Nacional de Saude Publica Sergio Arouca (ENSP).

No presente artigo serao apresentadas as estimativas de DALY, YLL e YLD do uso/dependencia de alcool e da cirrose de etiologia nao viral, isto e, a cirrose atribuida ao alcool e a outras causas. Uma taxa de desconto de 3%, proposta na metodologia do GBD, foi incorporada nos calculos de mortalidade (YLL) e morbidade (YLD) para os dois agravos.

Resultados

A Tabela 1 apresenta o DALY de cada grande grupo de agravos (I, II e III) nas diferentes regioes do pais em 2008. Observa-se que mais de 70% da carga de doenca no pais foram atribuidos ao Grupo II, o que ocorreu tambem em todas as regioes. A tabela apresenta ainda o DALY de "uso/ dependencia de alcool" e da "cirrose por alcool e outras causas", com a respectiva porcentagem do total. O uso/dependencia de alcool foi responsavel por 1.1 milhao de DALY no Brasil, o que representa 3% do total da carga de doenca no pais. A mesma proporcao foi observada em todas as regioes, exceto no centro-oeste, onde o DALY por alcool foi de 4%. O DALY para cirrose por alcool e outras causas foi de aproximadamente 536 mil no Brasil, representando 1% do total de carga de doenca no pais em 2008. A regiao sul foi a regiao que apresentou maior DALY absoluto, seguida pelo nordeste.

Ao se considerar as dez primeiras causas de DALY para homens segundo grupo etario, o alcool ocupou a segunda, terceira, e sexta posicoes nas faixas etarias de 15-29 anos, 30-44 anos e 45-59 anos, respectivamente (Figura 1). A cirrose por alcool e outras causas, por sua vez, esta entre as dez primeiras causas de DALY em homens nos grupos de 30-44; 45-59 e 60-69 anos (oitava, quinta e oitava posicoes, respectivamente). Nao foi apresentado o ranqueamento para as mulheres, pois os dois agravos em questao nao estavam entre as dez primeiras causas de DALY no sexo feminino em nenhuma das faixas etarias.

Figura 2 mostra o YLD, YLL e DALY por 100.000 habitantes segundo idade para os dois agravos. Para o YLD, maiores taxas sao observadas para o uso/dependencia do alcool, especialmente na faixa de idade entre 15 e 29 anos. Para a cirrose alcoolica, maiores valores de YLD sao encontradas na faixa de 45-59 anos, decrescendo a partir de entao. No que diz respeito ao YLL, taxas superiores sao observadas para a cirrose por alcool. Em ambos os agravos, a faixa etaria com maiores taxas de YLL e a de 45-59 anos. Ao analisar o DALY, percebe-se que maiores taxas sao observadas para uso/dependencia de alcool durante as faixas etarias iniciais, principalmente entre 15 e 29 anos, sendo superada pela cirrose na faixa dos 45-59 anos. Assim, a partir do 45 anos de idade, maiores taxas de DALY sao atribuidas a cirrose alcoolica.

A Figura 3 mostra que a maior contribuicao da carga de doenca por uso/dependencia de alcool e por YLD (83%), o que ocorre em todas as faixas de idade. Observa-se, entretanto, aumento da participacao do YLL com o avancar da idade. Quanto a faixa etaria, DALY por alcool teve maior impacto no grupo de 15-29 anos (47,5%), seguido por 30-44 e 44-59 anos (27,4% e 19.4% do DALY, respectivamente). No que diz respeito a distribuicao por sexo, percebe-se que maiores proporcoes de DALY sao encontradas entre os homens, com pouca variacao entre as faixas etarias (relacao homem: mulher de 2,3).

A cirrose por alcool e outras causas tem a maior fracao do DALY representada pelo YLL (75%), o que e verificado em todas as faixas etarias (Figura 4). O impacto da cirrose no grupo etario de 15-29 anos foi pequeno (4,4%), enquanto que o grupo de 44-59 anos apresentou a maior proporcao (40,2%), seguido pelas faixas de 30-44 e 60 anos ou mais (27,4% e 20,4%, respectivamente). Para a cirrose, assim como para a dependencia do alcool, maiores fracoes de DALY foram encontradas entre os homens (relacao homem: mulher de 4,6).

Discussao

No ECDB-2008, as doencas nao transmissiveis (Grupo II) foram responsaveis pela maior parcela do DALY no pais (77%). Nos ultimos anos, o fenomeno da transicao epidemiologica acarreta mudanca no padrao de morbimortalidade na populacao brasileira (18). Nota-se, assim, a reducao do adoecimento populacional pelas doencas infecto -parasitarias e o aumento por agravos nao transmissiveis. As doencas neuropsiquiatricas, por exemplo, representavam 18,6% do DALY no Brasil em 199818, passando a 27,8% em 200810. Neste grupo insere-se o uso/dependencia de alcool, que no presente estudo foi responsavel por 3% do DALY nacional, com variacao regional de 3 a 4%; frente aos 0,7% observados no GBD-20102. Em relacao ao ranqueamento mundial do DALY em 2010, o uso/dependencia de alcool encontrava-se na 35a posicao e na 17a, ao se considerar apenas a categoria Tropical Latin America, a qual inclui Brasil e Paraguai (2). No Brasil, em 1998, o alcool ocupava a 11a posicao do ranqueamento (4), ja em 2008, entre os homens ele ocupou a 3a posicao, enquanto que para as mulheres a 13a.

Em relacao a cirrose hepatica, o ECDB-2008 introduziu uma importante alteracao metodologica, ao avaliar o agravo em categorias etiologicas. Isso dificulta a comparacao ao ranqueamento do estudo anterior, relativo a 1998, que seguia a metodologia tradicional do GBD (4) e colocava a cirrose hepatica na 17a posicao para ambos os sexos. O presente artigo trata apenas da categoria "cirrose por alcool e outras causas de cirrose", nao avaliando a cirrose de etiologia viral. A categoria etiologica em questao foi responsavel por 1% do DALY nacional e aparece entre as 20 primeiras causas apenas para os homens, ocupando a 11a posicao. Ja no GBD-2010 (2), a cirrose por alcool foi responsavel por 0,6% do DALY total.

Cabe ressaltar que no ECDB-2008 nao se separa a cirrose atribuida ao alcool das outras causas de cirrose. Estas ultimas incluem, por exemplo, doencas metabolicas, geneticas e autoimunes, muitas com comportamento epidemiologico distinto da hepatopatia decorrente do alcool. A abordagem em categorias separadas nao foi possivel devido a escassez de dados nacionais sobre a prevalencia da cirrose alcoolica. Uma das poucas fontes de dados disponivel e o inquerito da Sociedade Brasileira de Hepatologia de 2001, no qual o alcool representava aproximadamente 60% das causas nao virais de cirrose (17). Assim, na categoria tratada no presente estudo, a cirrose alcoolica provavelmente representa a maior parcela de casos. Neste contexto, o percentual do DALY atribuido a cirrose alcoolica no Brasil poderia se aproximar do percentual mundial (0,6%) (6), ao contrario do uso/dependencia do alcool, que apresenta percentuais mais elevados no pais, conforme mostrado anteriormente.

Tanto o uso/dependencia de alcool como a cirrose hepatica sao agravos reconhecidamente mais frequentes no sexo masculino (2,7,14). Segundo a OMS, 6,2% das mortes em homens sao atribuiveis ao alcool, enquanto para as mulheres, esta porcentagem e de 1,1% (1). Em 2010, as mortes por cirrose atribuida ao alcool representaram 0,9% do total de obitos no mundo, sendo 0,7% para mulheres e 1,2% para homens (19). Ainda em 2010, a cirrose alcoolica foi responsavel por 0,8% do total de DALY em homens e por 0,4% do total de DALY em mulheres (6). Os dados do presente estudo reforcam esta preponderancia masculina, uma vez que os dois agravos estao entre as dez primeiras causas de DALY em homens, mas nao em mulheres. Por essa razao, foram apresentados apenas os dados do sexo masculino, que representa assim um grupo de maior risco para ambos os agravos.

Alem disso, quando sao analisadas as curvas de distribuicao do DALY por faixa etaria neste estudo, observa-se que a carga do alcool tem maior impacto em faixas etarias mais jovens, enquanto o maior impacto da cirrose e mais tardio, na faixa de 45-59 anos. No estudo do GBD-2010, os disturbios relacionados ao uso do alcool apresentavam maior carga nas idades de 25-50 anos, sofrendo declinio gradual a partir de entao (20). Ja para a cirrose, a curva mundial tambem mostra maior impacto da doenca entre 45-59 anos de idade, com declinio mais evidente apos este intervalo (2). A semelhanca das curvas nacionais e as do estudo mundial esta provavelmente relacionada a historia natural dos agravos: o alcool e considerado importante fator de risco para a cirrose, havendo uma relacao entre o seu consumo e o desenvolvimento de lesao hepatica (7). Assim, o maior acometimento das faixas etarias iniciais pelo alcool se refletiria em mais casos de cirrose alcoolica nas faixas etarias posteriores.

Para o alcool, o YLD foi o componente com maior proporcao no DALY, enquanto para a cirrose, o YLL foi o principal. Esta distribuicao tambem foi observada no estudo GBD-2010 (20). Samokhvalov et al. (21) realizaram uma revisao sistematica da literatura a respeito da incapacidade relacionada ao uso abusivo do alcool. Embora tenham encontrado heterogeneidade nos estudos, mudancas no estado emocional, nos relacionamentos sociais e na memoria foram importantes atributos de incapacidade observados. Ao avaliar o alcool como fator de risco para cirrose, Rehm et al. (7) verificaram que o seu consumo esta relacionado ao maior impacto na mortalidade pela doenca hepatica que a morbidade.

Ainda sao escassos os estudos epidemiologicos sobre o uso/dependencia de alcool e cirrose hepatica no pais. Ao produzir estimativas de YLL, YLD e DALY para o Brasil e suas regioes, o presente estudo auxilia a caracterizacao do perfil de morbimortalidade e, portanto, do impacto destes agravos na populacao. Ademais, permite a analise comparativa, por meio da distribuicao por sexo e faixa etaria, do comportamento do uso/dependencia de alcool e cirrose, caracterizando este processo de adoecimento no Brasil, bem como da subsidios para acoes governamentais.

Por outro lado, algumas limitacoes devem ser elencadas. Primeiramente, ainda ha uma escassez de estudos populacionais sobre a tematica, exigindo o uso de parametros a partir de varios estudos para a construcao dos indicadores. Alem disso, os estudos utilizados para a estimacao dos parametros, como o inquerito de hepatites (16), foram realizados nas capitais brasileiras e extrapolados para o restante do pais, podendo nao retratar adequadamente as demais cidades.

Outro ponto a se destacar e a ausencia de dados sobre a distribuicao por faixa etaria para os casos prevalentes de cirrose na populacao, o que tornou necessario o uso da distribuicao deste agravo a partir do SIM. Por fim, a ausencia de dados especificos para a cirrose alcoolica nao permitiu a desagregacao da categoria alcool e outras. Assim, apesar da maior parcela da categoria ser decorrente do alcool, deve-se ressaltar que ha tambem influencia de outras enfermidades hepaticas que podem ter comportamento epidemiologico distinto da cirrose alcoolica.

O uso/dependencia de alcool e uma das principais preocupacoes do servico de saude, ja que observa-se hoje um inicio de uso cada vez mais precoce e muitas vezes associados a situacoes de risco, como o dirigir sob o efeito do alcool (14). Desta forma, o presente estudo fornece subsidios para acoes preventivas ao abuso de alcool, ao demonstrar maior DALY na faixa etaria de 15 a 29 anos, apontando para a relevancia de acoes especificas para este grupo etario. Geralmente, nesta faixa etaria ocorrem constantes mudancas na vida, como o ingresso a universidade, maior convivio com os amigos (antes o circulo social era baseado no ambiente familiar) e a entrada no mercado de trabalho. Estas situacoes podem gerar efeitos estressores que podem associar-se ao maior uso de alcool (22,23). Assim, acoes preventivas nestas faixas etarias como limitar a venda de bebidas alcoolicas ao sobretaxar e restringir local/horario podem auxiliar na reducao do uso/ dependencia de alcool (24).

Por outro lado, a cirrose por alcool e outras causas apresentou maiores taxas na faixa etaria de 45 a 59 anos. Este dado nos sugere que acoes que reduzam o consumo de alcool nas faixas etarias iniciais podem minimizar o impacto deste agravo nas mais avancadas, dada a historia natural destes agravos. Ressalta-se, tambem, a necessidade de um servico de saude preparado para o diagnostico precoce e o tratamento adequado da dependencia do alcool a fim de prevenir o efeito posterior da cirrose na vida dos pacientes.

Finalmente, o presente estudo aponta alguns desdobramentos. Dado que o uso de alcool e um importante fator de risco para doencas hepaticas (25), torna-se necessario o computo da fracao da cirrose atribuivel ao alcool, visando conhecer a sua influencia no adoecimento populacional e propor acoes preventivas. Outro ponto a se destacar e a carencia de estudos de base populacional, bem como daqueles de carater longitudinal para obter melhor definicao do perfil do adoecimento por estas causas na populacao. Sugere-se tambem o investimento em estudos de custo-efetividade, nos quais o impacto de diferentes intervencoes nestes agravos seja avaliado.

Colaboradores

FB Portugal, MR Campos, JR Carvalho, LS Flor, JMA Schramm e MFS Costa participaram igualmente de todas as etapas de elaboracao do artigo.

Agradecimentos

Agradecemos ao Departamento de Ciencia e Tecnologia do MS pelo financiamento deste estudo; a toda equipe do Nucleo de Pesquisa em Metodos Aplicados aos Estudos de Carga Global de Doenca, especialmente a Roberta Benitez Freitas Passos, ao Iuri Costa Leite e ao Joaquim Valente. Agradecemos, tambem, aos hepatologistas participantes das discussoes do consenso de especialistas, pela contribuicao ao presente estudo: Angelo Alves de Mattos (RS), Cristiane Alves Villela-Nogueira (RJ), Francisco Jose Dutra Souto (MT), Henrique Sergio Moraes Coelho (RJ), Jorge Andre de Segadas-Soares (RJ) e Renata de Mello Perez (RJ); bem como a equipe do inquerito nacional de hepatites, coordenada por Leila Maria Moreira Beltrao Pereira, pelos esclarecimentos e detalhamento dos dados do estudo.

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Artigo apresentado em 09/03/2014

Aprovado em 03/08/2014

Versao final apresentada em 05/08/2014

Flavia Batista Portugal [1]

Monica Rodrigues Campos [1]

Juliana Ribeiro de Carvalho [2]

Luisa Sorio Flor [1]

Joyce Mendes de Andrade Schramm [1]

Maria de Fatima dos Santos Costa [3]

[1] Escola Nacional de Saude Publica, Fiocruz. R. Leopoldo Bulhoes 1480, Manguinhos. 21041-210 Rio de Janeiro RJ Brasil. flaviabportugal@gmail.com

[2] Servico de Pronto Atendimento, Hospital do Cancer, Instituto Nacional do Cancer.

[3] Departamento de Informacao e Documentacao, Instituto Fernandes Figueira, Fiocruz.

Tabela 1. DALY (a)--no absoluto e percentuais segundo regiao do Brasil
e grupos de doencas, 2008.

Region            DALY         DALY            DALY             DALY
                  Total       Group I        Group II         Group III

                                                         %

North          2,728,319.97     18%      1,949,395.08   71%      10%
Northeast     11,142,080.51     16%      8,391,663.22   75%       9%
Southeast     15,487,347.64     11%     12,310,421.98   79%       9%
South          5,177,988.94     11%      4,071,152.11   79%      10%
Center-West    2,421,925.03     12%      1,825,057.22   75%      12%
Brazil        36,957,662.09     13%     28,547,689.61   77%      10%

                    Uso nocivo e dependencia
                          de alcool

Regiao             DALY       % DALY/   % DALY/
                               total    Group II

Norte             87,224.66     3%         4%
Nordeste         360,111.59     3%         4%
Sudeste          461,870.49     3%         4%
Sul              145,499.22     3%         4%
Centro Oeste      87,420.79     4%         5%
Brasil         1,142,126.75     3%         4%

                  Cirrose por alcool e outras
                            causas

Regiao             DALY       % DALY/   % DALY/
                               total    Group II

Norte            29,895.16      1%         2%
Nordeste        173,533.59      2%         2%
Sudeste         227,041.53      1%         2%
Sul              75,639,89      1%         2%
Centro Oeste     30,058.35      1%         2%
Brasil          536,168.52      1%         2%

(a) DALY (Disability Adjusted Life Years).
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Title Annotation:FREE THEMES/TEMAS LIVRES; articulo en ingles
Author:Portugal, Flavia Batista; Campos, Monica Rodrigues; de Carvalho, Juliana Ribeiro; Flor, Luisa Sorio;
Publication:Ciencia & Saude Coletiva
Date:Feb 1, 2015
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