Elsevier

The Lancet

Volume 388, Issue 10049, 10–16 September 2016, Pages 1081-1088
The Lancet

Articles
The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

https://doi.org/10.1016/S0140-6736(16)30579-7Get rights and content

Summary

Background

With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013.

Methods

We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs).

Findings

Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86–0·94) to 1·45 million (1·38–1·54); YLLs from 31·0 million (29·6–32·6) to 41·6 million (39·1–44·7); YLDs from 0·65 million (0·45–0·89) to 0·87 million (0·61–1·18); and DALYs from 31·7 million (30·2–33·3) to 42·5 million (39·9–45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990.

Interpretation

Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health.

Funding

Bill & Melinda Gates Foundation.

Introduction

Infectious viral hepatitis is an important challenge to health worldwide. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are endemic in many low-income countries.1, 2 They usually cause self-limiting hepatitis but occasionally lead to fulminant liver failure and, in rare cases of immunosuppression, chronic HEV infection. Hepatitis B virus (HBV) and hepatitis C virus (HCV) also cause acute illness but more commonly lead to progressive liver fibrosis, cirrhosis, and an increased risk of liver cancer (specifically hepatocellular carcinoma).3, 4, 5

Effective vaccines for HAV and HBV have been available for more than two decades, and an HEV vaccine was licensed in China in 2011, but is not widely available.6 More recently, major improvements in antiviral therapies for HBV and HCV have been made. In the absence of a vaccine, progress in HCV treatment has been particularly important. New short-course oral treatments can achieve cure in most patients, including those previously considered difficult to treat, although long-term follow-up data are not yet available.7, 8 Together, these advances overcome many barriers to the control and treatment of viral hepatitis in low-income countries and are set to be important components of a new global health strategy.9 However, a better understanding of the burden of disease is required to guide these efforts.

The Global Burden of Disease (GBD) Study is a systematic effort to estimate health loss due to diseases, injuries, and risk factors by age, sex, and geography for timepoints from 1990 to 2013. It is the most comprehensive effort to estimate causes of mortality and morbidity, and their relative importance. GBD quantifies health loss using disability-adjusted life-years (DALYs), a summary metric combining premature death and non-fatal health outcomes.10 The GBD Study estimated the burden resulting from the acute sequelae of HAV, HBV, HCV, and HEV infections, and the chronic sequelae (ie, cirrhosis and liver cancer) of HBV and HCV infections. Still, the total burden of viral hepatitis was not clearly recognised in previous GBD reports because estimates for acute disease, cirrhosis, and liver cancer were categorised in separate parts of the GBD schedule of diseases and injuries.11 Building on estimates for the individual sequelae, we aimed to estimate the global burden of disease due to viral hepatitis, investigate the changes in disease burden between 1990 and 2013, and explore the extent to which disease burden affects low-income and lower-middle-income countries.

Research in context

Evidence before this study

On Oct 5, 2015, we searched PubMed for ““Hepatitis, Viral, Human”[Mesh] AND (burden OR DALY OR QALY OR HALE OR YLL OR YLD)”, with no restrictions on language or date of publication, and found 1445 publications. We excluded any studies that did not report original estimates of the frequency or burden of disease related to hepatitis A, B, C, or E infection, any studies that were restricted to special subpopulations (eg, injection drug users and people living with HIV), and any studies that did not produce estimates for an area larger than a country. 20 articles met our search criteria: two studies of hepatitis A virus seroprevalence; three studies of hepatitis B virus (HBV) seroprevalence; 12 studies of hepatitis C virus (HCV) that reported estimates of seroprevalence, prevalence of viraemia, incidence, or mortality; one study of hepatitis E virus (HEV) incidence and mortality; one study reporting estimates of cirrhosis and liver cancer due to HBV and HCV; and one study of liver cancer due to HBV and HCV. We found no studies that reported original estimates of the total burden of viral hepatitis, and no studies reporting global estimates of a comprehensive health gap metric (ie, disability-adjusted life-years or quality-adjusted life-years) for any of the four hepatitis viruses.

Added value of this study

We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer due to HBV and HCV, by age group, sex, and country from 1990 to 2013. Although sequela-specific hepatitis burden estimates have been published previously, our study is the first formal attempt to estimate the total burden of viral hepatitis, using systematic data gathering and robust statistical methods, and the trends in that burden over time. To our knowledge, this study is the first to explore the drivers of change in the burden of hepatitis and the effect of hepatitis in different country income levels. The effect of viral hepatitis has not been clearly recognised in previous GBD reports because estimates for acute disease, cirrhosis, and liver cancer have been reported separately. This paper is the first to place the burden of viral hepatitis in the context of overall global health.

Implications of all the available evidence

Our results show that viral hepatitis is one of the leading causes of death and disability worldwide, and causes at least as many deaths annually as tuberculosis, AIDS, or malaria. By contrast with most other communicable diseases, hepatitis has risen in importance since the first GBD Study in 1990. As WHO launches a major new effort to tackle viral hepatitis, these data are of crucial importance to global health policy.

Section snippets

Overall approach

We estimated mortality and morbidity due to acute viral hepatitis for the four most important viruses—HAV, HBV, HCV, and HEV—and the mortality and morbidity due to cirrhosis and liver cancer secondary to HBV and HCV. We aggregated burden from these hepatitis-attributable causes and decomposed trends to assess changes resulting from changing demographics versus changing age-specific rates (see appendix p 8 for details of decomposition methods).

Prevalence modelling (acute infection)

We obtained anti-HAV IgG, HBsAg, anti-HCV IgG, and

Results

Between 1990 and 2013, the number of deaths worldwide attributable to viral hepatitis increased by 63% (95% UI 52–75), YLLs due to viral hepatitis increased by 34% (24–46), YLDs increased by 34% (29–40), and DALYs increased by 34% (24–46; table 1). However, when these trends were decomposed to remove the effect of demographic trends (ie, changing population sizes and age structures), the underlying age-specific rates declined between 1990 and 2013: YLL rates declined by 20% (8–30), YLD rates

Discussion

To our knowledge, this study is the first attempt to formally estimate the burden of viral hepatitis using systematic data gathering and robust statistical methods. Our results show that viral hepatitis is one of the leading causes of death and disability worldwide, and causes at least as many deaths annually as tuberculosis, AIDS, or malaria. HBV and HCV account for more than 90% of viral hepatitis-related deaths and disability, and are the focus of renewed international efforts to combat

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