HCV Tops HBV as Leading Cause of Cirrhosis, Global Burden Projected to Increase

Dang Shuang-Suo, MD

Credit: Baishideng Publishing Group

Despite a global downward trend in the age-standardized rate of liver cirrhosis from 1990 - 2019, a recent study found the number of cases continued to rise during this time period, with hepatitis C virus (HCV) replacing hepatitis B virus (HBV) as the leading cause of cirrhosis worldwide.¹

Using data from the Global Burden of Disease (GBD) study, the present study provides an updated assessment of cirrhosis prevalence trends across 204 countries over the next 20 years and suggests the disease burden will continue to increase, largely attributed to HCV infection and global increases in alcohol consumption.¹

“Our study is the first to report on changing trends in liver cirrhosis at the global, regional, and national levels over 30 years, and predicts changes over the next 20 years,” Dang Shuang-Suo, MD, director of the department of infectious diseases at the Second Affiliated Hospital of Xi'an Jiaotong University in China, and colleagues wrote.¹ “Furthermore, the targeted analysis of the etiology, risk factors, and the impact of HDI and SDI on ASR, could further guide national healthcare policy development and the implementation of related interventions.”

A progressive condition that worsens over time as more scar tissue develops, cirrhosis slows the liver's ability to process blood, metabolize nutrients, filter out toxins, and produce bile and essential blood proteins. It poses a major global health concern due to its growing burden and associated poor health outcomes, but its incidence varies widely and is not well described.²

Using the latest GBD data, this study analyzed and evaluated the disease burden posed by liver cirrhosis in 204 countries and regions around the world from 1990 - 2019, additionally predicting the changing trends in the next 20 years. Investigators extracted data on incidence, deaths, age-standardized incidence and deaths, summary exposure value, and risk factors for morbidity associated with cirrhosis by country and territory from 1990 - 2019 from the Global Health Data Exchange Query Tool.¹

They assessed this data using age-standardized rates based on the world standard population in the GBD database, additionally using estimated annual percentage change (EAPC) and average annual percentage change (AAPC) to assess age-standardized rates over time. Trends in the incidence of cirrhosis in 2019-2039 were predicted using Nordpred and BAPC model packages in the R software.¹

Globally, the age-standardized rate of cirrhosis incidence decreased by 0.05% per year from 25.7/100,000 in 1990 to 25.3/100,000 in 2019. In 2019, Moldova (80 per 100000; 95% uncertainty interval [UI], 71.7 − 86.3) had the greatest age-standardized incidence rate, followed by Mongolia (79.6 per 100000; 95% UI, 66.4 − 94.2) and Egypt (78.7 per 100000; 95% UI, 62.3–99), whereas Papua New Guinea (6.1 per 100000; 95% UI, 4.9 − 7.2) had the lowest age-standardized incidence rate. Egypt had the highest age-standardized death rate (126.7 per 100000; 95% UI: 87.3 − 169.5), followed by Mongolia (72.9 per 100000; 95% UI, 56.9 − 91.3).¹

Investigators pointed out the burden of cirrhosis varied by gender. Globally, the number of deaths, death rate, and age-standardized death rate of liver cirrhosis was significantly lower in females than in males.¹

Additionally, they noted the leading causes of cirrhosis changed between 1990 and 2019. In 1990, the top 3 causes of cirrhosis were hepatitis B (28.2%), other causes (24.3%), and hepatitis C (23.2%). However, in 2019, the top 3 causes changed to hepatitis C (26.9%), hepatitis B (25.4%), and alcohol use (21.3%). Of note, liver cirrhosis caused by hepatitis C mostly occurred in North America and high-income North America, accounting for 41.1% in 1990 and increasing to 50.8% in 2019.¹

Investigators observed a 14% global increase in alcohol use, which contributed to 49.3% of disability-adjusted life years and 48.4% of global deaths from liver cirrhosis. Drug use, on the other hand, remained stable, increasing by 2.7% globally. However, investigators called attention to a 101% increase in summary exposure value attributable to drug use in North America, accounting for 41.6% of disability-adjusted life years and 39.4% of deaths.¹

Using the Nordpred and the BAPC software packages of the R software, investigators predicted the number and incidence of cirrhosis will persistently increase from 2019 - 2039. Based on the Nordpred model analysis, the incident number of liver cirrhosis cases will increase from 1,317,848.92 in 1990–1994 to 2,409,435.31 in 2035–2039. Similarly, the BAPC analysis indicated that the incident number of liver cirrhosis cases will grow from 1,273,961 in 1990 to 3,438,491 in 2039.¹

Investigators outlined several potential limitations to these findings, including a lack of analysis of disability-adjusted life years and death trends related to cirrhosis, inability to account for smoking’s impact on cirrhosis due to its exclusion from GBD data, and delayed effects of exposure risk.¹

“The global burden of cirrhosis will continue to increase, and countries should adopt broader and more effective approaches to prevent cirrhosis based on its most common causes,” investigators concluded.¹

References:

1. ^{Wang Y, Wang M, Liu C, et al. Global burden of liver cirrhosis 1990-2019 and 20 years forecast: results from the global burden of disease study 2019. Ann Med. 2024;56(1):2328521. doi:10.1080/07853890.2024.2328521}
2. ^{Cleveland Clinic. Cirrhosis of the Liver. Diseases & Conditions. July 26, 2023. Accessed May 14, 2024. https://my.clevelandclinic.org/health/diseases/15572-cirrhosis-of-the-liver}