The burden of cirrhosis and other chronic liver disease in the middle east and North Africa (MENA) region over three decades | BMC Public Health

In this study, we assessed the burden of cirrhosis and other chronic liver disease within the MENA region from 1990 to 2021 by analyzing data from the GBD dataset. Our analysis reveals a pressing need for national healthcare policymakers to confront the escalating incidence rates by developing and implementing targeted interventions. To the best of our knowledge, this is the first study to utilize the 2021 iteration of the GBD dataset to quantify the burden of cirrhosis and other chronic liver disease in the MENA region. Overall, our findings indicate a marked increase in incidence, escalating from 3,417,410 cases in 1990 to 7,344,030 in 2021, which translates to a 114.9% increase alongside a 8.3% rise in the ASIR from 1076.1 to 1165.3 per 100,000 individuals. This increase was primarily driven by the sharp rise in MASLD, which saw a 150.9% increase in incident cases and a 22.2% rise in ASIR. In contrast, other causes, including chronic hepatitis B and C, as well as alcohol-related cirrhosis, showed declining trends in ASIR. These trends of incidence were observed in both males and females across most etiologies. Interestingly, despite the growing incidence of cirrhosis and other chronic liver disease, there was a discernible decrease in overall disease burden, as evidenced by a reduction in the age-standardized death rates from 50.8 to 23.2 per 100,000 individuals and the age-standardized DALYs rate from 1161.8 to 565.1 per 100,000 individuals. Qatar showcased the most notable annual decline in age-standardized death rates at -2.88%, while Oman exhibited the highest annual increase in ASIR at 0.64%. This paradoxical trend of increasing incidence yet declining mortality and morbidity rates mirrors global patterns, emphasizing the public health challenges and opportunities for advancement within the MENA region.

In observing trends of increasing total raw death counts alongside declining age-standardized death and DALY rates, our findings echo the dual narrative of global health progress against cirrhosis mortality and the persistent challenge it represents, especially in the MENA region. More specifically, this mirrors the pattern described by Mokdad et al. in their analysis of GBD 2010 data across 187 countries from 1980 to 2010, noting an increase in mortality despite a decrease in age-standardized death rates similar to our study’s findings [13]. The rise in the total number of deaths attributed to cirrhosis in our study period likely results from demographic shifts, including population growth and aging [20]. Another comprehensive study spanning 195 countries from 1990 to 2017 found a global decrease in cirrhosis age-standardized death and DALY rates, aligning with our observations [20]. It also noted lower death and DALY rates in regions with higher SDI, such as Pacific Asia and North America, underscoring a global escalation in the cirrhosis burden due to increased deaths, DALYs, and age-standardized prevalence of cirrhosis. Despite a notable decrease in age-standardized death rates in the MENA region, mortality rates remain significantly higher than the global, with Egypt presenting the highest age-standardized death rate despite a 22.4% reduction from 1990 to 2017 [20]. These findings underscore the intricate relationship between demographic factors, healthcare interventions, and the cirrhosis burden.

Furthermore, the rising incidence of non-HCV related liver disease, particularly MASLD, highlights a critical and growing challenge within the MENA region’s healthcare infrastructure. Despite the initiation of public health programs aimed at various cirrhosis causes, MASLD emerges as a significant, yet largely unaddressed, contributor to the regional disease burden, with ASIR rates marking the largest increase in our analysis [22]. This observation is consistent with findings by Wang et al., [19] who reported a global uptick in MASLD ASIR, specifying an EAPC of 0.1. Their study notably highlights the MENA region—and Egypt in particular—as a hotspot for MASLD incidence and mortality, identifying the highest mortality rates in middle-SDI countries and the lowest in high-SDI settings, with a negative correlation observed between SDI and death rates (r = − 0.403, p < 0.001).¹⁹ This emerging trend of MASLD not only accentuates the pressing need for targeted healthcare strategies but also calls for a deeper investigation into how cirrhosis morbidity intersects with socioeconomic determinants. Such an analysis is crucial for comprehensively addressing the intricate demands of healthcare enhancement in the MENA region.

Our investigation into the correlation between cirrhosis and other chronic liver disease morbidity and socioeconomic factors within the MENA region has yielded unexpected results, diverging from established literature that show a strong link between socioeconomic status and liver disease burden. Historically, studies have demonstrated that low socioeconomic status is associated with an increased risk of various liver diseases, including cirrhosis, primary liver cancer, and nonalcoholic liver disease [23,24,25,26]. Such populations are often more susceptible to reaching advanced stages of liver disease and bear a disproportionate burden of liver cancer [27]. This correlation is well-documented across different global contexts, from Europe to Asia [23, 25, 28], suggesting a universal trend where socioeconomically disadvantaged groups face heightened risks and poorer health outcomes related to liver disease. The absence of a significant correlation in our findings may indicate unique regional dynamics within the MENA context or perhaps reflect variances in data collection, socioeconomic measures, or the multifaceted nature of healthcare access and quality across these countries. It raises critical questions about the interplay between socioeconomic factors and health outcomes in the region, suggesting that other determinants, such as healthcare policies, public health initiatives, or even genetic predispositions, may play a more significant role in influencing cirrhosis morbidity in the MENA region than previously thought. Furthermore, this relationship can be discussed in the special context of the MENA region, an area that has been subject to political turmoil, armed conflict, and migration [29, 30]. Overall, this discrepancy shows the need for a deeper investigation into how socioeconomic disparities contribute to the incidence and progression of liver diseases in MENA, including factors such as alcohol consumption patterns, which have been identified elsewhere as being influenced by socioeconomic status. This nuanced understanding is essential for developing targeted interventions that address not only the clinical aspects of liver disease but also the socioeconomic dimensions that exacerbate health disparities.

Public health implications

Effective prevention and early detection are pivotal in the management of chronic liver diseases (CLD), necessitating robust screening protocols. In the United States, evolving hepatitis C screening recommendations now advocate for universal, one-time screening of all individuals over 18 years old and all pregnant persons, contingent on a prevalence greater than 0.1%. This approach is underpinned by the cost-effectiveness of screening and the advent of direct-acting antiviral (DAA) agents for hepatitis C treatment [31]. Similarly, screening for MASLD in primary care settings targets individuals with metabolic risk factors and/or type II diabetes mellitus, reflecting a proactive stance towards early identification and management [32]. However, the MENA region exhibits a notable scarcity in screening recommendations and implementation for at-risk populations, highlighting a critical gap in CLD prevention strategies. Bridging this gap requires leveraging the successes and lessons learned from the US and other regions to tailor and implement effective screening protocols within MENA, accommodating the unique healthcare infrastructure and population health needs of the region.

While liver biopsy remains the definitive standard for cirrhosis diagnosis, its invasive nature limits its utility, particularly for ongoing disease monitoring. The emergence of non-invasive testing (NITs) has revolutionized the diagnosis and management of CLD both in the United States and globally [33]. In Lebanon, a retrospective study of 620 patients using FibroScan identified MASLD as the leading cause of liver disease [34]. While non-invasive testing (NIT) methods, such as the Fibrosis-4 (FIB-4) index and aspartate aminotransferase to platelet ratio index (APRI), are generally accessible, affordable, and straightforward to perform, access to more advanced diagnostics like transient elastography and specialized fibrosis seromarkers may remain limited. Although healthcare systems in affluent countries such as the UAE and Saudi Arabia typically provide broad insurance coverage, variability in healthcare delivery and infrastructure can still affect the consistent availability of these diagnostics, showing the need for improved access strategies [35]. These challenges underscore the urgent need to enhance diagnostic procedures for MASLD and MASH within the region. This imperative to improve diagnostics dovetails with the region’s pressing demand for liver transplantation (LT), further illustrating the interconnected challenges of managing CLD in the MENA and the critical role of advancing diagnostic and treatment capacities to address these needs comprehensively [36].

Moreover, the demand for LT in the MENA region is acute, with the need estimated at over 50 per million population, significantly exceeding the capacity of LT centers [37]. Since the introduction of deceased donor (DDs) transplantation in 1986 [38], the landscape of LT in the MENA has evolved. However, with the exception of Iran, living donors (LDs) predominate, even where DD donation is legally permitted. This reliance on LDs, compounded by a scarcity of DDs, financial burdens borne out-of-pocket, and insufficient social support, exacerbates the challenges of meeting the LT demand in the region [39].

Addressing these challenges involves strengthening screening programs, expanding access to NITs, and enhancing LT infrastructure. Integrating hepatitis and metabolic risk screening into primary care could support earlier detection, particularly if accompanied by targeted public awareness initiatives. Financial barriers to diagnostics might be reduced through subsidies or partnerships with private insurers, improving accessibility. Regional collaboration on transplant networks may also offer a way to alleviate donor shortages by pooling expertise and resources. While the successes of DD LT programs in Iran provide useful frameworks, solutions will need to be adapted to the specific healthcare systems and challenges within each country. Thoughtfully pursuing these strategies holds promise for mitigating the burden of cirrhosis and other chronic liver disease and improving long-term outcomes across the region.

Strengths and limitations

This study represents a significant advancement in understanding the burden of cirrhosis and other chronic liver disease in the MENA region, primarily by being the first to apply the 2021 iteration GBD dataset for a comprehensive analysis spanning nearly three decades. Its strengths lie in offering a detailed exploration of cirrhosis and other chronic liver disease incidence, death, and DALY trends, differentiated by etiology, thereby shedding light on the primary drivers of the disease within a very understudied region in public health research. Additionally, by comparing the MENA data with global trends, the study places the regional findings in a broader context, emphasizing unique challenges and the critical need for targeted healthcare interventions. The inclusion of both mortality and morbidity trends offers a holistic view of the disease’s impact, crucial for assessing healthcare outcomes and the effectiveness of existing strategies.

However, the study’s reliance on secondary GBD data introduces potential limitations related to the accuracy and completeness of the dataset, which could influence the findings. The regional focus, while valuable, might obscure country-specific nuances and variations in the burden across the MENA region due to diverse healthcare infrastructures and policies. Additionally, the study’s observation of an unexpected lack of significant correlation between cirrhosis and other chronic liver disease morbidity and socioeconomic factors suggests possible data gaps or complexities in the interplay between disease incidence and socioeconomic determinants. These limitations highlight the need for cautious interpretation of the findings and suggest areas for further research, particularly in refining disease management strategies and enhancing healthcare policy effectiveness within the MENA region.

Our study utilizes the standard definitions established by the GBD to align with global research efforts and facilitate cross-study comparisons. However, a key limitation lies in the broad categorization of “cirrhosis and other chronic liver diseases,” which includes various liver conditions that may not have progressed to cirrhosis, potentially overestimating the burden. Furthermore, autoimmune, cryptogenic, and parasitic causes of liver disease, such as schistosomiasis, are grouped under generalized categories like “other causes.” This aggregation limits the ability to isolate the contributions of these specific etiologies, particularly in regions where parasitic infections are endemic, such as Egypt. These limitations highlight challenges in capturing the true burden and epidemiological patterns of liver disease across different geographic and clinical contexts.

Future research

The findings from this study highlight the pressing need for extensive research to uncover the root causes of cirrhosis and other chronic liver disease across the MENA region, evaluate the impact of existing healthcare measures, and investigate pioneering treatments. The increasing incidence of cirrhosis and other chronic liver disease fueled notably by MASLD, alongside the substantial pressure it places on healthcare infrastructures, mandates a concentrated research effort on modifiable risk factors and disease progression mechanisms. Such insights would facilitate the crafting of precise prevention methodologies capable of either mitigating or reversing the escalating trend of chronic liver disease.

Furthermore, the demand for longitudinal research is paramount to generate robust data concerning the long-term prognosis for cirrhosis patients within the MENA area. These studies are vital for the assessment of intervention efficacy in real-world settings, including the impact of vaccination drives, initiatives aimed at curtailing alcohol use, and the application of direct-acting antiviral agents for hepatitis C treatment. Analysis focusing on the cost-effectiveness of these strategies will provide invaluable guidance for health policymakers in optimizing resource distribution.

In addition, developing novel treatment strategies that align with the unique demographic, genetic, and environmental characteristics of the MENA population is essential. This includes exploring the role of precision medicine in cirrhosis management and assessing the effectiveness of emerging therapeutic compounds. A promising research avenue involves enhancing non-invasive diagnostic techniques, which are pivotal for early detection and effective management of cirrhosis. By refining these methods, the dependence on liver biopsies could be reduced, leading to improved patient care and outcomes.

Finally, while we calculated incidence and other metrics by country, we did not explore the specific reasons behind the observed trends at the national level. Drawing meaningful conclusions about the drivers of these variations is beyond the scope of this regional-level analysis. We believe that country-specific data would provide more nuanced insights and enable a better understanding of these patterns. Future research focused on individual countries is needed to identify the underlying factors contributing to these trends and inform tailored public health strategies.