Liver cirrhosis has been regarded as the major cause of global health burden. The number of deaths due to liver cirrhosis is increasing gradually [6]. However, because of the heterogeneous pattern in risk factor of different countries, the number of patients who died from liver cirrhosis markedly varies [14]. In the study, we demonstrated the key findings on liver cirrhosis mortality from GBD 2017. For the first time, we comprehensively estimated the trends of liver cirrhosis mortality for 195 countries and 5 SDI regions between 1990 to 2017. In general, mortality of liver cirrhosis increased 47.15%. The trends were mainly dominated by an increase of HCV caused liver cirrhosis, with a smaller contribution from alcohol use and NASH. Notably, the number of deaths from NASH induced liver cirrhosis has increased 90.74%, which was highest among all etiologies. Thus, the global health community should recognize the importance of controlling liver cirrhosis risk factors and pay more attention to the liver cirrhosis caused by alcohol consumption and NASH[6].
HBV caused liver cirrhosis was a major health burden worldwide. Previous study indicated that about 248 million people suffered with HBV infection in 2010 [15]. Our study showed that about 383.97 thousand people died from HBV caused liver cirrhosis in 2017. Additionally, the mortality of HBV caused liver cirrhosis widely varied between countries. In some countries, HBV is the leading cause of liver cirrhosis, especially in East Asia and south Asia [15]. Our study demonstrated that the ASR of Easter Europe increased 3.69% per year. Contrary, the ASR of Western Sub-Saharan Africa decreased 2.02% per year. This amazing variation might be partly explained by varying risk factors and transmission routes across countries. Additionally, our study showed that India and China had the largest number of deaths due to HBV related liver cirrhosis. However, the mortality in India increased 102.6% from 1990 to 2017, while the mortality in China decreased 7.6%. This might be related with promoting HBV vaccine, screening of blood products and obtaining safe injection methods. Moreover, socioeconomic development and improvement in people's cognition might also be related to the number of deaths from liver cirrhosis caused by HBV. Unfortunately, 76 of 195 countries demonstrated an increase trend of ASR, although the availability of an effective vaccine and potent antiviral treatments. It might be related with national HBV prevention policy, national immigration policy, national medical insurance policy and national blood transfusion and blood donation policy [16–18]. Consequently, these countries should be recommended to reorient their HBV prevention strategies [19, 20]. Additionally, ensuring blood safety and medical device safety was also important for reducing mortality of liver cirrhosis caused by HBV [16, 21]. Finally, developing the anti-HBV drugs might provide another method to reduce mortality of liver cirrhosis [22].
Similar with previous studies, HCV still was the most important risk factors for liver cirrhosis [23, 24]. In contrast to liver cirrhosis mortality caused by HBV, the ASR of liver cirrhosis mortality caused by HCV increased and decreased only in low SDI region. It might be caused by absence of effective vaccine. Moreover, lack of treatment and poor efficacy were also closely related to the increase trend of mortality. Though the prevalence remained low in most European countries and America, but the ASR had a more significant increase in Eastern Europe, Central Asia and North America–high income [25–28]. Fortunately, direct-acting antiviral therapy had been on the market since 2014 and was effective in more than 90% of HCV patients [29, 30]. Moreover, ensuring the safety of blood transfusion, injection drug use and therapeutic injections were equally important for blocking HCV transmission [31]. Although the ASR has been increasing nowadays, the EAPC value was significantly lower than that of other causes, and negative growth of ASR is likely to occur in the future.
The overall ASR of liver cirrhosis mortality caused by alcohol has been minor increased, but has decreased in low and high SDI regions. In our study, the increase was more remarkable in Eastern Europe, Central Asia and North America–high income. This result was similar to those of previous global survey [32]. In our study, the ASR of liver mortality caused by alcohol decreased in Sub-Saharan Africa, though it increased in most regions. According to a previous global survey, the alcohol consumption was 17.1 liters per drinker in 2005, and the alcohol consumption was lowest in Africa by shown in the adult per capita consumption of alcohol by country [32]. This result obtained by Liu et al was consistent with our result [32]. It might be related to the living habits, beliefs and economic development of local people. Thus, developing policies to limit alcohol consumption was necessary for reducing mortality of liver cirrhosis caused by alcohol and improving population-health outcome. Moreover, we needed to pay more attention to the drinking problem of young people and formulated relevant policies [33, 34].
Although the mortality of liver cirrhosis caused by hepatitis decreased, the ever-increasing mortality of liver cirrhosis caused by NASH posed a continuing threat. In our study, the EAPC of liver cirrhosis mortality caused by NASH was highest among all etiologies. Moreover, the ASR increased in 4 SDI regions except for low SDI region, and significantly increased in Asia. The increase trend might be related with heavy and salty meat diet and westernized lifestyle [35]. Similar results also demonstrated that higher prevalence rate was found in China and other Asia countries in males and obese population [36]. Based on a research which indicated that the prevalence of NAFLD was higher in regions with a GDP less than 50000 yuan and more than 100000 yuan in China, the burden of liver cirrhosis mortality caused by NASH also might be closely related with national and personal economic levels [35]. Thus, systematic treatment of metabolic diseases and loss of weight might effectively reduce the liver cirrhosis mortality caused by NASH in patients. Additionally, we should closely monitored the patients suffered with liver cirrhosis caused by multiple causes, especially whose suffered with NASH and hepatitis [37].
In addition, our study showed that EAPC was negatively corelated with baseline ASR (< 45/100000), and indicated that countries with lower ASR had a higher mortality of liver cirrhosis. It might be explained as follow. Firstly, the smaller the ASR, the more significant impact on the EAPC induced by ASR change. Secondly, the country with lower ASR might pay less attention to liver cirrhosis. Finally, with the focus on liver cirrhosis, EAPC increased with the increase of ASR, though there was no statistical significance. The HDI (< 0.77) was positively correlated with EAPC. This may be because with the improvement of living standards and medical technology, patients with liver cirrhosis who were missed in the past have been diagnosed. As the HDI gradually increased, people became more aware of liver cirrhosis, and invested more money and time in prevention and treatment, so the EAPC declined.
Although the GBD estimates demonstrated the burden of liver cirrhosis mortality, several limitations should be noted. First, some liver cirrhosis patients not included in the GBD database may affect the results. Second, due to the data scarcity of GBD data, multi-etiological liver cirrhosis was not considered in this study. The interaction of several etiologies might play a role in promoting liver cirrhosis. For instance, alcohol consumption could worsen liver cirrhosis caused by hepatitis [38, 39]. Additionally, obesity and diabetes also increased the risk of liver cirrhosis caused by HCV [40, 41].
In summary, liver cirrhosis remains a huge threat to public health. Though the ASR of liver cirrhosis mortality caused by HBV decreased, the number of patients who died from liver cirrhosis due to HBV was high, especially in developing countries. The ASR of liver cirrhosis mortality caused by HCV still increased, though the direct-acting antiviral therapy for HCV patients has been used since 2014. Additionally, liver cirrhosis due to alcohol consumption and NASH were a global health concern that cannot be ignored. Thus, developing policies to limit alcohol consumption and advocate healthy living was important to reduce the mortality and improve population-health outcome, especially in several ‘‘high-risk” regions. By conducting this study, we can roughly illustrate the disease burden of liver cirrhosis mortality worldwide and formulate more reasonable and effective prevention strategies.