Liver cirrhosis is a form of liver dysfunction resulting from multiple factors. The common causes are infection with hepatitis viruses (such as hepatitis B virus[HBV] and hepatitis C virus[HCV]) and alcohol-related liver disease (1). Liver cirrhosis is the 11th most common cause of death worldwide, with ~2 million people dying of liver cirrhosis every year. It has been reported that >630,000 patients had a diagnosis of liver cirrhosis in the United States, with a prevalence rate of ~0.27% and a cirrhosis-related mortality rate of 26.4% per 2-year interval between 1999 and 2010 (2). The progression of compensated liver cirrhosis can lead to decompensation, and on this basis, it can progress to hepatocellular carcinoma. The 5 year cumulative incidence of cirrhosis ranges 8–20% in untreated chronic hepatitis B virus patients. Among those with cirrhosis, the 5 year cumulative risk of hepatic decompensation is 20% (3). The annual risk of HCC in patients with cirrhosis has been reported to be 2–5% (4). According to a study conducted in 2010, liver cirrhosis has become a major global health and economic challenge (5). The economic burden of patients with liver cirrhosis includes both direct medical expenditure (involving drugs and other hospitalization expenses) and indirect medical expenditure (involving an inability to work or a low work efficiency, and a reduced quality of life) (6). Several studies estimate the burden of chronic liver disease in the United States to be in the range of $2.5 billion, with the indirect cost of $10.6 billion (7, 8). Therefore, there is an urgent need for prevention strategies, and the implementation of effective measures should be based on evidence from health economic analyses.

China has the greatest disease burden of liver cirrhosis in the world (9). In China, the number of patients with liver cirrhosis accounts for 20% of the total number of patients with chronic liver disease, most of whom are aged between 20 and 50 years (10). Approximately 50% of deaths due to liver cancer and 15% of deaths due to liver cirrhosis worldwide occur in China (11). In China, although the prevalence of HBV in the general population had dropped to 7.2% by 2006, there remained 97 million HBV carriers (12). Approximately 150 million people are infected with HCV worldwide, of whom ~ 10 million are Chinese patients. Currently, there is no effective cure. Treatment mainly focuses on etiological and symptomatic management, which can only alleviate the disease (13, 14). It is not possible to predict the development and prognosis of liver cirrhosis and determine whether the received treatment measures are effective; therefore, patients are likely to experience illness uncertainty in relation to the disease (15). Illness uncertainty is likely to lead to the deterioration of patients' medical behavior and to interruption of disease treatment. Furthermore, it can seriously affect the rehabilitation process and disease prognosis, increase the risk of readmission, and ultimately increase the economic burden on patients. According to recent reports, the readmission rate for patients with liver cirrhosis has ranged from 20 to 37% for 30 days hospitalization and from 21 to 53% for 90 days hospitalization (16–19). The high readmission rate seriously affects patient quality of life, leading to increased medical expenditures.

Few studies have examined medical expenditure trends in patients with liver cirrhosis in China. Therefore, this study aimed to analyze data collected from multicenter medical institutions to estimate the medical expenditure related to liver cirrhosis between 2012 and 2020, and assess the drivers for such medical expenditure among patients with liver cirrhosis. The study results may help guide medical decision-making and provide better medical protection for such patients.

In this study, the medical expenditure of patients with liver cirrhosis gradually increased from 2012 to 2020, and the average annual growth rate in total medical expenditure was 7.65%. This increase in medical expenditure implied that some indirect expenses, such as patients' non-medical expenses, patient family care, lost work, transportation, and board and lodging were also likely to have increased. Our results showed that liver cirrhosis imposed a heavy economic burden on both individuals and society and that medical expenditure varied greatly among different subgroups of patients with liver cirrhosis.

In our study, the average medical expenditure for liver cirrhosis in 2020 was 18,461 CNY. According to data from the National Bureau of Statistics in 2019 (data not updated for 2020), Chongqing's gross domestic product (GDP) ranked 17th among the 31 provinces in China, which was at a medium level (23). Therefore, our results may be closer to the average national cost. According to the average household population (2.6 persons) and the per capita disposable income of rural residents (16,021 CNY) in 2019, the average medical cost per patient with cirrhosis was 44.3% of the average annual family income of rural households, indicating that the economic burden imposed due to liver cirrhosis was relatively high for individual patients' families in China, especially for low-income families. In addition, once advanced liver cirrhosis develops, a patient's medical expenditure will be higher. A cost study showed that compared with the mild stage of liver cirrhosis, costs increased 1.6 times with decompensated cirrhosis, 1.9 times with hepatocellular carcinoma, and 3.4 times with liver transplant, respectively (24). Xu et al. reported that the average medical expenditure of patients with liver cancer from 2009 to 2011 was as high as 35,248 CNY (95% confidence interval, 34,304–36,193) (25).

We found that the medical expenditure of patients with UEMI, NCMS, and URMI insurance types was significantly higher than that of those with other medical insurance and full self-pay. The UEMI is the most established medical insurance program in China, dating back to the mid-1990s (26). At the beginning of the 21st century, the Chinese government established two more insurance programs, namely, the NCMS for rural residents and the URMI for self-employed and unemployed urban residents (27). It has been reported that the medical expenses of older adults had increased from an average of $204.77 in 2005 to $696.23 in 2014. By 2014, the proportion of medical expense reimbursement for older adults in the rural NCMS had increased significantly from 30.6% in 2005 to 56.1% in 2014 (28). In 2008, the number of individuals insured with URMI was 118.26 million, which had increased to 376.89 million in 2015. The per capita pooling fund of URMI was 140 CNY in 2008, decreasing to 130 CNY in 2009, and then increasing annually, reaching 515 CNY in 2015 (29). In view of the increasing demand for higher quality medical care, the NCMS and the URMI still have great potential for improvement. With an aging population and the gradual increase in medical expenses and other complex factors, the UEMI, NCMS, and URMI are facing pressure on fund payments. Therefore, it is necessary to formulate specific policies to improve the social medical insurance system so that more people can access affordable medical care services.

We found that the average medical expenditure per patient increased 1.61 times from 2012 to 2020, which was consistent with results reported in other studies. Desai et al. analyzed the national data of inpatients with liver cirrhosis from 2008 to 2014 and found that hospitalization expenses increased 30.2% from 2008 to 2014, reaching USD $7.37 billion (30). We also found that the LOS time trend per patient began to increase gradually after 2018. A possible reason for this is that, with improvement in national medical insurance policies and enhanced disease awareness among individuals, an increasing number of patients with severe liver disease (see Supplementary Figure S2A) choose to go to hospital, with a view to improving their quality of life and delaying progression of the disease through treatment (31, 32).

In our study, we compared medical expenditure time trends concerning patients with liver cirrhosis among various patient subgroups. Patients aged ≤ 49 years had the highest average medical expenditure. The population of patients with severe liver diseases such as liver cirrhosis, liver failure, and liver cancer is gradually becoming younger; therefore, these patients usually need more comprehensive treatment measures after the first diagnosis (33, 34). The average medical expenditure was highest when the LOS was ≥15 days. Extending the LOS will inevitably increase the medical expenditure of patients, which is consistent with the results of other studies (35, 36). In addition, we also found that the difference in medical expenditure between a LOS ≥15 days and other LOS subgroups became increasingly larger (see Supplementary Figure S2B). This might be related to more modern medical equipment and more sophisticated medical services. The average medical expenditure of male patients was higher than that of female patients, higher in patients who smoked than in those who did not, and higher in patients who consumed alcohol than in those who did not. This might be attributed to men generally having unhealthy lifestyle habits such as smoking, excess alcohol consumption, and an unhealthy diet (37), all of which seriously affect the metabolic capacity of the liver and increase the risk of aggravation. Therefore, measures need to be taken in response to these challenges, such as increasing the frequency of monitoring for men, encouraging smoking and alcohol consumption cessation, and undertaking active treatment and preventive measures to avoid disease deterioration, thereby reducing the economic burden.

Our data showed that the proportion of drug costs had increased annually, possibly because patients with liver cirrhosis have many complications and are prone to recurring attacks. Patients develop complications such as abdominal infection, upper gastrointestinal bleeding, and hypoproteinemia, and symptomatic treatments such as blood transfusion and albumin transfusion are required (38, 39). Patients with liver cirrhosis have multiple recurrent infections and require treatment with many potent antibiotics. Furthermore, due to the advanced nature of treatment, the frequency of expensive drug use, such as biological drugs, has increased gradually (40), which has led to an increase in the proportion of drug expenses.

This study had several limitations. First, the patient data included in this study were all obtained from six tertiary hospitals in Chongqing, China, which may have led to selection bias and reduced the generality of the data. Second, this study only collected data on hospitalization medical expenditure within the study hospitals; however, some patients may have been diagnosed and treated in other hospitals, meanwhile, we were unable to collect patients' outpatient expenditure information. so our data may underestimate the economic burden of liver cirrhosis. Third, we were also unable to collect patients' income information, so we were unable to analyze the relative financial burden of medical expenditure for patients with liver cirrhosis from 2012 to 2020. Further research is needed to address these limitations and provide a more comprehensive understanding of the medical expenditure of patients with liver cirrhosis.

Nevertheless, a strength of our study was its use of patient-level data, which covered a spectrum of patients and settings across various developmental and socioeconomic levels. Through analyzing the source of medical expenditure, we determined factors that had an important effect on medical expenditure, which can provide a reference for formulating effective measures to reduce the economic burden on individuals, families, society, and the government.

In conclusion, there is a heavy economic burden on patients with liver cirrhosis, on their families, and on society. Our findings indicated that the medical expenditure of patients with liver cirrhosis increased significantly from 2012 to 2020; therefore, formulating targeted measures to reduce the personal burden on these patients is needed.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Committee of the People's Hospital of Chongqing Banan District. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

JT and XT: concept and design. JT: drafting of the manuscript. JT and YH: collected data. JT and XX: statistical analysis. DQ, QZ, JC, and LZ: administrative, technical, and material support. All authors contributed to the article and approved the submitted version.

This study was funded by Chongqing Science and Health Joint Medical Research Project (2020GDRC016).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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