Trends in the burden of hospitalised patients with cirrhosis in Switzerland: a cross-sectional study of cirrhosis-related hospitalisations between 1998 and 2020

Background

Chronic liver disease (CLD), especially cirrhosis, is an increasing cause of morbidity and mortality, responsible for 2.4% of all deaths in 2017, compared with 1.9% in 1990.1 The ageing of the population has an important effect, considering that age-standardised mortality decreased by 22% between 1980 and 2010,2 but the increase in prevalence of obesity and diabetes additionally contributes to the growing burden of CLD.3 Multiple data show a shift in the aetiologies of cirrhosis from viral hepatitis to alcohol-related liver disease (ARLD) and non-alcoholic fatty liver disease (NALFD), especially in Western Europe, the USA and Australia.1 3–9 In 2010, ARLD was the major cause of cirrhosis-related mortality and disability adjusted life years (DALYs) globally.10 CLD and cirrhosis are also major causes of hospital admission and of increase in healthcare costs.11–14 Hirode et al reported that CLD was responsible of over 80 billion US$ in hospitalisation costs in the USA between 2012 and 2016.15 During the same study period, there was an increase of over 20% in CLD-related hospitalisation and of 26% in inpatient hospitalisation costs. Another study also showed a growing economic burden of CLD between 1996 and 2016, namely due to inpatients costs.16 Moreover, CLD patients have an increasing number of comorbidities adding to the complexity of their management.9

The HEPAHEALTH Project guided by the European Association for the Study of the Liver concluded that in Switzerland, the age-standardised prevalence of cirrhosis was over 600 per 100 000, with an age-standardised mortality for liver disease of approximately 10 per 100 000 in 2016.17 However, the trends of hospitalisations for cirrhosis in Switzerland are not well known. Projections for Switzerland estimated that by 2030, the prevalence of NAFLD would increase to 24.3% of the population, with an expected increase in secondary cirrhosis and liver-related mortality.18 These estimations are in line with those established for Australia and Canada,19 20 and predict a major economic burden on the healthcare system.21 Therefore, understanding the trends of hospitalisations for cirrhosis in Switzerland is important to determine the current load on the inpatient system and to anticipate further impacts on the health system.

This study aimed to (1) analyse the trends in hospitalisations for cirrhosis in Switzerland between 1998 and 2020 and (2) assess the evolution of comorbidities, in-hospital mortality, length of stay (LOS) and related costs.

Methods

Results

Trends of cirrhosis-related hospitalisations

The yearly number of cirrhosis-related hospitalisations more than doubled from 1631 in 1998 to 4052 in 2020; expressed as rate per 100 000 hospitalisations, the increase was smaller, from 257 to 369 per 100 000, a 44% increase (figure 1).

Figure 1

Evolution of cirrhosis-related hospitalisations per 100 000 hospitalisations between 1998 and 2020.

Table 1 (and online supplemental etable 5) shows the trends of cirrhosis-related hospitalisations from 1998 to 2020 according to age categories, sex, origin, LOS, ICU stay and in-hospital mortality. Age category 45–64 years was the most frequent but decreased from 57.1% in 1998 to 47.2% in 2020, while the proportion of age category 65–84 years increased from 28.3% to 43.9% in the same period (P for trend <0.001). Men represented 2 out of 3 hospitalisations, and Swiss nationals represented over 75% of hospitalisations. These proportions remained stable during the study period.

View this table:

Table 1

Trends of cirrhosis-related hospitalisations between 1998 and 2020 (summary table)

The Lake Geneva region had the highest proportion of cirrhosis-related hospitalisations, but it decreased from 38.9% in 1998 to 25.2% in 2020 (P for trend <0.001). The hospitalisation rate per 100 000 inhabitants increased in all regions except in Lake Geneva. Comparison of the hospitalisation rates by regions showed higher rates in the Italian (Ticino) and French (Lake Geneva)-speaking parts of Switzerland (figure 2 and online supplemental etable 6).

Figure 2

Cirrhosis-related hospitalisations per 100 000 inhabitants according to hospital region.

The median LOS decreased from 11 days in 1998 to 8 days in 2020, while the proportion of hospitalisations with an ICU stay increased from 9.8% to 15.6% (both P for trend <0.001).

Table 2 shows the trends in causes of cirrhosis between 2012 and 2020 (online supplemental efigure 2). ARLD was the leading and increasing cause of cirrhosis, from 44.1% in 2012 to 47.9% in 2020 (P for trend <0.001). NAFLD was the second cause of cirrhosis at 42.7% in 2020 without a significant trend from 2012 to 2020. HCV was the third cause of cirrhosis and decreased from 12.3% to 3.2% in 2020 (P for trend <0.001). NASH documentation increased from 1.2% in 2012 to 4.2% in 2020 (P for trend <0.001). HBV-related cirrhosis decreased from 3.4% to 2.2% in 2020 (P for trend 0.001). Other aetiologies of cirrhosis (online supplemental etable 2) accounted for a low proportion of hospitalisations, representing 3.5% at the end of our study period, and without any notable trend.

View this table:

Table 2

Trends of aetiologies of cirrhosis, hepatocellular carcinoma and comorbidities from 2012 to 2020

Cirrhosis-related complications were reported in 56.9% of cirrhosis-related hospitalisations in 2012 and increased to 61.4% in 2020 (P for trend 0.008). Cirrhosis-related hospitalisations with a diagnosis of HCC increased from 24.4% in 2012 to 27.9% in 2020 (P for trend<0.001). As shown in table 2, the percentage of hospitalisations with coronary artery disease, congestive heart failure, chronic kidney disease and diabetes as comorbidities increased. Chronic kidney disease and diabetes were the most frequent, reported in 29.1% and 27.4% of all cirrhosis-related hospitalisations in 2020, respectively.

Discussion

Our findings show that cirrhosis-related hospitalisations increased in absolute numbers and in proportion to the total hospitalisations from 1998 to 2020 in Switzerland. Patients hospitalised for cirrhosis had an increasing median age, more comorbidities, more cirrhosis-related complications and a rising proportion of HCC. However, the median LOS and the in-hospital mortality decreased during the same study period.

The increasing burden of hospitalisations for cirrhosis is in line with prior literature that showed similar trends of increasing age, comorbidities and complications of cirrhosis in the USA15 22 and Australia.9 Another cross-sectional study in Germany showed a significant increase in all hospital admissions of patients with cirrhosis between 2005 and 2018.23

There were significant geographical differences in hospitalisation rates between the seven administrative regions of Switzerland, with more cirrhosis-related hospitalisations in the Italian and French-speaking parts of Switzerland. Social differences could explain the geographical variance in hospitalisation rate, as supported by data from the Swiss Federal Office of Statistics that show differences in alcohol consumption with more daily intake of alcohol in the Italian and French-speaking regions compared with the German-speaking regions.24 Similar geographical differences have been described in Germany.23 Origin did not seem to affect the rate of cirrhosis-related hospitalisations, as the majority of patients were Swiss nationals, in a proportion similar to that found in the general population.25

ARLD was the leading and probably underestimated aetiology of cirrhosis, as alcohol overconsumption may not have always been documented. ARLD was an increasing cause of cirrhosis in Switzerland, a finding also reported in the USA,22 26 and in Germany,23 but not in Australia.9 In another study in Portugal, ARLD did not increase but represented over 70% of cirrhosis-related hospitalisations between 2010 and 2017.27 Alcohol consumption per capita is the highest in the European region but with notable differences between countries3 and with a decreasing trend in Switzerland.28 One likely explanation for the increasing ARLD-related cirrhosis is the increasing age of patients as supported by data showing that people over 65 in Switzerland had the heaviest proportion of daily drinking, without notable change from 1992 to 2017.29

The determination of the NAFLD aetiology by exclusion could have conducted to an overdiagnosis of NAFLD. Multiple cross-sectional studies using similar databases had comparable difficulties to determine NAFLD because of the absence of specific ICD-10 codes.9 23 27 30 31 However, based on the available data, we chose this approach to approximate the burden of NAFLD in cirrhosis-related hospitalisations, as previously performed.15

As ARLD and NAFLD accounted for most cases of cirrhosis-related hospitalisations in our study, there is an urgent need for interventions at an individual and a population level to reduce the burden of cirrhosis in Switzerland. Interventions could be aimed at promoting healthy lifestyle, discouraging heavy alcohol intake, increasing price of alcohol and sugar-sweetened beverages, restricting alcohol and unhealthy food marketing, as well as improving screening and treatment of ARLD and NAFLD. A large and comprehensive review of preventive measures for the burden of liver disease has been published by Pimpin et al.3

HCV-related cases of cirrhosis demonstrated a steady decrease from 2012 to 2020 in Switzerland. The same trend has been described in Germany,23 Portugal27 and Spain,32 and is most probably related to the efficacy of the new antiviral therapies. However, other countries could not show the same decrease in HCV-related cirrhosis,9 15 most probably because affected patients do not benefit of universal access to treatment.

In-hospital mortality decreased in our study period, in line with the decrease from 11.6% in 2005 to 9.5% in 2018 reported in Germany.23 Still, the evolution of cirrhosis-associated mortality was reported variably in the literature, with an increasing global mortality1 but a decreasing age-adjusted mortality.2 The decreasing in-hospital mortality in our study with an ageing and more comorbid population is encouraging and has also been described in Portugal.27 One explanation could be linked to improved care pathways and more intensive inpatient care as suggested by the increase in costs. Multiple developments in the pharmacological and interventional treatment of complications of cirrhosis have been achieved and have been implemented in international guidelines for the management of cirrhosis.33–35 Application of these guidelines as well as the increase in liver transplantation, which increased substantially during our study period,36 37 could have contributed to the decreasing in-hospital mortality.

Analysis of the cirrhosis-related in-hospital costs displayed an increasing economic burden of cirrhosis between 2012 and 2020. Notably costs increased more than the number of admissions with a 70% increase in costs for only a 38% increase in hospitalisations with available information on healthcare expenditures. The proportion of costs related to hospitalisations with ICU stay in our study could suggest that increasing intensity of inpatient care may explain part of the rising costs. Furthermore, the increasing age, comorbidities and complications of cirrhosis during our study period could add to the rise in costs as reported by Hirode et al.15 Additionally, our study only focused on cirrhosis-related hospitalisations and Gu et al emphasised the important role of cirrhosis as a comorbidity in their cross-sectional study where over 50% of admissions with cirrhosis between 2005 and 2018 were with cirrhosis as a comorbidity.23 The increasing economic burden of cirrhosis has been described in the USA with a larger increase of in-hospital costs than in ambulatory care.16 The heavy economic burden of cirrhosis documented in our study emphasises the importance of preventing hospitalisations in patients with cirrhosis and improving ambulatory care. Previous studies have proposed tools to improve screening, quality of care, management of cirrhosis and follow-up after discharge with some of them proving cost-effective.14 38–41

Our study has multiple strengths, including a large sample of hospitalisations for cirrhosis on a prolonged period of >20 years. The Swiss Hospital Statistics is a national database with reliable demographic data and use of ICD-10 codes for definition of cirrhosis has been shown to be accurate.42 43 There are, however, limitations, also linked to the retrospective design of the study and the use of a hospital discharge database. Indeed, diagnoses depend on the quality of documentation by treating physicians and there can be some missing data or inaccuracy in documentation. Consequently, the quality of data available for the determination of aetiologies of cirrhosis, comorbidities and complications of cirrhosis was impacted by missing data or lack of precise documentation. Obesity for example was only scarcely reported which precluded use of the new metabolic dysfunction-associated steatotic liver disease (MASLD) definition in place of NAFLD. Despite consensus on the new MASLD definition,44 we used the NAFLD definition because of the exclusion method adopted, corresponding to the nomenclature used at the time of the data collection. Also, use of DRG linked to ICD-10 codes for billing purpose since 2012 in Switzerland introduced economic incentives associated with documentation that can favour some diagnoses and underestimate others. Thus, the increase of NASH-related cirrhosis, cirrhosis-related complications and costs could also be linked to a learning effect of coding staff. Another limitation is related to the anonymised database which renders impossible to ascertain the rehospitalisation rate. Therefore, our study focused on hospitalisations for cirrhosis but not on cirrhotic patients because the number of hospitalisations for each single patient could not be assessed. As an exploratory cross-sectional study, no correction for multiple testing was performed. Still, had a Bonferroni correction been applied considering the 27 tests performed, the resulting threshold would be 0.002, which would not change most of our findings. Finally, costs were only available for part of the admissions, without details regarding distribution of the costs nor explanation of the cause for missing data. Therefore, the impact of the latter on the overall economic burden could not fully be ascertained.

In conclusion, cirrhosis-related hospitalisations and related costs increased in Switzerland from 1998 to 2020 but in-hospital mortality decreased despite patients getting older. ARLD and NAFLD were the two leading causes of cirrhosis and should prompt for interventions at an individual and population level to reduce the burden of cirrhosis on the healthcare system.