The management of chronic liver diseases (CLDs) and cirrhosis represents a substantial public health burden in the United States. Over the past 2 decades, the prevalence of cirrhosis has doubled, and it is conservatively estimated that approximately 50,000 Americans die of CLD-related or cirrhosis-related complications each year (1–3). The costs of caring for this population are high: these patients are medically complex, require resource-intensive management, and frequently develop a progressive disease course that culminates in hepatic failure or death (4). Reduced quality of life and poor work productivity further contribute to over $10 billion in annual indirect costs (5), and unplanned healthcare utilization results in over 325,000 emergency department (ED) visits and 650,000 hospitalizations/year in the United States (6–9).
There has been relatively limited evaluation of national-level trends in expenditure on CLDs and cirrhosis over time. This is particularly relevant considering the substantial changes in both CLD epidemiology and advances in therapy that have occurred since the 1990s. First, there have been shifts in the relative contribution of viral hepatitis, alcohol-associated liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD) to the prevalence of CLDs (10–13). Second, innovations in liver transplantation, management of cirrhosis-related complications, and multidisciplinary comprehensive CLD care have improved the hepatology landscape over the past 2 decades. Third, changes in healthcare coverage and the infrastructure of health systems influence the way in which patients with CLD or cirrhosis access care (14). Understanding the implications of these changes on trends in healthcare expenditures is crucial for establishing public health priorities and planning future resource allocation for patients with CLDs and cirrhosis.
Therefore, we evaluated national-level patterns in healthcare spending and drivers of change in healthcare spending among patients with CLDs or cirrhosis between 1996 and 2016 in the United States, overall, by setting of care, by payer, and by age.
Data sources and study population
Healthcare spending and health service utilization were estimated using publicly available data from the US Disease Expenditure (DEX) 2016 Project (15). Over 180 primary data sources (including administrative records, insurance claims, and household surveys) were used to model estimates of spending across 154 health conditions, 38 age and sex groups, and multiple settings of care (ambulatory, inpatient, ED, and nursing facility care) (see Table 1, Supplementary Digital Content 1, https://links.lww.com/AJG/C4). All estimates were adjusted for comorbidities and differences between charged and payment data and then scaled to the official estimate of US healthcare spending from the National Health Expenditure Accounts to ensure that no spending was double counted. Final estimates are reflective of actual expenditures, track with each disease state, and are adjusted for inflation, expressed in 2016 US dollars. Age-specific prevalence and disease-related mortality from CLDs and cirrhosis were extracted from the Global Burden of Disease (GBD) 2017 Study (16). The GBD Study summarized age-specific and sex-specific epidemiologic metrics for 354 conditions using over 1,600 data sources in the United States, including hospital and claims data. Bayesian meta-regression was used to model estimates of prevalence and incidence and log-linear interpolation was used to determine rates for years without direct data collection, expressed as point estimates with 95% uncertainty intervals.
These 2 data sources were used to abstract estimates of annual healthcare spending on CLDs and cirrhosis (DEX project) and age-specific prevalence and mortality from CLDs and cirrhosis in the United States (GBD 2017) between 1996 and 2016. The DEX condition assignments were based on the International Classification of Disease (ICD)-GBD condition map, so these 2 sources are comparable (15,16). Diagnostic assignment based on ICD coding (either ICD-9 or ICD-10 depending on the source-year) was used to link spending to the DEX/GBD health conditions, using probabilistic reassignment for data deficiencies. Diagnostic codes used for mapping (see Table 2, Supplementary Digital Content 1, https://links.lww.com/AJG/C4) capture cirrhosis, sequelae of cirrhosis (including ascites, varices, jaundice, and liver transplantation), and other CLDs (including chronic viral hepatitis, inflammatory hepatic and cholestatic diseases, alcohol-related liver diseases, and metabolic liver disorders). Separate estimates by individual CLD etiologies were not available.
The primary outcome was annual healthcare spending on CLDs and cirrhosis. Trends were analyzed by age group (<20, 20–44, 45–64, and ≥65 years) and by setting of care (ambulatory care, inpatient care, ED care, and nursing facility care). The results were stratified by private insurance, public insurance, and out-of-pocket payment. As a secondary objective, we evaluated the drivers of change in ambulatory and inpatient healthcare spending for patients with CLDs and cirrhosis. Drivers of change were available for data between 1996 and 2013 (17). Changes in spending were categorized as (i) adjustment for the total US population size, (ii) adjustment for the proportion of the population in each age and sex group to account for differences in population aging, (iii) changes in disease prevalence and incidence, (iv) changes in service utilization, and (v) changes in service price and intensity.
Trends in healthcare spending overall and by strata were calculated as population-standardized annualized rates of change from 1996 to 2016 (the year-to-year change required to reflect total change in spending observed between 1996 and 2016). Joinpoint regression was used to assess for inflection points in temporal trends, testing whether a segmented line with inflections at joinpoints modeled the data better than a linear relationship. The grid search method was used with model selection based on the permutation test with 4,499 permutations and overall significance level of 0.05; a minimum difference of 5% between consecutive annual percent change (APC) segments was selected a priori with a minimum of 2 observations required between joinpoints to avoid overfitting.
All analyses were performed using Stata 14.2 (StataCorp LLC, College Station, TX) and Joinpoint Regression Program 4.0.1 (Statistical Research and Applications Branch, National Cancer Institute, USA).
Overall healthcare spending and prevalence
Table 1 summarizes annualized rates of change in healthcare spending for patients with CLDs or cirrhosis. From 1996 to 2016, there was an overall 4.3%/year (95% confidence interval [CI], 2.8%–5.8%) increase in healthcare spending to a total of $32.5 billion (95% CI, $27.0–$40.4 billion) in 2016. Temporal trends in total healthcare spending and disease prevalence are summarized in Figure 1. Annual spending per patient with CLDs or cirrhosis increased from $478/year in 1996 to $707/year in 2016. However, this trend was nonlinear: spending was stable from 1996 to 2000, increased significantly from 2000 to 2008 (APC 6.8% [95% CI, 6.1%–7.5%]), but then decreased from 2008 to 2016 (APC −1.7% [95% CI, −2.1% to −1.2%]) (Figure 2).
Trends in healthcare spending by setting of care and age
Healthcare spending by treatment setting and across age groups is summarized in Table 1 and Figure 3. Overall, the greatest proportion of spending was attributable to inpatient care (62.9% [95% CI, 57.1%–68.9%]), followed by ambulatory services (17.4% [95% CI, 12.3%–22.6%]). The greatest annualized rate of change was observed for ED-related care (11.2%/year). There was significant variability in temporal trends in spending by healthcare setting (Figure 2), whereas spending on inpatient or ED services were either stable or increasing over time; there was a 9.1%/year (95% CI, −10.7% to −7.5%) decrease in ambulatory spending from 2011 to 2016.
Most spending occurred in patients of 45–64 years old (Figure 3). A total of 28.4% (95% CI, 25.1%–32.1%) of spending for patients with CLDs or cirrhosis was in elderly patients of ≥65 years old, although the increase in spending overall was primarily driven by an annualized increase rate of change of 5.1% (95% CI, 3.4%–6.8%) in patients less than 65 years old compared with 2.7% (95% CI, 1.2%–4.2%) in patients of ≥65 years old. Adjusting for disease prevalence, the most significant increase in healthcare spending was observed among patients of 20–44 years old (APC 6.9% [95% CI, 6.1%–7.7%] from 2000 to 2008 and APC 0.9% [95% CI, 0.4%–1.4%] from 2008 to 2016) (Figure 2).
Healthcare spending by payer
Healthcare spending stratified by payer is summarized in Table 2. In 2016, a total of 39.9% (95% CI, 32.5%–50.4%) of spending on CLDs or cirrhosis was from public payers compared with 56.2% (95% CI, 45.2%–63.8%) by private payers. Changes in spending by different payers over time were primarily driven by a 4.9%/year increase in private payer spending for inpatient care (compared with 3.2%/year for public insurance) and an 11.4%/year increase in public payer spending for ED care (compared with 10.9%/year for private insurance). Out-of-pocket costs remained substantial and were estimated at $1.3 billion (95% CI, $848 million–$2.1 billion) in 2016.
Drivers of change in healthcare spending
Data to evaluate drivers of change for healthcare spending in inpatient and ambulatory settings were available for 1996–2013 and are summarized in Supplementary Digital Content 1 (see Table 3, https://links.lww.com/AJG/C4). Overall, there was a net increase in inpatient spending of $2.13 billion/year between 1996 and 2013, which was primarily attributable to a significant increase in the price and intensity of acute care services (APC 17.8%/year [95% CI, 14.5%–21.6%]). Changes in population size and age, as well as increases in disease incidence and prevalence, also increased inpatient costs over time. By contrast, the relative price and intensity and service utilization contributing to ambulatory costs were stable.
Mortality From CLDs or cirrhosis
The annual overall mortality from CLDs or cirrhosis in the United States increased from 40,254 (95% CI, 38,373–41,233) deaths/year in 1996 to 66,394 (95% CI, 63,490–68,323) deaths/year in 2016. The unadjusted increase in mortality rose by 2.6%/year (95% CI, 2.5%–2.6%). After adjusting for increasing disease prevalence, the change in mortality rate for patients with CLDs or cirrhosis increased from 13.8 deaths/10,000 population in 1996 to 14.7 deaths/10,000 population in 2016, reflecting a slight although statistically significant increase in mortality of 0.3%/year (95% CI, 0.3%–0.4%).
Over the past 2 decades, there has been a substantial increase in overall spending in the United States for the management of CLDs and cirrhosis, now accounting for over $32 billion annually and 1.2% of total US healthcare expenditures. For context, this exceeds spending on other GI conditions such as inflammatory bowel disease (0.9%), peptic ulcer disease (0.2%), and colorectal cancer (0.4%). Here, we demonstrate that most of the spending for patients with CLDs and cirrhosis occurs in hospital, and there has been a disproportionate increase in acute care inpatient and ED spending, whereas a plateau and subsequent decline in ambulatory spending has been observed. The primary drivers of these trends have been drastic increases in the price and intensity of inpatient-based care with reduced service utilization in the outpatient setting. Despite increased spending, a concurrent decrease in mortality among patients with CLDs or cirrhosis has not been observed. These findings suggest that potentially greater focus should be directed at upstream, preventative, ambulatory interventions rather than downstream, resource-intensive, and acute management of complications resulting from end-stage liver disease.
Acute care inpatient resource utilization accounts for more than 60% of all spending related to CLDs and cirrhosis. Several factors have likely contributed to the increase in cost of acute care management. First, this population of patients is getting sicker over time: even compared with 2012, patients with CLDs admitted in 2016 were older, more likely to have cirrhosis and cirrhosis-related complications, and have more comorbidities (including coronary artery disease, congestive heart failure, chronic kidney disease, and diabetes) (18). The costs of managing a more complex patient population are expected to be high because these patients are at risk for both disease-related and iatrogenic complications, such as renal decompensation, Clostridium difficile infection, and gastrointestinal bleeding (6,19). Second, we demonstrated that the increased intensity and price of inpatient care was the primary driver of increased healthcare spending in patients with CLDs or cirrhosis. Several important, albeit costly, advances in acute care of CLDs have been achieved in the past 20 years. We highlight a few notable examples, including the development of novel antibiotics such as rifaximin for treatment of hepatic encephalopathy (20); new antivirals for viral hepatitis; novel technologies such as transjugular intrahepatic portal systemic shunts and balloon-occluded retrograde transvenous obliteration for managing portal hypertension (21–23); and better support for multiorgan failure with vasoactive therapy, renal replacement, mechanical ventilation, and artificial liver support (24,25). Second, there has been a centralization of inpatient care from rural/nonteaching hospitals to academic centers over time. In an analysis of the US National Inpatient Sample, Kim et al. (26) showed that the proportion of patients discharged with decompensated cirrhosis from urban teaching hospitals has increased from 45.6% in 2005–2006 to 61.0% in 2013–2014 (P < 0.001). This parallels the progressively more complex management algorithms and interventions for patients with CLDs and cirrhosis that require multidisciplinary and tertiary/quaternary care-level support.
Another important advancement has been the establishment of liver transplantation as the gold standard therapy for patients with end-stage CLDs. More liver transplants are now being performed in the United States than ever before because of growing indications for liver transplantation, substantive improvements in the process for organ allocation and conservation, surgical technique, posttransplant care, and postoperative immunosuppression, resulting in favorable graft survival despite transplanting sicker patients (27,28). However, the average cost of liver transplantation in the United States ($163,438 USD [95% CI, $145,277–$181,598]) is approximately $60,000 more than in comparable Organization for Economic Cooperation and Development countries, stemming from inefficiencies in the US health system rather than patient-related, disease-related, or healthcare quality-related factors (29).
Although we found that spending for patients with CLDs and cirrhosis increased overall, there was actually a decrease in per patient spending after 2008 because of a plateauing in total healthcare expenditures combined with a continued rise in disease prevalence. A growing burden of both CLDs and cirrhosis has been observed in the United States (30–32), although the causes of CLDs have shifted: there has been a significant decrease in the prevalence of HCV-related cirrhosis, but the prevalence of NAFLD increased from 20.0% in 1988–1994 to 31.9% in 2013–2016 (33). Changing distributions coincide with the development of highly effective DAAs for HCV, whereas rising rates of metabolic syndrome, type 2 diabetes mellitus, and obesity have resulted in sobering models suggesting potentially over 130% increases in NAFLD-related decompensated cirrhosis, hepatocellular carcinoma, and liver-related death by 2030 (34,35). Similar trends favoring advanced presentations of ALD are also being observed: the proportion of patients with advanced ALD-related fibrosis has tripled, hospitalizations secondary to alcoholic cirrhosis have increased by more than 32.8%, and ALD-related liver transplantation has increased by 63.4% in the United States since 2000 (36).
In addition to considering changes in the epidemiology of CLDs, healthcare expenditure trends must also be interpreted in the context of the larger economic landscape. Most notably, the global financial crisis of 2008 resulted in substantial and protracted contractions to the international and US economies. According to the International Monetary Fund, the United States experienced a 2.5% decrease in gross domestic product (GDP) in 2008 and slower growth rates in GDP after the financial crisis (37). These results generally mirror what is observed in Figures 1 and 2, with near exponential from 2000 to 2008, followed by a reduction in spending after 2008. Furthermore, when considering CLD-related and cirrhosis-related spending as a proportion of the total US GDP, healthcare-related expenditures in this population have remained relatively stable between 1996 and 2016, ranging between 0.15% and 0.22%.
These changes in the epidemiology of CLDs and cirrhosis combined with stagnant spending in the ambulatory setting highlight a potential gap in care utilization. The focus on inpatient and ED spending in patients with CLDs and cirrhosis is disproportionate compared with other similar chronic health conditions, where patients experience a high burden of comorbidity and inpatient utilization. For example, in-hospital costs as a proportion of total expenditures for congestive heart failure (60.0%–51.5%) and chronic obstructive pulmonary disease (43.1%–29.1%) have decreased dramatically from 1996 to 2016 (15), whereas the proportion of spending in patients with CLDs and cirrhosis (65.0%–62.5%) has remained stable. Despite significant increases in total acute care spending for inpatient and ED-related management, a corresponding decrease in mortality rates for CLDs and cirrhosis has not been observed. Although the stable mortality despite increasing disease prevalence may reflect more effective management strategies, as previously highlighted, it also emphasizes that most acute care interventions are directed at managing unexpected and often life-threatening complications in patients with decompensated liver disease. In these extremely sick patients, even significant therapeutic advances have not drastically changed mortality on a population level.
Because no effective antifibrotic therapies currently reverse end-stage hepatic fibrosis, focusing on prevention of disease progression may be more cost-effective (38). This is where investment in high-quality, multidisciplinary, and accessible ambulatory care services is paramount to optimize interventions such as weight reduction and metabolic syndrome management for patients with NAFLD, counseling on high-risk alcohol consumption, pharmacologic prophylaxis for variceal bleeding and spontaneous bacterial peritonitis, updating vaccinations, and screening for hepatocellular carcinoma (39,40). Furthermore, investing resources in ambulatory care to prevent inpatient readmissions should be prioritized: Nguyen et al. (41) showed that only a small fraction of high-need, high-cost patients with CLDs contribute disproportionately to hospitalization-related costs, with 10% of patients with CLDs in the highest decile contributing to 36% of hospitalization costs and the top 1% of patients with CLDs spending nearly 10 days in hospital each month. Focusing on ambulatory strategies that address this population's needs and prevent readmission may be a cost-effective method of reducing inpatient spending long-term.
Importantly, our study evaluated only direct medical costs associated with the management of patients with CLDs and cirrhosis. However, direct medical costs account for only a proportion of the total economic burden of these diseases. O'Hara et al. (42) evaluated the cost of nonalcoholic steatohepatitis in Europe and the United States in the GAIN Study. Not only were the per-patient costs for managing nonalcoholic steatohepatitis highest in the United States compared with other European countries, but the mean direct medical costs accounted for only half of the indirect costs (€ 2,763/patient vs € 5,509/patient, respectively). The economic burden from lost wages and productivity, absenteeism, or impairment because of CLDs and cirrhosis is substantial.
Our study has several strengths. We evaluated the economic impact of CLDs and cirrhosis over a 2-decade time frame, using data from nationally representative sources aimed at capturing the overall burden of healthcare spending for the purposes of informing US health policy. However, we also acknowledge some important limitations. First, although we have reported national-level spending estimates, these data are provided in aggregate and mapped to the health condition of “CLDs and cirrhosis” in the DEX project framework. Therefore, we cannot directly evaluate spending by important subgroups such as by CLD etiology, degree of fibrosis, presence of hepatic decompensation, or transplantation status. The lack of granularity in the data precludes more detailed evaluation, although the scope of this work captures national-level costs across multiple payers, age groups, and settings of care. Second, given the complexity and vast scale of healthcare spending in the United States, the DEX project data are susceptible to potential biases in modeling assumptions and case definitions. For example, it may not capture costs associated with the management of incarcerated individuals and homeless populations, many of whom may be at risk for CLDs and cirrhosis because of lifestyle factors. In addition, ICD-based administrative coding definitions are imperfect, although previous work has shown high positive predictive values for ICD-9 and ICD-10 codes similar to those used in this analysis (43,44). Third, several important advances in pharmacologic therapy have occurred after 2010, and the full effects of these interventions have likely not yet been appreciated. Updated analyses are required because more data become available. Similarly, delineating specific high-value spending on interventions such as variceal or HCC screening and liver transplantation as compared to lower-value interventions is not possible. This is especially relevant because these data cannot be used to define the number of life-years gained or quality-adjusted life-years because the DEX project was primarily focused on quantifying total spending, rather than assessing specific health states used in calculating quality-adjusted life-years.
In summary, the economic burden of healthcare spending in the United States for patients with CLDs or cirrhosis is substantial. Spending is disproportionately directed toward acute management, with over 60% of total expenditures attributable to inpatient care, reflecting substantial advancements that have been made in CLD and cirrhosis care over the past several decades. Although overall spending has increased since the 1990s, temporal trends in per patient spending have begun to change in the past decade, notably with reductions in ambulatory care spending. However, given the increasing prevalence and changing face of CLDs and cirrhosis, our study highlights that more attention may need to be paid to preventative and ambulatory care services to reduce hospitalizations, ED visits, and readmissions for this high-need, high-cost population.
CONFLICTS OF INTEREST
Guarantor of the article: Christopher Ma, MD, MPH, and Siddharth Singh, MD, MS.
Specific author contributions: Study concept and design: C.M., S.S.; Acquisition of data: A.S.Q., N.H.N.; Analysis and interpretation of data: C.M., A.S.Q., N.H.N., S.S.; Drafting of the article: C.M.; Critical revision of the article for important intellectual content: all authors; Approval of the final article: all authors.
Financial support: N.H.N. was supported by NIDDK (T32DK007202) and NLM (T15LM011271). S.S. was supported by NIDDK (K23DK117058).
Potential competing interests: C.M.—no relevant conflicts of interest to declare; A.S.Q.—no relevant conflicts of interest to declare; N.H.N.—no relevant conflicts of interest to declare; I.S.—no relevant conflicts of interest to declare; S.E.C.—research grants from Boehringer Ingelheim, Genfit, Allergan, and Sequana Medical; personal fees from Intercept Pharmaceuticals, Eisai, AstraZeneca, Paladin Labs outside the submitted work; AAS—research grants from Gilead and Intercept; M.G.S.—advisory board and speaker fees from Gilead Sciences, Intercept, Novartis, CymBay, and Abbott; research funding and clinical trial support from Gilead Sciences, Intercept, Novartis, CymaBay, GSK, Pfizer, Astra Zeneca, Novo Nordisk, Genfit; A.T.—no relevant conflicts of interest to declare; S.K.A.—no relevant conflicts of interest to declare; S.S.—research grants from AbbVie, Janssen, and personal fees from Pfizer for ad hoc grant review.
WHAT IS KNOWN
- ✓ The burden of chronic liver diseases (CLDs) and cirrhosis in the United States is increasing.
- ✓ Healthcare costs associated with managing CLDs and cirrhosis are substantial.
WHAT IS NEW HERE
- ✓ Over $32 billion is spent each year to manage CLDs and cirrhosis, with over 60% of the costs attributed to acute inpatient care.
- ✓ Increasing intensity and price of inpatient care is the primary driver of changes in spending for patients with CLDs and cirrhosis over the past 20 years.
- ✓ Increasing acute care and decreasing ambulatory spending despite no changes in CLD-related and cirrhosis-related mortality highlight that additional investment in upstream interventions is required for these patients.
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