The nationwide trends in hospital admissions, deaths, and costs related to hepatitis C stratified by psychiatric disorders and substance use: an analysis of United States hospitals between 2016 and 2019

Abstract

Background & Aims:

Hepatitis C virus (HCV) is a prominent liver disease that often presents with mental illness. We stratify the HCV population and review its healthcare burden on the United States hospital system.

Methods:

The United States National Inpatient Sample (NIS) was used to select admissions related to HCV between 2016 and 2019. Weights were assigned to discharges, and trend analyses were performed. Strata were formed across demographics, comorbidities, psychiatric and substance use conditions, and other variables. Outcomes of interest included hospitalization incidences, mortality rates, total costs, and mean per-hospitalization costs.

Results:

From 2016 to 2019, there were improvements in mortality and hospitalization incidence for HCV, as well as a decline in aggregate costs across the majority of strata. Exceptions that showed cost growth included admissions with multiple psychiatric, stimulant use or poly-substance use disorders, and a history of homelessness. Admissions with no psychiatric comorbidities, admissions with no substance use comorbidities, and admissions with housing and without HIV comorbidity showed decreasing total costs. Along per-capita mean costs, admissions with comorbid opioid use, bipolar, or anxiety disorder showed significant increases. No significant trends in per-capita costs were found in admissions without mental illness diagnoses.

Conclusions:

Most strata demonstrated decreases in hospitalization incidences and total costs surrounding HCV; however, HCV cases with mental illness diagnoses saw expenditure growth. Cost-saving mechanisms for these subgroups are warranted.

Introduction

Hepatitis C virus (HCV) is a prominent, progressive cause of hepatic morbidity, resulting in fibrosis and ultimately cirrhosis if left untreated (1,2). As recently as 2015, the Polaris Observatory estimated the global prevalence of HCV to be approximately 1% (3). HCV prevalence in the United States (US) nearly matches the global average of 1%, but this is comparatively higher than that of Canada and Western Europe (2–4). While there is still work to do, the US has made progress in its fight against HCV, especially since 2014 and with the advent of direct-acting antivirals (5,6). Nationally, the largest age cohort contributing to HCV prevalence is persons born between 1945 and 1965, the reason for this being a history of injection drug and blood transfusion before 1992, the year in which HCV blood screening became available (2,7). Today, the US HCV patient population is characterized by a bimodal distribution of infection, with a subpopulation of older iatrogenic infections and a newer cohort of injection drug use related illness (6). State-level analysis gives evidence to this trend, with regions such as Appalachia contributing larger proportions of patients, theoretically because of higher prevalence of injection drug use (2,4).

Beyond substance use disorder, psychiatric illnesses in the HCV patient are not uncommon (8–10). Higher rates of homelessness and HIV diagnosis are also observed, especially among HCV persons who inject drugs (PWID) (11). Management of these conditions becomes complex and requires a multidisciplinary approach, involving psychiatric, primary, and medical care services to manage social determinants and comorbidity (12,13). Due to consultations from a wide range of specialties, these specific HCV patients may accrue increased hospitalization expenses, thus giving rise to greater costs at the population level (14, 15, 16). Co-occurring psychiatric comorbidities could also prolong hospital length of stay, further exacerbating financial burdens (17, 18). Therefore, it is imperative to review healthcare costs associated with these especially vulnerable HCV patient subgroups.

We use a national hospital registry to review expenditures of HCV-related admissions. In an effort to characterize increasing or decreasing trends, we stratify across demographic, psychiatric, and medical comorbidities. We aim to identify population subgroups that are associated to disproportionate cost burden and may be amenable to cost saving strategies.

Methods

Study Data

Data in this study was accessed from the National Inpatient Sample (NIS), made available through the HCUP-AHRQ sponsorship. The NIS extracts data from multiple State Inpatient Databases (SID), and in doing so, it queries approximately 20% of discharges from each hospital in each SID. Care centers not captured by the NIS include rehabilitation and long-term acute care hospitals, psychiatric wards, and other mental health institutions. NIS charge information was converted to reflect costs via inflation-adjusted charge-to-cost ratios, to calculate the costs per hospitalization. Weights were applied to each hospitalization contained in the SID universe. Weights were derived from attributable year information, NIS-distributed hospital identifiers, and survey-weighting methodology. Using these figures, cumulative annual and per-hospitalization mean costs were calculated. Cases between 2016 and 2019 were considered for analysis.

Study Variables and Analysis Procedure

ICD-10 based codes were used to create variables and strata, with groupings made across demographics, socioeconomic status (SES) and hospital characteristic variables, psychiatric, medical, substance use and social comorbidities, comorbid liver diseases, and liver complications. The HCV study population was composed of admissions diagnosed with this condition (HCV) at discharge, according to the ICD-10 system. Hospitalizations including other liver diseases, such as alcoholic liver disease, hepatocellular carcinoma, hepatitis B, or non-alcoholic fatty liver disease were included. Comorbidity and liver complication variables were coded as binary yes/no factors (e.g., presence of coronary artery disease, yes or no). Other categorical information concerned admission demographics, SES, and hospital characteristics.

Trends for this data were assessed for the time period from 2016 to 2019. Reported against the denominator of every 100,000 US hospitalizations, annual hospitalization incidences and mortality rates were found for each designated stratum. Within each strata category (e.g., age, medical comorbidity, liver complication, etc.), the proportion of total cases contributed by each individual stratum was derived (e.g., those with ages between 18 and 34 years contributed 12.85% of the HCV-related admission total in 2016). Mortality rates against the hospitalization annualized incidence were also calculated. Regarding expenditure analyses, the mean, median (with upper and lower quartiles) and total costs were determined, along with 95% confidence intervals. For each stratum, linear regression curves for the hospitalization incidence, mortality rate, cost analyses, and percent difference between each consecutive year (e.g., difference in the values between 2017 versus 2016, divided by the value of 2016) were described. Significance for these values was measured using goodness-of-fit (R2) and p-value statistics. All p-values below 0.05 were considered to be statistically significant. The random forest method was used to take missing and random-type data into consideration. Data pertaining to demographics, SES variables, liver complications, and psychiatric comorbidity was visualized using bar charts, with significant findings highlighted. Statistical analyses were performed using R version 4.1.2.

Furthermore, sensitivity analyses were conducted to better identify admissions directly related to HCV morbidity, rather than admissions characterized by HCV but with stable hepatic function. The study cohort was grouped according to HCV onset (acute, chronic, and cirrhosis present), as well as priority diagnoses, with admissions categorized by having HCV within their top ten, top fifteen, or top twenty diagnoses. The supplementary tables describe these data.

Results

Hospitalization Incidences

Across all cohorts, incidence rates of hospitalizations related to HCV were estimated to be 632,580, 625,515, 596,090, and 554,365 for the years 2016 through 2019, respectively (R2=0.92, p=0.04). These cohorts under investigation saw decreasing trends, with admissions of ages between 50 and 64 years of age attaining significance (R2=0.99, p=0.003). Male (R2=0.93, p=0.04) and female (R2=0.92, p=0.04) sex strata, as well as admissions categorized as White (R2=0.94, p=0.03), Black (R2=0.95, p=0.03), or Asian (R2=0.98, p=0.01) also showed significantly decreasing patterns. Notably, admissions with ages older than 65 showed a significantly increasing trend (R2=0.95, p=0.02), as well as admissions with simultaneous non-alcoholic fatty liver disease (R2=0.97, p=0.01). Psychiatric comorbidity strata showed significant decreases in hospitalization incidences for admissions with concurrent bipolar disorder (R2=0.91, p=0.05), schizophrenia (R2=0.91, p=0.05), and depression (R2=0.98, p=0.01). Regarding substance use disorder comorbidities, admissions with stimulant use disorder saw a significant increase in hospitalizations (R2=0.99, p=0.005). Admissions with opioid use disorder was the largest substance use comorbidity subset and showed a borderline significant decreasing trend (R2=0.89, p=0.06). Social comorbidity strata exhibited a decreasing incidence in those with HIV (R2=0.98, p=0.01) and an increasing incidence in those who were homeless (R2=0.99, p=0.007). Admissions without any psychiatric disorder diagnoses, admissions without any substance use disorder diagnoses, and admissions without social-related comorbidities all showed significantly decreasing trends (without psychiatric comorbidity: R2=0.97, p=0.02; without substance use disorder: R2=0.99, p=0.004; without social comorbidity: R2=0.95, p=0.03). Further information of hospitalization incidence related to SES, liver diseases and complications, and other organ comorbidities are described in Table 1.

Table 1.

Admission Rates Associated with HCV in US Hospitals

Year	2016		2017			2018			2019			r2		p-value
Total Admissions	Total: 632,580 Total per 100,000: 1,773.15 (1,713.02 – 1,833.28)		Total: 625,515 Total per 100,000: 1,747.32 (1,686.83 – 1,807.81)			Total: 596,090 Total per 100,000: 1,677.83 (1,617.36 – 1,738.30)			Total: 554,365 Total per 100,000: 1,565.16 (1,510.47 – 1,619.85)			Total: 0.92 Total per 100,000: 0.93 (0.92 – 0.93)		Total: 0.04 * Total per 100,000: 0.04 * (0.03 * – 0.04 *)
Demographics	Rate per 100,000 admissions	Stratum percentage (%)	Rate per 100,000 admissions	Stratum percentage (%)	Percent difference (%)	Rate per 100,000 admissions	Stratum percentage (%)	Percent difference (%)	Rate per 100,000 admissions	Stratum percentage (%)	Percent difference (%)	r2 for Rate per 100,000 admissions	r2 for Stratum percentage (%)	p-value for Rate per 100,000 admissions	p-value for Stratum percentage (%)
Age
18 to 34	227.79	12.85	241.17	13.80	5.87	240.79	14.35	−0.16	220.33	14.08	−8.49	0.08	0.70	0.71	0.16
35 to 49	333.42	18.80	332.42	19.02	−0.30	324.24	19.33	−2.46	309.79	19.79	−4.46	0.87	0.97	0.07	0.01*
50 to 64	914.49	51.57	854.56	48.91	−6.55	780.41	46.51	−8.68	695.04	44.41	−10.94	0.99	1.00	0.003**	0.001**
greater than 65	297.45	16.77	319.18	18.27	7.31	332.39	19.81	4.14	340.00	21.72	2.29	0.95	1.00	0.02*	0.002**
Gender
Male	1,086.55	61.28	1,071.86	61.34	−1.35	1,026.64	61.19	−4.22	960.42	61.36	−6.45	0.93	0.03	0.04*	0.84
Female	686.61	38.72	675.46	38.66	−1.62	651.19	38.81	−3.59	604.75	38.64	−7.13	0.92	0.03	0.04*	0.84
Race
White	1,109.24	62.56	1,086.68	62.19	−2.03	1,054.37	62.84	−2.97	993.36	63.47	−5.79	0.95	0.66	0.03*	0.19
Black	376.04	21.21	368.14	21.07	−2.10	344.86	20.55	−6.32	320.28	20.46	−7.13	0.96	0.92	0.02*	0.04*
Hispanic	201.13	11.34	205.65	11.77	2.25	197.71	11.78	−3.86	174.58	11.15	−11.70	0.67	0.05	0.18	0.77
Asian or Pacific Islander	19.62	1.11	19.15	1.10	−2.41	18.20	1.08	−4.97	17.31	1.11	−4.89	0.98	0.03	0.009**	0.83
Other	67.12	3.79	67.70	3.87	0.86	62.70	3.74	−7.39	59.63	3.81	−4.89	0.86	0.02	0.07	0.86
Medical Comorbidities
Coronary Artery Disease	10.54	0.59	11.20	0.64	6.28	10.19	0.61	−9.04	9.26	0.59	−9.11	0.60	0.06	0.23	0.76
Congestive Heart Failure	18.91	1.07	33.13	1.90	75.23	37.46	2.23	13.08	38.64	2.47	3.13	0.82	0.91	0.10	0.04*
Chronic Kidney Disease	71.81	4.05	65.62	3.76	−8.63	62.23	3.71	−5.16	58.37	3.73	−6.20	0.98	0.66	0.010**	0.19
Chronic Obstructive Pulmonary Disease	90.50	5.10	86.26	4.94	−4.68	80.98	4.83	−6.12	73.05	4.67	−9.79	0.98	0.99	0.01*	0.003**
Diabetes	56.27	3.17	54.32	3.11	−3.47	49.20	2.93	−9.42	45.15	2.88	−8.24	0.97	0.95	0.01*	0.03*
Hypertension	260.24	14.68	247.30	14.15	−4.97	233.68	13.93	−5.51	216.10	13.81	−7.52	0.99	0.90	0.003**	0.05*
≥ 2 Comorbidities	691.76	39.01	670.98	38.40	−3.00	647.65	38.60	−3.48	609.49	38.94	−5.89	0.98	0.00	0.01*	0.99
None	573.13	32.32	578.52	33.11	0.94	556.43	33.16	−3.82	515.10	32.91	−7.43	0.78	0.37	0.12	0.39
Liver Etiologies
Alcoholic Cirrhosis	173.28	9.77	166.59	9.53	−3.87	151.91	9.05	−8.81	141.12	9.02	−7.10	0.98	0.92	0.009**	0.04*
Hepatocellular Carcinoma	38.78	2.19	40.21	2.30	3.69	37.86	2.26	−5.85	36.93	2.36	−2.45	0.53	0.70	0.27	0.16
Hepatitis B	45.83	2.58	43.65	2.50	−4.76	43.36	2.58	−0.66	38.31	2.45	−11.64	0.86	0.38	0.07	0.38
Non-Alcoholic Fatty Liver Disease	20.74	1.17	22.61	1.29	9.02	25.33	1.51	12.03	26.37	1.68	4.10	0.97	0.99	0.01*	0.005**
≥ 2 Etiologies	26.26	1.48	26.68	1.53	1.57	27.51	1.64	3.14	27.32	1.75	−0.72	0.80	0.97	0.11	0.01*
None	1,468.25	82.80	1,447.59	82.85	−1.41	1,391.85	82.96	−3.85	1,295.11	82.75	−6.95	0.92	0.01	0.04*	0.90
Liver Complications
Ascites	17.18	0.97	17.03	0.97	−0.91	16.45	0.98	−3.37	15.36	0.98	−6.64	0.89	0.93	0.06	0.04*
Cirrhosis	271.46	15.31	249.69	14.29	−8.02	232.20	13.84	−7.00	221.80	14.17	−4.48	0.98	0.62	0.01*	0.21
Encephalopathy	7.83	0.44	10.55	0.60	34.60	8.73	0.52	−17.25	7.58	0.48	−13.12	0.06	0.01	0.75	0.92
Hepatorenal Syndrome	1.04	0.06	0.84	0.05	−19.20	0.83	0.05	−0.92	0.95	0.06	13.91	0.14	0.02	0.63	0.85
Varices	5.44	0.31	4.67	0.27	−14.21	4.04	0.24	−13.42	3.70	0.24	−8.43	0.97	0.90	0.01*	0.05
≥ 2 Complications	156.07	8.80	152.37	8.72	−2.38	143.61	8.56	−5.75	132.12	8.44	−8.00	0.95	0.99	0.02*	0.007**
≥ 3 Complications	44.74	2.52	49.71	2.84	11.11	45.77	2.73	−7.93	41.33	2.64	−9.69	0.28	0.05	0.47	0.78
≥ 4 Complications	7.11	0.40	9.26	0.53	30.32	8.37	0.50	−9.57	7.61	0.49	−9.13	0.01	0.28	0.91	0.47
≥ 5 Complications	0.60	0.03	0.70	0.04	15.88	0.61	0.04	−13.34	0.48	0.03	−20.69	0.44	0.21	0.34	0.54
None	1,261.68	71.15	1,252.53	71.68	−0.73	1,217.23	72.55	−2.82	1,134.24	72.47	−6.82	0.86	0.87	0.07	0.07
Psychiatric Comorbidities
Bipolar Disorder	89.28	5.03	87.22	4.99	−2.30	83.06	4.95	−4.77	74.18	4.74	−10.69	0.91	0.83	0.05*	0.09
Depression	179.24	10.11	170.64	9.77	−4.80	154.77	9.22	−9.30	137.21	8.77	−11.34	0.98	0.99	0.01*	0.004**
Anxiety	129.66	7.31	132.42	7.58	2.13	130.70	7.79	−1.30	123.93	7.92	−5.18	0.44	0.98	0.34	0.01*
Stress-Related Disorder †	20.34	1.15	20.50	1.17	0.82	20.93	1.25	2.07	20.74	1.32	−0.91	0.65	0.96	0.19	0.02*
Schizophrenia	28.51	1.61	28.31	1.62	−0.69	26.09	1.56	−7.84	23.60	1.51	−9.54	0.91	0.83	0.05*	0.09
≥ 2 Comorbidities	258.09	14.56	267.55	15.31	3.67	274.01	16.33	2.41	263.69	16.85	−3.77	0.20	0.99	0.55	0.007**
None	1,068.05	60.23	1,040.67	59.56	−2.56	988.26	58.90	−5.04	921.81	58.90	−6.72	0.97	0.89	0.02*	0.06
Substance Use Comorbidities
Cocaine	55.74	3.14	57.24	3.28	2.69	57.34	3.42	0.17	52.90	3.38	−7.74	0.28	0.80	0.47	0.11
Marijuana	56.10	3.16	56.54	3.24	0.78	51.55	3.07	−8.82	46.39	2.96	−10.02	0.86	0.70	0.07	0.16
Opioid	235.55	13.28	233.75	13.38	−0.76	225.33	13.43	−3.60	209.66	13.40	−6.95	0.89	0.64	0.06	0.20
Stimulant	46.63	2.63	53.40	3.06	14.51	64.98	3.87	21.69	72.97	4.66	12.30	0.99	0.98	0.005**	0.009**
≥ 2 Comorbidities	172.89	9.75	198.07	11.34	14.56	217.20	12.95	9.66	206.17	13.17	−5.08	0.66	0.93	0.18	0.04*
None	1,206.24	68.03	1,148.33	65.72	−4.80	1,061.43	63.26	−7.57	977.07	62.43	−7.95	0.99	0.96	0.004**	0.02*
Social Comorbidities
HIV	93.34	5.26	85.35	4.88	−8.56	78.84	4.70	−7.63	65.78	4.20	−16.56	0.98	0.97	0.01*	0.01*
Homelessness	102.38	5.77	115.33	6.60	12.64	129.25	7.70	12.08	136.73	8.74	5.79	0.99	1.00	0.007**	0.002**
≥ 2 Comorbidities	8.84	0.50	9.61	0.55	8.66	9.71	0.58	1.06	9.63	0.62	−0.86	0.61	0.99	0.22	0.007**
None	1,568.59	88.46	1,537.03	87.97	−2.01	1,460.02	87.02	−5.01	1,353.02	86.45	−7.33	0.95	0.99	0.03*	0.007**
Socioeconomic Status
Median Household Income
Quartile 1	769.31	43.39	759.96	43.49	−1.22	716.88	42.73	−5.67	674.76	43.11	−5.88	0.94	0.36	0.03*	0.40
Quartile 2	442.17	24.94	448.97	25.69	1.54	442.77	26.39	−1.38	394.52	25.21	−10.90	0.58	0.09	0.24	0.70
Quartile 3	349.25	19.70	330.22	18.90	−5.45	324.14	19.32	−1.84	313.22	20.01	−3.37	0.95	0.13	0.02*	0.63
Quartile 4	212.43	11.98	208.17	11.91	−2.01	194.03	11.56	−6.79	182.66	11.67	−5.86	0.96	0.70	0.02*	0.16
Insurance Type
Medicare	612.40	34.54	604.69	34.61	−1.26	578.86	34.50	−4.27	546.19	34.90	−5.64	0.94	0.49	0.03*	0.30
Medicaid	725.57	40.92	733.77	41.99	1.13	707.48	42.17	−3.58	659.63	42.14	−6.76	0.76	0.69	0.13	0.17
Private Insurance	240.00	13.54	215.27	12.32	−10.30	198.80	11.85	−7.65	176.15	11.25	−11.40	0.99	0.95	0.003**	0.02*
Other	195.19	11.01	193.58	11.08	−0.82	192.68	11.48	−0.47	183.19	11.70	−4.92	0.77	0.94	0.12	0.03*
Hospital Region
Northeast	362.32	20.43	357.57	20.46	−1.31	333.92	19.90	−6.61	298.94	19.10	−10.48	0.91	0.85	0.05*	0.08
Midwest	315.33	17.78	318.31	18.22	0.95	310.87	18.53	−2.34	286.67	18.32	−7.79	0.70	0.62	0.16	0.21
South	714.55	40.30	698.37	39.97	−2.26	678.25	40.42	−2.88	644.51	41.18	−4.97	0.97	0.61	0.02*	0.22
West	380.95	21.48	373.07	21.35	−2.07	354.78	21.15	−4.90	335.05	21.41	−5.56	0.97	0.15	0.02*	0.61

^*p < 0.05,

^**p < 0.01,

^***p < 0.001

^†This includes PTSD and adjustment disorder

Mortality Rates

Mortality rates tended to decrease throughout the 4-year study period. While cases with multiple extrahepatic morbidities suffered the highest mortality rates, they saw a significantly decreasing pattern throughout the study period (R2=0.92, p=0.04). Both strata of admissions with HCV as their sole liver pathology and admissions with co-presenting alcoholic liver disease experienced significantly declining death rates (R2=0.95, p=0.03 and R2=1.00, p<0.001 respectively), as well as admissions complicated by cirrhosis (R2=0.99, p=0.003). Similar results were found in hospitalizations with concurrent anxiety disorder (R2=1.00, p<0.001) and those with HIV (R2=0.94, p=0.03). Hospitalizations without any psychiatric comorbidity, without any substance use comorbidity, and without any social comorbidity showed significant reductions in mortality (R2=0.96, p=0.02, R2=0.96, p=0.02, and R2=0.96, p=0.02, respectively). Additional trends describing HCV mortality rates are found in Table 2.

Table 2.

Mortality Rates Associated with HCV in US Hospitals

Year	2016		2017			2018			2019			r2		p-value
Total Deaths	Total: 16,955 Total per 100,000: 47.53		Total: 16,660 Total per 100,000: 46.54			Total: 15,350 Total per 100,000: 43.21			Total: 14,445 Total per 100,000: 40.78			r2 for Total: 0.95; r2 for Total per 100,000: 0.96		p-value for Total: 0.02 *; p-value for Total per 100,000: 0.02 *
Demographics	Mortality rate per 100,000 admissions	Proportion percentage (%)	Mortality rate per 100,000 admissions	Proportion percentage (%)	Percent difference (%)	Mortality rate per 100,000 admissions	Proportion percentage (%)	Percent difference (%)	Mortality rate per 100,000 admissions	Proportion percentage (%)	Percent difference (%)	r2 for Mortality rate per 100,000 admissions	r2 for Proportion percentage (%)	p-value for Mortality rate per 100,000 admissions	p-value for Proportion percentage (%)
Age
18 to 34	1.51	0.66	1.89	0.78	24.57	2.00	0.83	5.99	1.93	0.88	−3.23	0.66	0.94	0.19	0.03*
35 to 49	5.19	1.56	5.24	1.58	1.00	4.95	1.53	−5.42	4.28	1.38	−13.66	0.77	0.70	0.12	0.16
50 to 64	28.62	3.13	26.87	3.14	−6.10	22.71	2.91	−15.47	20.51	2.95	−9.70	0.98	0.68	0.01*	0.17
greater than 65	12.21	4.10	12.54	3.93	2.75	13.54	4.07	7.94	14.06	4.14	3.85	0.97	0.11	0.02*	0.66
Gender
Male	30.68	2.82	30.94	2.89	0.84	29.40	2.86	−4.97	27.60	2.87	−6.13	0.83	0.37	0.09	0.39
Female	16.85	2.45	15.60	2.31	−7.39	13.81	2.12	−11.51	13.19	2.18	−4.50	0.97	0.78	0.02*	0.12
Race
White	28.09	2.53	26.72	2.46	−4.87	24.97	2.37	−6.56	23.83	2.40	−4.56	0.99	0.77	0.003**	0.13
Black	10.69	2.84	10.35	2.81	−3.22	9.25	2.68	−10.66	9.43	2.94	1.99	0.81	0.04	0.10	0.80
Hispanic	6.05	3.01	6.48	3.15	7.04	5.85	2.96	−9.66	4.97	2.85	−15.13	0.62	0.49	0.21	0.30
Asian or Pacific Islander	0.85	4.36	1.06	5.54	24.16	1.03	5.65	−3.21	0.86	4.98	−16.18	0.00	0.18	0.98	0.57
Other	1.84	2.74	1.93	2.85	4.98	2.11	3.37	9.52	1.69	2.84	−19.76	0.03	0.14	0.82	0.62
Comorbidities
Coronary Artery Disease	0.28	2.66	0.36	3.24	29.55	0.31	3.04	−14.74	0.30	3.20	−4.25	0.00	0.48	0.98	0.31
Congestive Heart Failure	1.33	7.04	1.82	5.48	36.37	1.83	4.88	0.76	2.02	5.22	10.34	0.83	0.67	0.09	0.18
Chronic Kidney Disease	3.38	4.70	3.10	4.73	−8.20	3.03	4.86	−2.41	2.63	4.50	−13.22	0.94	0.17	0.03*	0.59
Chronic Obstructive Pulmonary Disease	2.92	3.22	2.78	3.22	−4.66	2.51	3.09	−9.87	2.09	2.86	−16.60	0.95	0.84	0.03*	0.08
Diabetes	1.72	3.06	1.73	3.19	0.47	1.55	3.15	−10.61	1.45	3.22	−6.08	0.88	0.66	0.06	0.18
Hypertension	5.52	2.12	5.38	2.17	−2.62	5.01	2.14	−6.83	4.88	2.26	−2.51	0.96	0.67	0.02*	0.18
≥ 2 Comorbidities	19.89	2.87	18.87	2.81	−5.12	17.99	2.78	−4.68	17.32	2.84	−3.70	0.99	0.17	0.004**	0.59
None	12.49	2.18	12.50	2.16	0.10	10.99	1.98	−12.07	10.09	1.96	−8.17	0.90	0.86	0.05	0.07
Liver Etiologies
Alcoholic Cirrhosis	9.43	5.44	8.53	5.12	−9.52	7.74	5.10	−9.30	6.89	4.88	−11.00	1.00	0.91	< 0.001***	0.05*
Hepatocellular Carcinoma	3.18	8.20	3.34	8.30	4.92	3.49	9.22	4.56	3.33	9.02	−4.55	0.38	0.73	0.38	0.15
Hepatitis B	1.01	2.20	1.42	3.26	41.18	1.35	3.12	−5.16	1.19	3.10	−12.23	0.10	0.46	0.68	0.32
Non-Alcoholic Fatty Liver Disease	0.27	1.28	0.29	1.30	10.15	0.28	1.11	−4.04	0.35	1.34	25.38	0.71	0.00	0.16	0.97
≥ 2 Etiologies	1.89	7.20	1.83	6.86	−3.30	1.97	7.16	7.69	1.89	6.93	−3.99	0.10	0.16	0.69	0.60
None	31.74	2.16	31.12	2.15	−1.97	28.37	2.04	−8.83	27.13	2.09	−4.37	0.95	0.51	0.03*	0.29
Liver Complications
Ascites	1.40	8.16	1.34	7.88	−4.33	1.27	7.70	−5.53	1.36	8.82	6.99	0.24	0.23	0.51	0.52
Cirrhosis	9.68	3.57	8.81	3.53	−9.00	8.23	3.55	−6.58	7.34	3.31	−10.84	0.99	0.66	0.003**	0.18
Encephalopathy	0.71	9.12	0.82	7.81	15.29	0.93	10.65	12.72	0.75	9.87	−19.45	0.08	0.29	0.72	0.46
Hepatorenal Syndrome	0.29	28.38	0.31	36.67	4.40	0.23	27.12	−26.72	0.40	41.79	75.54	0.17	0.32	0.59	0.43
Varices	0.24	4.38	0.28	5.99	17.24	0.24	5.92	−14.35	0.25	6.87	6.21	0.00	0.85	0.95	0.08
≥ 2 Complications	9.78	6.27	9.15	6.00	−6.48	8.30	5.78	−9.24	7.65	5.79	−7.85	1.00	0.87	0.002**	0.07
≥ 3 Complications	4.27	9.56	4.44	8.94	3.90	4.28	9.35	−3.67	3.37	8.16	−21.14	0.58	0.62	0.24	0.21
≥ 4 Complications	1.02	14.40	1.22	13.12	18.77	1.17	13.95	−3.87	0.95	12.43	−19.03	0.08	0.56	0.71	0.25
≥ 5 Complications	0.13	20.93	0.11	16.00	−11.42	0.13	20.93	13.36	0.16	32.35	22.60	0.52	0.53	0.28	0.27
None	19.99	1.58	20.06	1.60	0.36	18.44	1.51	−8.08	18.56	1.64	0.69	0.75	0.03	0.14	0.82
Psychiatric Comorbidities
Bipolar Disorder	1.30	1.46	1.38	1.59	6.09	1.39	1.68	0.76	1.14	1.54	−17.93	0.28	0.23	0.47	0.52
Depression	3.13	1.74	3.27	1.92	4.57	3.04	1.96	−6.99	2.60	1.89	−14.55	0.65	0.46	0.19	0.33
Anxiety Disorder	2.90	2.24	2.64	1.99	−9.01	2.39	1.83	−9.37	2.10	1.70	−12.08	1.00	0.98	< 0.001***	0.010**
Stress-Related Disorder †	0.25	1.24	0.20	0.95	−22.49	0.28	1.34	43.95	0.38	1.84	35.41	0.62	0.59	0.21	0.23
Schizophrenia	0.53	1.87	0.80	2.81	49.48	0.65	2.48	−18.68	0.62	2.63	−4.05	0.02	0.38	0.86	0.38
≥ 2 Comorbidities	2.51	0.97	2.46	0.92	−2.01	2.84	1.04	15.65	2.43	0.92	−14.59	0.01	0.01	0.90	0.92
None	36.90	3.46	35.80	3.44	−2.99	32.61	3.30	−8.91	31.51	3.42	−3.37	0.96	0.21	0.02*	0.54
Substance Use Comorbidities
Cocaine	1.21	2.16	1.01	1.76	−16.57	0.97	1.69	−3.44	1.06	2.00	9.03	0.35	0.10	0.41	0.68
Marijuana	0.93	1.65	0.84	1.48	−9.40	0.61	1.17	−27.79	0.68	1.46	11.97	0.74	0.33	0.14	0.43
Opioid	3.92	1.67	4.15	1.77	5.71	3.81	1.69	−8.06	3.76	1.79	−1.54	0.39	0.38	0.37	0.38
Stimulant	0.90	1.92	0.94	1.75	4.33	1.41	2.17	50.39	1.10	1.51	−21.76	0.36	0.15	0.40	0.61
≥ 2 Comorbidities	1.65	0.96	1.76	0.89	6.41	2.25	1.04	27.95	2.16	1.05	−4.08	0.78	0.53	0.12	0.27
None	38.92	3.23	37.85	3.30	−2.75	34.16	3.22	−9.76	32.03	3.28	−6.22	0.96	0.07	0.02*	0.74
Social Comorbidities
HIV	2.59	2.78	2.40	2.81	−7.35	2.00	2.53	−16.81	1.92	2.92	−3.93	0.94	0.01	0.03*	0.89
Homelessness	0.90	0.88	0.84	0.73	−6.57	0.87	0.68	4.12	0.92	0.67	5.16	0.13	0.80	0.64	0.10
≥ 2 Comorbidities	0.01	0.16	0.07	0.73	398.28	0.06	0.58	−19.39	0.16	1.61	175.84	0.80	0.79	0.11	0.11
None	44.02	2.81	43.23	2.81	−1.80	40.28	2.76	−6.82	37.79	2.79	−6.18	0.96	0.25	0.02*	0.50
Socioeconomic Status
Median Household Income
Quartile 1	20.32	2.64	19.53	2.57	−3.92	17.86	2.49	−8.53	18.21	2.70	1.97	0.81	0.02	0.10	0.87
Quartile 2	11.41	2.58	12.40	2.76	8.72	11.75	2.65	−5.25	9.83	2.49	−16.39	0.41	0.18	0.36	0.58
Quartile 3	9.73	2.79	8.74	2.65	−10.11	8.66	2.67	−1.01	7.75	2.47	−10.46	0.92	0.84	0.04*	0.09
Quartile 4	6.07	2.86	5.87	2.82	−3.34	4.94	2.55	−15.79	5.00	2.74	1.16	0.84	0.35	0.08	0.41
Insurance Type
Medicare	18.89	3.09	17.67	2.92	−6.48	17.45	3.01	−1.23	17.31	3.17	−0.83	0.79	0.18	0.11	0.58
Medicaid	16.34	2.25	16.59	2.26	1.54	14.30	2.02	−13.83	13.23	2.01	−7.49	0.86	0.81	0.08	0.10
Private Insurance	7.20	3.00	6.65	3.09	−7.71	6.25	3.14	−6.01	5.17	2.93	−17.32	0.95	0.04	0.02*	0.79
Other	5.09	2.61	5.63	2.91	10.64	5.21	2.70	−7.49	5.08	2.77	−2.40	0.05	0.09	0.78	0.70
Hospital Region
Northeast	8.40	2.32	7.53	2.11	−10.33	6.66	1.99	−11.58	6.55	2.19	−1.60	0.92	0.21	0.04*	0.54
Midwest	7.36	2.33	8.10	2.54	10.10	7.67	2.47	−5.32	7.00	2.44	−8.71	0.17	0.14	0.59	0.63
South	19.68	2.75	18.73	2.68	−4.82	17.18	2.53	−8.25	16.71	2.59	−2.73	0.97	0.70	0.02*	0.16
West	12.10	3.18	12.18	3.26	0.70	11.70	3.30	−3.98	10.52	3.14	−10.07	0.77	0.02	0.12	0.87

^*p < 0.05,

^**p < 0.01,

^***p < 0.001

^†This includes PTSD and adjustment disorder

Total Annual Costs

Between 2016 and 2019, the total annual costs were found to show a decreasing trend of $8,997.60, $8,837.72, $8,409.10, and $8215.35 million US dollars for all strata combined (R2=0.97, p=0.02). Decreasing trends were also noted in granular strata analyses. The cohort with an admission age greater than 65 years saw an increasing trend (R2=0.96, p=0.02), and a decreasing pattern was found in the cohort with admission ages between 50 and 64 (R2=0.99, p=0.004). Additionally, strata of admissions with male sex, as well as White, Black, and Hispanic groups all showed significant declines over the four-year period. Admissions with concurrent alcoholic liver disease experienced a decreasing trend in total expenditures, but those with concurrent non-alcoholic fatty liver disease experienced an increase (R2=0.99, p=0.008 andR2=0.97, p=0.02 respectively). Of the psychiatric comorbidities, the strata of admissions diagnosed with depression had a significantly decreasing trend (R2=0.99, p=0.005), and admissions without a simultaneous mental illness exhibited a similarly significant decline in costs (R2=0.97, p=0.01). Admissions with multiple psychiatric comorbidities, however, showed an increasing trend that reached significance (R2=0.91, p=0.045). Amongst queried substance use disorder strata, the stimulant use and multiple comorbidities cohorts observed significant increasing trends (R2=0.99, p=0.006 andR2=0.95, p=0.03 respectively), which contrasted with the significantly decreasing pattern exhibited in the cohort with no substance use comorbidity (R2=0.98, p=0.011). Marijuana use was the sole substance use disorder strata demonstrating decreases in costs (R2=0.89, p=0.05). Admissions with HIV exhibited decreasing expenditures (R2=1.00, p=0.002), but those experiencing homelessness showed an increasing pattern (R2=0.97, p=0.02). Admissions without social comorbidity saw improvement in terms of decreasing costs (R2=0.98, p=0.01). Further total cost analyses are found in Table 3, and bar charts detailing linear regressions across demographics, SES information, liver complication, social comorbidity, and psychiatric and substance use disorders are shown in Figures 1 through 4, respectively.

Table 3.

Total Cost Associated with HCV in US Hospitals

Year	2016		2017			2018			2019			r2	p-value
Total Cost (in million dollars)	8,997.60		8,837.72			8,409.10			8,215.35			0.97	0.02 *
Demographics	Total (in million dollars)	(95% confidence interval)	Total (in million dollars)	(95% confidence interval)	Percent difference (%)	Total (in million dollars)	(95% confidence interval)	Percent difference (%)	Total (in million dollars)	(95% confidence interval)	Percent difference (%)	r2 for Total (in million dollars)	p-value for Total (in million dollars)
Age
18 to 34	817.64	(748.88 – 886.41)	879.57	(813.59 – 945.54)	7.57	913.98	(843.70 – 984.27)	3.91	876.39	(801.34 – 951.44)	−4.11	0.46	0.32
35 to 49	1,471.26	(1,386.98 – 1,555.53)	1,525.35	(1,427.75 – 1,622.95)	3.68	1,458.89	(1,361.81 – 1,555.96)	−4.36	1,429.85	(1,330.95 – 1,528.75)	−1.99	0.38	0.38
50 to 64	4,958.54	(4,718.79 – 5,198.28)	4,588.74	(4,362.38 – 4,815.11)	−7.46	4,132.57	(3,937.59 – 4,327.55)	−9.94	3,847.94	(3,664.44 – 4,031.43)	−6.89	0.99	0.004 **
greater than 65	1,750.15	(1,662.87 – 1,837.43)	1,844.06	(1,745.94 – 1,942.18)	5.37	1,903.65	(1,807.54 – 1,999.77)	3.23	2,061.18	(1,951.85 – 2,170.51)	8.27	0.96	0.02 *
Gender
Male	5,787.50	(5,508.50 – 6,066.40)	5,638.39	(5,354.60 – 5,922.18)	−2.58	5,352.97	(5,090.96 – 5,614.98)	−5.06	5,268.71	(5,004.80 – 5,532.62)	−1.57	0.96	0.02 *
Female	3,210.10	(3,064.50 – 3,355.70)	3,199.32	(3,046.91 – 3,351.73)	−0.34	3,056.13	(2,915.03 – 3,197.23)	−4.48	2,946.64	(2,802.03 – 3,091.26)	−3.58	0.92	0.04 *
Race
White	5,316.68	(5,067.56 – 5,565.79)	5,235.26	(4,971.69 – 5,498.83)	−1.53	5,031.27	(4,787.47 – 5,275.07)	−3.90	4,970.13	(4,707.71 – 5,232.55)	−1.22	0.96	0.02 *
Black	2,035.01	(1,868.77 – 2,201.25)	1,970.58	(1,801.99 – 2,139.17)	−3.17	1,807.78	(1,657.73 – 1,957.84)	−8.26	1,769.07	(1,623.90 – 1,914.24)	−2.14	0.95	0.03 *
Hispanic	1,115.56	(1,015.91 – 1,215.21)	1,110.72	(1,013.31 – 1,208.14)	−0.43	1,064.12	(963.98 – 1,164.25)	−4.20	999.02	(903.85 – 1,094.20)	−6.12	0.89	0.06 *
Asian or Pacific Islander	139.75	(117.99 – 161.51)	133.31	(113.87 – 152.75)	−4.61	135.26	(107.09 – 163.42)	1.46	122.33	(102.37 – 142.28)	−9.56	0.77	0.12
Other	390.59	(332.96 – 448.21)	387.84	(325.91 – 449.77)	−0.70	370.67	(319.51 – 421.83)	−4.43	354.80	(308.36 – 401.24)	−4.28	0.93	0.03 *
Comorbidities
Coronary Artery Disease	56.52	(50.81 – 62.22)	63.35	(57.05 – 69.64)	12.09	66.68	(58.37 – 74.99)	5.25	51.63	(46.17 – 57.10)	−22.56	0.05	0.78
Congestive Heart Failure	163.50	(145.04 – 181.95)	240.48	(220.71 – 260.25)	47.09	277.27	(252.72 – 301.82)	15.30	306.57	(274.99 – 338.15)	10.57	0.95	0.03 *
Chronic Kidney Disease	483.37	(442.80 – 523.95)	417.59	(384.58 – 450.60)	−13.61	376.73	(347.75 – 405.70)	−9.79	372.61	(340.37 – 404.85)	−1.09	0.88	0.06
Chronic Obstructive Pulmonary Disease	431.51	(407.88 – 455.14)	430.12	(405.20 – 455.03)	−0.32	402.82	(378.65 – 426.99)	−6.35	378.89	(355.92 – 401.85)	−5.94	0.91	0.05 *
Diabetes	297.00	(273.05 – 320.95)	286.72	(264.96 – 308.48)	−3.46	258.12	(241.82 – 274.42)	−9.97	256.30	(238.42 – 274.19)	−0.70	0.90	0.05 *
Hypertension	1,293.07	(1,221.90 – 1,364.24)	1,238.20	(1,168.37 – 1,308.03)	−4.24	1,138.16	(1,075.14 – 1,201.18)	−8.08	1,110.50	(1,047.31 – 1,173.69)	−2.43	0.96	0.02 *
≥ 2 Comorbidities	3,857.17	(3,677.90 – 4,036.45)	3,694.60	(2,330.35 – 3,875.57)	−4.21	3,549.20	(3,384.37 – 3,714.03)	−3.94	3,431.97	(3,272.98 – 3,590.97)	−3.30	0.99	0.003 **
None	2,415.45	(2,291.25 – 2,539.64)	2,466.66	(3,513.63 – 2,602.96)	2.12	2,340.12	(2,209.03 – 2,471.22)	−5.13	2,306.88	(2,162.98 – 2,450.77)	−1.42	0.65	0.19
Liver Etiologies
Alcoholic Cirrhosis	940.42	(891.97 – 988.87)	881.73	(831.59 – 931.86)	−6.24	803.70	(761.99 – 845.40)	−8.85	765.21	(725.58 – 804.84)	−4.79	0.99	0.008 **
Hepatocellular Carcinoma	279.39	(243.25 – 315.52)	288.08	(254.84 – 321.33)	3.11	263.36	(232.98 – 293.75)	−8.58	254.93	(223.48 – 286.38)	−3.20	0.71	0.16
Hepatitis B	251.83	(228.30 – 275.37)	259.17	(232.33 – 286.02)	2.91	259.25	(225.66 – 292.84)	0.03	229.23	(208.56 – 249.89)	−11.58	0.38	0.38
Non-Alcoholic Fatty Liver Disease	116.13	(104.78 – 127.48)	121.46	(111.14 – 131.78)	4.59	136.57	(124.42 – 148.72)	12.44	148.68	(135.70 – 161.65)	8.87	0.97	0.02 *
≥ 2 Etiologies	171.23	(153.21 – 189.25)	165.92	(148.35 – 183.49)	−3.10	162.54	(147.93 – 177.16)	−2.03	176.64	(156.99 – 196.29)	8.67	0.07	0.73
None	7,238.58	(6,914.43 – 7,562.74)	7,121.35	(6,787.24 – 7,455.46)	−1.62	6,783.67	(6,471.03 – 7,096.32)	−4.74	6,640.67	(6,321.81 – 6,959.52)	−2.11	0.96	0.02 *
Liver Complications
Ascites	142.32	(127.13 – 157.51)	153.39	(136.20 – 170.57)	7.78	145.20	(131.04 – 159.35)	−5.34	161.76	(139.88 – 183.64)	11.41	0.55	0.26
Cirrhosis	1,418.28	(1,343.11 – 1,493.46)	1,277.08	(1,207.34 – 1,346.83)	−9.96	1,187.90	(1,129.31 – 1,246.49)	−6.98	1,166.18	(1,108.79 – 1,223.57)	−1.83	0.91	0.05 *
Encephalopathy	46.90	(40.52 – 53.27)	70.70	(55.98 – 85.42)	50.75	48.63	(42.90 – 54.35)	−31.21	49.48	(42.72 – 56.24)	1.76	0.03	0.84
Hepatorenal Syndrome	14.51	(8.00 – 21.02)	9.50	(6.55 – 12.45)	−34.53	10.68	(6.03 – 15.33)	12.40	12.22	(8.91 – 15.54)	14.49	0.11	0.66
Varices	43.91	(28.11 – 59.71)	27.58	(23.58 – 31.59)	−37.18	29.62	(23.55 – 35.69)	7.38	27.16	(19.69 – 34.63)	−8.30	0.61	0.22
≥ 2 Complications	890.59	(834.45 – 946.73)	855.05	(803.66 – 906.43)	−3.99	794.73	(744.78 – 844.68)	−7.05	750.35	(703.57 – 797.13)	−5.58	0.99	0.004 **
≥ 3 Complications	318.05	(289.26 – 346.84)	333.72	(299.70 – 367.74)	4.93	292.48	(267.86 – 317.10)	−12.36	280.97	(254.45 – 307.49)	−3.94	0.67	0.18
≥ 4 Complications	64.09	(54.44 – 73.75)	80.95	(68.08 – 93.82)	26.30	69.55	(59.37 – 79.73)	−14.08	67.63	(55.08 – 80.18)	−2.76	0.00	0.99
≥ 5 Complications	11.88	(5.09 – 18.67)	8.22	(4.21 – 12.22)	−30.82	9.34	(5.89 – 12.78)	13.65	5.49	(3.53 – 7.44)	−41.25	0.77	0.12
None	6,047.06	(5,768.65 – 6,325.46)	6,021.53	(5,730.10 – 6,312.96)	−0.42	5,820.98	(5,539.99 – 6,101.96)	−3.33	5,694.10	(5,410.42 – 5,977.79)	−2.18	0.93	0.03 *
Psychiatric Comorbidities
Bipolar Disorder	359.01	(338.00 – 380.02)	355.54	(332.65 – 378.43)	−0.97	348.43	(325.78 – 371.08)	−2.00	321.84	(301.93 – 341.76)	−7.63	0.83	0.09
Depression	848.63	(798.72 – 898.54)	802.14	(754.24 – 850.03)	−5.48	727.38	(684.57 – 770.20)	−9.32	683.10	(640.05 – 726.14)	−6.09	0.99	0.005 **
Anxiety Disorder	645.86	(611.71 – 680.02)	667.78	(632.09 – 703.47)	3.39	678.59	(639.49 – 717.69)	1.62	652.71	(616.73 – 688.69)	−3.81	0.08	0.73
Stress-Related Disorder †	107.88	(95.99 – 119.76)	114.02	(98.71 – 129.33)	5.70	105.19	(95.12 – 115.26)	−7.74	118.90	(106.87 – 130.94)	13.03	0.26	0.49
Schizophrenia	166.60	(137.11 – 196.09)	168.20	(144.33 – 192.07)	0.96	143.87	(123.79 – 163.96)	−14.46	137.24	(117.84 – 156.65)	−4.61	0.85	0.08
≥ 2 Comorbidities	1,065.96	(1,010.31 – 1,121.61)	1,119.89	(1,054.77 – 1,185.01)	5.06	1,135.60	(1,069.43 – 1,201.76)	1.40	1,159.41	(1,093.44 – 1,225.39)	2.10	0.93	0.04 *
None	5,803.64	(5,520.79 – 6,086.49)	5,610.15	(5,328.73 – 5,891.57)	−3.33	5,270.03	(5,013.10 – 5,526.97)	−6.06	5,142.14	(4,878.36 – 5,405.93)	−2.43	0.97	0.01 *
Substance Use Comorbidities
Cocaine	245.90	(225.54 – 266.27)	244.24	(224.24 – 264.25)	−0.68	244.16	(224.67 – 263.66)	−0.03	238.01	(218.65 – 257.38)	−2.52	0.78	0.12
Marijuana	252.94	(234.50 – 271.39)	249.39	(230.78 – 268.01)	−1.40	230.18	(212.92 – 247.44)	−7.70	198.64	(185.28 – 211.99)	−13.70	0.89	0.05
Opioid	1,088.06	(1,015.44 – 1,160.68)	1,141.96	(1,062.03 – 1,221.89)	4.95	1,125.28	(1,046.05 – 1,204.51)	−1.46	1,122.37	(1,037.33 – 1,207.42)	−0.26	0.24	0.51
Stimulant	230.43	(207.05 – 253.82)	257.60	(228.69 – 286.50)	11.79	295.77	(267.14 – 324.41)	14.82	340.72	(311.20 – 370.23)	15.19	0.99	0.006 **
≥ 2 Comorbidities	709.02	(655.17 – 762.87)	819.88	(756.63 – 883.13)	15.64	914.60	(840.68 – 988.52)	11.55	944.39	(859.83 – 1,028.96)	3.26	0.95	0.03 *
None	6,471.22	(6,177.45 – 6,764.99)	6,124.65	(5,837.35 – 6,411.94)	−5.36	5,599.10	(5,354.35 – 5,843.84)	−8.58	5,371.22	(5,130.08 – 5,612.35)	−4.07	0.98	0.01 *
Social Comorbidities
HIV	500.96	(454.28 – 547.64)	467.46	(419.73 – 515.19)	−6.69	421.81	(377.65 – 465.97)	−9.77	382.14	(342.07 – 422.22)	−9.40	1.00	0.002 **
Homelessness	466.50	(419.00 – 514.00)	511.06	(460.90 – 561.23)	9.55	558.83	(498.06 – 619.60)	9.35	645.91	(578.58 – 713.25)	15.58	0.97	0.02 *
≥ 2 Comorbidities	43.42	(35.69 – 51.16)	44.23	(7,455.07 – 52.85)	1.87	44.05	(37.31 – 50.78)	−0.43	53.10	(40.07 – 66.13)	20.56	0.65	0.19
None	7,986.70	(7,633.33 – 8,340.08)	7,814.96	(35.61 – 8,174.85)	−2.15	7,384.41	(7,062.93 – 7,705.89)	−5.51	7,134.20	(6,812.44 – 7,455.96)	−3.39	0.98	0.01 *
Socioeconomic Status
Median Household Income
Quartile 1	3,646.70	(3,416.30 – 3,877.10)	3,577.11	(3,346.10 – 3,808.12)	−1.91	3,347.38	(3,125.48 – 3,569.28)	−6.42	3,297.66	(3,072.60 – 3,522.73)	−1.49	0.93	0.03 *
Quartile 2	2,140.40	(2,041.10 – 2,239.70)	2,219.55	(2,104.37 – 2,334.73)	3.70	2,161.61	(2,055.19 – 2,268.03)	−2.61	1,994.09	(1,886.37 – 2,101.81)	−7.75	0.45	0.33
Quartile 3	1,881.70	(1,777.30 – 1,986.00)	1,779.34	(1,677.52 – 1,881.16)	−5.44	1,731.57	(1,637.86 – 1,825.29)	−2.68	1,753.47	(1,652.51 – 1,854.44)	1.26	0.71	0.16
Quartile 4	1,328.80	(1,217.30 – 1,440.20)	1,261.71	(1,144.65 – 1,378.78)	−5.05	1,168.53	(1,071.95 – 1,265.11)	−7.39	1,170.12	(1,071.52 – 1,268.73)	0.14	0.89	0.05
Insurance Type
Medicare	3,311.11	(3,158.95 – 3,463.26)	3,261.82	(3,100.15 – 3,423.49)	−1.49	3,066.54	(2,928.76 – 3,204.33)	−5.99	3,062.35	(2,916.50 – 3,208.19)	−0.14	0.88	0.06
Medicaid	3,525.55	(3,312.14 – 3,738.96)	3,561.26	(3,329.77 – 3,792.75)	1.01	3,441.81	(3,219.69 – 3,663.94)	−3.35	3,387.03	(3,167.48 – 3,606.58)	−1.59	0.76	0.13
Private Insurance	1,300.20	(1,214.11 – 1,386.28)	1,170.70	(1,097.41 – 1,243.98)	−9.96	1,069.76	(1,003.74 – 1,135.78)	−8.62	961.16	(892.99 – 1,029.33)	−10.15	1.00	0.001 **
Other	860.73	(784.36 – 937.10)	843.95	(766.52 – 921.37)	−1.95	830.98	(760.81 – 901.15)	−1.54	804.81	(738.58 – 871.04)	−3.15	0.98	0.01 *
Hospital Region
Northeast	1,804.20	(1,616.50 – 1,991.90)	1,796.16	(1,603.85 – 1,988.47)	−0.44	1,658.42	(1,486.55 – 1,830.28)	−7.67	1,650.92	(1,478.90 – 1,822.94)	−0.45	0.84	0.08
Midwest	1,396.30	(1,258.80 – 1,533.70)	1,431.76	(1,287.29 – 1,576.23)	2.54	1,449.02	(1,297.05 – 1,600.99)	1.21	1,361.92	(1,225.91 – 1,497.93)	−6.01	0.08	0.71
South	3,205.30	(2,936.30 – 3,474.40)	3,113.19	(2,848.04 – 3,378.33)	−2.87	2,979.69	(2,736.71 – 3,222.67)	−4.29	2,906.86	(2,650.46 – 3,163.27)	−2.44	0.99	0.006 **
West	2,591.80	(2,381.90 – 2,801.70)	2,496.61	(2,265.24 – 2,727.98)	−3.67	2,321.97	(2,119.63 – 2,524.32)	−7.00	2,295.64	(2,082.11 – 2,509.18)	−1.13	0.94	0.03 *

^*p < 0.05,

^**p < 0.01,

^***p < 0.001

^†This includes PTSD and adjustment disorder

Figure 1.

Inflation-adjusted total and mean costs and trends for HCV patients, stratified by demographic descriptors.

Figure 4.

Inflation-adjusted total and mean costs and trends for HCV patients, stratified by psychiatric and substance use disorder comorbidities.

Mean Costs

Mean costs per-hospitalization were calculated for HCV related admissions. Generalized increasing trends were noted throughout the strata. The age group of admissions between 18 and 34 years old showed significantly greater per-capita costs (for 18- to 34-year-olds: R2=0.94, p=0.03). Significantly increasing expenses among psychiatric comorbidities and substance use comorbidities included the bipolar disorder cohort (R2=0.95, p=0.03), anxiety disorder cohort (R2=0.95, p=0.03) and opioid use disorder cohort (R2=0.97, p=0.02). The strata of admissions without psychiatric diagnoses, as well as the strata of admissions without substance use comorbidities, did not show a significantly increasing or decreasing trend. No patterns attained significance in the social comorbidity strata. The above findings and additional breakdown of patterns in liver etiologies, complications and comorbidities can be found in Table 4. Likewise, bar charts detailing linear regressions of mean costs across demographics, SES information, liver complication, and psychiatric and substance use disorders are shown in Figures 1 through 4. Supplementary Table 1 includes information concerning the median costs of these hospitalizations.

Table 4.

Mean Costs Associated with HCV in US Hospitals

Year	2016		2017			2018			2019			r2	p-value
Demographics	Mean Cost (in dollars)	(95% confidence interval)	Mean Cost (in dollars)	(95% confidence interval)	Percent difference (%)	Mean Cost (in dollars)	(95% confidence interval)	Percent difference (%)	Mean Cost (in dollars)	(95% confidence interval)	Percent difference (%)	r2 for Mean Cost (in dollars)	p-value for Mean Cost (in dollars)
Age
18 to 34	10,061.44	(9,457.27 – 10,665.60)	10,187.82	(9,721.83 – 10,653.81)	1.26	10,684.26	(10,184.12 – 11,184.40)	4.87	11,230.05	(10,574.97 – 11,885.14)	5.11	0.94	0.03 *
35 to 49	12,368.69	(11,921.56 – 12,815.83)	12,818.09	(12,299.74 – 13,336.44)	3.63	12,664.50	(12,148.37 – 13,180.62)	−1.20	13,031.17	(12,495.25 – 13,567.09)	2.90	0.72	0.15
50 to 64	15,198.59	(14,792.90 – 15,604.27)	14,999.82	(14,580.32 – 15,419.31)	−1.31	14,905.04	(14,530.18 – 15,279.91)	−0.63	15,630.90	(15,202.84 – 16,058.96)	4.87	0.23	0.52
greater than 65	16,492.96	(16,016.10 – 16,969.83)	16,139.14	(15,654.42 – 16,623.86)	−2.15	16,120.36	(15,667.99 – 16,572.73)	−0.12	17,115.85	(16,570.38 – 17,661.33)	6.18	0.26	0.49
Gender
Male	14,930.40	(14,516.10 – 15,344.70)	14,694.42	(14,266.15 – 15,122.70)	−1.58	14,676.12	(14,275.78 – 15,076.47)	−0.12	15,488.45	(15,021.05 – 15,955.85)	5.54	0.32	0.44
Female	13,105.20	(12,748.50 – 13,461.90)	13,231.01	(12,856.54 – 13,605.47)	0.96	13,209.98	(12,864.31 – 13,555.64)	−0.16	13,756.83	(13,355.16 – 14,158.51)	4.14	0.73	0.15
Race
White	13,435.29	(13,063.34 – 13,807.24)	13,457.74	(13,066.87 – 13,848.60)	0.17	13,431.41	(13,076.50 – 13,786.31)	−0.20	14,126.12	(13,683.97 – 14,568.26)	5.17	0.59	0.23
Black	15,169.10	(14,605.28 – 15,732.92)	14,952.43	(14,378.00 – 15,526.86)	−1.43	14,755.01	(14,248.01 – 15,262.01)	−1.32	15,594.75	(15,035.55 – 16,153.96)	5.69	0.15	0.61
Hispanic	15,546.80	(14,768.64 – 16,324.97)	15,087.28	(14,368.98 – 15,805.58)	−2.96	15,149.74	(14,499.48 – 15,800.00)	0.41	16,156.25	(15,358.38 – 16,954.11)	6.64	0.25	0.50
Asian or Pacific Islander	19,964.26	(17,894.48 – 22,034.05)	19,447.10	(17,620.78 – 21,273.41)	−2.59	20,921.42	(17,991.67 – 23,851.18)	7.58	19,955.47	(17,824.20 – 22,086.75)	−4.62	0.09	0.70
Other	16,311.89	(15,091.62 – 17,532.16)	16,003.44	(14,573.35 – 17,433.54)	−1.89	16,640.55	(15,169.65 – 18,111.45)	3.98	16,799.24	(15,353.25 – 18,245.22)	0.95	0.59	0.23
Comorbidities
Coronary Artery Disease	15,031.11	(13,608.21 – 16,454.01)	15,797.84	(14,447.08 – 17,148.61)	5.10	18,418.94	(16,415.41 – 20,422.47)	16.59	15,742.08	(14,282.94 – 17,201.22)	−14.53	0.17	0.59
Congestive Heart Failure	24,239.49	(22,119.28 – 26,359.69)	20,276.81	(18,965.97 – 21,587.65)	−16.35	20,831.78	(19,465.81 – 22,197.74)	2.74	22,401.83	(20,480.30 – 24,323.37)	7.54	0.13	0.64
Chronic Kidney Disease	18,867.08	(17,716.83 – 20,017.32)	17,777.54	(16,822.89 – 18,732.19)	−5.77	17,038.81	(16,085.36 – 17,992.27)	−4.16	18,022.15	(16,899.57 – 19,144.74)	5.77	0.31	0.44
Chronic Obstructive Pulmonary Disease	13,365.57	(12,832.80 – 13,898.35)	13,928.72	(13,318.36 – 14,539.08)	4.21	14,001.26	(13,368.60 – 14,633.92)	0.52	14,642.93	(13,989.74 – 15,296.13)	4.58	0.93	0.04 *
Diabetes	14,794.58	(13,884.88 – 15,704.28)	14,745.11	(13,902.71 – 15,587.51)	−0.33	14,766.58	(14,043.72 – 15,489.44)	0.15	16,029.01	(15,190.31 – 16,867.71)	8.55	0.58	0.24
Hypertension	13,927.94	(13,461.61 – 14,394.27)	13,986.22	(13,486.36 – 14,486.08)	0.42	13,709.45	(13,205.88 – 14,213.02)	−1.98	14,508.75	(13,952.02 – 15,065.48)	5.83	0.31	0.44
≥ 2 Comorbidities	15,629.38	(15,231.58 – 16,027.18)	15,381.34	(11,499.16 – 15,806.19)	−1.59	15,424.94	(15,048.77 – 15,801.11)	0.28	15,897.96	(15,498.42 – 16,297.50)	3.07	0.22	0.54
None	11,813.50	(11,416.97 – 12,210.04)	11,910.47	(14,956.50 – 12,321.78)	0.82	11,837.65	(11,443.95 – 12,231.35)	−0.61	12,644.24	(12,140.83 – 13,147.65)	6.81	0.62	0.21
Liver Etiologies
Alcoholic Cirrhosis	15,212.27	(14,691.67 – 15,732.86)	14,785.39	(14,246.06 – 15,324.72)	−2.81	14,891.53	(14,401.01 – 15,382.04)	0.72	15,308.76	(14,786.98 – 15,830.53)	2.80	0.04	0.80
Hepatocellular Carcinoma	20,194.15	(18,511.81 – 21,876.48)	20,012.80	(18,562.28 – 21,463.33)	−0.90	19,580.99	(18,091.79 – 21,070.20)	−2.16	19,490.16	(17,695.77 – 21,284.56)	−0.46	0.94	0.03 *
Hepatitis B	15,402.68	(14,431.07 – 16,374.28)	16,587.11	(15,394.21 – 17,780.01)	7.69	16,828.99	(15,124.17 – 18,533.81)	1.46	16,892.06	(15,856.37 – 17,927.75)	0.37	0.76	0.13
Non-Alcoholic Fatty Liver Disease	15,693.14	(14,481.85 – 16,904.44)	15,004.68	(14,000.75 – 16,008.60)	−4.39	15,174.42	(14,080.81 – 16,268.03)	1.13	15,918.50	(14,900.33 – 16,936.68)	4.90	0.06	0.75
≥ 2 Etiologies	18,274.26	(16,891.61 – 19,656.90)	17,373.73	(16,132.78 – 18,614.69)	−4.93	16,628.40	(15,562.55 – 17,694.26)	−4.29	18,257.45	(16,755.12 – 19,759.78)	9.80	0.02	0.87
None	13,819.24	(13,467.39 – 14,171.09)	13,742.09	(13,369.55 – 14,114.62)	−0.56	13,718.53	(13,374.37 – 14,062.68)	−0.17	14,476.67	(14,071.45 – 14,881.89)	5.53	0.49	0.30
Liver Complications
Ascites	23,217.00	(21,135.00 – 25,298.99)	25,166.03	(22,886.84 – 27,445.23)	8.39	24,841.33	(22,795.01 – 26,887.66)	−1.29	29,735.37	(26,229.79 – 33,240.95)	19.70	0.79	0.11
Cirrhosis	14,644.90	(14,178.96 – 15,110.84)	14,287.46	(13,823.89 – 14,751.03)	−2.44	14,399.64	(13,974.80 – 14,824.48)	0.79	14,844.47	(14,408.18 – 15,280.75)	3.09	0.14	0.63
Encephalopathy	16,778.83	(14,654.68 – 18,902.97)	18,727.21	(14,920.41 – 22,534.02)	11.61	15,686.37	(13,996.58 – 17,376.17)	−16.24	18,429.88	(16,089.82 – 20,769.95)	17.49	0.03	0.83
Hepatorenal Syndrome	39,211.90	(21,687.48 – 56,736.31)	31,663.02	(23,175.12 – 40,150.91)	−19.25	36,193.81	(20,890.51 – 51,497.10)	14.31	36,490.49	(28,163.88 – 44,817.10)	0.82	0.02	0.85
Varices	22,633.00	(14,417.59 – 30,848.41)	16,517.72	(14,317.31 – 18,718.13)	−27.02	20,642.09	(16,548.67 – 24,735.50)	24.97	20,734.64	(15,057.58 – 26,411.69)	0.45	0.01	0.92
≥ 2 Complications	15,994.78	(15,326.25 – 16,663.31)	15,675.97	(15,083.71 – 16,268.22)	−1.99	15,576.82	(14,945.68 – 16,207.95)	−0.63	16,034.86	(15,353.02 – 16,716.70)	2.94	0.00	0.99
≥ 3 Complications	19,928.03	(18,688.06 – 21,167.99)	18,753.67	(17,395.32 – 20,112.03)	−5.89	17,987.74	(16,882.03 – 19,093.45)	−4.08	19,191.93	(17,861.58 – 20,522.27)	6.69	0.22	0.53
≥ 4 Complications	25,283.78	(22,175.05 – 28,392.51)	24,420.07	(21,543.17 – 27,296.97)	−3.42	23,378.40	(20,435.09 – 26,321.72)	−4.27	25,094.97	(21,083.90 – 29,106.04)	7.34	0.06	0.76
≥ 5 Complications	55,241.02	(25,616.81 – 84,865.22)	32,866.58	(20,433.93 – 45,299.22)	−40.50	43,434.54	(28,475.31 – 58,393.78)	32.15	32,270.33	(22,622.48 – 41,918.18)	−25.70	0.48	0.30
None	13,434.62	(13,081.47 – 13,787.77)	13,429.38	(13,050.53 – 13,808.24)	−0.04	13,460.46	(13,109.45 – 13,811.47)	0.23	14,173.77	(13,761.12 – 14,586.43)	5.30	0.63	0.21
Psychiatric Comorbidities
Bipolar Disorder	11,271.93	(10,786.53 – 11,757.33)	11,386.36	(10,824.68 – 11,948.05)	1.02	11,807.24	(11,202.59 – 12,411.89)	3.70	12,248.96	(11,686.88 – 12,811.05)	3.74	0.95	0.03 *
Depression	13,271.25	(12,721.08 – 13,821.41)	13,131.49	(12,613.20 – 13,649.78)	−1.05	13,228.73	(12,710.97 – 13,746.48)	0.74	14,055.48	(13,450.09 – 14,660.86)	6.25	0.55	0.26
Anxiety Disorder	13,963.12	(13,486.04 – 14,440.21)	14,086.73	(13,590.19 – 14,583.27)	0.89	14,613.76	(14,065.27 – 15,162.25)	3.74	14,869.86	(14,331.83 – 15,407.90)	1.75	0.95	0.03 *
Stress-Related Disorder †	14,869.15	(13,405.05 – 16,333.25)	15,534.05	(13,641.51 – 17,426.59)	4.47	14,148.09	(13,044.97 – 15,251.21)	−8.92	16,188.06	(14,809.87 – 17,566.25)	14.42	0.14	0.62
Schizophrenia	16,381.90	(13,646.86 – 19,116.93)	16,595.70	(14,615.64 – 18,575.75)	1.31	15,520.22	(13,619.53 – 17,420.91)	−6.48	16,416.78	(14,404.59 – 18,428.97)	5.78	0.07	0.74
≥ 2 Comorbidities	11,577.08	(11,208.03 – 11,946.14)	11,692.35	(11,289.88 – 12,094.82)	1.00	11,665.08	(11,272.27 – 12,057.90)	−0.23	12,414.07	(11,981.36 – 12,846.78)	6.42	0.68	0.17
None	15,231.46	(14,805.06 – 15,657.86)	15,058.99	(14,631.30 – 15,486.69)	−1.13	15,009.85	(14,612.50 – 15,407.20)	−0.33	15,749.53	(15,271.42 – 16,227.65)	4.93	0.33	0.43
Substance Use Comorbidities
Cocaine	12,366.34	(11,720.92 – 13,011.75)	11,920.06	(11,275.73 – 12,564.40)	−3.61	11,986.43	(11,352.03 – 12,620.84)	0.56	12,704.16	(11,998.34 – 13,409.99)	5.99	0.15	0.62
Marijuana	12,637.57	(11,920.33 – 13,354.82)	12,321.77	(11,657.56 – 12,985.98)	−2.50	12,567.94	(11,835.62 – 13,300.25)	2.00	12,089.95	(11,444.44 – 12,735.46)	−3.80	0.52	0.28
Opioid	12,947.70	(12,426.38 – 13,469.02)	13,646.73	(13,048.95 – 14,244.51)	5.40	14,056.35	(13,464.75 – 14,647.95)	3.00	15,114.11	(14,455.55 – 15,772.68)	7.53	0.97	0.02 *
Stimulant	13,852.36	(13,004.08 – 14,700.64)	13,476.22	(12,421.72 – 14,530.71)	−2.72	12,812.40	(12,019.96 – 13,604.84)	−4.93	13,183.03	(12,442.30 – 13,923.75)	2.89	0.61	0.22
≥ 2 Comorbidities	11,495.18	(10,911.54 – 12,078.82)	11,563.08	(10,986.99 – 12,139.17)	0.59	11,852.49	(11,278.18 – 12,426.80)	2.50	12,932.48	(12,178.48 – 13,686.47)	9.11	0.80	0.11
None	15,037.82	(14,633.01 – 15,442.63)	14,898.74	(14,498.38 – 15,299.10)	−0.92	14,847.78	(14,483.13 – 15,212.44)	−0.34	15,520.61	(15,098.81 – 15,942.41)	4.53	0.35	0.41
Social Comorbidities
HIV	15,043.88	(14,347.11 – 15,740.66)	15,298.99	(14,400.64 – 16,197.34)	1.70	15,059.20	(14,156.97 – 15,961.43)	−1.57	16,400.89	(15,438.80 – 17,362.99)	8.91	0.59	0.23
Homelessness	12,772.05	(11,974.54 – 13,569.56)	12,378.92	(11,681.50 – 13,076.33)	−3.08	12,169.63	(11,438.82 – 12,900.44)	−1.69	13,336.98	(12,565.85 – 14,108.12)	9.59	0.14	0.63
≥ 2 Comorbidities	13,762.70	(11,920.10 – 15,605.29)	12,858.62	(13,823.51 – 14,777.41)	−6.57	12,766.71	(11,559.01 – 13,974.41)	−0.71	15,571.88	(12,599.19 – 18,544.57)	21.97	0.28	0.47
None	14,272.17	(13,896.20 – 14,648.15)	14,202.96	(10,939.82 – 14,582.40)	−0.48	14,236.11	(13,891.03 – 14,581.20)	0.23	14,886.95	(14,477.73 – 15,296.17)	4.57	0.55	0.26
Socioeconomic Status
Median Household Income
Quartile 1	13,287.20	(12,871.40 – 13,703.00)	13,148.48	(12,729.28 – 13,567.69)	−1.04	13,142.96	(12,739.76 – 13,546.17)	−0.04	13,798.05	(13,324.07 – 14,272.03)	4.98	0.40	0.36
Quartile 2	13,568.80	(13,200.70 – 13,936.80)	13,809.65	(13,368.50 – 14,250.79)	1.78	13,741.53	(13,369.40 – 14,113.67)	−0.49	14,270.52	(13,818.49 – 14,722.56)	3.85	0.77	0.12
Quartile 3	15,102.40	(14,590.60 – 15,614.30)	15,051.73	(14,546.70 – 15,556.76)	−0.34	15,036.25	(14,567.40 – 15,505.09)	−0.10	15,805.59	(15,227.22 – 16,383.95)	5.12	0.53	0.27
Quartile 4	17,533.20	(16,701.10 – 18,365.30)	16,931.23	(16,005.84 – 17,856.61)	−3.43	16,951.18	(16,137.43 – 17,764.93)	0.12	18,086.76	(17,203.83 – 18,969.69)	6.70	0.16	0.61
Insurance Type
Medicare	15,155.56	(14,748.96 – 15,562.16)	15,068.22	(14,623.73 – 15,512.71)	−0.58	14,911.10	(14,536.80 – 15,285.40)	−1.04	15,829.77	(15,366.46 – 16,293.07)	6.16	0.35	0.41
Medicaid	13,620.05	(13,188.69 – 14,051.41)	13,557.41	(13,058.78 – 14,056.04)	−0.46	13,693.30	(13,232.26 – 14,154.35)	1.00	14,497.10	(13,963.89 – 15,030.31)	5.87	0.66	0.19
Private Insurance	15,185.67	(14,538.95 – 15,832.38)	15,191.03	(14,594.53 – 15,787.54)	0.04	15,146.03	(14,551.21 – 15,740.85)	−0.30	15,405.66	(14,677.47 – 16,133.86)	1.71	0.46	0.32
Other	12,360.62	(11,719.89 – 13,001.35)	12,178.17	(11,627.55 – 12,728.80)	−1.48	12,139.05	(11,665.13 – 12,612.97)	−0.32	12,403.70	(11,938.76 – 12,868.63)	2.18	0.01	0.91
Hospital Region
Northeast	13,957.80	(13,176.70 – 14,738.90)	14,031.96	(13,150.00 – 14,913.92)	0.53	13,979.16	(13,164.79 – 14,793.54)	−0.38	15,592.39	(14,628.49 – 16,556.29)	11.54	0.61	0.22
Midwest	12,412.00	(11,828.70 – 12,995.20)	12,564.79	(11,938.49 – 13,191.10)	1.23	13,119.83	(12,406.38 – 13,833.27)	4.42	13,413.34	(12,748.92 – 14,077.76)	2.24	0.96	0.02 *
South	12,573.80	(11,962.20 – 13,185.50)	12,452.49	(11,874.36 – 13,030.63)	−0.97	12,365.64	(11,868.14 – 12,863.14)	−0.70	12,733.76	(12,098.43 – 13,369.08)	2.98	0.10	0.68
West	19,070.70	(18,111.70 – 20,029.70)	18,693.55	(17,674.82 – 19,712.29)	−1.98	18,421.79	(17,499.10 – 19,344.48)	−1.45	19,344.77	(18,224.36 – 20,465.19)	5.01	0.03	0.83

^*p < 0.05,

^**p < 0.01,

^***p < 0.001

^†This includes PTSD and adjustment disorder

Sensitivity Analyses

A sensitivity analysis describing the patient cohort according to HCV onset (acute, chronic, cirrhotic stage) and priority diagnosis (HCV within the top ten, fifteen, or twenty diagnoses) is included in Supplementary Tables 2 through 7. In general, trends remained similar in these analyses, including for the psychiatric, substance use, and social comorbidity strata.

Discussion

Using data from a national, US hospital-based registry, the healthcare burden of HCV between the years of 2016 and 2019 was reviewed, with special attention to this condition’s cost implications. Improvements were seen in regard to lower hospitalization incidences, mortality rates, and aggregate costs across many strata. Exceptions to this pattern included admissions with comorbid psychiatric and substance use disorders. Entries with admission ages older than 65, as well as those with concurrent non-alcoholic fatty liver disease, were characterized by increased hospitalization incidences. This finding correlates with the natural aging of persons born between 1945 and 1965, and as HCV patients grow older, increasing trends in cases can be expected in advanced-age strata (2). Additionally, there has been a steep rise in non-alcoholic fatty liver disease prevalence within the United States independent of HCV (19). Increasing rates of non-alcoholic fatty liver disease and HCV dual-diagnoses could be a by-product of shifting chronic liver disease trends.

Strata-specific analysis of expense data revealed that entries with admission ages between 18 and 34 years, comorbid opioid use disorder, bipolar disorder, or anxiety disorder showed per-capita mean cost growth, inverse to decreasing trends in poor outcomes. Aggregate costs showed increasing trends in patients with stimulant use, polysubstance use, and poly-psychiatric disorders. Meanwhile, patients without the queried mental illness diagnoses experienced decreasing patterns. Admissions documented to be patients experiencing homelessness also saw cost growth; however, decreases were observed among HIV-comorbid patients. Data from health economic analyses prior to the DAA era showed similar findings, in that expenditure decreases were not uniform across HCV patients (20). Even with the arrival of these therapies, it appears that certain groups continue to require higher treatment spending.

DAAs have been considered to be a primary driver behind the improvements in US HCV clinical and economic outcomes, and their arrival motivated the World Health Organization’s HCV global elimination targets of a 90% reduction in new infection incidence and 65% liver-related mortality reduction by 2030 (21,22). This therapy’s impact must be contextualized in the US health insurance system to further illustrate the studied economic burden of HCV. The multi-payer design of insurance introduces insurer variability, with an analysis of U.S.-based pharmacy data between 2016 and 2017 revealing that absolute denial for DAA occurred at a rate of 52.4% by commercial insurers and 14.7% by the public program Medicare (23). The U.S.-based Medicaid program rations DAA access according to a patient’s sobriety history and fibrosis severity (24). These restrictions have the potential to introduce treatment disparities on the basis of insurance providers via limiting patient accessibility to DAA. Consequently, the proportions of patients receiving DAA therapy fluctuate between insurance types, with a 2022 report from the CDC finding that DAA treatment initiation within one year of a positive HCV RNA test was 23%, 28%, and 35% in Medicaid, Medicare, and private insurance recipients, respectively (25).

Insurance barriers contingent on such clinical characteristics differ across countries; for instance, Australia was one of the first countries to institute DAA access for all, regardless of fibrosis stage or substance use (26,27). It has been argued that US and other countries’ treatment restrictions are a result of prohibitively expensive regimens (26). Exorbitant DAA prices does not appear to solely be a US problem; globally, a price analysis by Barber et al (2020) showed that the ratio of the US GDP per capita over DAA regimen was comparable to that of other countries (e.g., the US GDP per capita to sofosbuvir ratio was 1.01, whereas it was 1.08 for the United Kingdom) (28). Eventual patent expiration and ensuing generic production could provide relief of these barriers, which will come in as soon as 2025 for many countries (26).

To elaborate on the cost implications of DAA therapy, the potential of becoming cured and avoiding costly complications must be balanced against DAA therapy’s high but temporary price. While DAA therapy is curative for over 95% of patients, chronic infection often progresses to costly interventions, such as liver transplant and frequent hospitalizations for decompensated cirrhosis (29–31). The price range for these medications is in the $20,000 to $30,000 dollar range before co-pays, a figure which outstrips the $10,000 to $20,000 per-capita admission mean cost presently reported (32). Still, the chronic nature of HCV and recurrent hospitalizations must be given appropriate attention. A state-level Medicare and Medicaid analysis suggested that early treatment of Medicaid recipients with DAAs resulted in cost-savings of approximately $1.0 billion dollars over 25 years, and a second review found that treatment of acute HCV could decrease costs by $3,655 per patient when considering viral transmissivity (32,33). Work by Mattingly et al (2020) considers the effect of HCV cure on reducing the rates of absenteeism, productivity, and patient/caregiver time, and this adjustment shows DAA regimens becoming cost-saving in both monetary and unmeasurable ways at both 10 and 20 years (34). Such investigations highlight the advantages of DAA therapy from a long-term economic standpoint.

Coverage of DAA therapy in the US can therefore be potentially cost-saving, but it is limited by the aforementioned financial barriers. As corroborated by this study’s granular analysis of trends among vulnerable subpopulations, additional challenges to DAA accessibility may disproportionately affect HCV costs among patient populations with substance use or psychiatric disorders, or those without stable housing. In a New York City-based cohort of 1024 patients, Al-Khazraji et al (2020) found that 816 patients presenting at a large academic medical center did not receive HCV-DAA treatment (80%), with primary reasons for nontreatment being poor adherence (67%), active substance use disorder (20%), and significant psychiatric illness (12.7%) (35). The potential overlap of these barriers was also noted, in that those with a substance use disorder could have poor adherence to regimens or psychiatric comorbidity (35,36). An HIV-HCV subcohort from their analysis demonstrated treatment rates of 6%, compared to rates of 23% in non-coinfected patients. This is despite the finding of the SIMPLIFY trial, in which 100 of 103 HCV-PWID patients were cured with a regimen of sofosbuvir and velpatasvir (37). These findings reveal patient subgroups that may be particularly impacted by the increasing cost and resource reported in this study.

Given the demonstrated efficacy of DAA treatment, work has been done to identify barriers to care in the PWID population in pursuit of equitable and effective treatment outcomes. Between 2012 and 2018, DAA initiation measurements in a population of 29,228 newly-infected HCV patients found a 24% therapy initiation rate among those with a substance use disorder, compared to a 34% rate for those without (38). Factors believed to be driving this disparity include a lack of care integration among mental and physical health providers, discriminatory drug and alcohol abstinence requirements for publicly-funded state programs, prior authorization requirements, provider bias, and lack of patient symptoms all being proposed as impeding access (35,39,40). Because of these barriers, patients may be more likely to remain infected, predisposing them to both present and future complications requiring expensive in-patient interventions. Furthermore, the complicated access to DAA therapy suggests that cost-savings for these populations may be delayed. With further evidence from this study of increasing cost-burdens, especially among these populations, the potential benefits of DAA therapy cannot be ignored.

While unrestricted access to DAA therapy will likely have to wait until patent expiration reduces cost, state-level policies may alternatively aid in modulating transmission. Implementation of needle-exchange programs (NEPs) is one intervention that has gained considerable support, with clear benefits in terms of preventing HIV transmission (41,42). Studies on sole-NEP intervention to prevent HCV, however, have been inconclusive, with meta-analysis showing mixed results (43–45). Notably, a systematic review conducted by Platt et al (2018) found high NEP coverage in Europe to be associated with a reduction in HCV acquisition risk, but no effect was observed in North America (46). Further, such policies are complicated to enact and study in the US because of state-to-state variability on NEP legality—over 20% of states still significantly restricted use as of 2019, but recent trends suggest that several governments may move toward broader availability (47). On a state-by-state level, there is evidence for NEP reducing HCV incidence. However, as access improves across the US, this intervention’s effect would need further analysis of its case and cost burden, alongside a comparison against DAA or NEP with DAA solutions to optimize a solution to reported disproportionate cost burdens (48).

Limitations

Limitations of the present study include the retrospective design and the use of the NIS database which is based on billing information. The ICD-10 codes used to select patients depend on the accuracy of the labeling physician. Therefore, the NIS could not correct for potential misclassification or coding errors. Furthermore, data regarding the sustained virological response is not included in the NIS variables. This limitation was addressed via sensitivity analyses of HCV onset-type (acute, chronic, with cirrhosis).

Conclusion

Incidence rates and total costs of HCV-related admissions and management are trending downward. However, increasing care costs in HCV patients, especially for those with psychiatric conditions, substance use disorder, and those without housing, indicate that the cost burdens of specific HCV population segments need to be addressed and improved to minimize expenditure of valuable expenditures.

Figure 2.

Inflation-adjusted total and mean costs and trends for HCV patients, stratified by hospital-related and socioeconomic variables.

Figure 3.

Inflation-adjusted total and mean costs and trends for HCV patients, stratified by liver-related complications.