Hepatitis D-Associated Hospitalizations in the United States: 2010–2018

Paul Wasuwanich; Catherine W. Striley; Saleem Kamili; Eyasu H. Teshale; Eric C. Seaberg; Wikrom Karnsakul

J Viral Hepat. 2022;29(3):218-226.

Conclusion

Hospitalizations of hepatitis D in the United States were uncommon with no significant changes in hospitalization rates overall in the 2010–2015 and 2015–2018 periods. Additionally, the burden of hepatitis D was disproportionately greater in certain demographics and geographic regions. Hepatitis D hospitalizations did not result in increased frequencies of mortality compared to HBV only hospitalizations; however, complications such as liver failure were significantly more frequent in the hepatitis D cohort. Nevertheless, we found that within the hepatitis D cohort, older age and the presence of alcoholic cirrhosis were both major risk factors of mortality. And while pregnant persons and their foetuses/neonates did not seem to be at increased risk for morbidity or mortality if they were infected with hepatitis D compared to HBV only, further research is needed with larger cohorts.

Hepatitis D appeared to be largely underdiagnosed in the United States. There is a need for routine hepatitis D testing after a confirmed chronic hepatitis B diagnosis, especially considering the severity of the disease as well as the future availability of hepatitis D-specific therapy.

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Abbreviations
CI, confidence interval; HBV, hepatitis B virus; HCUP, Healthcare Cost and Utilization Project; HCV, hepatitis C virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; ICD-9, International Classification of Diseases, Ninth Revision; ICD-10, International Classification of Diseases, Tenth Revision; IQR, interquartile range; IRR, incidence rate ratio; OR, odds ratio.

Acknowledgements
We would like to thank Dr. Philip Spradling and Dr. Nelson Adekoya from the Centers for Disease Control and Prevention for reviewing and providing important feedback on this study. Open Access funding enabled and organized by Projekt DEAL.

Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Table 1. Demographic characteristics of nationwide hepatitis D hospitalizations and hepatitis B hospitalizations (without hepatitis D) as controls
Characteristics	Hepatitis D	Hepatitis B only	p-value
Number of hospitalizations, N	3035	413,355
Age, years, median (IQR)	53 (45–61)	53 (43–62)	.554
Sex			.012
Male, N (%)	2011 (66.3)	253,358 (61.3)
Female, N (%)	1024 (33.7)	159,997 (38.7)
Race/Ethnicity			<.001
Non-Hispanic White, N (%)	1308 (43.1)	171,956 (41.6)	.787
Non-Hispanic Black, N (%)	693 (22.8)	108,899 (26.3)	.021
Hispanic, N (%)	440 (14.5)	34,597 (8.4)	<.001
Asian or Pacific Islander, N (%)	315 (10.4)	55,997 (13.5)	.012
Native American, N (%)	29 (1.0)	2212 (0.5)	.169
Other/Unknown, N (%)	250 (8.2)	39,694 (9.6)	.358
Region of hospital			<.001
Northeast, N (%)	1256 (41.4)	102,797 (24.9)	<.001
Midwest, N (%)	360 (11.9)	65,336 (15.8)	.007
South, N (%)	802 (26.4)	156,097 (37.8)	<.001
West, N (%)	617 (20.3)	89,125 (21.6)	.459
Type of hospital			.094
Rural, N (%)	105 (3.5)	21,343 (5.2)	.058
Urban non-teaching, N (%)	703 (23.2)	101,047 (24.4)	.432
Urban Teaching, N (%)	2222 (73.2)	289,249 (70.0)	.096
Unknown, N (%)	5 (0.2)	1716 (0.4)	N/A

Note: National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), 2010–2015.
The time period did not include the full year of 2015 due to the transition from ICD-9 to ICD-10 codes on September 1st, 2015. This table included data from January 1st, 2010 to September 1st, 2015.
p-values for subcategories of Race/Ethnicity, Region of Hospital, and Type of Hospital were provided below the overall p-value for that category. Bold indicates statistically significant p-values p < .05.
Abbreviations: ICD-9, International Classification of Diseases, Ninth Revision; ICD-10, International Classification of Diseases, Tenth Revision; N/A, Not Available.

Table 2. Morbidity and mortality characteristics of hepatitis D hospitalizations and hepatitis B hospitalizations (without hepatitis D) as controls
Characteristics	Hepatitis D	Hepatitis B only	p-value
Number of hospitalizations, N	3035	413,355
Age, years, median (IQR)	53 (45–61)	53 (43–62)	.554
Length of hospital stay, days, median (IQR)	4 (2–7)	4 (2–7)	.585
Deaths, N (%)	112 (3.7)	15,161 (3.7)	.995
Hepatic complications
Liver failure, N (%)	198 (6.5)	18,779 (4.5)	.018
Hepatic neoplasm, N (%)	188 (6.2)	20,508 (5.0)	.161
Non-alcoholic cirrhosis, N (%)	622 (20.5)	62,643 (15.2)	<.001
Biliary cirrhosis, N (%)	0 (0.0)	310 (0.1)	.497
Portal hypertension, N (%)	393 (12.9)	28,303 (6.8)	<.001
Hepatic encephalopathy, N (%)	50 (1.6)	4154 (1.0)	.115
Ascites, N (%)	500 (16.5)	44,593 (10.8)	<.001
Jaundice, N (%)	60 (2.0)	8139 (2.0)	.985
Extra-hepatic complications
Acute kidney failure, N (%)	522 (17.2)	66,570 (16.1)	.461
Chronic kidney disease, N (%)	498 (16.4)	76,855 (18.6)	.163
Anorexia, N (%)	25 (0.8)	3518 (0.9)	.928
Haematemesis HBV, N (%)	30 (1.0)	3781 (0.9)	.879
Other organ failure, N (%)	623 (20.5)	88,800 (21.5)	.568
Haematological complications
Thrombocytopenia, N (%)	667 (22.0)	74,534 (18.0)	.012
Coagulopathy, N (%)	153 (5.0)	16,366 (4.0)	.171
Co-infections
HIV, N (%)	376 (12.4)	57,974 (14.0)	.250
HCV, N (%)	959 (31.6)	121,542 (29.4)	.235
Risk factors
H/O of injection drug use, N (%)	276 (9.1)	28,892 (7.0)	.044
Diabetes, N (%)	667 (22.0)	95,205 (23.0)	.535
Solid organ transplantation, N (%)	118 (3.9)	11,122 (2.7)	.068

Note: National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), (2010–2015).
p-values were calculated for significant differences using chi-squared test, Fisher's exact test and Mann–Whitney U test.
The time period did not include the full year of 2015 due to the transition from ICD-9 to ICD-10 codes on 1 September 2015. This table included data from 1 January 2010 to 1 September 2015. Bold indicates statistically significant p-values p < .05.
Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; H/O, history of; IQR, interquartile range.

Table 3. Risk factors for mortality in hepatitis D hospitalizations
Risk factors		Crude odds ratio (95% CI)	Crude p-value	Adjusted odds ratio (95% CI)	Adjusted p-value
Demographics
Age	≥65 (vs <65)	2.71 (1.11–6.58)	0.028	3.79 (1.24–11.60)	.020
Sex	Female (vs. Male)	0.87 (0.35–2.16)	0.772	1.07 (0.44–2.63)	.878
Race/Ethnicity	White (vs. Other)	1.75 (0.73–4.16)	0.209	1.39 (0.58–3.34)	.456
Co-infection
HIV	Yes/No	0.28 (0.04–2.11)	0.217	0.40 (0.05–3.08)	.379
HCV	Yes/No	1.39 (0.59–3.27)	0.456	1.96 (0.77–4.96)	.158
Co-morbidity
Alcoholic cirrhosis	Yes/No	2.81 (1.00–7.94)	0.051	3.37 (1.04–10.92)	.044
Diabetes	Yes/No	1.59 (0.47–3.15)	0.695	0.95 (0.33–2.77)	.924

Note: National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), (2010–2015). Bold indicates statistically significant p-values p < .05.
Abbreviations: CI, confidence interval; HCV, hepatitis C virus; HIV, human immunodeficiency virus.

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Hepatitis D-Associated Hospitalizations in the United States: 2010–2018

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