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

Disclosures

J Viral Hepat. 2022;29(3):218-226. 

In This Article

Results

Out of a total of 324,527,181 estimated hospitalizations in the United States between 2010 and 2018, we identified 3825 hospitalizations with a diagnosis of hepatitis D. In the same period, there were 413,355 hospitalizations with a diagnosis of hepatitis B without hepatitis D (HBV only). In the hepatitis D cohort, the median age was 53 years with an IQR of 45–61 years, and 2011 (66.3%) were male. The race/ethnic distribution was 1308 (43.1%) non-Hispanic White, 693 (22.8%) non-Hispanic Black, 440 (14.5%) Hispanic, 315 (10.4%) Asian or Pacific Islander, 29 (1.0%) Native American and 250 (8.2%) other/unknown. The majority of hepatitis D-associated hospitalizations occurred in the Northeast region (41.4%), and when examining the type of hospital, most (73.2%) occurred in urban teaching hospitals. The median age and distribution of hospital type were similar to the HBV only cohort (p = .554 and p = .094, respectively). However, compared to the HBV only cohort, the hepatitis D cohort had a greater proportion of males, 66.3% versus 61.3% (p = .012). Additionally, the hepatitis D cohort had a significantly different race/ethnicity distribution compared to the HBV only cohort (p < .001), with the greatest difference in the proportion of Hispanics, 14.5% versus 8.4% ; proportions of non-Hispanic Blacks and Asian or Pacific Islanders were significantly lower compared to the HBV only cohort. Furthermore, the regional distribution of hepatitis D-associated hospitalizations was significantly different from HBV only hospitalizations (p < .001), with a greater fraction of hepatitis D-associated hospitalizations in the Northeast region, 41.4% versus 24.9% (Figure S1). These results were summarized in Table 1.

The hospitalization rate of hepatitis D did not change significantly over time during the 2010–2015 period (IRR = 1.01; 95% CI = 0.96–1.06; p = .679) nor in the 2015–2018 period (IRR = 1.09; 95% CI = 0.92–1.29; p = .306). The hospitalization rate of hepatitis D ranged from 13.8 per 10,000,000 to 20.7 per 10,000,000 in the 2010–2015 period and from 6.9 per 10,000,000 to 8.4 per 10,000,000 in the 2015–2018 period (Figure 1). The hospitalization rate of HBV only did not change significantly during the 2010–2015 period (IRR = 1.00; 95% CI = 1.00–1.21; p = .195); however, during the 2015–2018 period, the hospitalization rate increased significantly over time (IRR = 1.04; 95% CI = 1.03–1.05; p < .001). The hospitalization rate of HBV only ranged from 2229.0 per 10,000,000 to 2447.7 per 10,000,000 in the 2010–2015 period and from 2275.5 per 10,000,000 to 2494.7 per 10,000,000 in the 2015–2018 period (Figure 2). Figure S2 displays the change over time in ICD-9 and ICD-10 diagnosis codes used for the diagnosis of hepatitis D. Rates of mortality over time were also examined between 2010 and 2018. Figure S3 illustrates the case-fatality rate of the hepatitis D cohort as compared to the HBV only cohort. Case-fatality rates of the hepatitis D cohort varied greatly year to year but were similar to that of the HBV only cohort overall.

Figure 1.

Hospitalization rates over time for hepatitis D. National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), 2010–2015 and 2015–2018. The vertical black line indicates the transition from the use of ICD-9 codes to ICD-10 codes on 1 September 2015. HBV, hepatitis B virus; HDV, hepatitis D virus; ICD-9, International Classification of Diseases, Ninth Revision; ICD-10, International Classification of Diseases, Tenth Revision

Figure 2.

Hospitalization rates over time for hepatitis B (without hepatitis D). National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), 2010–2015 and 2015–2018. The vertical black line indicates the transition from the use of ICD-9 codes to ICD-10 codes on 1 September 2015. ICD-9, International Classification of Diseases, Ninth Revision; ICD-10, International Classification of Diseases, Tenth Revision

Detailed analysis was conducted on a six-year period (2010–2015), examining the clinical characteristics of the hepatitis D-associated hospitalizations comparison with HBV only hospitalizations. Compared to the HBV only cohort, the hepatitis D cohort had significantly greater frequencies of liver failure (6.5% vs. 4.5%; p = .018), non-alcoholic cirrhosis (20.5% vs. 15.2%; p < .001), portal hypertension (12.9% vs. 6.8%; p < .001), ascites (16.5% vs. 10.8%; p < .001) and thrombocytopenia (22.0% vs. 18.0%; p = .012). Additionally, history of injection drug use was significantly more common in the hepatitis D cohort compared to the HBV only cohort, 9.1% versus 7.0%, respectively (p = .044). However, there were no significant differences between the two cohorts in the age of patients, length of hospital stay and deaths (Table 2).

Of the 3035 hepatitis D-associated hospitalizations in the 2010–2015 period, 59 (1.9%) involved pregnancy, and of those 59 pregnancies, 49 (83.1%) resulted in deliveries. The median age was 29 years (IQR: 27–31). The race/ethnic distribution was 15 (25.4%) non-Hispanic White, 20 (33.9%) non-Hispanic Black, 0 (0.0%) Hispanic, 20 (33.9%) Asian or Pacific Islander, 0 (0.0%) Native American and ≤10 other/unknown. The geographic distribution was 15 (25.4%) in the Northeast, ≤10 in the Midwest, 20 (33.9%) in the South and 15 (25.4%) in the West. Thirty-five (59.3%) were hospitalized at an urban teaching hospital, 20 (33.9%) at an urban non-teaching hospital and ≤10 at a rural hospital. Of the 59 pregnant persons, 25 (42.4%) had a history of caesarian delivery. There were no reported maternal deaths, but there were maternal morbidities including abnormal glucose tolerance and coagulation defects, as well as foetal/neonatal morbidities including abnormal heart rate/rhythm, preterm delivery and post-term delivery. The median length of hospital stay for these pregnant persons was 3 days (IQR: 2–3). However, the frequencies of these morbidities and the length of stay were not significantly greater than pregnancies in the HBV only cohort. Of note, the proportion of pregnancies in the hepatitis D cohort was found to be significantly smaller than in the HBV only cohort (p < .001) (Table S1). Upon close examination of each pregnancy hospitalization in the hepatitis D cohort, we found that each hospitalization had unique mothers; there were no cases of rehospitalizations in this subgroup.

During the 2010–2015 period, 112 (3.7%) of the 3,035 hepatitis D-associated hospitalizations resulted in death of the patient. Risk factors for mortality including demographics (age, sex and race/ethnicity), co-infections (HIV and HCV) and co-morbidities (alcoholic cirrhosis and diabetes) were examined. In the multivariate (adjusted) analysis, being over 65 years of age (OR = 3.79; 95% CI = 1.24–11.60; p = .020) and having a diagnosis of alcoholic cirrhosis (OR = 3.37; 95% CI = 1.04–10.92; p = .044) were both found to significantly increase the odds of mortality within the hepatitis D cohort. Other risk factors were not significantly associated with mortality (Table 3).

We conducted further analysis on liver transplantation within these cohorts during the 2010–2015 period. There were 73 (2.4%) liver transplantations in the hepatitis D cohort and 5365 (1.3%) liver transplantations in the HBV only cohort (p = .015). Of those with liver failure, 23 (11.6%) from the hepatitis D cohort and 3500 (18.6%) from the HBV only cohort had liver transplantation (p = .236). Of those with hepatic encephalopathy, 0 (0%) from the hepatitis D cohort and 79 (1.9%) from the HBV only cohort had liver transplantation (p = .657). Of those with jaundice, 0 (0%) from the hepatitis D cohort and 138 (1.7%) from the HBV only cohort had liver transplantation (p = .648). And of those with failure of other organs (non-liver and non-renal), ≤10 from the hepatitis D cohort and 1145 (1.3%) from the HBV only cohort had liver transplantation (p = .796).

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