Table 1.
Demographic characteristics and patient outcomes among all US patients with hepatitis of unknown etiology from October 1, 2021 – September 30, 2022, stratified by underlying condition category (N=377).
| Stratified by whether the patient had underlying conditions that could contribute to their hepatitis*,† | ||||
|---|---|---|---|---|
| Overall | ||||
| Characteristic | No. (%) | No | Possibly | Likely |
| All patients | N=377 | N=259 | N=59 | N=22 |
| Age, years, median (IQR) | 2.8 (1.2–5.0) | 2.9 (1.5–5.1) | 3.1 (1.2–5) | 1.7 (0.5–3.0) |
| Sex | ||||
| Male | 192 (51%) | 134 (52%) | 28 (47%) | 11 (50%) |
| Female | 184 (49%) | 125 (48%) | 31 (53%) | 11 (50%) |
| Unknown | 1 (<1%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Race and ethnicity ‡ | ||||
| Hispanic or Latino | 153 (41%) | 110 (43%) | 24 (41%) | 9 (41%) |
| White, non-Hispanic | 130 (35%) | 90 (35%) | 20 (34%) | 7 (32%) |
| Black, non-Hispanic | 38 (10%) | 25 (10%) | 7 (12%) | 4 (18%) |
| Asian, non-Hispanic | 11 (3%) | 10 (4%) | 0 (0%) | 0 (0%) |
| Multiple, non-Hispanic | 10 (3%) | 5 (2%) | 4 (7%) | 0 (0%) |
| American Indian/Alaskan, non-Hispanic | 6 (2%) | 4 (2%) | 2 (3%) | 0 (0%) |
| Hawaiian/Other Pacific Islander, non-Hispanic | 4 (1%) | 3 (1 %) | 0 (0%) | 1 (5%) |
| Unknown/missing | 25 (7%) | 12 (5%) | 2 (3%) | 1 (5%) |
| Outcome | ||||
| Hospitalized | 347 (92%) | 244 (94%) | 50 (85%) | 21 (95%) |
| Length of stay (days) | 4 (2–9) | 4 (2–8.5) | 3.5 (2–9) | 3 (2–18) |
| Received liver transplant | 21 (6%) | 15 (6%) | 3 (5%) | 0 (0%) |
| Died | 9 (2%) | 5 (2%) | 2 (3%) | 2 (9%) |
| Measure of severity of acute hepatitis § | ||||
| Patients with completed chart abstraction§ | 332 (88%) | 250 (97%) | 57 (97%) | 21 (95%) |
| AST, median (IQR) | 1761 (717–3577) | 2076 (806–3763) | 1268 (645–2931) | 890 (552–2037) |
| ALT, median (IQR) | 1662 (667–2994) | 1846 (784–3279) | 1010 (565–2134) | 906 (626–1567) |
| INR, median (IQR) | 1.3 (1.1–1.9) | 1.3 (1.1–2.0) | 1.3 (1.0–1.6) | 1.2 (1.1–1.5) |
| Hepatomegaly | 113 (34%) | 89 (36%) | 17 (30%) | 7 (33%) |
| Splenomegaly | 36 (11%) | 28 (11%) | 4 (7%) | 4 (19%) |
| Ascites | 38 (11%) | 28 (11%) | 6 (11%) | 4 (19%) |
| Acute hepatitis with acute liver failure# | 84 (25%) | 68 (27%) | 14 (25%) | 2 (10%) |
| ALF based on coding** | 63 (19%) | 51 (20%) | 9 (16%) | 2 (10%) |
| Hepatic encephalopathy# | 39 (12%) | 30 (12%) | 9 (16%) | 0 (0%) |
| Hepatic lymphohistiocytosis# | 4 (1%) | 1 (<1%) | 2 (4%) | 1 (5%) |
| Signs and symptoms during illness or prior to hepatitis onset § | ||||
| Any respiratory | 165 (50%) | 127 (51%) | 28 (49%) | 8 (38%) |
| Cough/rhinorrhea | 137 (41%) | 104 (42%) | 24 (42%) | 7 (33%) |
| Congestion | 67 (20%) | 48 (19%) | 12 (21%) | 7 (33%) |
| Any gastrointestinal | 279 (84%) | 217 (87%) | 46 (81%) | 14 (67%) |
| Vomiting | 211 (64%) | 166 (66%) | 34 (60%) | 10 (48%) |
| Diarrhea | 160 (48%) | 130 (52%) | 21 (37%) | 9 (43%) |
| Abdominal pain | 143 (43%) | 114 (46%) | 23 (40%) | 6 (29%) |
| Any systemic | 296 (89%) | 227 (91%) | 51 (89%) | 15 (71%) |
| Fatigue | 205 (62%) | 163 (65%) | 32 (56%) | 10 (48%) |
| Decreased appetite | 204 (61%) | 162 (65%) | 33 (58%) | 8 (38%) |
| Fever | 165 (50%) | 121 (48%) | 30 (53%) | 12 (57%) |
| Hepatitis signs and symptoms | 215 (65%) | 180 (72%) | 28 (49%) | 7 (33%) |
| Jaundice | 190 (57%) | 161 (64%) | 24 (42%) | 5 (24%) |
| Dark-colored urine | 87 (26%) | 75 (30%) | 11 (19%) | 1 (5%) |
| Days from gastrointestinal, respiratory, or systemic sign/symptom onset to presentation for hepatitis illness | ||||
| Gastrointestinal to hepatitis presentation, days, median (IQR) | 3 (1–7) | 3 (1–7) | 3 (1–6) | 1 (1–4) |
| Respiratory to hepatitis presentation, days, median (IQR) | 4 (2–9) | 4 (2–10) | 3 (2–8) | 4 (2–14) |
| Systemic signs/symptoms to hepatitis presentation, days, median (IQR) | 3 (1–6) | 3 (1–6) | 2 (1–5) | 1 (0–2) |
| Gastrointestinal, respiratory, or systemic signs/symptoms to hepatitis presentation, days, median (IQR) | 4 (2–8) | 4 (2–8) | 4 (2–7) | 2 (0–10) |
Abbreviations: ALF = acute liver failure; ALT= alanine aminotransferase; AST= aspartate transaminase; IQR= interquartile range;
Underlying condition strata: “No”: Those with no underlying medical conditions or underlying medical conditions unlikely to contribute to hepatitis, “Possibly”: Those with some underlying medical conditions that in the right circumstances, possibly could contribute and/or result in worsening hepatitis, “Likely”: patients with significant or specific comorbid medical conditions that likely could directly cause and/or contribute to hepatitis.
Four patients with underlying conditions marked unknown and 33 without complete medical record abstraction could not be classified into one of the underlying condition strata.
Race and ethnicity data were obtained from parental report, if available, and if parental report was not available then race and ethnicity were obtained from the medical chart abstraction.
The denominators for all measures of severity of acute hepatitis and for signs and symptoms during illness or prior to hepatitis onset only included patients with completed chart abstractions.
Acute liver failure, hepatic encephalopathy, and hepatic lymphohistiocytosis were defined based on documentation written from the chart abstraction indicating these outcomes occurred.
Acute liver failure based on coding was defined as INR >1.5 AND hepatic encephalopathy or INR >2 (without hepatic encephalopathy)