Acute Fulminant Hepatic Failure Associated with Parvovirus B19 Infection in an Immunocompetent Adult
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- Huang, R.J., Varr, B.C. & Triadafilopoulos, G. Dig Dis Sci (2012) 57: 2811. doi:10.1007/s10620-012-2110-y
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Case Presentation and Evolution
A previously healthy 21-year-old female presented with epigastric pain, nausea, vomiting, arthralgias, and decreased appetite. Three weeks before presentation, she had developed cough, fevers, chills, and coryza immediately following a similar illness in her 4-year-old daughter. Although in the interval her respiratory symptoms had resolved, she continued to experience fevers, chills, and arthralgias. Three days before presentation she began to notice mid-epigastric pain, severe headache, profound nausea, and non-bilious, non-bloody vomiting. She denied other sick exposures, alcohol use, illicit drug use, or recent travel history.
At an outside hospital, an aspartate aminotransferase level (AST) of 954 U/L (normal value, 10–32 U/L), alanine aminotransferase level (ALT) of 1,300 U/L (0–30 U/L), total bilirubin level of 3.9 mg/dL (normal value, 0.2–1.2 mg/dL), and alkaline phosphatase level of 98 U/L (normal value, 30–120 U/L) were reported. She was discharged home with instructions to return if symptoms worsened.
One day later, she presented to Stanford University Medical Center with worsening symptoms. On physical examination she was visibly jaundiced, in significant distress, with right-upper to mid-epigastric tenderness to palpation, but without peritoneal signs. Repeat laboratories revealed AST of 9,348 U/L, ALT of 9,337 U/L, total bilirubin level of 2.4 mg/dL, alkaline phosphatase level of 109 U/L, and an international normalized ratio (INR) of 3.1 (normal value, 0.8–1.20), with anemia and thrombocytopenia (hemoglobin = 10.6 g/DL; platelet count = 140 × 103/μL; WBC = 8.2 × 103/μL). A right-upper quadrant ultrasound revealed marked concentric gallbladder wall thickening, a nonspecific finding but suggestive of underlying hepatitis. There were no gallstones, pericholecystic fluid, or evidence of intra- or extrahepatic biliary dilatation found, and portal flow was normal.
The patient was admitted with a diagnosis of acute hepatitis. Antibody and serum DNA polymerase chain reaction testing for HIV, hepatitis A, B, and C were negative. DNA polymerase chain reaction testing for adenovirus, cytomegalovirus, and Epstein-Barr virus were negative, as was urine nucleic acid testing for C. trachomatis and N. gonorrhoeae. Acetaminophen level was <2.0 μg/mL (normal value, <2.0 μg/mL). Urine toxicology screen was negative. The anti-nuclear antibody result and anti-smooth muscle antibody results were negative at the laboratory detection threshold. The serum IgG level was 1,270 mg/dL (normal range, 800–1,800 mg/dL) and ceruloplasmin level was 18 mg/dL (normal range 20–35 mg/dL). Ferritin was elevated at >10,000 ng/mL (upper limit of detection), indicating an acute inflammatory process. Serum iron was normal at 117 μg/dL (normal range 50–175 μg/dL), and TIBC slightly decreased at 194 μg/dL (normal range 250–410 μg/dL). HFE gene testing for C282Y, H63D, and S65C were ultimately negative.
Normal ranges and laboratory values from our patient over an 84-h time period from initial presentation at an outside hospital (0 h)
AST (10–32 U/L)
ALT (0–30 U/L)
Bilirubin (0.2–1.2 mg/dL)
Alk. Phos. (30–120 U/L)
Albumin (3.5–5.0 g/dL)
Human parvovirus B19 is a member of the Erythrovirus genus, the predominant parvovirus pathogen in humans. First linked to clinical disease in 1981, infection can produce a wide variety of manifestations including erythema infectiosum in children, aplastic crisis in patients with underlying hemolytic anemia, and chronic bone marrow failure in immunocompromised hosts . Parvovirus B19 has been established as an uncommon cause of acute hepatitis in children and infants [2–5]. Moreover, parvovirus B19 has been established as a co-infectant in chronic hepatitis B and C virus infections, often predicting worsened outcome [6–8]. However, the ability of parvovirus B19 to cause acute hepatitis in immunocompetent adults remains controversial, with a report questioning this association . To our knowledge there have been eight case reports in the literature implicating parvovirus B19 as a cause of acute hepatitis in immunocompetent adults [10–17].
In the majority of the reported cases, the elevation in liver enzymes has been mild. Among the eight previously reported cases, the highest recorded values for AST and ALT were both below 2,000 U/L, with the majority of recorded values below 500. In contrast, in our case the AST and ALT values both peaked at above 9,000 U/L, indicating a rapid and severe degree of hepatocyte necrosis not previously seen. Moreover, in the previously reported cases, the duration of hepatic dysfunction was generally prolonged. For instance, in the case reported by Pardi et al. the duration of abnormal liver enzymes extended up to 102 days, and in the case reported by Ho et al., the duration of illness extended up to 10 weeks. In contrast, our patient demonstrated a very rapid increase in liver enzyme values and concomitant clinical deterioration within the first 24 h of presentation. The degree of acuity in this case is also evidenced by the very high level of the acute phase reactant ferritin associated with severe coagulopathy and hypoalbuminemia, all suggestive of impending liver failure.
In other cases, a suppressed hematopoiesis was reported, with neutropenia, anemia, and thrombocytopenia present in various degrees [11, 13, 17]. In our case, much more mild degrees of anemia and thrombocytopenia were observed. Interestingly, Krygier et al.  also reported minimal hematologic abnormalities where, similar to this case, their patient experienced a very rapid decline ultimately requiring orthotopic transplantation. Whether the degree of hematologic abnormality can be correlated with acuity of hepatic dysfunction is an intriguing possibility.
The mechanism(s) through which parvovirus B19 elicits hepatocyte dysfunction and necrosis remains unknown. One hypothesis maintains that direct viral invasion of hepatocytes leads to subsequent caspase-mediated apoptosis . Parvovirus may be able to directly infect hepatocytes through interaction with P antigen, a cellular receptor present on both hepatocytes and erythrocytes .
In conclusion, there is increasing evidence that parvovirus B19 is causative in the development of acute viral hepatitis in immunocompetent adults, with and without concomitant hematologic abnormalities. Here we describe a case of acute fulminant hepatic failure secondary to parvovirus B19 infection, with the highest plasma aminotransferase concentrations reported to date. Given its rarity, parvovirus B19 is likely under-diagnosed as a cause of acute hepatic injury; as such, this report will encourage clinicians to consider this virus as a potential etiology for acute hepatitis in adult patients.
Parvovirus B19 may cause acute viral hepatitis in immunocompetent adults, with and without concomitant hematologic abnormalities.
In most cases, parvovirus B19 hepatitis is preceded by an upper respiratory viral syndrome, followed by mild liver function test abnormalities that may last for several weeks.