Acute fulminant hepatitis with bone marrow failure in an adult due to parvovirus B19 infection
Authors: Li Sun, Jiu–Cong Zhang
Journal: Hepatology (2011)

Infection by parvovirus B19 is widespread and can be associated with a wide range of different pathologies and clinical manifestations.1 It mainly causes the childhood exanthema erythema infectiosum and an influenza-like condition with polyarthropathy.2 In rare cases, parvovirus B19 infection has been associated with hepatic dysfunction and hematologic disease in adult.3, 4 We describe here a case of acute fulminant hepatitis with bone marrow failure in a healthy adult following asymptomatic infection with B19 virus. A previously healthy 34-year-old woman without history of previous liver disease, exposure to toxic agents, or alcohol abuse reported to our practice after 20 days of fever; a week of yellowish staining of sclera, skin, and urine; and wrist and ankle joint pain on both sides (Table 1, day 1). She was hospitalized and given oral doses of prednisone and ibuprofen in addition to 5 days of intravenous infusion of penicillin and erythromycin. Her joint pain decreased, but the fever remained, the highest body temperature being 107.6°F. After maculopapules appeared on her back with significant pruritus (Figure 1) and her laboratory results worsened (Table 1, day 7), she was transferred to our facility. Physical examination revealed jaundice, fever, and hepatomegaly. Rheumatoid factor, alpha-1-antitrypsin level, antinuclear antibody, double-stranded DNA antibody, liver-kidney microsomal type 1 antibody, smooth muscle actin antibody, blood culture, and tuberculin tests were unrevealing. Abdominal ultrasound revealed only homogeneous enlargement of the liver and spleen, and chest radiographs and abdominal computed tomography scans were noncontributory. Serology was negative for hepatitis A, B, C, D, E, or G virus; cytomegalovirus; Epstein–Barr virus; rubella virus; herpes virus; chlamydia; syphilis; mycoplasma; brucella; toxoplasma; or human immunodeficiency virus. Liver protectants such as glycyrrhizin and reduced glutathione for injection were initiated for the diagnosis of acute fulminant hepatitis because hepatic damage became exacerbated (Table 1, day 17). Piperacillin and tazobactam were used for anti-infection; albumin prepared from human plasma was used for supporting therapy. The patient's liver chemistry values gradually improved, but a hemolytic anemia developed, and nadir blood counts included hemoglobin 87 g/L, platelet count 9 × 109/L, prothrombin activity 16.7%, and white blood cell count 0.25×109/L. Bone marrow aspiration revealed decreased cellularity, meeting the diagnostic criteria for bone marrow failure. Subsequently, the patient was treated with combination therapy consisting of an intravenous infusion of immunoglobulin, dehydrohydrocortisone, and subcutaneous injections of granulocyte colony-stimulating factor. By 3 months after the start of therapy, she had achieved a complete recovery from hematopoiesis as confirmed by way of bone marrow analysis. Maculopapule appeared on back of the patient with significant pruritus. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] To clarify the causative infectious agent associated with bone marrow failure, we performed serological analysis. Immunoglobulin M and G antibodies against parvovirus B19 measured by way of enzyme-linked immunosorbent assay (IBL, Hamburg, Germany) and B19-DNA measured by nested polymerase chain reaction were positive. Based on these findings, we attributed the fulminant hepatitis and bone marrow failure to asymptomatic B19 infection. This appears to be the first adult patient reported to have acute fulminant hepatitis and bone marrow failure caused by B19 virus infection. To date, the notion of B19 virus as a causative agent of hepatic dysfunction has not been fully accepted, and there is literature questioning this association.5 However, evidence in favor of this association continues to accumulate,2 and our recent practice also reveals the tropism of B19 virus in adult patients with liver disease.1 We believe the recognized clinical spectrum of B19 infection continues to expand, particularly in adult cases, and B19 infection should be considered part of the differential diagnosis in any patient presenting with liver dysfunction. Li Sun M.D., Ph.D.*, Jiu-Cong Zhang M.D.*, * Department of Infectious Diseases, PLA Centres for the Treatment of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.