Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation

Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation.     

Secondary Symptomatic Parvovirus B19 Infection in a Healthy Adult

Parvovirus B19 is a common infection in adults and children. There are reports of secondary parvovirus infection in immunocompromised persons, but no reports of symptomatic secondary infection in healthy persons. We describe a healthy 39-year-old woman who presented with fever, rash, and arthralgia. Her symptoms were thought most compatible with parvovirus B19 infection, but she reported prior positive parvovirus antibody 2 years earlier during prenatal care. Tests were therefore also sent for HIV, streptococcal infection, hepatitis C, and Lyme disease. Testing revealed both elevated IgG and IgM antibodies for parvovirus B19; previously, the patient was positive only for IgG. On a subsequent visit she related that a community outbreak of parvovirus developed in her town and church group. We believe this case demonstrates that a symptomatic secondary infection with parvovirus can occur in healthy persons, and that prior positive antibody test does not preclude the development of acute infection.     

Rheumatoid purpura in adults and parvovirus B19 infection: fortuitous association or parvovirus B19-induced vasculitis?

INTRODUCTION: Henoch-Schoenlein purpura has been reported to be associated with parvovirus B19 infection, particularly in children and rarely in adults. We report the case of a 42-year-old patient presenting with this association. EXEGESIS: A 42-year-old patient was admitted to our medical center because of lower limb purpura. Henoch-Schoenlein purpura diagnosis was confirmed on histological findings (kidney biopsy) and concomitantly parvovirus B19 infection was proved by serological test (IgM+). Association of Henoch-Schoenlein purpura and parvovirus B19 infection has already been described. However, none of the reported studies demonstrated clearly the link between these two diseases. With regard to this observation, we wonder about the systematic use of the parvovirus B19 serological test in patients presenting first Henoch-Schoenlein purpura. Indeed, parvovirus B19-induced vasculitis is habitually controlled with intravenous immunoglobulins. CONCLUSION: A prospective study should explore the link between Henoch-Schoenlein purpura and primary parvovirus B19 infection. Moreover, we should evaluate intravenous immunoglobulins' efficacy in Henoch-Schoenlein purpura associated with active parvovirus B19 infection in order to improve the prognosis of this disease.     

人微小病毒B19感染所致肝损害19例临床分析

目的探讨B19病毒感染所致肝损害的临床表现、实验室检查特点及治疗与转归。方法对人微小病毒B19感染患者19例的临床资料进行回顾性分析。结果在人微小病毒B19感染的19例患者,主要症状有乏力(12例)、黄疸(10例)、脾肿大(10例),伴有发热(10例)、皮疹(6例)及肌肉关节疼痛(6例),有6例伴有如下疾病或并发症:如妊娠(1例)、急性肝功能衰竭(2例)、精神分裂症(1例)、急性骨髓停滞(1例)和肺炎(1例)。以血清天门冬氨酸氨基转移梅(AST)升高为主,黄疸大多数表现为轻到中度,容易出现凝血酶原活动度(PTA)下降,但胆碱脂酶(CHE)下降不明显。经积极对症支持治疗,肝功能等各项指标正常后治愈出院。人微小病毒B19可致肝功能受损,导致急性肝炎或急性重型肝炎。结论对临床上非甲～戊型肝炎病人,应注意检查血清抗B19病毒IgM。该病毒感染是一个急性或亚急性过程,呈良性经过,有自愈倾向。     

Parvovirus B19 in an immunocompetent adult patient with acute liver failure: an underdiagnosed cause of acute non-A-E viral hepatitis.

There are occasional pediatric reports of parvovirus B19-associated transient acute hepatitis and hepatic failure. A case of a 34-year-old immunocompetent woman who developed severe and prolonged but self-limited acute hepatitis and myelosuppression following acute parvovirus B19 infection is reported. Parvovirus B19 may be the causative agent in some adult cases of acute non-A-E viral hepatitis and acute liver failure.     

HEPATITIS-ASSOCIATED APLASTIC ANEMIA AND ACUTE PARVOVIRUS B19 INFECTION: A REPORT OF TWO CASES AND A REVIEW OF THE LITERATURE

Hepatitis-associated aplastic anemia is rare in general, but occurs in up to 28% of patients receiving liver transplantation for fulminant non-A, non-B hepatitis. Cases are commonly young men with mild hepatitis but severe aplastic anemia. Although cases have been reported in association with hepatitis A, B, and C, most appear to be due to a non-A-B-C virus. We report two cases of acute hepatitis subsequently complicated by marrow hypoplasia in patients with acute parvovirus B19 infection. Hepatic manifestations of parvovirus B19 infection range from liver chemistry abnormalities to fulminant hepatic failure and aplastic anemia. Our cases demonstrate a less severe form of hepatitis-associated aplastic anemia, and together with other data, suggest that parvovirus B19 is at least one cause of hepatitis-associated aplastic anemia, and may be a heretofore underrecognized hepatotrophic virus.     

Infection with parvovirus B19

Human parvovirus B19 is common and widespread. Major manifestations of B19 infection are transient aplastic crisis, erythema infectiosum, hydrops fetalis, acute and chronic rheumatoid-like arthropathy and, in the immunocompromised host, chronic or recurrent bone marrow infection. Less common presentations include skin eruptions, isolated cytopenias, vasculitis, hepatitis, and neuropathies. Increasing awareness of the clinical manifestations of B19 infection makes parvovirus B19 an emerging virus. B19 may persist in healthy or immunocompromised individuals. B19 has been suggested as a candidate agent in rheumatic diseases.     

Parvovirus B19 infection after renal transplantation

Despite improvements in the management of transplanted patients, viral infections following transplantation remain significant causes of morbidity and mortality. New laboratory techniques have improved the diagnosis of pathogenic viral infections following transplantation such as parvovirus B19 infections. Anemia is the principal abnormality associated with parvovirus B19 infection but other complications have been reported such as hepatitis, glomerulonephritis, myocarditis or arthritis. In immunocompromised patients, infection, which may remain undiagnosed by serological tests is usually assessed by PCR. Patients may spontaneously recover. However, in the absence of specific antiviral therapy, intravenous immunoglobulin appears to be the more efficacious treatment.     

Infection and musculoskeletal conditions: Viral causes of arthritis

Several viruses cause postinfectious arthritis. The disease is a typical manifestation of arthritogenic alphaviruses, rubella virus and human parvovirus B19. In addition, arthritis is not uncommon after infection by HIV, cytomegalovirus, hepatitis B virus, hepatitis C virus, or Epstein-Barr virus (EBV). Also prolonged arthritis may result from viral infections, particularly with alphaviruses and human parvovirus B19. Viruses such as EBV and B19 may have significant roles in initiating chronic arthropathies, which in some cases may be indistinguishable from rheumatoid arthritis.     

Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients

In the course of 6 years, 23 otherwise healthy patients with acute febrile illness and leukopenia were diagnosed as having acute parvovirus B19 infection. Five of these patients had agranulocytosis associated with acute parvovirus B19 infection and one had chronic agranulocytosis due to persistent parvovirus B19 infection. The diagnosis was made after positive anti-parvovirus B19 IgM antibodies were found in all of the patients and viral DNA was detected by PCR in four patients. Neutropenia and agranulocytosis appear to be much more frequently associated with parvovirus B19 infection than previously reported.     

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.     

Human parvovirus B19: historical and clinical review

Human parvovirus B19 has been associated with disease only for the past few years. First isolated from sera obtained for studies on hepatitis B in 1975, it was not until 1981 that infection with this small, single-stranded DNA virus was related to aplastic crisis associated with hemolytic anemia. A nonspecific viral prodrome, the occurrence in family members, and epidemics of aplastic crisis suggested the infectious etiology. Human parvovirus infection has since been associated with arthritis, erythema infectiosum (fifth disease), fetal death, and hydrops fetalis. Through the use of recently developed serologic tests, epidemics of erythema infectiosum and parvoviral infection have been related not only to aplastic crisis but also to intrauterine infection and hydrops; DNA hybridization studies have allowed the detection of viral DNA in serum and tissue extracts. Studies have been hampered by the lack of an ability to culture the virus, but this is now possible utilizing bone marrow culture and erythropoietin. This article is a historical and clinical review of human parvovirus infection and disease and considers potential questions regarding their consequences.     

Persistent parvovirus B19 infection detected by specific CD4+ T‐cell responses in a patient with hepatitis and polyarthritis

We, here, report the case of a parvovirus B19 infection in an immunocompetent male patient presenting with acute hepatitis and polyarthritis. To follow the course of infection, we used a previously established enzyme‐linked immunosorbent spot assay (ELISPOT) technique to detect CD4+ T cells specific for viral proteins. Even though symptoms of arthritis and hepatitis resolved in the immunocompetent individual within a few weeks, viral DNA in serum and CD4+ T cells specific for the viral protein VP1 unique region were still detectable more than 6 month after the onset of symptoms, thus pointing to a persistent state of infection. On the basis of this observation, we hypothesize that the intensity of liver involvement correlates with the likelihood of developing persistent parvovirus B19 infection. The described ELISPOT technique to detect virus‐specific CD4+ T cells provides an excellent tool to analyse the state of parvovirus B19 infection for future studies to test this hypothesis.     

Transmission of symptomatic parvovirus B19 infection by clotting factor concentrate

The risk of acquiring diseases from transfusion of blood and blood products is well recognized and the issue of parvovirus in haemophiliacs is not a new one. We report two patients with haemophilia acquiring iatrogenic parvovirus B19 infection, resulting in life-threatening sepsis in one, an immunocompetent adult. Over the last 10 years there has been great progress in manufacturing safer products with regard to enveloped viruses such as HIV, hepatitis B and C. A recent outbreak across Europe of hepatitis A in haemophiliacs treated with plasma-derived factor VIII concentrates has made haemophilic treaters concerned about the known (parvovirus B19 and hepatitis A) and the unknown non-lipid enveloped viruses that may be contained in the clotting factor concentrates, because these are resistant to the existing viral inactivating techniques. The possibility of HIV itself mutating into a non-lipid enveloped virus emphasizes the need to seek and use safer products.     

Fifth (human parvovirus) and sixth (herpesvirus 6) diseases

Fifth (erythema infectiosum) and sixth (roseola infantum) diseases are common rash illnesses of childhood that have long been recognized in clinical medicine. The discovery of the viruses that cause these illnesses has revealed relationships with other syndromes. Primary infection with the agent of erythema infectiosum, human parvovirus B19, is associated with transient aplastic crisis in hemolytic anemia, arthropathy in adults, chronic anemia in immunocompromised patients, and nonimmune fetal hydrops in pregnant women. The only documented illness associated with primary infection with human herpesvirus 6 is roseola or exanthema subitum in young children. However, reactivated infections in adults and immunocompromised patients may be associated with serious illness such as encephalitis/encephalopathy, and bone marrow suppression leading to transplant failure or graft-versus-host disease. Diagnostic studies for both viruses have been limited, although reliable serologic tests for human parvovirus B19 have recently become available. Diagnosis of human herpesvirus 6 remains problematic, because current tests cannot differentiate primary from reactivated disease. This is more of an issue for the putative relationship of these viruses to more chronic conditions, such as rheumatologic disease for human parvovirus B19 and multiple sclerosis for human herpesvirus 6. The relationship between the viruses and these conditions remains controversial, and better diagnostic tests and further information on viral pathogenesis for both viruses are required in order to make a reliable judgment in this regard.     

Human parvovirus B19 in patients with aplastic anemia

Aplastic anemia is characterized by pancytopenia with hypoplastic bone marrow. Various factors including viral infections have been implicated as the precipitating factors. Human parvovirus B19 has been associated with red-cell aplasia, leukopenia, and thrombocytopenia. The present study was carried out to determine the role of parvovirus B19 in aplastic anemia patients. Twenty-seven aplastic anemia patients and 20 healthy controls were tested for the presence of parvovirus B19 infection by detecting parvovirus B19-specific IgM by ELISA and viral DNA by PCR. Parvovirus B19 IgM and viral DNA were detected in significantly higher numbers of patients in comparison to the controls (40.7% vs. 5%, P < 0.01; 37% vs. 0%, P < 0.001, respectively). The presence of parvovirus DNA in aplastic anemia patients indicates active or recent infection. However, more studies are needed to explore the mechanism of bone-marrow aplasia due to human parvovirus B19 infection.     

Renal involvement of human parvovirus B19 in an immunocompetent host.

Human parvovirus B19, which is most commonly known to cause erythema infectiosum in children, is also known to cause infection in adults, with complications ranging from a self-limited polyarthropathy in immunocompetent patients to hydrops fetalis in pregnant women, transient aplastic crises in patients with chronic hemolytic anemias, and chronic aplastic anemia in immunocompromised hosts. We describe a previously healthy immunocompetent woman who presented with manifestations of acute parvovirus B19 infection.     

Life-threatening human parvovirus B19 infection transmitted by intravenous immune globulin

Infection of human parvovirus B19 (B19) is usually a self-limiting febrile illness, but can sometimes be life-threatening under certain circumstances, such as aplastic crisis in patients with haemolytic anaemia, hydrops fetalis in pregnant women and fulminant hepatitis. B19 can be transmitted through respiratory secretions, transplacentally and by transfusion of blood or blood products. In the present case, administration of intravenous immune globulin (i.v.Ig) transmitted B19 infection and consequently caused pure red cell aplasia and aggravation of hepatitis to fulminant hepatitis. Our case may raise important questions as to the safety of i.v.Ig and possible contamination by B19.