Parvovirus B19 Infection Mimicking Autoimmune Hepatitis: A Brief Report

Abstract

Background Parvovirus B19 can cause a variety of manifestations, mainly in children but occasionally in adults. Parvovirus hepatitis is an uncommon manifestation and is usually mild and self-limited. Parvovirus-related acute severe hepatitis and fulminant hepatitis, including acute liver failure, are rare presentations and can mimic other common causes of hepatitis. We hereby report a case of parvovirus-related severe hepatitis in adolescent girls.

Case Report A 17-year-old girl presented with fever and upper respiratory symptoms, followed by onset of jaundice. Her general and systemic physical examinations were unremarkable except for pallor and icterus. On evaluation, she had severe anemia and hepatocellular pattern of jaundice (the maximum value of total bilirubin was 53, and aspartate and alanine transaminase were 756 and 256, respectively). The etiological workup revealed negative markers for typical viral hepatitis. Still, the autoimmune profile revealed a positive antinuclear antibody, and her liver biopsy was also consistent with autoimmune hepatitis. Because of severe anemia and the absence of other hepatic decompensation, systemic viral illness with hepatic involvement was considered, and workup in the same line revealed parvovirus serology positivity. A final diagnosis of parvovirus-related acute severe hepatitis with aplastic crisis was considered, and she was managed with a short course of oral steroids. She responded well to treatment; clinical and biochemical parameters showed improvement on subsequent follow-up. Even after a prolonged follow-up of 1.5 years, she is in clinical and biochemical remission, further confirming the diagnosis of parvovirus-related acute hepatitis.

Conclusion Parvovirus can cause severe hepatitis and should be considered in the differential diagnosis of hepatitis of unknown etiology, especially if there is concomitant hematological involvement.

Keywords

acute severe hepatitis - parvovirus hepatitis - autoimmune hepatitis - case report

Introduction

Human parvovirus, a member of the Parvoviridae family, is a nonenveloped deoxyribonucleic acid virus. Infection of parvovirus B19 is globally prevalent, with infection being widespread among children and relatively uncommon in adults.[1] The virus spreads primarily through respiratory droplets; secondary infections occur through household contacts. Parvovirus-related diseases can be grouped into common and uncommon, with common ones being—fifth disease in children, arthropathy in adults, transient aplastic crisis in patients with increased erythroid proliferation (underlying hemolytic disease), persistent anemia in patients with immunocompromised or immunodeficiency status, and hydrops fetalis in fetus. Uncommon presentations can include hepatitis, myocarditis, meningoencephalitis, vasculitis, and Guillain–Barre syndrome. The manifestations could be due to viremia, virus-related cytotoxic effects, and immune-mediated injury.[1]

There is sufficient evidence to suggest that parvovirus B19 infection can cause a spectrum of liver diseases, from elevation of transaminases to acute hepatitis to fulminant hepatic failure and even chronic hepatitis. It can also cause fatal macrophage activating syndrome and fibrosing cholestatic hepatitis. Presentation as acute hepatitis or fulminant liver failure has been mainly reported in the pediatric age groups but has also been reported in adults, albeit infrequently. In adults, parvovirus B19 hepatitis course is less severe and shows complete and spontaneous remission. Fulminant hepatic failure induced as a result of acute B19 infection remains a rare clinical entity and may be underreported due to infrequent testing and lack of awareness. We report a similar case of parvovirus infection presenting as acute severe hepatitis and initially misdiagnosed as autoimmune hepatitis (AIH), but subsequently, a proper diagnosis could be made, and unnecessarily prolonged immunosuppression could be prevented.[2]

Case Summary

A 17-year-old girl with no comorbidities or addictions presented with low-grade fever associated with dry cough and myalgia for 4 days, followed by the onset of jaundice. There was no history of change in the sensorium, gastrointestinal (GI) bleeding, itching, or abdominal distension. There was no past or family history of jaundice. She denied a history of prescription as well as alternative medication intake. She was initially evaluated elsewhere and found to have hemoglobin of 5 g/dL with normal platelet and total leukocyte counts. She received two units of packed red blood cell transfusion and was referred to our center.

On general physical examination, she was found to have icterus, and per abdomen examination, it revealed hepatosplenomegaly. However, there were no stigmata of chronic liver disease. Ultrasound of the abdomen revealed a liver span of 16 cm with normal echotexture and mild splenomegaly. Liver biochemistry revealed total bilirubin of 40 mg/dL with raised transaminases suggestive of hepatocellular jaundice, and her coagulation parameters were preserved. Etiological workup for jaundice revealed negative serology for hepatotropic viruses (including surface antigen, anti-hepatitis C virus antibody, and immunoglobulin M [IgM] for hepatitis A and E virus). AIH profile revealed positive antinuclear antibody (ANA; titer 1:40) but negative for antismooth muscle antibody and liver-kidney microsomal antibody. Serum IgG was marginally above upper limit normal (1678 mg/dL; normal range 700–1600 mg/dL). Her serum ceruloplasmin was within the normal limit (27 mg/dL), and slit lamp examination was negative for the Kayser–Fleischer ring. Anemia workup revealed a normal iron profile and vitamin B12 levels, but indirect and direct Coombs tests were positive. Her other hemolytic workup, including serum lactate dehydrogenase and glucose-6 phosphate dehydrogenase, were within normal limits, and peripheral blood film did not show any evidence of hemolysis. Upper GI endoscopy showed no varices or portal hypertensive changes. Serial investigations revealed worsening of jaundice, as tabulated in [Table 1]. She underwent a liver biopsy because of high suspicion of AIH, which showed interface hepatitis and ductular proliferation suggestive of AIH ([Fig. 1]). Her simplified AIH score was 5, and she was started on steroids and ursodeoxycholic acid. She showed both clinical and biochemical responses to the initial treatment and was referred to the gastroenterology department for further management. Given her atypical initial presentation with severe anemia and respiratory symptoms to begin and preserved coagulation parameters and absence of any other decompensation despite very high bilirubin, a possibility of acute fulminant hepatitis secondary to atypical viral infection was kept, and samples were sent for atypical virus panel (Epstein–Barr virus [EBV], cytomegalovirus [CMV], varicella-zoster virus, herpes simplex virus, and parvovirus IgM). Her parvovirus serology was found to be positive, and a final diagnosis of parvovirus-related aplastic anemia with acute severe hepatitis was kept. The patient improved symptomatically with the normalization of liver enzymes and cytopenia on serial investigations, and steroids were gradually tapered over the next 6 weeks. Even after one and half years of follow-up, there was no relapse, further confirming the diagnosis of parvovirus-related acute hepatitis.

Table 1 Serial investigations of the patient showing improvement with the treatment

Investigations at various interval	Baseline investigations	Investigations after 2 weeks (prednisolone started)	Investigations after 3 weeks	Investigations at 6 weeks follow-up (prednisolone tapered and stopped)	Investigations at 6 months of follow-up	Investigations at 18 months of follow-up
Hemoglobin (g/dL)	8.7	8.7	8.8	10	11.2	10.9
TLC (per cumm)	3380	4000	5900	6000	7800	7300
Plt (in lacs)	2.1	2.2	2.9	3	3.3	2.9
Bilirubin (T/D)	40/21	53/24	13.8/9.2	2.3/1.4	0.9/0.2	0.8/0.2
AST/ALT/ALP	756/256/41	614/136/106	144/120/-	131/89/193	31/27/112	28/33/104
TP/ALB	8.0/3.2	7/3.52	6.9/3.8	6.1/3.6	7.1/4.4	7.2/4.3
INR	1.3	1.3	1.14	0.98	1.04	1.0

Abbreviations: ALB, albumin; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; Bilirubin (T/D), total and direct bilirubin; INR, international normalization ratio; Plt, platelet count; TLC, total leukocyte count; TP, total protein.

Fig. 1 Histopathological examination of the liver biopsy specimen showed an expanded portal tract with interface hepatitis with the presence of chronic inflammatory cells (lymphocytes - red arrow, plasma cells - black arrow) along with ductular proliferation (green arrow) (hematoxylin and eosin, 200 × ).

Discussion

Parvovirus B19 is an erythrovirus of the Parvoviridae family and can lead to various clinical presentations in pediatric and adult age groups. Its primary mode of transmission is through respiratory droplets, but it can also spread through blood transfusions and the placental routes. The principal member of the Parvoviridae family, parvovirus B19 is an erythrovirus, spreads predominantly in erythroid progenitor cells and a small number of other cells, such as fetal liver, stem cells and bone marrow cells, and megakaryocytic leukemia cell lines maintained with erythropoietin. B19 can also infect hepatocytes because of globosides and glycosphingolipids in their cell membrane, like erythroid precursors. Parvovirus B19 predominantly affects school-going children, and less frequent manifestations are seen in pregnant women, immunocompromised individuals of all ages, and people who suffer from different types of hematological disorders. Parvovirus B19 infection can present with a variety of clinical diseases and syndromes. The viral infection is suspected in cases of sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients. It is confirmed by either positive serology, polymerase chain reaction analysis, or in situ hybridization in a biopsy specimen.[3]

Liver involvement is uncommon in parvovirus infection, but it can range from mild elevation of transaminases to fulminant liver failure. According to a study by Mih ́aly et al, parvovirus B19-related hepatitis may occur in 4.1% of patients infected by this virus.[4] Around 50 cases of B19-related hepatitis have been reported in the literature, with the majority being acute hepatitis and being self-limiting with excellent prognosis. However, the prognosis becomes grave if it progresses to fulminant hepatitis and acute liver failure (ALF). Its mechanism of injury is via two mechanisms: (1) direct cytotoxicity—via NS1-cyclin-dependent kinase activation of caspase 3 and 9 and (2) immune-mediated interferon gamma, tumor necrosis factor-α, interleukin-2 receptors, and reduced interleukin-1. Limited data are available regarding hepatic involvement due to parvovirus and is mainly reported as case reports or small case series.[5] [6] [7] Hepatitis due to atypical viral infection is to be suspected when there is other system involvement like in CMV or EBV colitis, pneumonitis, and pharyngitis may be present, while in case of parvovirus, there is hematological system involvement like in the index case. Our case was initially misdiagnosed as AIH because of positive ANA, suspected autoimmune hemolytic anemia because Coombs test was positive, and liver biopsy was also suggestive. Liver biopsy in parvovirus hepatitis displays cellular and canalicular cholestasis, apoptosis, and variable amounts of necrosis depending upon the immune status of the host and the severity of liver involvement and can mimic AIH. However, the clinical presentation was atypical for AIH and Coombs test could be falsely positive due to a recent blood transfusion. Moreover, due to the absence of stigmata of chronic liver disease/portal hypertension (normal platelet count, no varices on endoscopy), a diagnosis of parvovirus hepatitis was considered, and steroids were tapered with advice to close follow-up. The patient is doing well, and there is no clinical or biochemical recurrence even after one and half years of follow-up, further confirming the diagnosis of parvovirus hepatitis.

There are no specific treatment guidelines for infection caused by the B19 virus, and most of the symptoms and elevation of liver enzymes presented during the infection stage resolve without any treatment. In case of acute and fulminant hepatitis, standard critical intensive care unit care is the same as for ALF management. Steroids are found to be beneficial in recovery in fulminant hepatitis cases. Combination therapy consisting of an intravenous infusion of immunoglobulin, dehydrohydrocortisone, and subcutaneous injections of granulocyte colony-stimulating factor for 3 months has been tried.[8] A case report published by Singh et al of a 16-year-old presenting with ALF was managed successfully by therapeutic plasma exchange.[9] This showed that this modality can be used as a bridge to liver transplant or recovery from this illness.

Conclusion

The case described here suggests that parvovirus B19 infection may be associated with the development of acute hepatitis. Infection with parvovirus B19 should be considered in the differential diagnosis of patients presenting with acute hepatitis of unknown etiology, especially in the presence of concomitant hematological involvement. Parvovirus hepatitis can mimic other common causes of hepatitis in the index case; it was confused by positive ANA titer and suggestive histopathology. Proper history and interpretation of investigations are essential as misdiagnosis as AIH could have resulted in antecedent risk of lifelong immunosuppression and stigma of chronic illness.

Conflict of Interest

None declared.

Acknowledgment

None.

Guarantor of Article

Dr. Chhagan Lal Birda.

Consent

An informed consent was obtained for the publication.

Permission to Reproduce Material from Other Sources

Not required.

Ethical Clearance and Informed Consent

Ethical approval was obtained from the institutional Ethics Boards. A written informed consent was obtained from the patient.

Authors' contributions

C.L.B., A.A., D.A., P.K., and J.G. contributed to the conception and design of the study. K.M., S.K.S., and C.L.B. were responsible for the generation, collection, assembly, analysis, and interpretation of data. The manuscript was drafted or revised by C.L.B., A.A., D.A., P.K., and J.G., while C.L.B. and A.A. conducted a critical revision for important intellectual content. All authors approved the final version of the manuscript.

• References

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Publikationsverlauf

Eingereicht: 17. Oktober 2024

Angenommen: 02. Februar 2025

Artikel online veröffentlicht:
24. März 2025