Elsevier

Journal of Hepatology

Volume 45, Issue 3, September 2006, Pages 361-369
Journal of Hepatology

Co-infection of human parvovirus B19 in Vietnamese patients with hepatitis B virus infection

https://doi.org/10.1016/j.jhep.2006.03.013Get rights and content

Background/Aims

Human parvovirus B19 (B19) has been identified in the serum of hepatitis B virus (HBV) infected patients. However, the effect of B19-infection on the course of HBV-associated liver disease has not previously been investigated. We examined the prevalence of B19-DNA in HBV-infected Vietnamese patients and analysed the association between co-infection and the clinical outcome of HBV-infection.

Methods

Serum samples from 399 HBV-infected patients and 64 healthy individuals were analysed for the presence of B19-DNA by PCR and DNA-sequencing.

Results

B19-DNA was detected in 99/463 (21.4%) individuals. The proportion of HBV-infected patients who were also co-infected with B19 was higher than the healthy controls (P < 0.001). B19-DNA was detected more frequently in patients with HBV-associated hepatocellular carcinoma compared to patients with acute and chronic HBV, HBV-associated liver cirrhosis and healthy subjects (P < 0.006). A positive correlation was also found between B19-DNA loads and both serum HBV–DNA loads and alanine aminotransferase (ρ > 0.250 and P < 0.05).

Conclusions

Our findings demonstrate that B19-infection is frequent in HBV-infected Vietnamese patients. Also, a significant correlation exists between HBV/B19 co-infection and a greater likelihood of progression to more severe hepatitis B-associated liver disease. Further studies are required to determine the role of B19-infection on HBV-associated pathogenesis.

Introduction

Infection with B19 is found worldwide and the prevalence of specific immunoglobulin G (IgG) antibodies against B19 increases with advancing age. Approximately 15% of children, 60% of adults and up to 85% in individual older than 70 years have serological evidence of B19-infection [1]. B19 is a member of the Erythroviruses within the family of Parvoviridae [1]. Parvoviruses are non-enveloped and are amongst the smallest DNA-containing viruses that are capable of infecting mammalian cells [2]. The genome of B19 consists of a linear single stranded DNA molecule of 5600 nucleotides [3], [4] which contains three open reading frames (ORFs) encoding the non-structural protein NS1 (77 kDa), the two structural proteins VP1 (84 kDa) and VP2 (58 kDa) [5].

The postulated cellular receptor for B19-infection is the red blood cell P-antigen which is necessary for B19 binding to the cell surface [6], [7], [8]. Although target cells of B19 are mainly erythroid progenitor cells which express high levels of P-antigen, non-erythroid cell lines, including fetal myocytes, follicular dendritic cells, endothelial cells, and primary hepatocytes can be infected by B19 [6], [7], [8], [9], [10], [11], [12], the latter raising the possibility that B19 may be capable of causing hepatitis.

B19 has a diverse spectrum of clinical manifestations including erythema infectiosum, hydrops fetalis, aplastic anaemia [13], [14] arthritis [15], myocarditis [16], [17], [18], vasculitic syndromes [19], [20], and neurological disorders [21].

In addition to this diverse clinical spectrum of disease, the detection of B19-DNA in liver specimens of patients with hepatitis has also implicated B19 as an etiological agent for hepatic inflammation [11], [22], [23], [24], [25], [26], [27]. However, the role of B19 as a possible pathogen causing fulminant, acute or chronic hepatitis is controversial [11], [28], [29], [30], [31]. It has been suggested that B19 may play a role in accelerating the course of hepatitis B and C-associated liver diseases [27], [31], [32] and this may be especially important in Asia where hepatocellular carcinoma (HCC) is related to HBV-infection in up to 90% of the cases [33]. In countries like Vietnam where approximately 26% of the population is seropositive for hepatitis B surface antigen (HBsAg) and where infection with B19 is also common the impact of HBV/B19 co-infection on the course of HBV-associated liver disease may be an important clinical problem. Recently, Hsu and colleagues reported that B19-IgM and -IgG antibodies were detected in 35.2% and 85.2% of Taiwanese patients infected with HBV, respectively [32]. Despite the apparent frequent occurrence of co-infection the role of B19 on pathogenesis of HBV has not previously been investigated.

Although the prevalence of HBV-infection in Vietnam is known, the rate of B19-infection in this population is not described. In this study we have therefore investigated the prevalence of B19-infection in a cohort of HBV-infected and healthy individuals from Vietnam and sought to determine the relationship of HBV/B19 co-infection on the course of HBV-associated liver disease.

Section snippets

Study subjects

Four hundred sixty-three Vietnamese individuals were included in this study. Of these, 311 were symptomatic HBV-infected patients with well-characterized clinical profiles, 88 were asymptomatic (ASYM) chronic HBV carriers with no liver disease and 64 were healthy individuals who had no evidence of HBV-infection (HBsAg-negative). Patients were enrolled at Tran Hung Dao Hospital, Bach Mai Hospital and 103 Military Hospital, Hanoi, Vietnam during 2000–2002. Chronic hepatitis B infection was

Clinical symptoms and liver parameters of HBV-infected Vietnamese

The clinical profiles and the results of serum biochemical analyses of the different clinical groups of HBV-infected Vietnamese patients are shown in Table 1. Patients with acute HBV-infection were significantly younger than those in the other HBV clinical categories (P < 0.001) but not compared to healthy controls. As expected, the serum ALT, AST, total bilirubin, and direct bilirubin levels were significantly higher in patients with AHB compared to other groups (P < 0.001). The prothrombin time

Discussion

Infection with B19 is common and this is reflected by the high seroprevalence of specific IgG antibodies against B19 in young children (5–15%), adults (60%) and adults over the age of 70 years (85%) [1]. Although antibody is prevalent in the general population, viremia or presence of viral DNA is rare. The frequency of B19-DNA blood donors has been estimated at rates of 1:167 to 1:35,000 [1]. In contrast, one study discovered B19-DNA in bone marrow of 4/45(9%) healthy subjects [40]. We have

Acknowledgements

We are grateful to Dr. Don LV, Dr. Thang HH, Dr. Nhuong DX, Mrs. Binh DT, Mrs. Thoa LT, Mss. Lam HT, and Mrs. Dung DT for their help in collecting samples. We thank Illmann S. for her excellence assistance and Dr. Szalay G. for her help in ELISA-technique. This work was supported by the Deutsche Krebshilfe, Grant No. 10-2142-Bo1, the Deutsche Forschungsgemeinschaft SFB/Transregio-19, TP B5. Nguyen Linh Toan was supported by a scholarship from project 322 of Vietnam Ministry of Education and

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