Volume 12, Issue 6 , Pages e67-e70, November 2008
Liver schistosomiasis: an unexpected finding in hepatitis B virus-related chronic hepatitis
Article Outline
Summary
Case report
We report the unusual case of an African patient who underwent a liver biopsy for a chronic HBV-related hepatitis, whose histological sample also unexpectedly revealed elements diagnostic for schistosomiasis. The patient was only mildly symptomatic for the Schistosoma infestation; stool examination confirmed the presence of parasitic eggs. Hepatitis B virus (HBV)–schistosomiasis co-infection is particularly rare in Western countries. Only the identification of some pathological elements atypical for HBV infection by means of step sections in the liver biopsy sample allowed us to disclose the unsuspected diagnosis.
Conclusions
Since migratory flows have increased, the number of foreign people being referred to our hospitals has increased. Patients coming from areas endemic for infectious diseases that are absent in Western countries must be carefully evaluated, taking into account possible unexpected co-infections, including in the setting of pathological studies of liver biopsies.
Keywords: Hepatitis B virus infection, Schistosomiasis, Liver biopsy
Introduction
During the last decade, the phenomenon of immigration into Europe of large numbers of people from Africa and from the Middle and Far East has led Western physicians to face considerable diagnostic challenges with infective and parasitic diseases not endemic in our countries.
The wide use of liver biopsy in the diagnosis of chronic viral hepatitis has led both clinicians and pathologists to take into account a lot of diseases that were once thought to be unusual in the differential diagnosis.
We describe herein the case of an African patient who underwent a liver biopsy for a chronic hepatitis B virus (HBV)-related hepatitis, whose histological sample also unexpectedly revealed elements diagnostic for schistosomiasis.
Case report
A 40-year-old man originating from the Gambia and a resident in Italy for 5 years, was admitted to Belcolle Hospital for intermittent pain, in all abdominal quadrants, accompanied with alternating constipation and mild diarrhea. There was no past medical history of episode of fever consistent with malaria infestation. He presented in good general condition, with no significant abnormalities on abdominal examination. Routine blood and urine tests showed no significant abnormality, except for elevated AST (102
IU/l) and ALT (163IU/l) serum levels (normal values: up to 46 and 56IU/l, respectively). γ-Glutamyl transpeptidase and alkaline phosphatase serum levels were in the normal range. HBV markers were as follows: HBsAg positive, anti-HBs antibody negative, anti-HBc IgG positive, HBeAg negative, and anti-HBe antibody positive. Anti-hepatitis C virus (HCV) antibody was negative, as well as anti-HIV antibody. HBV-DNA determination: 37328IU. Results of stool culture were negative. A colonoscopy was performed: only a slight hyperemia of the rectal mucosa was found, with no specific findings on histological examination of the biopsies.
An ultrasound-guided biopsy (using a 18-G cutting needle) was performed on the right liver lobe to establish the stage of HBV-related liver disease. A liver sample of 4.5cm (fixed in 10% buffered formalin) was processed, and 5-μm step sections were stained with hematoxylin and eosin (H&E), Gomori, and with immunostain for HBsAg and HBcAg. On light microscopy, a mild to moderate lymphoplasmacytic infiltrate was detected in the portal tracts, with numerous eosinophils and macrophages forming epithelioid granulomas, sometimes with giant cells (Figure 1). Clumps of dark brown pigment were evident in the portal macrophages; this pigment was birefringent under polarized light in a red–yellow color, indistinguishable from malarial hemozoin pigment. No significant piecemeal necrosis or lobular activity was present (grade 2, according to Ishak et al.).1 The liver architecture was preserved; most of the portal tracts were enlarged, but no septae extended far into the lobule, nor were areas of bridging evident (stage 2, according to Ishak et al.).
Figure 1.
Schistosoma egg (arrow) surrounded by eosinophils, plasma cells, and macrophages.
Immunohistochemical staining showed the presence of HBsAg in the cytoplasm of 30% of the liver cells (Figure 2), while HBcAg was not detected. The presence of a large number of eosinophils in the portal tracts, epithelioid granulomas, and hemozoin pigment are not characteristic of HBV infection, but rather suggest a diagnosis of malaria or schistosomiasis. Step sections showed foreign material with the appearance of parasitic eggs within the granulomas (Figure 1, Figure 3), with brown shell and spine and a circular ring of nuclei, reminiscent of Schistosoma.
Figure 2.
Immunohistochemical intracytoplasmic staining for hepatitis B surface antigen.
Figure 3.
Parasitic egg (arrow) with brown shell and spine, partially altered due to overlapping of eosinophils and macrophages.
At this point, a parasitologic examination identified Schistosoma mansoni eggs in the stools. Treatment to eradicate the parasite was administered orally: praziquantel, 40mg/kg in two doses over a single day. Symptoms improved within a week. A repeat parasitologic stool examination, performed after one month, was negative for Schistosoma mansoni eggs.
Due to the elevated AST and ALT serum levels, the high titer of HBV-DNA, the HBV marker serology (anti-HBe positivity), and the mild necroinflammation activity, the patient was given oral anti-viral treatment with entecavir, 1mg daily. This dosage was chosen because of the presence of a high viral load. The patient was not pretreated with lamivudine. After a 5-month antiviral therapy, the viral load was negative. The patient is still taking entecavir.
Discussion
Liver biopsy is indicated in the diagnosis of a wide range of hepatic diseases, among which chronic viral hepatitis has an important place.2 When nothing more than abnormal liver biochemistry is present, a liver biopsy may reveal a wide range of hepatic diseases of assorted nature and extent.3
The possibility of a liver biopsy revealing an unsuspected secondary pathology or an alternative diagnosis is well known; this is reported to range from 2.4% to 3.7%.4, 5 More frequently, such unexpected findings consist of fatty liver disease, iron overload, and intra-hepatic cholestasis.4, 5 In our patient, the liver biopsy was only performed in order to grade and stage the HBV-related chronic liver disease suspected on the basis of serological findings. But the inflammatory infiltrate detected in the portal tracts was not characteristic of HBV-related chronic hepatitis, nor was the dark brown pigment present in macrophages and Kupffer cells, which suggested different diagnostic hypotheses such as malaria or schistosomiasis. The malaria hypothesis, even of the low-grade falciparum type, was excluded since the patient had lived permanently in Italy for many years, never traveling abroad. Accordingly, a thick and thin blood smear was not performed. It is known that when malaria parasitemia subsides, the hemozoin pigment shifts to the portal tract macrophages and is subsequently cleared after a variable time-period.6 The hypothesis of a malaria infestation occurring before the patient's immigration to Italy was also excluded, because of the absence of any significant fever episode in the anamnesis. The provenance of the patient from tropical Africa, a region endemic for various parasitic diseases, prompted pathologists to perform step sections on the liver biopsy sample to search for elements suggestive of other infestations. In this way, elements typical of a diagnosis of schistosomiasis were found, besides the findings of chronic HBV hepatitis. This co-infection is considered very unusual in our health units, since it is not mentioned in any of the recent surveys on this topic.3, 4, 5
Schistosomiasis is a parasitic infestation caused by flatworms localized mainly in the gut (Schistosoma mansoni, Schistosoma mekongi, Schistosoma japonicum) and in the genitourinary tract (Schistosoma haematobium). This disease is endemic in 74 African, South American, Caribbean, and Asian countries. According to the World Health Organization, approximately 200 million people are infested worldwide.7 Human infection is initiated when cercariae penetrate intact skin during immersion in fresh water where infected snails live. The organism begins its transformation, and migrates through the venous or lymphatic vessels to the lungs and to the intestine. Most of these infestations, if symptomatic, cause abdominal pain and diarrhea. In some Schistosoma cases with intestinal involvement (about 25–50%, particularly in hyperendemic areas), the eggs pass into the portal circulation. They are trapped in the portal tracts, causing a granulomatous inflammatory response inducing perisinusoidal inflammation and periportal fibrosis.
In endemic countries the Schistosoma–HBV co-infection is well known. In a population of HBsAg-positive blood donors in Brazil,8 35.5% of patients had schistosomiasis elements in their liver biopsy samples. An interaction between schistosomiasis and viral hepatitis B has often been suggested, but controversial data are present in the literature. The reciprocal influence of these two diseases has not yet been definitively established, even in experimental animal models,9 in which the two diseases seem to run parallel courses. Also, a lack of interaction with schistosomiasis has been found in patients with HCV-related hepatitis, whose histological scores do not differ according to the presence or the absence of schistosomal infection.10 Some studies conducted in the Far East in order to verify the hypothesis of a role of Schistosoma japonicum infestation in the development of hepatocellular carcinoma (HCC) in HBV patients, have tended to exclude this possibility.11, 12 Rather, it would be the complication with HBV infection (through chronic hepatitis and liver cirrhosis) that represents the major factor involved in the development of HCC in patients infested with Schistosoma japonica. On the other hand, there are several reports indicating that HBV or HCV and Schistosoma mansoni co-infections are associated with accelerated deterioration of hepatic function and a higher risk of HCC than that attributable to HBV alone.13, 14 An explanation for these discrepancies could be either in the different activities or in the various populations of the virus-related hepatitis, or the number or reinfestations due to Schistosoma. In our patient, for example, the damage likely due to HBV-related hepatitis was limited (grade 2, stage 2), and the inflammatory reaction to Schistosoma infestation was circumscribed around the eggs, probably due to the absence of reinfestations (since he had lived for a long time in Italy). No interference on safety and immunogenicity of a recombinant hepatitis B vaccine has been reported in Egypt in patients affected with Schistosoma mansoni.15
In Western countries, where snails representing the intermediate hosts of schistosomiasis do not live, no native case is possible, and such a disease is considered very uncommon. All detected cases are imported by tourists who have traveled in endemic areas or by people who have immigrated from such countries. Migratory flows have especially increased the number of foreign people being referred to our hospitals. Hence, patients coming from areas endemic for infectious diseases that are absent in Western countries must be carefully evaluated, taking into account possible unexpected co-infections, including in the setting of the interpretation of liver biopsies. Western pathologists may be not completely confident with the diagnosis of schistosomiasis because of its rarity. A thoughtful approach to liver biopsy interpretation when uncharacteristic elements are found may suggest different hypotheses, allowing the correct diagnosis to be established.
Ethical approval: The ethics committee of our institution approved this work.
Conflict of interest: No conflict of interest to declare.
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- . Hepatocellular carcinoma and schistosomiasis japonica. A clinicopathologic study of 59 autopsy cases of hepatocellular carcinoma associated with chronic schistosomiasis japonica. Acta Pathol Jpn. 1986;36:525–532
- Immunohistochemical detection of HBsAg and HBcAg in the liver of patients with schistosomiasis japonica complicated by hepatocellular carcinoma. J Tongji Med Univ. 1991;11:141–144
- . Risk factors for hepatocellular carcinoma in Egypt: the role of hepatitis-B viral infection and schistosomiasis. Anticancer Res. 1999;19:4565–4569
- Hepatitis B and C virus markers among patients with hepatosplenic mansonic schistosomiasis. Rev Inst Med Trop Sao Paulo. 2000;42:313–320
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PII: S1201-9712(08)01370-2
doi:10.1016/j.ijid.2008.04.013
© 2008 International Society for Infectious Diseases. Published by Elsevier Inc. All rights reserved.
Volume 12, Issue 6 , Pages e67-e70, November 2008
