Parasites of the liver - epidemiology, diagnosis and clinical management in the European context.

Parasites in the liver cause significant global morbidity and mortality, as they can lead to recurrent cholangitis, cirrhosis, liver failure and cancer. Due to climate change and globalisation, their incidence is increasing, especially in Europe. The correct diagnosis of a hepatic parasite is often delayed because clinicians are unfamiliar with respective entities. Therefore, in this review, we aim to provide clinicians with a comprehensive clinical picture of hepatic parasites and to bring these neglected parasitic liver diseases to the wider attention of hepatology stakeholders in Europe and around the world.

Genetic algorithms identify individuals with high risk of severe liver disease caused by schistosomes.

Schistosomes induce severe hepatic disease, which is fatal in 2-10% of cases, mortality being higher in cases of co-infection with HBV or HCV. Hepatic disease occurs as a consequence of the chronic inflammation caused by schistosome eggs trapped in liver sinusoids. In certain individuals, the repair process leads to a massive accumulation of fibrosis in the periportal spaces. We and others have shown that genetic variants play a crucial role in disease progression from mild to severe fibrosis and explain why hepatic fibrosis progresses rapidly in certain subjects only. We will review here published findings concerning the strategies that have been used in the analysis of hepatic fibrosis in schistosome-infected individuals, the genetic variants that have associated with fibrosis, and variants in new pathways crucial for fibrosis progression. Together, these studies show that the development of fibrosis is under the tight genetic control of various common variants with moderate effects. This polygenic control has made it possible to develop models that identify schistosome-infected individual at risk of severe hepatic disease. We discuss the performances and limitations of these models.

First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.

Nonspecific CD8+ T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8+ T Cell-Mediated Clusters against Malaria Liver-Stage Infection.

CD8+ T cells are the major effector cells that protect against malaria liver-stage infection, forming clusters around Plasmodium-infected hepatocytes and eliminating parasites after a prolonged interaction with these hepatocytes. We aimed to investigate the roles of specific and nonspecific CD8+ T cells in cluster formation and protective immunity. To this end, we used Plasmodium berghei ANKA expressing ovalbumin as well as CD8+ T cells from transgenic mice expressing a T cell receptor specific for ovalbumin (OT-I) and CD8+ T cells specific for an unrelated antigen, respectively. While antigen-specific CD8+ T cells were essential for cluster formation, both antigen-specific and nonspecific CD8+ T cells joined the clusters. However, nonspecific CD8+ T cells did not significantly contribute to protective immunity. In the livers of infected mice, specific CD8+ T cells expressed high levels of CD25, compatible with a local, activated effector phenotype. In vivo imaging of the liver revealed that specific CD8+ T cells interact with CD11c+ cells around infected hepatocytes. The depletion of CD11c+ cells virtually eliminated the clusters in the liver, leading to a significant decrease in protection. These experiments reveal an essential role of hepatic CD11c+ dendritic cells and presumably macrophages in the formation of CD8+ T cell clusters around Plasmodium-infected hepatocytes. Once cluster formation is triggered by parasite-specific CD8+ T cells, specific and unrelated activated CD8+ T cells join the clusters in a chemokine- and dendritic cell-dependent manner. Nonspecific CD8+ T cells seem to play a limited role in protective immunity against Plasmodium parasites.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer.

BACKGROUND: Anisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review. CASE PRESENTATION: The case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin. CONCLUSION: The present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.

Hepatic paragonimiasis in a 15-month-old girl: a case report.

BACKGROUND: Paragonimiasis, particularly hepatic paragonimiasis (HP), is a type of zoonotic parasitic disease rarely encountered in infants. There have been only a few reports of HP, and no case of HP has been reported in an infant. CASE PRESENTATION: A 15-month-old girl presented with persistent mild fever with a duration of 1 month, hepatomegaly, and low-density lesions in the right hepatic lobe on abdominal ultrasound and computer tomography. Pathological examination and serum antibody detection were performed to verify HP. The diagnosis of HP was established based on findings of Charcot-Leyden crystals on liver lesion biopsy and antibodies against paragonimus westermani detected by enzyme-linked immunosorbent assay. After initiation of praziquantel (75 mg/kg/day for 3 days), all clinical findings promptly improved and the patient was discharged. CONCLUSION: It is very important to consider paragonimiasis in the clinical examination of infants from an area with paragonimiasis epidemic presenting with fever, hepatomegaly, low-density lesions in the liver.

Schistosomal portal hypertension: Randomized trial comparing endoscopic therapy alone or preceded by esophagogastric devascularization and splenectomy.

UNLABELLED:  Background. Upper gastrointestinal bleeding is a major cause of morbidity and mortality in patients with portal hypertension secondary to schistosomiasis mansoni. AIM: To evaluate the efficacy of combined surgery and sclerotherapy versus endoscopic treatment alone in the prophylaxis of esophageal variceal rebleeding due to portal hypertension in schistosomiasis. MATERIAL AND METHODS: During a two-years period consecutive patients with schistosomiasis and a recent bleeding history were evaluated for prospective randomization. Absolute exclusion criteria were alcoholism or other liver diseases, whereas platelet count < 50,000/mm3, INR > 1.5 or presence of gastric varices were relative exclusion criteria. By random allocation 25 (group A) have received endoscopic sclerotherapy for esophageal varices alone and 22 (group B) combined treatment: esophagogastric devascularization with splenectomy followed by sclerotherapy. Interim analysis at 24 months has shown significant statistical differences between the groups and the randomization was halted. RESULTS: Mean age was 38.9 ± 15.4 years and 58.46% were male. Mean follow-up was 38.6 ± 20.1 months. Endoscopic comparison of the size of esophageal varices before and after treatment did not show significant differences among the two groups. Treatment efficacy was assessed by the rate of recurrent esophageal variceal bleeding, that was more common in group A- 9/25 patients (36.0%) vs. 2/22 (9.0%) in group B (p = 0.029). Other complications were odynophagia, dysphagia and esophageal ulcer in group A and ascites and portal vein thrombosis in the surgical group. CONCLUSION: In portal hypertension due to schistosomiasis, combined surgical and endoscopic treatment was more effective for the prevention of recurrent esophageal variceal bleeding.

Molecular diagnosis of Eimeria stiedae in hepatic tissue of experimentally infected rabbits.

The early detection of Eimeria stiedae in the hepatic tissue of experimentally infected rabbits was investigated using molecular assay. Forty 6-week-old male New Zealand rabbits were divided into two groups. Group A (30 animals) was infected with 2.5 × 10(4) sporulated oocysts of E. stiedae per animal on Day 0 and Group B (10 animals) was used as the uninfected controls. Three animals from Group A and one from Group B were sacrificed at 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27 days post infection (PI). Gross and microscopic post-mortem findings were recorded. Polymerase chain reaction (PCR) of the E. stiedae internal transcribed spacer 1 genomic region was conducted on blood, liver tissue, and feces from the Group A experimentally infected animals. Macroscopically, the liver showed irregular yellowish white nodules pathognomonic to E. stiedae infection beginning on Day 15 PI. Hepatomegaly and ascites were obvious from Day 21-24 PI. The presence of different E. stiedae schizonts and gametocytes in the histopathological sections of the biliary epithelium were evident on Day 15 PI. The E. stiedae PCR was first positive in liver tissues on Day 12 and in fecal samples on Day 18 PI, but the blood samples were negative. In conclusion, the PCR can be used for early diagnosis and control of E. stiedae schizonts before shedding of the oocysts in feces.

Hepatobiliary and pancreatic ascariasis-sonographic pictorial essay on four pediatric cases with acute biliary colic.

Hepatobiliary and pancreatic ascariasis occur due to migration of the round worm ascaris lumbricoides through the bile duct orifice finally reaching the common bile duct, main pancreatic duct, intrahepatic ducts or gallbladder. These resulted in acute epigastric and right hypochondriac region colicky pain. Ultrasound is the investigation of choice in hepatobiliary ascariasis. We present here sonographic images on four pediatric patients with acute biliary colic.

Long-term outcome after liver transplantation for hepatic schistosomiasis: a single-center experience over 15 years.

Our objective was to study the long-term outcomes of patients who had undergone liver transplantation because of schistosomiasis at our institute over the last 15 years. Four hundred forty-one patients underwent liver transplantation at our institute, and 14 did so for schistosomiasis. The survival of patients who underwent transplantation for schistosomiasis was compared with that of patients who underwent transplantation for other liver diseases. Survival curves were drawn via the Kaplan-Meier method and were compared with the log-rank test. P < 0.05 was considered significant. All 14 patients were male, and the average age was 56.8 ± 8.4 years. The average Model for End-Stage Liver Disease score was 18.2 ± 5.6, and the average Child-Pugh score was 10.6 ± 1.2. All patients had splenomegaly; pretransplant variceal bleeding occurred in 7 patients (50%), and portal vein thrombosis was diagnosed in 5 patients (36%). Patient survival was 75% 1 year after transplantation and 75% at the end of follow-up because no patients were lost after the first year. Patients who underwent transplantation for other causes achieved survival rates of 86% and 76% 1 and 10 years after transplantation, respectively. There was no significant survival difference between the 2 groups (P = 0.66). All patients who survived the early posttransplant period had functioning liver grafts with no reported diagnoses of schistosomiasis in the new grafts. In conclusion, liver transplantation for patients with schistosomiasis has a favorable outcome with no risk of reactivation.

Schistosoma mansoni-Related Hepatosplenic Morbidity in Adult Population on Kome Island, Sengerema District, Tanzania.

Schistosomiasis is one of the important neglected tropical diseases (NTDs) in Tanzania, particularly in Lake Victoria zone. This baseline survey was a part of the main study of integrated control of schistosomiasis and soil-transmitted helminths (STHs) aimed at describing morbidity patterns due to intestinal schistosomiasis among adults living on Kome Island, Sengerema District, Tanzania. Total 388 adults from Kome Islands (about 50 people from each village) aged between 12 and 85 years, were examined by abdominal ultrasound according to the Niamey protocol. Liver image patterns (LIPs) A and B were considered normal, and C-F as distinct periportal fibrosis (PPF). The overall prevalence of PPF was 42.2%; much higher in males than in females (47.0% in male vs 34.4% in females, P=0.007). Abnormal increase of segmental branch wall thickness (SBWT) and dilated portal vein diameter (PVD) were also more common in males than in females. Hepatosplenomegaly was frequently encountered; 68.1% had left liver lobe hepatomegaly and 55.2% had splenomegaly. Schistosoma mansoni-related morbidity is quite high among adults in this community justifying the implementation of integrated control strategies through mass drug administration, improved water supply (pumped wells), and health education that had already started in the study area.

Hepatic cysticercosis: a rare entity.

Hepatic cysticercosis is a very rare entity; only four cases have been reported to date. High-resolution ultrasonography of the abdomen is the initial and most reliable modality for evaluation of hepatic cysticercosis. Medical therapy is the mainstay of treatment. We report a case of hepatic cysticercosis in a 28-year-old male who presented with right upper quadrant pain, fever, and jaundice. The article also describes the imaging patterns of hepatic cysticercosis based on different stages of evolution.

Parasites of the liver: A global problem?

Parasitic liver diseases can be caused by trematodes, cestodes, nematodes, and protozoa. This pathology is significant because millions of people in different parts of the world have liver parasites, which can manifest themselves in the development of inflammation, liver cysts, cholecystitis, cholelithiasis, pancreatitis and liver cirrhosis that are often threatening their lives. The International Agency for Research on Cancer considers three species of trematodes, Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis, to be carcinogens. Complex modern examination methods, in some cases including extensive screening of large populations, are required for diagnosing liver parasites. Treatment of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic measures. There is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.

Hepatobiliary Ascariasis in a Piglet.

PURPOSE: Ascariasis caused by the helminth Ascaris suum is the most common parasitosis of swine worldwide and it may involve all age categories of pigs. The present study reports an unusual localization of A. suum worms in the biliary system of a piglet slaughtered for human consumption. METHODS: The liver was subjected to ultrasound scan and pathological examination. The isolated worms were morphologically examined and the DNA was extracted for the molecular identification of the species involved. RESULTS: A total of 43 preadult nematodes were found within the gallbladder and the bile ducts. Parasites were morphologically identified as belonging to the genus Ascaris and molecularly as A. suum. At gross examination, the liver was moderately enlarged, with the bile ducts severely dilated. A chronic inflammatory infiltrate was noted, often centered around ectatic bile ducts (up to 5 mm in diameter), lined by hyperplastic epithelium and filled with sections of nematodes. The worm sections showed smooth cuticle, coelomyarian musculature, and an intestinal tract lined by columnar, uninucleated cells within a pseudocoelom. The ex vivo ultrasonographic examination of the liver allowed the visualization of several nematodes in the bile duct lumen and could be suggested for in vivo diagnosis. Unfortunately, the absence of the intestine did not allow to define the pathogenesis of the infection. CONCLUSION: Although, given the unusual nature of this finding, it is difficult to identify predisposing factors for this A. suum localization, it suggests that ascariasis should be considered in the differential diagnosis of pigs with hepatobiliary disease.

Comparison of covariate adjustment methods using space-time scan statistics for food animal syndromic surveillance.

BACKGROUND: Abattoir condemnation data show promise as a rich source of data for syndromic surveillance of both animal and zoonotic diseases. However, inherent characteristics of abattoir condemnation data can bias results from space-time cluster detection methods for disease surveillance, and may need to be accounted for using various adjustment methods. The objective of this study was to compare the space-time scan statistics with different abilities to control for covariates and to assess their suitability for food animal syndromic surveillance. Four space-time scan statistic models were used including: animal class adjusted Poisson, space-time permutation, multi-level model adjusted Poisson, and a weighted normal scan statistic using model residuals. The scan statistics were applied to monthly bovine pneumonic lung and "parasitic liver" condemnation data from Ontario provincial abattoirs from 2001-2007. RESULTS: The number and space-time characteristics of identified clusters often varied between space-time scan tests for both "parasitic liver" and pneumonic lung condemnation data. While there were some similarities between isolated clusters in space, time and/or space-time, overall the results from space-time scan statistics differed substantially depending on the covariate adjustment approach used. CONCLUSIONS: Variability in results among methods suggests that caution should be used in selecting space-time scan methods for abattoir surveillance. Furthermore, validation of different approaches with simulated or real outbreaks is required before conclusive decisions can be made concerning the best approach for conducting surveillance with these data.

Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

Previously, we demonstrated unique protein expression patterns in 20-week-Schistosoma mansoni-infected CBA/J mice with moderate splenomegaly syndrome (MSS) or hypersplemomegaly syndrome (HSS). To better understand the development of severe pathology, we compared the two-dimensional differential in-gel electrophoresis (2D-DIGE) proteomic signatures of livers from uninfected mice and mice infected for 6, 8, 12, or 20 weeks and found significant changes in collagen isoforms, interleukin-2 (IL-2), cytokeratin 18, hydroxyproline, S. mansoni phosphoenolpyruvate carboxykinase, major urinary protein isoforms, and peroxiredoxin 6. Cytokeratin 18, hydroxyproline, and connective tissue growth factor (CTGF) were chosen for analysis in mouse and human sera using targeted biochemical assays. Consistent with the liver analysis, cytokeratin 18, CTGF, and hydroxyproline were significantly elevated in sera from mice with HSS compared to those from uninfected mice or mice with MSS. Moreover, cytokeratin 18 and CTGF were found to be markers for subjects with hepatosplenic and intestinal schistosomiasis, respectively, while serum hydroxyproline was a strong indicator of fibrosis for severe HS. These findings indicate that schistosome-associated changes to the liver can be detected in the serum and reveal the potential for cytokeratin 18 to be used as a diagnostic marker for early detection of hepatosplenic schistosomiasis.

Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid.

Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 µg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

Ultrasound versus biological markers in the evaluation of periportal fibrosis in human Schistosoma mansoni.

In this paper, the authors review the literature and share their experience of the principal biological markers of fibrosis for the evaluation of periportal fibrosis (PPF) caused by mansoni schistosomiasis. These biological markers are compared to diagnostic ultrasound (US) scans as means of grading PPF. We also review procollagen type I and III, collagen type IV, laminin, hyaluronic acid (HA), immunoglobulin G, platelets, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase as markers of the disease. Although there are several good markers for evaluating PPF and portal hypertension, such as HA, platelets or APRI, none can yet replace US. These markers may, however, be used to identify patients at greater risk of developing advanced disease in endemic areas and determine who will need further care and US studies.

[Multiple liver lesions accompanied by eosinophilia - a case report of fascioliosis]. / Multiple Leberherde und Eosinophilie - ein Fallbericht einer Fasciola hepatica-Infektion.

Fascioliosis is a zoonotic disease caused by Fasciola hepatica (common liver fluke). Initial clinical symptoms are frequently non-specific. Even after the development of liver tumors, a range of different underlying disorders will have to be considered. The rare cause of a parasitosis is not always included in the differential diagnostic work up. We report on a 41-year-old truck driver from Middle East who was admitted at our hospital due to ongoing upper abdominal pain, fatigue, night sweat and nausea lasting for weeks. Diagnostic investigation showed leucocytosis, high erythrocyte sedimentation rate, elevated liver values and IgE as well as blood eosinophilia. Radiological findings of the computed tomography were bilateral pulmonary lesions 3 mm in size and multiple hepatic lesions up to 4.5 cm in diameter. Due to the suspicion of a malignant disease, a liver biopsy was planned but cancelled after parasitological serology (Western blot and ELISA) revealed IgG-antibodies against F. hepatica. Detailed history gave evidence of a recent parasitological infection during a stay in Turkey with consumption of vegetable which were grown and washed with water from the local river. Eggs of the parasite could neither be found in analysis of duodenal secretion nor in examination of fecal culture. However, confirmation for the infection with F. hepatica was proved with another positive serology. The treatment with Triclabendazole (Egaten(®)) for two days with a total dosage of 2000 mg was followed by a remarkable recovery of the patient's symptoms and decrease of eosinophilia in the blood count just one month after treatment and normalization after four months.