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.

Prophylactic versus therapeutic role of the transplanted CD34+ Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.

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.

Diagnosis and clinical management of hepatosplenic schistosomiasis: A scoping review of the literature.

BACKGROUND: Hepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking. CONCLUSIONS: Most interventions have been developed on the basis of individual groups' experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.

Fungal and Parasitic Infections of the Liver.

Hepatosplenic candidiasis and other fungal infections of the liver are uncommon in healthy individuals; however, high index of suspicion is essential in immunocompromised patients with prolonged fever. Parasitic infections are protozoan or helminthic; their distribution and epidemiology are variable among different world regions. Clonorchiasis, opisthorchiasis, fascioliasis, and ascariasis are helminthic infections that commonly involve the biliary systems. Signs and symptoms of cholangitis require prompt management to relieve biliary obstruction; addition of antihelminthic agents is essential. Parasitic infections are mostly transmitted to humans by fecally contaminated food and water. Proper hand and food sanitation measures are essential in preventing disease transmission.

Capillaria hepatica infestation.

Capillaria hepatica is a very rare zoonotic infestation which primarily infests rodents and is rarely found in humans. The presenting features are fever of unknown origin, hepatomegaly and peripheral eosinophilia. Liver biopsy remains the cornerstone of diagnosis. Treatment of choice is Albendazole and outcome is generally good.

Disease and medicine in the armies of British India, 1750-1830: the treatment of fevers and the emergence of tropical therapeutics.

The East India Company's extensive medical establishment was noted for innovation and experimentation, it tested economical mass remedies. The service's control of its patients was significant, prefiguring the birth of the clinical anatomical medicine of Paris of the 1790s. The unique environment created a distinctive medical discipline: the medicine of warm climates. This chapter focuses on fever in particular; attention was focused on malfunction of the liver and the favoured treatment was purgation via mercury. The dominance of this method resulted partly from senior military officers imposing their views on the juniors.

Factors affecting illness in the developing world: chronic disease, mental health and traditional medicine cures.

This is a case report of a 24-year-old Ethiopian woman with a medical history of hepatosplenic schistosomiasis. She suffers from chronic liver failure and portal hypertension. She has been hospitalised for 'hysteria' in the past but did not receive follow-up, outpatient treatment or psychiatric evaluation. After discontinuing her medications and leaving her family to use holy water, a religious medicine used by many Ethiopians, she was found at a nearby monastery. She was non-communicative and difficult to arouse. The patient was rushed to nearby University of Gondar Hospital where she received treatment for hepatic encephalopathy and spontaneous bacterial peritonitis. Her illness is the result of neglected tropical disease, reliance on traditional medicine as opposed to biomedical services and the poor state of psychiatric care in the developing world.

[The worm in the liver]. / Der Wurm in der Leber.

Patients with parasitic involvement of the liver are a small group of patients in European countries. In the differential diagnosis of "hepatic mass" "pain in the right upper abdomen" "biliary obstruction" or "abnormal liver function tests" parasites are, if at all, considered last. In most health care centers diagnostic and management experience is limited with respect to these diseases. They should therefore been taken care of by specialized centers. In most countries these are centers for tropical diseases. Important components of the work up of patients with parasitic diseases are: risk assessment (place of origin, travel and exposure), geographic distribution of the parasites, incubation period, prepatent period, laboratory investigations (eosinophilia, IgE, direct parasitological diagnosis) and imaging studies. Important parasites with liver involvement will be presented: schistosomiasis, echinococcosis, fascioliasis, toxocariasis.

Angiostrongylus vasorum Causing Severe Granulomatous Hepatitis with Concurrent Multiple Acquired PSS.

A 14 mo old female Jack Russell terrier presented with a 12 hr history of vomiting and inappetence. She was subsequently diagnosed with multiple acquired portosystemic shunts during an exploratory celiotomy. Gross and histopathological hepatic abnormalities were consistent with chronic disease, including features suggestive of portal hypertension that was potentially caused by migrating and resident Angiostrongylus vasorum larvae. Fecal analysis and polymerase chain reaction of hepatic tissue confirmed the presence of Angiostrongylus vasorum . The dog recovered clinically following empirical treatment and supportive care. A lack of parasite burden was confirmed 9 wk postdiagnosis; however, serum biochemical analysis at that time was suggestive of ongoing hepatic dysfunction.

Hepatic schistosomiasis.

Schistosomiasis is a major, worldwide cause of morbidity and mortality. Disease from the organism Schistosoma mansoni results from egg deposition in the liver, intestines, and other organs and is associated with an intense, granulomatous response from the human host. Clinical manifestations range from mild to severe intestinal forms, and hepatosplenic schistosomiasis, which is associated with hepatic fibrosis, portal hypertension, esophageal varices, and splenomegaly. This article presents information about the epidemiology, immunopathogenesis and clinical aspects of the disease, the relationship between hepatic schistosomiasis and viral infections, diagnosis, therapy, and control strategies for schistosomiasis.

Serum and urinary ribonuclease in children with schistosomal hepatic fibrosis.

Serum and urinary RNase activity was determined in 15 normal children and in 52 children in various clinical stages of schistosomal hepatic fibrosis. The activity of serum RNase was compared with that of serum GOT, GPT and AP. The activity of serum and urinary RNase in the different schistosomal groups was significantly higher than in healthy children. The elevated levels of serum and urinary RNase activity were possibly due to malnutrition with tissue catabolism, zinc-deficiency and liver cell injury. Treatment with Astiban and protein-rich diet resulted in a significant decrease in serum and urinary RNase activity and an in significant drop in serum GOT, GPT and AP. Serum and urinary RNase appear to be more sensitive indices for evaluating the early metabolic disturbances in schistosomal patients than GOT, GPT or AP. Our findings also showed that the severity of cases could be graded according to the level of urinary RNase.

Schistosomiasis as an important determining factor for the response of Egyptian patients with chronic hepatitis C to therapy with recombinant human alpha-2 interferon.

The aim of the present study was to compare the response to recombinant human alpha-2 interferon therapy in 2 groups of Egyptian patients having chronic hepatitis C with or without associated schistosomiasis. Group 1 included 36 patients with associated intestinal schistosomiasis, and group 2 included 24 patients without schistosomiasis. All patients had abnormal serum aminotransferase levels and were negative for hepatitis B surface antigen and anti-hepatitis core antibody, but positive for hepatitis C virus antibody in serum. All patients received interferon at a dose of 3 million units subcutaneously 3 times a week for 6 months and were followed up clinically, biochemically and haematologically during this treatment period and for 6 months thereafter. A second liver biopsy was obtained from every patient after the completion of interferon therapy. Both the percentage of complete response with return to normal of alanine aminotransferase levels during therapy and the overall response rate at 6 months (when patients with a partial response were also included as responders) were significantly lower (P < 0.001) in group 1 (14% and 33% respectively) than in group 2 (63% and 71% respectively). The liver histology also improved significantly in group 2 (46%) compared with group 1 (14%) after completion of therapy (P < 0.05). On the other hand the overall relapse rate in responders, by 6 months after cessation of therapy, was significantly higher (P < 0.05) in group 1 (92%) than in group 2 (59%). These results show that the presence of associated schistosomiasis has to be considered as an important factor in determining the response of Egyptian patients with chronic hepatitis C to therapy with interferon.

Dynamic analysis of T-lymphocyte function in relation to hepatopathologic changes and effect of interleukin-12 treatment in mice infected with Schistosoma japonicum.

We analyzed the dynamics of splenic T-lymphocyte function in relation to hepatopathologic changes in C3H/Hc mice, experimentally infected with Schistosoma japonicum. Vigorous granuloma formation was observed at 7 wk postinfection. At 10 wk postinfection, granuloma formation entered into the down-modulation stage, as represented by the diminished granuloma size. The Th2 response was activated when eggs appeared in the liver, whereas Th1 responses were depressed and the proliferation of T lymphocytes was decreased. The level of IgG antibodies to the worm and egg antigens rose continually after infection. Interleukin-12 treatment of infected mice inhibited Th2 responses and T-cell proliferation, decreased granuloma formation and fibrosis, but had no effect on the fecundity of the worms. These data suggest that egg deposition is the major factor driving Th2 responses, depressing Th1 cytokine expression as well as T-cell proliferation in S. japonicum-infected mice.

Results of sclerotherapy for bleeding esophageal varices in patients with schistosomal liver disease. A retrospective study.

BACKGROUND/AIMS: The aims of the study were to evaluate results of injection sclerotherapy in patients with liver schistosomiasis inducing bleeding esophageal varices and to review ultrasonographic features of the liver disease as well as endoscopic characteristics of the esophageal disease in order to assess any interrelationship between them. METHODOLOGY: A total of 34 patients with active or recent history of hematemesis and Schistosoma mansoni infection had emergency or elective endoscopic sclerotherapy. Each underwent ultrasound examination to assess hepatosplenic involvement and staging, and were followed-up with upper digestive endoscopy every 4 months. RESULTS: Obliteration or reduction of the varices in small columns was achieved in 82.3% of cases. During the follow-up period (mean: 10.4 +/- 2.1 months; range: 4-16 months) rebleeding was noted in 2 patients and 2 patients died due to variceal hemorrhage. The relationship between the ultrasonographic periportal fibrosis grade and the endoscopic variceal grade or varices localization was very strong (P < 0.001). A significant difference between grade 1 vs. 3 and 1 vs. 2 of periportal fibrosis and the presence of red signs was also found (P < 0.008). CONCLUSIONS: In view of the results obtained in terms of success rate in obliterating varices, rebleeding and mortality rates, a longitudinal study could be justified to assess the usefulness of prophylactic sclerotherapy for the prevention of the first variceal hemorrhage and in the attempt to prolong survival in patients with Schistosoma-induced esophageal varices.

Specific treatment of hepatosplenic schistosomiasis can increase T-lymphocyte reactivity.

It has been recognized that Schistosoma mansoni infection causes depression of T-cell responsiveness. In this study we have evaluated whether immunodepression associated to schistosomiasis could be reverted by specific treatment. T-cell immune response was assessed by means of intradermal tests using recall antigens in a group of 22 patients with hepatosplenic schistosomiasis, one year after treatment with oxamniquine and compared with a group of untreated hepatosplenic patients. Only 27% of treated patients presented complete anergy to all tested antigens, in marked contrast to 80% unresponsiveness showed by hepatosplenic patients without treatment. Although most of the treated individuals showed some response to the tested antigens, in some individuals this unresponsiveness still persisted after treatment. Anergy was not found in any normal individual of the control group. It was concluded that Schistosoma mansoni infected patients may recover their normal immune responsiveness after the elimination of the worm by treatment.

Hepatosplenic schistosomiasis: a review.

BACKGROUND: Schistosomiasis is a granulomatous disease that is caused by infection with schistosomes. It is a major health threat in tropical and subtropical countries. Due to increased movement, all residents of the universe are at risk of contracting this infection. The infection goes through several stages, but the most life-threatening form and leading cause of mortality is hepatosplenic schistosomiasis (HSS). It is a chronic complication, which develops as a consequence of inflammatory response. This complication has not been adequately addressed or attended the and as a consequence most of patients presenting with this complication in our settings die. OBJECTIVES: To review literature on hepatosplenic schistosomiasis, to give the state-of-the-art management of HSS, to give our own experience on management of this complication and hence impart knowledge to medical personnel on HSS. DATA SOURCE: Literature is from Medline database and experience from gastroenterology clinics. Our own experience has been blended on top. STUDY SELECTION AND DATA EXTRACTION: We have selected material, which have been verified and can be applicable in resource poor-countries, where this problem is a major health threat. DATA SYNTHESIS: Based on published studies and meta-analyses and our own experience we have been able to draw conclusions on the current understanding of the subject. CONCLUSION: Hepatosplenic schistosomiasis is a deadly complication and occurs mainly in poor countries. Regular reviews and updates of our knowledge is important to enable stakeholders of health sector understand the problem and develop strategies on its management.

Biliary ascariasis with acute hemorrhagic pancreatitis: a case report.

A case of acute hemorrhagic pancreatitis associated with biliary ascariasis in a 35 year old man is reported. Clinical presentation and laboratory investigation along with management outcome are discussed.

[Sclerotherapy of single non-parasitic liver cyst]. / Leczenie obliteracyjne pojedynczych niepasozytniczych torbieli watroby.

Single, non-parasitic liver cysts, usually asymptomatic, accidental finding during ultrasound examination require treatment only if they attain larger diameter and upper right quadrant symptoms could not be explained by other pathology. Treatment options include surgical enucleation, open or laparoscopic unroofing or percutaneous emptying usually associated with injection of sclerotising agent. From May 1995 to June 1997 10 patients with single, symptomatic, non-parasitic cysts of the liver were treated at the 2nd Department of General Surgery, Collegium Medicum of Jagiellonian University. Ultrasound and gastroscopy excluded other pathology of upper GI tract that might be responsible for the symptoms. Under ultrasound guidance samples of cysts content were collected for cytology, bilirubin concentration and bacteriology. Injection of the contrast medium revealed no contact of the cyst's cavity with the biliary tree. 5 patients were excluded from the protocol due to leakage of contrast in to fee peritoneal cavity. Other 5 were submitted to sclerotherapy by injection of 95% ethanol after introduction of fine drain into the cyst's cavity under ultrasound guidance; in two patients procedure was performed once, in two twice and in one tree times. In 4 patients complete or nearly complete resolution of symptoms was achieved, in one with big cyst treatment failed. We observed no complication. Owing to satisfying results we may conclude that this minimally invasive method might be attempted before more aggressive treatment would be employed.