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The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors.

Clostridium difficile infection (CDI) is an increasingly problem in everyday clinical practice. The most important risk factor of this infection is antibiotics use. The incidence of Clostridium difficile associated diarrhea (CDAD) in patients after renal transplantation is estimated to be about 6% in the early postoperative period. Due to the applied immunosuppression and frequent infections requiring intensive, broad spectral antibiotics, the later prevalence of CDAD may remain at a similar level. Massive diarrhea caused by Clostridium difficile may lead to fluctuations in immunosuppressive drugs concentration, in renal transplant patients. The authors present a case study of a 23-year old patient after kidney transplantation from deceased donor, with diagnosed polymorphic PTLD (Post-Transplant Lymphoproliferative Disorder). During biological treatment with rituximab in this patient 4 recurrences of CDI were observed. In this article the clinical manifestation of recurrent CDAD are presented. The authors discuss therapeutic procedure with fidaxomicin use, its results and influence on immunosuppressive drugs concentration.

Post transplant lymphoprolipherative disorder (PTLD) is a very severe, life threatening complication after organ transplantation. In adults after kidney transplantation the frequency of this complication is 0.3-3%; whereas in children 0.4-10%. Epstein-Barr virus infection discovered in 90% of patients, as a result of immunosuppression, plays an important role in the PTLD etiology. There is a coincidence between heavy immunosuppression, especially its cumulative doses, and the increased risk of lymphoprolipherative disorder. The clinical manifestation of PTLD may present as: mononucleosis like syndrome (fever, pharyngitis, tonsillar enlargement, lymphadenopathy), or as a rapid progressive course presenting with severe acidosis, lymphadenopathy, dysfunction of graft and other internal organs, where infiltration may mimic tumour like appearance. The present paper discusses methods and effectiveness of PTLD treatment, which aims to restore effectiveness of the immunological system, elimination of neoplastic cells and EBV.

Lymphoproliferative disorders (LPD) occur often in EBV-infected patients, especially in solid-organ and haematopoietic stem cell transplant recipients. The risk of developing LPD ranges from 1 to 25% and depends on the type of transplantation. We are presenting the case of a 9-year-old boy with acute myelogenous leukaemia in second remission, who developed LPD after matched unrelated donor bone marrow transplantation (MUD BMT) not identical in two loci. On day 50 after BMT the patient presented with fever and symptoms of paronychia. Two weeks later, bilateral cervical tenderness and adenopathy and hepatosplenomegaly developed. Bone marrow biopsy confirmed continuing remission. An extensive infection workup, including bacterial, mycotic and CMV infection yielded negative results. Basing on clinical picture and suspecting LPD, EBV-PCR was performed. The patient was found to have extremely high EBV DNA levels (4.905.152 genomes/mcg) in the peripheral blood. On days 64 and 73 after BMT, the patient received two doses of rituximab (MabThera) (375 mg/m(2)) After the first dose of rituximab EBV DNA copy numbers decreased to 707.723/mcg. However the patient's general condition was worsening; 71 days after BMT increasing aplasia and symptoms of venoocclusive disease (VOD) developed. The patient received two doses of defibrotide (Novarid). Despite of intensive therapy, progressive hepatic failure and increasing pulmonary oedema led to the patient's death, on day 96 after BMT.

Recipients of renal transplants have an increased risk of developing secondary malignancies. About 4% of patients who underwent kidney transplantation will develop cancer, and 1% of transplanted patients will develop lymphoproliferative disorders. According to clinical analyses and laboratory data, the main reason for increased risk of developing malignant disease in this group of patients, is their immunocompromised status due to immunosuppressive treatment. So called "strong" immunosuppressive drugs like antilymphocytic globulin (ALG), antithymocytic globulin (ATG), or monoclonal globulin OKT3 seem to favor the development of secondary malignancies much more than other drugs, like: corticosteroids, azathioprine (AZA), or cyclosporine (CsA). Secondary lymphoproliferative disorders are usually connected with reactivation of Ebstein-Barr virus infection. Patients with early onset (<1 year after the transplantation) have a favorable clinical course after withdrawal of immunosuppression. The subset of late-onset (>1 year) has usually much more aggressive clinical course and patients require intensive treatment. The general recommendation in these patients is to stop or to reduce the immunosuppressive treatment and to continue the chemotherapy in full dose. This treatment is often complicated by severe infections, but it offers a chance to achieve remission without worsening the function of transplanted organ. In this paper we are presenting five patients with secondary lympho- or myeloproliferative disorders after kidney transplantation and give an overview of the recent literature in this field.

Unlabelled: Epstein-Barr virus (EBV) infections in immunosuppressed patients cause the severe clinical problems. Posttransplant lymphoproliferative disease (PTLD) might occur as a result of the latent EBV activation., Objective: Occurrence of active EBV infection in heart and bone marrow transplant patients., Methods: 68 serum samples obtained from 13 allogenic bone marrow and 20 heart transplant patients were tested by IF and ELISA methods. Antibodies against VCA, EA and EBNA antigens were measured., Results: All patients showed the presence of anti-VCA IgG antibodies, thus all were seropositive. Three patients (9%) showed primary EBV infection while in 12 (36%) patients virus reactivation or reinfection was confirmed., Conclusions: 1. EBV infection in immunosuppressed patients is mainly caused by latent virus reactivation. 2. Type of EBV infection can be confirmed serologically only by the detection of specific anti-VCA, EA and EBNA antibodies. 3. The risk of PTLD in transplant patients creates the need for frequent monitoring.