1/864. hepatitis c virus in peripheral blood mononuclear cells from a chronically infected patient receiving liver graft from infected donor. BACKGROUND: In hepatitis c virus (HCV)-positive patients receiving HCV-positive liver allografts either the donor or recipient strain overtakes the other strain. Whether these changes are reflected in peripheral blood mononuclear cell (PBMC)-associated virus is unknown. methods: We analyzed by single-strand conformation polymorphism and sequencing HCV rna from serum and PBMCs from a liver transplant recipient whose indigenous strain was replaced by the donor strain. RESULTS: Only the recipient strain was detectable in serum and PBMCs 3 and 5 days after transplantation; at day 7 and 8, a mixture of both was present in the PBMCs, but only recipient strain was detectable in serum. This coincided with the peak presence of donor dna in recipient PBMCs. From day 14 on, HCV sequences in serum and PBMCs were indistinguishable. CONCLUSIONS: Overtake phenomenon in the setting of liver transplantation from infected donors to infected recipients is manifested in PBMCs. cells released from infected graft carry donor HCV strain. ( info) |
2/864. Wilson's disease coexisting with viral hepatitis type C: a case report with histological and ultrastructural studies of the liver. Histopathological and ultrastructural findings in the liver of a female patient who suffered from Wilson's disease (WD) and viral hepatitis type C (HCV) are reported. light and electron microscopy examinations demonstrated a variety of morphological alterations--many of them frequently seen in livers of patients with WD and others that can be found in cases presenting HCV infection. The influence of coexistence of these two diseases on morphological changes is discussed. ( info) |
3/864. Combining IgG and interferon alpha-2b in chronic hepatitis c virus infection. Treatment of chronic active hepatitis c virus (HCV) liver disease remains unsatisfactory. Interferon alpha 2b (IFN) has shown favorable though often unsustained effects. Besides its antiviral properties, IFN is a recognized immune modulator. We present data showing the favorable evolution of a case treated with IFN and IgG. Besides the antibody repertoire, the influence of IgG on the immune network is increasingly considered. The complex interactions resulting from combining drugs with immunomodulatory properties, such as IFN and different IgG preparations, may sound confusing. However, it might provide an insight into the outcome of chronic HCV infection, in which, evidently, immune components are heavily implicated. Prolonged treatment, with high-dose intravenous immunoglobulin (IVIG) seemed to be effective, either independently or by potentiating IFN. ( info) |
4/864. Development of myasthenia gravis after interferon alpha therapy. Interferon (IFN) alpha is now used in the treatment of some malignant diseases and chronic viral hepatitis. There have been several reports of development of autoantibodies and autoimmune diseases or the deterioration of preexisting disorders in patients under treatment. We enclose a case of myasthenia gravis (MG) which developed after six weeks of treatment as fluctuating bilateral ptosis, intermittent diplopia, and mild weakness of limb and neck muscles. A test dose of edrophonium chloride was administered, resulting in improved muscle strength. Elevated anti acetylcholine receptor (AChR) antibody titer was found. Single fiber electromyography showed an increased jitter from extensor digitorum communis, frequently accompanied by transmission blocking. Repetitive electric 3 Hz stimulation of the abductor pollicis brevis muscle, revealed an abnormal decrement of 28% in compound motor action potential. myasthenia gravis was diagnosed and the patient was given pyridostigmine, immunoglobulines and prednisone with benefit. Six months latter he developed an acute myasthenic crisis with severe respiratory failure and high anti AChR antibody titer. IFN-alpha can induce MG or simply manifests a preexisting subclinical disease, but otherwise its therapeutic efficacy in MG has been shown in experimental and clinical studies. Autoimmune mechanisms, as the release of different cytokines as IFN, by immunocompetent cells, may be involved in the pathogenesis of both MG and chronic active hepatitis. Autoantibody production against postsynaptic membrane structures by IFN-alpha could be the underlying pathophysiology. ( info) |
5/864. Ileal varices associated with recurrent bleeding in a patient with liver cirrhosis. We report a rare case of massive and recurrent bleeding from ileal varices in a patient with hepatitis c virus-positive liver cirrhosis. A 66-year old woman, who had undergone laparotomy and blood transfusion 36 years before (because of an extrauterine pregnancy) and endoscopic sclerotherapy for esophageal varices 1 year previously, was admitted to our hospital with loss of bright red blood per rectum. The bleeding was massive and recurrent, and frequent blood transfusions were required. Endoscopic studies failed to find the bleeding site. In the venous phase of selective superior mesenteric angiography, mesenteric varices in the lower part of the abdominal cavity were observed. laparotomy was performed to control the repeated bleeding which had lasted for more than 1 month. Varices communicating with the right ovarian vein were found on the ileal wall and segmental resection of the ileum was performed. Histological examination demonstrated a massive varicose vein and several dilated veins in the submucosa. The patient's postoperative course was favorable, with no hemorrhagic events during a follow-up of more than 6 months after surgery. Ileal varices should be considered in the diagnosis of a patient who presents with lower gastrointestinal bleeding and portal hypertension. ( info) |
6/864. Diffuse recidivant alveolar hemorrhage in a patient with hepatitis c virus-related mixed cryoglobulinemia. A case of diffuse and recidivant alveolar hemorrhage is presented in a patient with hepatitis c virus-related type II mixed cryoglobulinemia with membranoproliferative glomerulonephritis. The patient was a 48-year-old white woman who suffered several outbreaks of pulmonary hemorrhage refractory to treatment with steroids, cyclophosphamide, azathioprine, plasmapheresis and interferon-alpha. The patient also presented persistent increased titers of immune complexes and rheumatoid factor with no histological hepatic alterations. Some considerations about evolution and treatment are given according to the updated physiopathology of this disease. ( info) |
7/864. Highly active antiretroviral therapy leading to resolution of porphyria cutanea tarda in a patient with AIDS and hepatitis c. The association between hiv infection and porphyria cutanea tarda (PCT) is not well established. Since almost all hiv-infected patients with PCT previously described in the literature had additional risk factors for PCT, it is still unclear if hiv infection and not a cofactor such as hepatitis c virus is the trigger for PCT in this population. We describe a patient with AIDS and hepatitis c who developed bullous lesions due to PCT. The cutaneous lesions persisted for 18 months and resolved after he was placed on highly active antiretroviral therapy for hiv. No other therapeutic interventions were undertaken, while exposure to other known precipitants remained unchanged. During follow-up, skin lesions reappeared when the patient discontinued antiretroviral therapy, but PCT lesions again resolved after he restarted highly active antiretroviral therapy and hiv infection was controlled. This case supports the hypothesis that a direct causative relationship exists between hiv and the development of PCT. ( info) |
8/864. Long-term administration of cyclosporin A to HCV-antibody-positive patients with dermatologic diseases. BACKGROUND: cyclosporine A (CYA) is an immunosuppressive agent which is being used in the treatment of an increasingly wide range of dermatologic diseases, but its use has been avoided in carriers of hepatitis c virus (HCV). methods: We administered small doses of CYA (maximum, 3 mg/kg/day) for a long time to treat dermatologic diseases in one HCV-antibody-positive patient with no HCV-rna in the blood, one patient with a small amount of HCV-rna in the blood, and two patients with large amounts of HCV-rna in the blood. RESULTS: skin lesions improved in all patients, but recurred upon complete or partial withdrawal of CYA. In the absence of HCV-rna in the blood, or when only a small quantity of HCV-rna was present in the blood, HCV-rna load showed no apparent change. In one patient with a large blood HCV-rna load, CYA dosage reduction was followed by increases in alanine aminotransferase (ALT) levels and decreases in blood HCV-rna. Aggravation of hepatitis due to immunologic reactivation was suspected in this patient. CONCLUSIONS: The reduction of CYA dosage is a key element in the use of this agent for cutaneous diseases. ( info) |
9/864. interferon-alpha may exacerbate cryoblobulinemia-related ischemic manifestations: an adverse effect potentially related to its anti-angiogenic activity. The discovery of the strong association between hepatitis c virus (HCV) infection and the development of mixed cryoglobulinemia has motivated active testing of antiviral-directed alternative therapies. Several trials have demonstrated that classic cryoglobulinemia-associated manifestations improve with interferon-alpha (IFNalpha) treatment. Herein we report on 3 HCV-infected patients with severe cryoglobulinemia-related ischemic manifestations who were closely followed up during IFNalpha therapy. Clinical evaluations with special attention to ischemic lesions, liver function tests, and cryocrit determinations were serially performed. In addition to prednisone and immunosuppressive agents, the patients received IFNalpha at 3 x 10(6) units, 3 times per week for 2 months, 3 months, and 4 months, respectively. In all 3 patients, systemic features improved, liver function results returned to normal, and cryocrit values decreased. However, ischemic lesions became less vascularized and ischemia progressed, leading to transmetatarsal and subcondylar amputation, respectively, in 2 of the patients and fingertip necrosis and ulcer enlargement in the third. skin biopsies performed before IFNalpha therapy and after 2 months of IFNalpha therapy in the third patient showed a significant decrease in subepidermal microvessels. When IFNalpha was discontinued, the lesions finally healed. cryoglobulinemia-related ischemic lesions may worsen during IFNalpha treatment, presumably through a decrease in inflammation-induced angiogenesis. The anti-angiogenic activity of IFNalpha may delay the appropriate healing of ischemic lesions. ( info) |
| To elucidate the role of host immune status in the evolution and complexity of hepatitis c virus (HCV) quasispecies, three chronic HCV-infected patients who underwent bone marrow transplantation (BMT) were studied. The three transplanted patients' sera were sampled at pre-BMT, 3 months after BMT, and 12 months after BMT and the nucleotide diversity and substitution of the hypervariable region (HVR) of HCV quasispecies were analyzed. The nucleotide diversity was high at the pre-BMT period (28.2-43.4 x 10(-2) nucleotide difference/site). HVR of HCV quasispecies then became homogeneous in the first 3 months after BMT (0.11-6.40 x 10(-2) nucleotide difference/site). The nucleotide diversity of HVR at 12 months after BMT of all three patients was higher than that of 3 months after BMT but still lower than that of pre-BMT (2.09-6.40 x 10(-2) nucleotide difference/site). The analysis on nucleotide substitution rate showed a higher value between pre-BMT and 3 months after BMT (0.624-0.708 nucleotide difference/site per year) than that between 3 months and 12 months after BMT (0.072-0.127 nucleotide difference/site per year). HCV rna titer decreased when the host had a low white cell count and increased accordingly. It was concluded that the evolution of HVR of HCV quasispecies related to the immune status of the host during BMT: after immunosuppression, an initial increase of viral populations was followed by the emergence of a dominant strain while the quasispecies gradually recovered as the immunity of the host gained its competence. ( info) |