TTV infection and its relation to serum transaminases in apparently healthy blood donors and in patients with clotting disorders who have been investigated previously for hepatitis C virus and GBV-C/HGV infection in Belgium.

A novel DNA virus, TT virus (TTV), has been proposed as a possible etiologic agent for non A-E hepatitis. The aim of the present study was to determine the prevalence of TTV infection using PCR in healthy blood donors and in patients with clotting disorders who have been investigated previously for GBV-C/HGV and HCV infection in Belgium. In this study, PCR using primers proposed by Takahashi et al. [(1998) Hepatology Research 12:233-239] proved far more sensitive than those used by Okamoto et al. [(1998) Journal of Medical Virology 56:128-132]. The sequence of the PCR products showed 87% identity to the published sequence. TTV was present in 29.7% of healthy blood donors, a figure intermediate between the low rate of infection observed in Scotland and the high rates in the Far East. TTV was detected in 46.5% of 127 patients studied with clotting disorders as compared to 79.5% for HCV and 11.8% for GBV-C/HGV infection. However, there was no impact on the level of serum transaminases. Treatment with interferon for HCV infection co-infected with TTV suppressed temporarily serum TTV DNA. Therefore, it was concluded that TTV DNA is detected frequently in serum of healthy blood donors in Belgium and more often in patients with clotting disorders. TTV does not cause liver disease or contribute to the severity of liver disease.

An experimental evaluation of three preoperative radiation regimens for resectable rectal cancer.

BACKGROUND: We investigated the degree of tumor cell killing after radiotherapy regimens commonly used in clinical practice in comparison with an accelerated schedule. METHODS: Mtln3 mammary adenocarcinoma tumor cells were inoculated subcutaneously in the hind leg of syngeneic Fischer 344 rats. Tumors were irradiated with 5 x 5 Gy in 5 days, 10 x 3 Gy over 10 days, or 5 x (2 x 3) Gy in 5 days. After excision of the irradiated tumors, the dye exclusion, a tetrazolium-based colorimetric and the clonogenic assays were used to determine tumor cell viability and surviving fractions. RESULTS: Estimated potential doubling time values indicate a rapid proliferation capacity, comparable with potential doubling time values in human rectal cancer. The dye exclusion and clonogenic assays revealed a significantly higher degree of cell killing after the hypofractionated and the accelerated regimens of, respectively, 5 x 5 Gy and 5 x (2 x 3) Gy over 5 days compared with 10 x 3 Gy over 10 days. CONCLUSIONS: A shorter treatment time offered the best therapeutic efficacy. The schedule involving two daily fractions of 3 Gy over 5 days should be less toxic than 5 x 5 Gy and may therefore provide a therapeutic advantage.

Aplastic anemia after transplantation for non-A, non-B, non-C fulminant hepatic failure: case report and review of the literature.

Aplastic anemia is a rare complication of liver transplantation (<1%). However, an increasing number of cases of aplastic anemia have been recently reported when liver transplantation is performed for non-A, non-B, non-C fulminant hepatic failure. The aim of this study is to reevaluate the importance and the incidence of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure, and to propose preventive measures, diagnostic and management guidelines to try to reduce the incidence, morbidity and mortality associated with this complication. In this report a case of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure is described. In addition, the pertinent literature on aplastic anemia after liver transplantation, since the first description of that complication in 1987, is reviewed. A 20-year-old woman developed aplastic anemia 14 weeks after liver transplantation for fulminant non-A, non-B, non-C hepatitis. After failure of G-CSF treatment, she was treated with intensive immunosuppression (FK 506, ATG, high-dose steroids). She is well 1 year post-transplantation, with normal liver tests and with bone marrow recovery. Through a Medline literature search (1988-1999), we identified 30 additional cases of aplastic anemia following liver transplantation for non-A, non-B, non-C fulminant hepatic failure. Of all liver transplantations performed for that indication at five participating centers, the mean incidence of aplastic anemia was 23.2%. Mean age was 10 years (1.2-29) and the male/female ratio was 4.6. For treating aplastic anemia, different modalities were used: ATG ( n=12), ALG ( n=1), OKT 3 ( n=1), G-CSF ( n=6), a 6-HLA-compatible bone marrow transplantation ( n=3), and none ( n=12). The mortality rate remains high (39%), with infections and bleeding as the two most frequent causes of death. Based on this literature review, we conclude that aplastic anemia is a relatively common complication of liver transplantation for non-A, non-B, non-C fulminant hepatic failure in children and young adults. An unknown viral agent operating through immune-mediated mechanisms is probably responsible. The myelotoxic environment inherent to transplantation (e.g. azathioprine, trimethoprim) probably has a cumulative effect. Preventive measures (e.g. not using myelotoxic drugs) should be adopted in high-risk children and young adults transplanted for non-A, non-B, non-C fulminant hepatic failure. Early detection of bone marrow depression, a low threshold for performing a bone marrow biopsy, and prompt treatment are pivotal. Intensive standard supportive care with broad-spectrum antibiotics and anti-fungal agents is essential during phases of pancytopenia. Although spontaneous recovery has been described under maintenance immunosuppression, increased immunosuppression, in particular with ATG, may reverse the aplastic anemia and promote bone marrow recovery. In unresponsive patients, six-HLA-identical bone marrow transplantation has been successful.