AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine ...AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.展开更多
The anemia of chronic kidney disease and hemodialysisis characterized by chronic inflammation and releaseof cytokines, resulting in the upregulation of the ironhormone hepcidin, also increased by iron therapy andreduc...The anemia of chronic kidney disease and hemodialysisis characterized by chronic inflammation and releaseof cytokines, resulting in the upregulation of the ironhormone hepcidin, also increased by iron therapy andreduced glomerular filtration, with consequent reduc-tion in iron absorption, recycling, and availability to theerythron. This response proves advantageous in theshort-term to restrain iron availability to pathogens, buultimately leads to severe anemia, and impairs the re-sponse to erythropoietin （Epo） and iron. Homozygosityfor the common C282Y and H63D HFE polymorphismsinfluence iron metabolism by hampering hepcidin re-lease by hepatocytes in response to increased ironstores, thereby resulting in inadequate inhibition othe activity of Ferroportin-1, inappropriately high ironabsorption and recycling, and iron overload. However, in hemodialysis patients, carriage of HFE mutations may confer an adaptive beneft by decreasing hepcidin release in response to iron infusion and infammation, thereby improving iron availability to erythropoiesis,anemia control, the response to Epo, and possibly sur-vival. Therefore, anti-hepcidin therapies may improve anemia management in hemodialysis. However, HFE mutations directly favor hemoglobinization indepen-dently of hepcidin, and reduce macrophages activation in response to inflammation, whereas hepcidin might also play a benefcial anti-infammatory and anti-micro-bic action during sepsis, so that direct inhibition of HFE-mediated regulation of iron metabolism may represent a valuable alternative therapeutic target. Genetic stud-ies may offer a valuable tool to test these hypotheses and guide the research of new therapies.展开更多
文摘AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.
文摘The anemia of chronic kidney disease and hemodialysisis characterized by chronic inflammation and releaseof cytokines, resulting in the upregulation of the ironhormone hepcidin, also increased by iron therapy andreduced glomerular filtration, with consequent reduc-tion in iron absorption, recycling, and availability to theerythron. This response proves advantageous in theshort-term to restrain iron availability to pathogens, buultimately leads to severe anemia, and impairs the re-sponse to erythropoietin （Epo） and iron. Homozygosityfor the common C282Y and H63D HFE polymorphismsinfluence iron metabolism by hampering hepcidin re-lease by hepatocytes in response to increased ironstores, thereby resulting in inadequate inhibition othe activity of Ferroportin-1, inappropriately high ironabsorption and recycling, and iron overload. However, in hemodialysis patients, carriage of HFE mutations may confer an adaptive beneft by decreasing hepcidin release in response to iron infusion and infammation, thereby improving iron availability to erythropoiesis,anemia control, the response to Epo, and possibly sur-vival. Therefore, anti-hepcidin therapies may improve anemia management in hemodialysis. However, HFE mutations directly favor hemoglobinization indepen-dently of hepcidin, and reduce macrophages activation in response to inflammation, whereas hepcidin might also play a benefcial anti-infammatory and anti-micro-bic action during sepsis, so that direct inhibition of HFE-mediated regulation of iron metabolism may represent a valuable alternative therapeutic target. Genetic stud-ies may offer a valuable tool to test these hypotheses and guide the research of new therapies.
