Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cidofovir and adefovir are members of a new class of antiviral compounds. They are acyclic phosphonate analogues of deoxynucleoside monophosphates. Both compounds undergo intracellular activation to form diphosphates that are potent inhibitors of viral DNA polymerases. Cidofovir has broad spectrum antiviral activity against herpesviruses, papillomaviruses and poxviruses, whereas adefovir has potent activity against retroviruses and certain DNA viruses, including herpesviruses and hepadnaviruses. Intravenous cidofovir is approved for treatment of cytomegalovirus retinitis in patients with AIDS. Cidofovir and adefovir are dianionic at physiological pH and have low oral bioavailability in animals and humans. After intravenous administration to HIV-infected patients, the pharmacokinetics of both drugs are independent of dose and are consistent with preclinical data. Systemic exposure is proportional to the intravenous dose and both drugs are cleared by the kidney and excreted extensively as unchanged drug in the urine. Intracellular activation of a small fraction (< 10%) of the dose by cellular kinases leads to prolonged antiviral effects that are not easily predicted from conventional pharmacokinetic studies. The observed rate of elimination of cidofovir and adefovir from serum may not reflect the true duration of action of these drugs, since the antiviral effect is dependent on concentrations of the active phosphorylated metabolites that are present within cells. For both drugs, > 90% of an intravenous dose is recovered unchanged in the urine over 24 hours. Metabolism does not contribute significantly to the total clearance of either drug. Concomitant oral probenecid decreases both the renal clearance of cidofovir and the incidence of nephrotoxicity, presumably by blocking its active tubular secretion. This is the basis of the clinical use of concomitant probenecid as a nephroprotectant during cidofovir therapy. Subcutaneous administration produces exposure equivalent to that following intravenous administration. Drug interaction studies with cidofovir are ongoing, but there is no evidence of an interaction between zidovudine and either cidofovir or adefovir. Clearance of cidofovir in patients with renal impairment showed a linear relationship to creatinine clearance. The low oral bioavailability of adefovir has led to the development of an oral prodrug, adefovir dipivoxil, currently in development for the treatment of HIV and hepatitis B infections.
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PMID:Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. 1009 59

Three patients with acute thrombotic thrombocytopenic purpura (TTP) (one associated with E. coli infection) received as primary treatment pooled fresh frozen plasma (FFP) virus inactivated by the solvent/detergent (SD) method, plus prednisolone. All three patients attained platelet counts of > 50 x 10(9)/l by days 7, 3 and 10, respectively. Serum creatinine became corrected in parallel. Neurological features were slow to resolve in one patient, and developed de novo during plasma infusion in another with rapid reversal once intensive plasma exchange with SDFFP was instituted. All patients are in stable remission > 1 years later. SDFFP was well tolerated with no febrile or other reactions, and all patients remained negative for markers of infection with HIV, hepatitis B and hepatitis C viruses. One patient was positive for antibodies for hepatitis A virus and parvovirus B19 prior to treatment. The other two patients remained antibody negative at the end of therapy.
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PMID:Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura. 1034 71

The clinical outcome of long-term renal allograft recipients in the Chinese population has not been reported previously. We analysed patients from the pre-cyclosporin era who had grafts that functioned for > 10 years. Forty-five patients (31 men, 14 women; mean age 30, follow-up duration 13.3 years), representing a 10-year graft survival of 53%, were included. Thirty-six patients (80%) received living-related allografts and 9 (20%) received cadaveric or living-unrelated renal transplantation. The mean serum creatinine at last follow-up was 1.36 mg/dl (range, 0.83-4.08). Major posttransplantation complications included: hypertension in 25 (56%), infection in 16 (36%), acute rejection in 15 (33%), lipid disorder in 13 (29%), liver disease in 7 (16%), osteonecrosis in 5 (11%), malignancy in 4 (9%), coronary artery disease in 3 (7%), and diabetes mellitus in 3 (7%). Five grafts were lost: 3 to chronic rejection, and 2 to patients with stable function who died of non-renal causes. Proteinuria correlated strongly with graft function and survival, and marginally with hypertension. In hepatitis B carriers, serum alpha-feto protein is useful in the early detection of hepatocellular carcinoma. We conclude that while patients in the pre-cyclosporin era can survive with excellent graft function beyond the first decade, the risk of complications leading to significant morbidity still remains even when patients are receiving minimal doses of immunosuppression in the second decade.
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PMID:Long-term renal allograft recipients from South-east Asia in the pre-cyclosporin era. 1035 40

With improvements in surgical techniques and management of postoperative complications, heart transplantation can now be performed with donors and recipients who were previously considered unsuitable. In this study, we report the results of heart transplantation with marginal donors and recipients in our hospital. From June 1993 through June 1998, we performed 79 heart transplantations. Marginal recipients were defined as those with high pulmonary vascular resistance (> 6 Wood units), severe renal impairment (serum creatinine > 2 mg/dL and creatinine clearance < 50 mL/min), or severe hepatic dysfunction (ALT and AST > 100 IU/L or serum bilirubin > 2.5 mg/dL). Marginal donors were those with any of the following conditions: old age (> 40 years), size mismatch (donor/recipient body weight ratio < 0.8), history of chronic alcohol use, previous cardiopulmonary resuscitation and hypotension, hepatitis B or C virus positivity, coronary artery disease, high-dose dopamine (> 10 micrograms.kg-1.min-1), or prolonged allograft ischemic time (> 4 hours). Of the 79 transplantations performed, 45 (58%) involved marginal recipients or donors. The 30-day mortality rate was 5%, and the 1-year and 5-year survival rates were 87% and 83%, respectively. The survival rates did not differ significantly between cases involving marginal donors or recipients and those involving nonmarginal donors and recipients. There were 27 marginal recipients (34%), only one of whom died during surgery. Five of six recipients with severe renal impairment needed short-term hemodialysis after transplantation. Recipients with high pulmonary vascular resistance had a higher incidence of early acute rejection (5/10 vs 22/69). Thirty-three (42%) of the patients received transplants from marginal donors, four of whom died during surgery; two died of acute vascular rejection, one of allograft failure caused by prolonged ischemic time, and one of bleeding secondary to preoperative sepsis and coagulopathy. These results show that heart transplantation may be performed in marginal recipients and donors, with acceptable operative mortality.
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PMID:Heart transplantation with marginal recipients and donors. 1057 34

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.
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PMID:Case studies in orthotopic liver transplantation for hepatitis B: a panel discussion. 1096 64

To evaluate the prevalence and incidence density of heavy proteinuria and chronic renal insufficiency (CRI) and the factors related to disease progression, 10,288,620 urinary screenings of elementary and junior high-school students from 1992 to 1996 were studied retrospectively. Urinary screening included pH, protein, occult blood, and glucose measurements. Blood sample analysis included total protein, albumin, A/G ratio, blood urea nitrogen, creatinine (Cr), antistreptolysin O titer, C3, cholesterol, hepatitis B virus surface antigen, IgA, and fasting blood sugar. The results showed that the 4-year prevalence of proteinuria was higher in girls than in boys (6.87x10(-4) vs. 4.83x10(-4) respectively). There were 189 cases with disease progression into CRI among the 10,288,620 students screened and followed continuously, with the prevalence of disease progression into CRI higher in boys than in girls (2.24x10(-5) vs. 1.41x10(-5) respectively). Of the 119 cases (63%) presenting with CRI since the first urine screening and blood sampling, only 14 had serum Cr levels higher than 6.0 mg/dl. There were 1,289 patients (10.5%) with proteinuria in 1992 and 705 patients (7.1%) in 1996. The absolute number of patients with heavy proteinuria decreased. The percentage of underlying glomerulonephritis in children on dialysis also decreased from 63.2% in 1992 to 47.0% in 1996. Logistic regression analysis showed that a persistent serum cholesterol level higher than 220 mg/dl, an albumin level lower than 3.5 g/dl, total protein less than 6 g/dl, and diastolic pressure higher than 90 mmHg were the significant risk factors for disease progression to CRI. We conclude that early detection of students with heavy proteinuria by mass urinary screening, early appropriate treatment, and monitoring of significant risk factors may help to decrease or delay the progression of renal disease, delay the introduction of dialysis in these predialysis CRI patients and maintain their growth and development.
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PMID:The prevalence of heavy proteinuria and progression risk factors in children undergoing urinary screening. 1097 5

Seroconversion rate following hepatitis B vaccination in patients of chronic renal failure (CRF) has been in the range of 10%-82% in various studies. Different approaches have been tried to improve seroconversion rate. We studied two schedule of hepatitis B vaccination, 0,1,2 (Group A) and 0,1,2,6 (Group B) in mild (creatinine 1.5 to 3.0 mg%), moderate (creatinine 3.0 to 6.0 mg%) and severe CRF (creatinine > 6.0 mg%). Between Oct. 93 to Oct. 95, 117 patients with CRF who were negative for HBsAg and anti-HBs were included in the study. Forty micrograms of recombinant vaccine "ENGIREX" (20 micrograms in each deltoid region) was given in both the groups. Number of cases of mild, moderate and severe CRF were 18, 15 and 42 in group A and 12, 13 and 17 in group B, respectively. One month after the last dose of vaccination, anti-HBs was measured using ELISA kit (Abbot Laboratories, India). Anti-HBs titres of > 10 IU/L were taken as criteria of positive seroconversion. In group A seroconversion rate was 87.5%, 66.6% and 35.7% in mild, moderate and severe CRF respectively while same results in group B were 100%, 77% and 36.36%, respectively. We conclude that patients of chronic renal failure should be vaccinated at very early stage of the disease using 40 micrograms of vaccine. Four doses schedule of 0,1,2,6 give better results than three doses schedule in early CRF.
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PMID:Comparison of two schedules of hepatitis B vaccination in patients with mild, moderate and severe renal failure. 1122 73

The biosocial background in which the hepatitis B virus (HBV) carrier state with membranous nephropathy (MN) develops was studied by evaluating HBV carriage and proteinuria among 195 family members and household contacts of 31 index HBV carrier children with MN. Unrelated individuals from the communities of these index cases who were negative for HBV served as controls (n = 123). HBV was determined by using third-generation enzyme-linked immunosorbent assay, slot-blot hybridization, and nested polymerase chain reaction. Patterns of proteinuria were determined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis; immunoglobulin G and haptoglobulin were suggestive of MN. Seventy-two members (36.9%) of the study group (n = 195) were HBV carriers; 21 of these carriers (29.2%) had proteinuria. Twenty-eight members (41.2%) of the study group who were HBV negative (n = 68) and 26.8% of the controls showed proteinuria. This lack of association between HBV carriage and proteinuria remained when controlled for sex and family relationship. HBV was not protective against the development of proteinuria. Proteinuria suggestive of MN was strongly associated with an abnormal protein-creatinine ratio (P: = 0.001), but was not significantly different between subjects and controls (8.7% versus 6.5%; P: = 0.5). Genetic influences or environmental exposures in these subjects may be responsible for the proteinuria, suggesting underlying glomerular basement membrane damage. Discordance between the HBV carrier state and patterns of proteinuria in the study group suggest that HBV and MN may not be causally related or may reflect exceptional interaction between specifically vulnerable individuals and HBV.
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PMID:Characterization of proteinuria in asymptomatic family members and household contacts of children with hepatitis B virus-associated membranous nephropathy. 1113 77

Hepatitis C virus (HCV) infection is common in the dialysis population and patients with chronic renal failure (CRF) not requiring dialysis. HCV is the most important cause of chronic liver disease in dialysis patients; however, its role has been underestimated by the lower aminotransferase activity in the dialysis population. Aminotransferase activity in patients with CRF not requiring dialysis has not been adequately addressed to date. The aim of this study is to investigate whether serum aminotransferase levels in predialysis patients with CRF are less than those obtained in healthy individuals and dialysis patients. We also analyzed the potential association between serum aminotransferase activity and demographic, clinical, and biochemical parameters. Aspartate (AST) and alanine aminotransferase (ALT) activity was greater in antibody to hepatitis C (anti-HCV)-positive than anti-HCV-negative patients with CRF not requiring dialysis (AST, 32.3 +/- 19 versus 18.1 +/- 8 IU/L [P = 0.0001]; ALT, 32.9 +/- 28 versus 17.7 +/- 11 IU/L [P = 0.00001], respectively). Predialysis patients with CRF had lower AST and ALT activity in comparison to healthy individuals (AST, 19.7 +/- 11.2 versus 20.4 +/- 6.8 IU/L [P = 0.00001]; ALT, 19.5 +/- 15.1 versus 21.7 +/- 11.3 IU/L [P = 0.00001], respectively). The difference was much greater after correction for viral markers: AST and ALT levels in hepatitis B surface antigen (HBsAg)-negative anti-HCV-negative predialysis patients with CRF were less than those in the healthy population (AST, 17.9 +/- 8 versus 20.4 +/- 6.8 IU/L [P = 0.00001]; ALT, 17.5 +/- 10 versus 21.7 +/- 11.3 IU/L [P = 0.00001], respectively). Comparison of AST and ALT activity between age-matched healthy and predialysis seronegative CRF groups showed lower AST and ALT values in the study population. HBsAg-negative anti-HCV-negative dialysis patients had lower AST and ALT activity than seronegative predialysis patients with CRF (AST, 16.6 +/- 11.6 versus 17.9 +/- 8 IU/L [P = 0.01]; ALT, 16.3 +/- 9.4 versus 17.5 +/- 10 [P = 0.041], respectively). Multivariate analysis in the predialysis CRF population showed an independent association between AST (P = 0.00001) and ALT (P = 0.00001) activity and anti-HCV positivity, and age was negatively linked to AST (P = 0.011) and ALT levels (P = 0.001). AST level was negatively related to serum creatinine level (P = 0.0001). In conclusion, HCV infection causes significant liver injury in predialysis patients with CRF. These patients have decreased aminotransferase activity compared with the general population. Dialysis patients show lower aminotransferase activity than predialysis patients with CRF. Because serum aminotransferase levels are commonly used to screen for liver disease in the dialysis and predialysis CRF population, recognition of liver damage may be hampered by the reduction in aminotransferase values in these patients. Studies aimed to clarify the pathogenesis of this phenomenon are in progress.
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PMID:Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis. 1168 54

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. The aim of this study is to elucidate the effectiveness of lamivudine for the treatment of HBV reactivation with or without fulminant hepatic failure in renal transplant recipients. Forty-two renal transplant recipients (30 men, 12 women) were enrolled onto this study. Eight patients presented with HBV reactivation without fulminant hepatic failure and were administered lamivudine (group I), 5 patients presented with HBV and hepatic failure and were administered lamivudine (group II), 5 patients presented with HBV and hepatic failure but were not administered lamivudine (group III), and 24 patients were asymptomatic HBV carriers who were not administered lamivudine (group IV). Lamivudine was administered at a dose of 100 or 150 mg once daily. A greater prevalence of recent use of a combination of antilymphocyte immunoglobulin (ALG) and methylprednisolone (MP) occurred in patients with hepatic failure (groups II and III) than those without hepatic failure (30% versus 6.3%; P = 0.043). However, there was no significant difference in the incidence of MP use alone (20% versus 25%; P = 0.746). Mortality rates for groups I, II, and III were significantly different (12.5%, 40%, 100%; P = 0.008). One patient in group I died of sepsis without evidence of HBV DNA, even in the terminal event. In group II, 3 of 5 patients (60%) were rescued by lamivudine therapy. In group III, without lamivudine treatment, there was a 100% mortality rate despite intensive plasmapheresis. HBV DNA was not detectable after lamivudine treatment in 7 of 8 patients in group I and 3 of 5 patients in group II. Creatinine levels did not change significantly during lamivudine treatment. Hepatitis B surface antigen and hepatitis B e antigen seroconversion rates after lamivudine treatment were 7.7% and 37.5%, respectively. We conclude that ALG is a potent trigger of HBV-related fulminant hepatic failure in renal transplant recipients, whereas lamivudine is an effective and lifesaving treatment. Prompt use of lamivudine is recommended in renal transplant recipients with evidence of HBV reactivation to prevent catastrophic fulminant hepatic failure.
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PMID:Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients. 1168 62


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