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Biomedical subjects

T L Wright

Publications and source records attributed to T L Wright.

At least 73 records · Page 4Linked to original sources
PubMed1997

Prophylaxis and treatment strategies for chronic viral hepatitis in liver transplant patients.

This article highlights the importance of hepatotropic viruses as pathogens in patients undergoing liver transplantation, their contribution to morbidity and mortality after transplantation, and the approach to treatment of these pathogens when they cause disease. Although many advances have been made in the management of viral hepatitis in the transplant setting, there remain unanswered questions about the long-term natural history of the disease. An understanding of the pathogenesis of infection in the setting of transplantation is emerging slowly but requires further investigation. New approaches to treating disease in patients with either HBV or HCV infection are under development and will likely focus on the use of combinations of antiviral and immunomodulatory agents.

Hepatitis, Chronic↗
PubMed1997

Hepatitis C infection in transplantation.

This review emphasizes the role of HCV in the transplant setting. Prolonged HCV infection results in end-stage liver disease and as such represents a common indication for liver transplantation. Recurrence of infection is almost universal after transplantation in those with viremia before transplantation. Acquired disease is uncommon but nevertheless important, particularly in organ populations in whom screening for infection is not routine. The natural history of post-transplantation disease suggests that the effect on graft or patient survival is minor, at least during short-term follow-up. Long-term follow-up is needed, as well as more detailed study of the factors contributing to severity of post-transplantation disease. Kidney transplant recipients are commonly infected with HCV prior to transplantation. HCV infection after transplantation is associated with an increased risk of liver disease and infectious complications, but its effect on survival is still controversial. Similarly, observations in recipients of other solid organ transplants, such as heart and lung, and bone marrow patients suggest that HCV infection usually is not a major cause of mortality in the first 5 to 10 years of follow-up. Many issues still need to be addressed. The most important is the identification of factors that contribute to disease progression. Finally, effective therapies to eradicate infection and prevent disease progression are awaited.

Graft Rejection↗
PubMed1997

Effects of metronidazole on Porphyromonas gingivalis biofilms.

Subgingival bacteria exist within a biofilm consisting of cells and extracellular matrix which may afford organisms protection from both antibiotics and components of the host immune system. MIC values for planktonic Porphyromonas gingivalis treated with metronidazole were compared with those obtained for the same strain in biofilms associated with hydroxyapatite (HA) surfaces. The treated biofilms were examined for growth and studied by scanning electron microscopy. A broth assay resulted in an MIC of 0.125 microgram/ml for metronidazole against P. gingivalis, P. gingivalis biofilms exhibited growth after treatment with 20 micrograms/ml metronidazole, which was 160 times the MIC for planktonic organisms. The results of this study indicate that biofilm-associated P. gingivalis may be resistant to metronidazole at concentrations which are usually attained by systemic administration.

Anti-Bacterial Agents↗
PubMed1997

Hepatitis C virus: quantitation and distribution in liver.

The optimal method for viral quantitation and the most appropriate site for determining viral load in patients with chronic hepatitis C virus (HCV) infection are unknown. We developed a method for measuring HCV RNA in the liver with the following features: 1) efficient extraction of RNA from tissue (89% of RNA recovered); 2) accurate amplification using branched DNA with strong concordance between a single sample tested on multiple occasions either in the same or in different runs; 3) good sensitivity (95%) and specificity (100%). HCV RNA was detected in as little as 2 mg of tissue, and viral load determined in a needle biopsy was representative of viral load in other parts of the liver. Within individual livers, 68% of the samples quantitated were within 1.5-fold of the geometric mean, and 95% were within 2.2-fold of the geometric mean. The mean ratio of virus in the liver and serum was 103, range 17.4-286. A delay of 30 minutes before freezing the liver tissue resulted in a reduction in the measured viral load in some, but not all instances. A sensitive, specific and reproducible method for quantitating HCV RNA in the liver has been developed. Measurement of viral load at one site was representative of viral load at other sites. While hepatic HCV RNA levels are consistently greater than serum levels, the ratio of liver of serum viral load varies widely. The clinical use of measurement of viral load in the liver remains to be defined.

Adult↗
PubMed1997

Antibody to GBV-C second envelope glycoprotein (anti-GBV-C E2): is it a marker for immunity?

The clinical significance of GB virus C (GBV-C E2) antibody is under investigation. The prevalence rates of GBV-C RNA and antibody to GBV-C E2 glycoprotein were determined in a population of 123 Egyptian anti-hepatitis C virus (HCV)-positive patients with chronic liver disease (CLD) who had not been treated previously with interferon. Sera were tested for GBV-C RNA by the LCx assay (Abbott Laboratories, North Chicago, IL), and for GBV-C E2 antibody by enzyme immunoassay. GBV-C RNA was present in 11.4% of patients. GBV-C E2 antibody was detected in 55.9% of GBV-C RNA-negative patients and in 2.2% of GBV-C RNA-positive patients (P = 0.006). GBV-C RNA was associated significantly with a history of schistosomiasis (relative risk [RR] = 5.83, 95% confidence interval [CI] 1.99-17.14, P < 0.005) but not with parenteral risk factors. The presence of GBV-C E2 antibody was not associated with age, gender, parenteral risk factors, schistosomal infection, or HCV viremia. The HCV genotype and level of viremia were similar in GBV-C anti-E2-positive and negative patients. There was a trend toward more severe histological disease with anti-E2 seropositivity (RR = 1.45, 95% CI 0.89-2.45, P = 0.11), an association which was independent of the evidence of schistosomiasis. It is concluded that GBV-C infection is common among HCV-infected Egyptian patients with CLD due to HCV infection. A significant negative correlation between the GBV-C viremia and GBV-C E2 antibody suggests that an antibody response is associated with viral clearance. This antibody response presumably occurs spontaneously, as none of the patients had received antiviral therapy. The unexpected association between GBV-C RNA and schistosomiasis suggests that nonparenteral or occult parenteral routes of GBV-C infection are likely to be important.

Adolescent↗
PubMed1996

Hepatitis B and C coinfections and persistent hepatitis B infections: clinical outcome and liver pathology after transplantation.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common complications after orthotopic liver transplantation (OLT), but the liver pathology and clinical outcomes of HBV infection with HCV coinfection have not been thoroughly examined. In this study, we used the polymerase chain reaction (PCR) to detect HBV and HCV in pre- and post-OLT sera of 38 patients and correlated the findings with clinical outcome and liver pathology. Of 13 patients who were HBV and HCV negative before OLT, 9 acquired HBV infection, and 4 developed acquired HBV and HCV coinfections after OLT. Persistent HBV infections were present in 10 patients. Three patients with pre-OLT HBV infections developed persistent HBV and acquired HCV coinfections after OLT; 5 with pre-OLT HCV infections developed acquired HBV and persistent HCV coinfections after OLT, and 7 had persistent HBV and HCV coinfections before and after OLT. Portal/periportal inflammation was the same in all groups; however, lobular inflammation and fibrosis were more severe in patients with persistent HBV infections and in those with acquired HBV and HCV coinfections. Two major histopathological patterns were present in patients with HBV and HCV coinfections, one with predominant features of HCV infection, and the other with those of HBV infection. Patients with post-OLT HBV and HCV coinfections had survival rates similar to those with acquired HBV infection, whereas patients with persistent HBV infections experienced more allograft loss caused by chronic hepatitis or fibrosing cytolytic hepatitis, and had a more dire clinical outcome than the others. Although the limited numbers reported in this study prevent a definitive conclusion, our data suggest that in patients with HBV and HCV coinfections, the presence of HCV may improve the clinical outcome as compared with the expected outcome of persistent HBV infection alone.

Adult↗
PubMed1996

Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia.

Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe posttransplantation liver disease than infection with non-1b genotypes. To address this issue, we evaluated the outcome in 124 patients who underwent liver transplantation for chronic HCV infection. The HCV genotype and/or serotype responsible for infection was determined by four different methods. HCV RNA was detected in serum samples by polymerase chain reaction (PCR) amplification, and quantified by branched DNA assay. Disease severity was expressed as a histological score (which included grading of portal inflammation, lobular activity, fibrosis, and cytopathic changes). Median duration of histological follow-up was 25 months (range 1-75 months). Genotype was assignable in 112 (92.5%) patients. Genotypes responsible for infection were as follows: 1a = 32.2%, 1b = 27.3%, 2a = 7.4%, 2b = 8.3%, 3a = 14%, and mixed infection (more than one subtype) = 3.3%. Level of viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and total histological score were not significantly different in patients infected with type 1b compared with patients infected with other genotypes. While duration of histological follow-up was greater in patients infected with type lb versus other types (P = .02), by univariate and multivariate analysis neither HCV genotype (lb versus others), level of viremia nor duration of histological follow-up were associated with disease severity. Moreover, there was no significant difference in the actuarial graft survival in patients infected with type lb compared with that of patients infected with non-lb types (82% and 87% at 3 years, respectively). Reanalysis using HCV genotype 1 showed no association with disease severity, graft survival, and patient survival. We conclude that HCV genotype 1 and subtype 1b are not associated with disease severity or graft survival in liver transplantation recipients.

Adult↗
PubMed1996

Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin.

Prophylactic hepatitis B immunoglobulin (HBIg) reduces the risk of reinfection in hepatitis B surface antigen (HBsAg)-positive liver transplant recipients. In the medical center of this study, high-dose HBIg immunoprophylaxis is administered at a fixed dose of 10,000 IU monthly, and in this study, the long-term efficacy of this treatment regimen was examined. Of 52 HBsAg-positive liver transplant recipients, 24 were administered HBIg immunoprophylaxis, and 28 were administered no specific therapy; the 2-year recurrence rates (defined by the reappearance of HBsAg) were 19% and 76%, respectively. Fifty-four percent of the HBIg-treated patients were positive for HBeAg or hepatitis B virus (HBV) DNA (by hybridization assay) pretransplantation. In patients administered monthly HBIg, intrapatient and interpatient variability in trough antibody to HBsAg (anti-HBs) titer was significant, highlighting the potential difficulties of using anti-HBs titer to guide therapy. Trough anti-HBs titers were less in patients who became HBsAg positive than in patients who remained HBsAg-negative (490 vs. 1290 mIU/mL) (P = .0001), reflecting either the cause or effect of HBV reinfection. Of 9 patients who remained HBsAg-negative and who were administered monthly HBIg for at least 1 year, HBV DNA by polymerase chain reaction amplification was detectable in the sera of 67%, the lymphocytes of 50%, and the liver of 57%. In conclusion, a fixed monthly dose of HBIg reduces the recurrence of HBs antigenemia, even in patients with indices of active viral replication pretransplantation. The presence of residual virus in the majority of patients administered HBIg suggests that long-term HBIg administration may be necessary.

Actuarial Analysis↗
PubMed1996

Interferon alfa for recurrent hepatitis B infection after liver transplantation.

Reinfection with hepatitis B virus (HBV) after liver transplantation is nearly universal in patients not receiving immunoprophylaxis. Because reinfection reduces graft and patient survival, treatment of recurrent infection is important. Interferon alfa (IFN-alpha) is an effective therapy for chronic hepatitis B infection in immunocompetent patients, but its efficacy in transplant recipients has not been established. Fourteen liver transplant recipients with recurrent hepatitis B infection (hepatitis B surface antigen [HBsAg] positive in serum; hepatitis on biopsy) were treated with IFN-alpha 2b (Intron A; Schering Inc, Kenilworth, NJ) 3 million units (MU) three times weekly for 23.5 weeks (median, range 4 to 41). The primary endpoint was loss of HBV DNA by the b-DNA assay (a virological response). Before treatment, all patients were HBV DNA positive and 9 were hepatitis B e antigen (HBeAg) positive. Pretreatment HBV DNA levels were 6,760 MEq/mL (median, range 2.0 to 11,888 MEq/mL). HBV DNA levels decreased significantly with treatment (P = .03). Four patients had a complete and sustained virological response. Virological responses did not consistently correlate with biochemical response because of concomitant hepatitis C. Two patients had a serological response; 1 lost HBeAg, another lost HBeAg and HBsAg. All responders remained HBV DNA negative in follow-up (mean, 32 months; range, 23 to 40), but 1 patient required retransplantation for cirrhosis. Of the nonresponders, 1 patient required retransplantation for chronic rejection, 3 required retransplantation for recurrent hepatitis B, 3 died with recurrent hepatitis B, and 3 are alive and remain HBV DNA positive. IFN-alpha can induce a sustained serological (14%) and virological response (29%) in liver transplant recipients with recurrent HBV infection.

Hepatitis B↗
PubMed1996

Therapy for chronic hepatitis B infection.

Interferon-alpha is currently the only therapy approved for treatment of chronic HBV in the United States and Europe. Interferon-alpha therapy causes loss of HBeAg and HBV DNA in approximately a third of treated patients, and the loss of these markers of active viral replication is associated with improvements in hepatic histology and ALT levels. However, the long-term effects of interferon-alpha on morbidity and mortality, and especially on the incidence of the complications of chronic HBV infection, remain to be defined. The currently available treatment for chronic HBV is far from perfect. Interferon therapy is usually associated with significant side effects and requires subcutaneous administration. Additionally, there are a large number of patients who either fail to meet criteria for treatment, or who, with therapy, fail to respond (at least 60% of all patients). Moreover, interferon treatment is expensive (approximately $5,000 for a 16 week course of 5MU daily). Hence the search continues for effective, orally-available and cost-efficacious therapy. Of the agents available, the nucleoside analogues appear to have the greatest promise. The availability of cell culture systems and animal models for studying potential anti-HBV drugs will aid in the future development of these agents. Therapeutic vaccines, and combination therapies (given either concurrently or sequentially) may also play a future role in the management of chronic HBV infection. While prevention of disease must be a primary goal in the war against this common infection, a continued focus must be maintained on the treatment of the approximately 300 million individuals world-wide with established chronic HBV infection.

Adjuvants, Immunologic↗
PubMed1996

Hepatitis G virus infection in patients with hepatitis C virus infection undergoing liver transplantation.

BACKGROUND & AIMS: Hepatitis G virus (HGV) is transmissible by blood transfusion, but its role in chronic liver disease is unknown. The aim of this study was to determine the prevalence of HGV infection in patients infected with hepatitis C virus (HCV) undergoing transplantation and evaluate the effects of HGV coinfection on the course of posttransplantation HCV infection. METHODS: One hundred twenty-four patients infected with HCV undergoing liver transplantation were studied. Serum samples were tested for HCV and HGV RNA; HCV RNA was quantitated by branched DNA assay, and HCV genotype was determined. RESULTS: The prevalence of pretransplantation and posttransplantation HGV infection was 24% and 28%, respectively. Pre-transplantation HGV infection was positively correlated with posttransplantation HGV infection (P < 0.001). Pretransplantation clinical features were not different in patients infected with HCV with and without HGV infection. Posttransplantation HCV RNA levels were not significantly different in patients with and without HGV coinfection, but HCV genotype 1b was more frequent in patients with HGV coinfection. There were no differences in the histological severity of posttransplantation liver disease, graft, and patient survival between patients with and without HGV infection. CONCLUSIONS: Although HGV coinfection is frequent in patients with end-stage HCV disease undergoing liver transplantation, there is no association between the presence of HGV coinfection and the severity of liver disease post-transplantation, graft, or patient survival.

Adult↗
PubMed1996

Cryoglobulinemia presenting after liver transplantation.

Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis C. Three patients undergoing transplantation for end-stage chronic hepatitis C in whom cryoglobulinemia with vasculitis developed after transplantation are described. Hepatitis C virus (HCV) infection was confirmed in the 3 patients by the presence of HCV RNA detected by polymerase chain reaction. The time interval between transplantation and the first expression of vasculitis was 1, 5, and 17 months. Type II cryoglobulins were detected in the sera of all 3 patients. All patients developed cutaneous vasculitis, requiring digital amputation in 1 case. Two patients developed membranoproliferative glomerulonephritis. Plasmapheresis and the addition of cyclophosphamide led to an improvement in the renal disease in 1 case, whereas no treatment was able to reverse the renal failure in the other case. One patient developed an autoimmune hemolytic anemia 4 years after transplantation. One patient died of multiorgan failure 5 months after transplantation. We propose that HCV-associated cryoglobulinemia could become clinically significant only after orthotopic liver transplantation, possibly due in part to posttransplant increase in viremia as reflected by HCV RNA levels. These results confirm previous observations suggesting that HCV infection is important etiologically in the pathogenesis of cryoglobulinemia.

Adult↗
PubMed1996

Hepatitis C virus detection by single-round PCR specific for the terminal 3' noncoding region.

A single-round PCR method with primers specific for the 3' noncoding region (NCR) of hepatitis C virus (HCV) has been developed. Using a double RNAzol-B extraction, a high-temperature reverse-transcription step with SuperScript II reverse transcriptase, and a 40-cycle two-temperature PCR with a TaqStart antibody hot-start procedure, we were able to detect a 92-nucleotide fragment of the recently discovered 98-nucleotide highly conserved sequence at the 3' terminus of the HCV genome. Direct sequencing of the PCR products confirmed the specificity of the PCR and demonstrated conservation in this region. Only one nucleotide change in 14 specimens was found. End point dilution titration of sera with known viral RNA titers showed the sensitivity of the single-round 3' NCR PCR to be comparable to those of the established nested 5' NCR assays (fewer than 25 HCV genome equivalents). To evaluate specificity and sensitivity, a panel of 116 serum samples characterized by nested 5'-end PCR, genotyping, and quantitative assays was tested. A high degree of concordance (96%) between the 3' NCR and 5' NCR PCR results was found. The sequence conservation at the 3' end of the HCV genome among common genotypes and the savings in time, labor, and reagents from a single-round PCR make this assay a useful addition to the detection systems available to identify and monitor HCV infection.

DNA Primers↗
PubMed1995

The impact of pretransplantation hepatitis C infection on the outcome of renal transplantation.

Controversy exists regarding the impact of pretransplantation HCV infection on the outcome of renal transplantation. We compared the prevalence of posttransplantation liver disease and graft and patient survival among kidney transplant recipients with and without anti-HCV at the time of transplantation. Pretransplantation sera from 103 randomly selected recipients of kidneys from anti-HCV-negative donors were tested for anti-HCV using a second generation ELISA. Twenty-three (22%) were positive for anti-HCV and 80 (78%) were negative. Anti-HCV-positive recipients had a longer time on dialysis (P = 0.003) and had a higher number of previous transplants (P = 0.01). Further, 61% of anti-HCV-positive patients had a history of liver disease compared with 13% of anti-HCV-negative patients (P < 0.001). HCV RNA was detected in the pretransplantation serum in 61% of anti-HCV positive recipients compared with 5% of anti-HCV-negative recipients (P < 0.001). Clinical follow-up on both anti-HCV-positive and -negative patients was obtained until December, 1993. Median posttransplantation follow-up among recipients with anti-HCV prior to transplantation (45 months) was shorter (P = 0.05) than that for recipients without anti-HCV (66 months). For recipients with anti-HCV prior to transplantation, the relative risk of posttransplantation liver disease was 5.0 (95% confidence intervals of 2.4 to 10.5); the relative risk of graft loss was 1.3 (95% confidence intervals of 0.6 to 2.6); the relative risk of death was 3.3 (95% confidence intervals of 1.4 to 7.9), and the relative risk of death due to sepsis was 9.9 (95% confidence intervals of 2.6 to 38.3). The results of this study demonstrate that pretransplantation HCV infection is associated with an increased risk of liver disease and death after renal transplantation. These results raise the question of whether anti-HCV-positive patients on dialysis should be offered renal transplantation as opposed to continuing dialysis.

Adult↗