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Biomedical subjects

T L Wright

Publications and source records attributed to T L Wright.

At least 91 records · Page 5Linked to original sources
PubMed1995

A controlled study of hepatitis C transmission by organ transplantation. The New England Organ Bank Hepatitis C Study Group.

Hepatitis C virus (HCV) can be transmitted by transplantation of cadaver organs from donors with antibody to HCV (anti-HCV); therefore, transplantation of organs from anti-HCV positive donors to anti-HCV-negative recipients has been discouraged. We have looked at outcomes in recipients of organs from anti-HCV positive and negative donors to determine whether this advice is well-founded. Stored sera from 716 consecutive cadaver organ donors procured by the New England Organ Bank between 1986 and 1990 were tested for anti-HCV by a first-generation ELISA (ELISA1); 13 (1.8%) were positive. 29 recipients who received organs from these donors were the study group. 37 donors were randomly selected from 703 ELISA1-negative cadaver organ donors. 74 recipients of organs from these 37 donors were the control group. Clinical records were reviewed and recipient sera were tested for anti-HCV with a second-generation ELISA (ELISA2), and HCV RNA was tested for by polymerase chain reaction. Median post-transplant follow-up was 42 and 49 months for study and control groups. Post-transplantation prevalence of anti-HCV and HCV RNA was 67% and 96% among recipients from anti-HCV-positive donors, and 20% and 18% among recipients from anti-HCV-negative donors (p < 0.001). Post-transplantation non-A, non-B hepatitis, graft loss, and death were observed in 55%, 52%, and 31% among recipients of organs from anti-HCV-positive donors, and 16%, 53%, and 33% among recipients from anti-HCV-negative donors. In a proportional hazards model, the relative risks for non-A, non-B hepatitis, graft loss, and death among recipients from anti-HCV-positive donors were 4.37 (95% CI 1.97-9.70), 0.93 (0.51-1.70), and 0.89 (0.41-1.93). Transmission of HCV infection by organ transplantation increased the risk of liver disease among recipients. However, after 3.5 years, donor HCV infection did not adversely affect patient survival or graft survival.

Adult↗
PubMed1995

Low incidence of intraspousal transmission of hepatitis C virus after liver transplantation.

Although the incidence of spousal transmission of hepatitis C virus (HCV) in chronic carriers is extremely low (1.4% to 8%), hepatitis C recurrence after liver transplantation is common with markedly increased serum HCV RNA levels. Thus, partners of these patients may be at higher risk of acquiring infection. This study evaluates the prevalence of spousal transmission of hepatitis C after liver transplantation. Twenty-two of 25 couples who were eligible agreed to the retrospective study. Twenty-two patients (17 males, 5 females) and spouses (5 males, 17 females) were studied with respective mean ages of 50.2 years (35 to 65 years) and 46.9 years (33 to 66 years). Liver enzymes, second-generation enzyme-linked immunosorbent assay (ELISA) for antibody to HCV (anti-HCV) and HCV RNA by polymerase chain reaction (PCR), and branched DNA assay were performed. HCV-associated antibodies were detected in 1 of 22 (5%) spouses and 21 of 22 (95%) patients (P < .0001). Nineteen of 22 (86%) patients tested positive by PCR with a mean value of 16,218,100 Eq/mL (464,700 to 51,980,000). All spouses including the only ELISA anti-HCV positive spouse tested negative by PCR (P < .0001). Eight of 21 spouses tested negative for anti-HCV pretransplantation, (13 of 21 pretransplantation were not tested). Estimated mean duration of hepatitis C infection in patients was 14 years (3 to 40 years). Mean patient follow-up posttransplantation was 654.5 days (141 to 1,959 days). Mean duration of marriage was 22.6 years (2.5 to 46 years). No risk factors other than exposure to index patients were observed in spouses. The incidence of spousal transmission of HCV in liver transplantation remains low (5%) and similar to chronic carriers of HCV.

Adult↗
PubMed1995

Detection of hepatitis C after liver transplantation. Four serologic tests compared.

To determine the best method for detecting HCV infection in immunosuppressed patients, stored frozen serum from 101 liver transplant recipients was tested for hepatitis C virus. Each sample was tested by four assays. HCV RNA was detected by both polymerase chain reaction (PCR) and branched DNA signal amplification. Antibody to HCV was determined using second-generation enzyme-linked immunoassay (EIA) and recombinant immunoblot assay. Forty one transplant recipients met the working definition for true positives of HCV infection. Of these "true positives," 98% were positive by HCV RNA PCR assay, 88% by b-DNA signal amplification assay, 88% by anti-HCV EIA, and 63% demonstrated two or more reactive bands on recombinant immunoblot. Five of 57 (9%) HCV-antibody negative recipients had HCV RNA detected by both methods. Of 44 HCV enzyme-linked immunoassay (EIA) repeatedly reactive samples, the recombinant immunoblot was negative in 2 and indeterminate in 13. HCV RNA was present in 9 of 13 recombinant immunoblot indeterminate sera. Nine EIA repeatedly reactive sera were negative by both tests for HCV RNA. In liver transplant recipients, HCV infection is best determined by measurement of HCV RNA. Antibody formation may be delayed or suppressed in a minority of patients despite > 10(9) equivalents/L (> 10(6)/mL) of HCV RNA in serum. Recombinant immunoblots with a single reactive band pattern often indicate HCV infection in immunosuppressed patients.

Hepacivirus↗
PubMed1995

Hepatitis C: an overview.

Hepatitis C virus (HCV) has been associated with acute and chronic posttransfusion and with sporadic non-A non-B (NANB) hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Cloning of the sequence encoding an antigenic component of HCV in 1989 led to the development of tests to detect antibody to HCV in serum. Viral HCV RNA can be detected and estimated with polymerase chain reaction (PCR) and branched-chain DNA (bDNA) signal amplification tests. The entire viral genome has been sequenced. The HCV envelope region varies considerably, and infections with mutant HCV have been described. Approximately 0.5-1.5% of healthy blood donors test positive, and HCV infection can be acquired by blood transfusion or i.v. drug abuse. Vertical and sexual transmission of the virus is rare, and the transmission mode remains obscure in a large group of patients. Acute hepatitis C is mild and often asymptomatic. Chronic hepatitis C has an indolent course but may progress to cirrhosis and HCC. Recombinant alpha interferon (IF) is used to treat chronic HCV disease, but no consensus has been reached on patient selection, dose, and duration of treatment. Approximately 50% of treated patients respond, but 50-80% of responders relapse over time. Liver transplantation in patients with end-stage, HCV-related liver disease is often followed by allograft infection. Short-term survival with reinfection is good, but the long-term consequences remain to be defined.

Blood Donors↗
PubMed1995

Long-term outcome in kidney transplant patients with hepatitis C (HCV) infection.

To assess the prevalence and long-term impact of HCV on kidney transplant recipients, we assayed 716 pre-transplant sera using a first-generation ELISA. The anti-HCV positive sera were confirmed by a 6-antigen radioimmunoassay (RIA). Patients were followed up for 5 years. Graft survival, function, evidence of chemical hepatitis (AST > 2x normal), patient mortality and cause of death were evaluated. The prevalence of anti-HCV antibody was 10.3%. In the 638 patients who were followed up for 5 years, there were no differences in graft function, graft survival, overall mortality, or death from sepsis or liver disease. Peak AST levels were significantly higher in anti-HCV positive patients compared to anti-HCV negative patients. At 5 years, the AST levels remained significantly higher in the anti-HCV positive group, however, this was only 6 U/1 > normal. Liver biopsies performed 3 to 7 years post-transplant in 80% of anti-HCV positive patients with chemical hepatitis showed 12% CAH, 50% mild hepatitis and 38% normal histology. Six (9.7%) patients seroconverted from anti-HCV positive to anti-HCV negative 2 to 5 years post-transplant. The presence of anti-HCV does not appear to alter long-term patient or graft survival, and histologic evidence of severe chronic liver disease was rare in anti-HCV positive patients with chemical hepatitis. From these results, the presence of anti-HCV antibody should not preclude kidney transplantation.

Adolescent↗
PubMed1995

Hepatitis C virus infection in the immunocompromised patient.

With this review we have attempted to highlight key issues in the diagnosis and management of HCV infection in immunocompromised patients. Much of the information is preliminary and will require careful assessment with prospective collection of data in large numbers of patients. With the advent of new assays, our ability to diagnose infection is accurate. We are still lacking sufficient data regarding the natural history of infection to aid substantially in the management of these patients. Finally, we desparately need new therapeutic approaches to this disease. Hopefully, with greater understanding of the replication of this virus and the mechanism of liver pathogenicity, novel approaches to treatment will be developed.

HIV Infections↗
PubMed1995

Hepatitis C infection in the transplant recipient.

This article highlights the increasing role of HCV in the transplant setting. Its importance in the liver transplant setting is clear. It produces end-stage liver disease and represents a common indication for transplant referral. Recurrent infection is nearly universal posttransplant in those with viremia pretransplant. Acquired disease is uncommon. The natural history of posttransplant disease suggests there is no significant impact of graft or patient survival, at least in the short-term. Long-term follow-up is needed, as well as more detailed study of the factors contributing to posttransplant disease. Kidney transplant patients commonly are infected with HCV prior to transplantation. Acquisition of infection through infected donors also serves as a source of HCV infection. HCV infection after transplantation is associated with an increased risk of liver disease but has no significant effect on short-term patient survival. The issues of organ allocation from anti-HCV-positive donors are particularly relevant to this patient population because maintenance dialysis always is a treatment alternative to transplantation. Much less information is available on other transplant groups, such as heart, lung, and bone marrow transplant recipients. There are many unanswered questions, especially with respect to the natural history of disease after 5 to 10 years of infection. The pathogenesis of infection in the transplant setting is emerging slowly but requires further investigation. Both direct viral cytopathicity and host-mediated immunity appear to play a role in liver injury. An increased understanding of pathogenicity will lead to improved management of patients with HCV infection both pre- and posttransplant.

Disease Transmission, Infectious↗
PubMed1994

"Occult" hepatitis B virus as source of infection in liver transplant recipients.

Hepatitis B virus (HBV) infection almost always recurs after liver transplantation in patients who were surface antigen (HBsAg) positive before surgery but apparent de novo acquisition of infection in a transplant setting has not previously been reported. We have used sensitive techniques to elucidate the origin of such infections in patients in a California transplantation programme. We tested post-transplant serum from 207 patients who had been HBsAg negative and found 20 to be HBsAg positive. The origin of infection was identified in 7 patients, being occult pre-transplant infection in 5 and occult infection in the donor in 2. No pre-transplant patient nor donor with demonstrable HBV DNA had serological markers of hepatitis B. Post-transplant HBV DNA was present in serum from 19 patients. Analysis of the variable pre-S region of HBV demonstrated 100% sequence homology between recipient liver and post-transplant serum (2 patients) and between donor serum and recipient post-transplant serum (2). There was only 84% homology between the 2 different patients infected with subtype adw. 19 patients are alive, 9 without histological evidence of hepatitis (mean follow-up 33 months), and survival was significantly greater than that of a group with recurrent HBV infection. Apparent acquisition of HBV infection with liver transplantation is not rare, and may be due to occult pre-transplant infection or occult infection in the donor. The post-transplant outcome of this infection tends to be benign but our findings do underscore the clinical relevance of HBV infection in the absence of serological markers.

Adolescent↗
PubMed1994

Interferon-alpha therapy for hepatitis C virus infection after liver transplantation.

The aims of this pilot study were to evaluate the safety and efficacy of interferon-alpha 2b for treatment of hepatitis C virus infection in liver transplant recipients, to monitor changes in hepatitis C virus RNA levels with treatment and to determine pretreatment parameters predictive of a complete response. Eighteen patients with documented hepatitis C virus viremia and histological evidence of hepatitis after liver transplantation received 3 million units of alpha interferon three times weekly for at least 4 mo. Pretreatment serum aminotransferase levels were at least 1.5 times the upper limit of normal and no patient had concomitant hepatitis B virus infection. Response to therapy was defined as normalization of both aspartate and alanine aminotransferase at the end of treatment. Five patients (28%) had a complete response, whereas 13 (72%) had persistent elevation of one or both aminotransferases (nonresponders). At the end of therapy, hepatitis C virus RNA levels were reduced in both responders and nonresponders (p = 0.043 and 0.039, respectively by Wilcoxon signed rank test). After cessation of treatment, aminotransferases remained normal in four of five responders but serum hepatitis C virus RNA levels returned to pretreatment levels in responders and nonresponders. There was no significant change in histological score with therapy. Responders were more likely than nonresponders to have low pretreatment hepatitis C virus RNA levels and low serum bilirubin (p = 0.0004 and 0.0077, respectively). Responders tended to have a prolonged interval between transplantation and initiation of therapy (p = 0.10 by rank logistic regression analysis). Side effects resulted in early cessation of therapy in two patients and dose reduction in six.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1994

Pruritus as a symptom of hepatitis C.

Recent isolation, cloning, and sequencing of the hepatitis C genome, which has led to the development of an enzyme-linked immunosorbent assay, has produced increasing recognition of a hepatic disease that frequently leads to potentially lethal, chronic active hepatitis. We describe four patients who had pruritus or in whom pruritus developed as a consequence of hepatitis C. The symptom of pruritus should be added to a growing list of cutaneous manifestations of this newly recognized inflammatory viral hepatitis.

Adult↗
PubMed1994

Screening and confirmatory testing of cadaver organ donors for hepatitis C virus infection: a U.S. National Collaborative Study.

Hepatitis C virus (HCV) can be transmitted by organ transplantation. Cadaver organ donors are screened for HCV infection by testing for antibodies to HCV (anti-HCV). The prevalence of HCV infection and performance of anti-HCV tests in detecting HCV infection in organ donors are unknown. Sera from 3078 cadaver organ donors were tested for anti-HCV by a first generation enzyme-linked immunosorbent assay (ELISA1). Sera from all 137 ELISA1 positive donors and a random sample of 92 ELISA1 negative donors were tested for anti-HCV by a second generation ELISA (ELISA2) and for HCV RNA by the polymerase chain reaction. Organ bank records were reviewed for risk factors associated with HCV infection. Follow-up was available on 70 recipients of organs from 42 ELISA2 positive donors. The prevalence of HCV RNA, extrapolated to all 3078 donors, was 2.4%. Liver disease, anti-HCV and HCV RNA were detected more frequently among recipients of organs from ELISA2 positive donors with HCV RNA than from ELISA2 positive donors without HCV RNA. Among donors, the sensitivity and negative predictive value of the ELISA2 for HCV RNA were 100%. However, despite a specificity of 98.1%, the positive predictive value was only 55.1%. Clinical and laboratory characteristics did not distinguish ELISA2 positive donors with and without HCV RNA. The presence of serum HCV RNA in organ donors predicts the risk of transmission of HCV infection. Discarding organs from ELISA2 positive donors would eliminate transmission, but organs from 1.88 percent of donors would be wasted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Antibody response to hepatitis C virus infection after liver transplantation.

OBJECTIVE: To determine whether liver transplantation and the subsequent immunosuppression affect the antibody response to hepatitis C virus (HCV) infection. METHODS: Sera from 46 patients were compared before and after liver transplantation for markers of HCV infection. Serum HCV RNA was determined by polymerase chain reaction (PCR). Anti-HCV antibody was determined by first- and second-generation immunoassays as well as a quantitative assay of the titer of anti-HCV core antibody. RESULTS: Among individuals who acquired hepatitis C infection in association with liver transplantation, only 15% (3/12) developed antibody to the core antigen and only 25% (3/12) reacted to any antigen present on the second-generation recombinant immunoblot assay after a mean follow-up period of 18 months. Thirty-eight percent (5/13) were positive, by the second-generation enzyme immunoassay (EIA-2) Whereas 94% (16/17) of the individuals who had detectable anti-HCV core antibodies pretransplant continued to have such antibodies after transplant, the titer of these antibodies declined an average of 4-fold. No significant change was seen in the antibody titer toward rotavirus, a common viral pathogen. Patients who acquired HCV infection or in whom the allograft became reinfected had a significantly increased incidence of posttransplant hepatitis (61% vs. 33%, respectively). CONCLUSIONS: Liver transplantation and posttransplant immunosuppression lead to an attenuated antibody response to hepatitis C viral infection. Currently available assays for anti-HCV antibodies may be unreliable in the posttransplant setting.

Adult↗
PubMed1994

Hepatitis C in HIV-infected patients with and without AIDS: prevalence and relationship to patient survival.

BACKGROUND: Limited information is available about the prevalence of hepatitis C virus in patients with human immunodeficiency virus in relation to specific risk factors or about the influence of hepatitis C virus coinfection on survival. This retrospective study addressed these questions. METHODS: The study population consisted of 512 predominantly non-intravenous drug-using male homosexuals, 224 of whom had AIDS. Samples positive for hepatitis C virus antibody by second-generation enzyme immunoassay were further tested by means of strip immunoblot assay, and for hepatitis C virus RNA by means of polymerase chain reaction amplification. A randomly selected set of enzyme immunoassay-negative samples was also tested for hepatitis C virus RNA and, if hepatitis C virus RNA positive, by a second-generation recombinant immunoblot assay. RESULTS: The prevalence of hepatitis C virus infection unaccounted for by intravenous drug use or transfusion was 11.7% by enzyme immunoassay, and 87% of sera positive by enzyme immunoassay were also positive by second-generation recombinant immunoblot assay or hepatitis C virus RNA analysis. Hepatitis C virus RNA was detectable in 53% of enzyme immunoassay-positive samples but in only about 1% of enzyme immunoassay-negative samples. Hepatitis C virus coinfection did not influence survival of HIV-infected patients with or without manifestations of AIDS. CONCLUSIONS: Hepatitis C virus infection in nontransfused, non-intravenous drug-using patients with HIV infection is several times more prevalent than in volunteer blood donors, suggesting homosexual transmission of hepatitis C virus. About half of patients seropositive for hepatitis C virus antibody have detectable hepatitis C virus RNA, and serologically occult hepatitis C virus viremia is rare. Hepatitis C virus coinfection does not appear to adversely influence survival.

Acquired Immunodeficiency Syndrome↗
PubMed1994

New approaches to treatment of chronic viral hepatitis.

Despite rapid progress in knowledge of the biology of hepatitis viruses, the ability to treat chronic infection is limited. In fact, interferon-alpha 2b is the only FDA-approved therapy for chronic HBV and chronic HCV. The authors report on the interferons and evolving therapies for chronic viral hepatitis and conclude with a discussion of liver transplantation.

Chronic Disease↗