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Biomedical subjects

D Gretch

Publications and source records attributed to D Gretch.

14 recordsLinked to original sources
PubMed2006

Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients.

Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3-6 were classified as having advanced fibrosis (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of > or = 2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80.

Adolescent↗
PubMed2000

Humoral immune response to hepatitis C after liver transplantation: assessment of a new recombinant immunoblot assay.

OBJECTIVE: The immune control of infection with hepatitis C virus (HCV) is poorly understood; vigorous antibody responses to viral proteins seem to coexist with the virus and thus whether they are neutralizing remains controversial. HCV-related liver failure is the leading indication for orthotopic liver transplantation (OLT) worldwide. Attenuated antibody responses in immunosuppressed patients and decreased reliability compared to assessment of HCV RNA has hampered the use of antibody testing post-OLT. The goals of this current analysis were twofold: to determine the sensitivity of a prototype strip immunoblot assay (RIBA 3.0, Chiron Diagnostics) for the diagnosis of HCV post-OLT; to determine if there was a correlation between antibody response and severity of histological recurrence. METHODS: The study was comprised of 76 HCV-positive individuals divided into three patient groups: liver allograft recipients with evidence of mild or no histological recurrence (n = 52), liver allograft recipients with evidence of severe HCV recurrence and allograft cirrhosis (n = 12), and nontransplant patients being enrolled in an induction interferon trial (n = 12). All transplant patients had histological follow-up of at least 1 yr. RESULTS: Sixty of the 64 (94%) HCV-positive OLT recipients had 1+ reactivity to two or more recombinant antigens; three of the patients who lacked a detectable response had minimal histological recurrence and one had severe recurrence. All nontransplant patients demonstrated 4+ reactivity to at least two antigens, and 55/64 (86%) OLT recipients demonstrated this same level of reactivity. Seven of the nine patients lacking this high level of reactivity had evidence of minimal recurrence. Furthermore, the mean (+/- SEM) level of antibody reactivity for c100 (p = 0.04) and NS5 (p = 0.01) were significantly lower for patients with mild recurrence after OLT, compared to the other groups. The level of antibody reactivity was unrelated to HCV genotype or viral load. CONCLUSIONS: The recently developed RIBA 3.0 assay for detection of antibodies to HCV appears to be highly sensitive for the diagnosis of HCV post-OLT. In general, the level of antibody reactivity was comparable in the transplant patients and in nonimmunosuppressed controls. The pathogenic implications of the relatively diminished humoral response in patients with mild recurrence post-OLT are discussed.

Antibody Formation↗
PubMed2000

Distinct patterns of glomerular disease in Lima, Peru.

AIM: We performed both a retrospective and prospective study to elucidate the types of glomerular diseases present in adults in Lima, Peru. MATERIAL AND METHODS: In the retrospective study, we analyzed 1,263 renal biopsies over a 10-year period (1985 -1995) that were processed at a central reference renal pathology laboratory in Lima. 101 cases were examined in the prospective study. RESULTS: The most common glomerular diseases observed were those due to systemic lupus erythematosus (30.2%), membranoproliferative glomerulonephritis (MPGN, 14.8%), and focal and segmental glomerulosclerosis (FSGS, 13.9%). Although mesangial-proliferative nephritis was observed in 9.5% of cases, IgA nephropathy was rare (0.9%). Examination of the year to year frequency showed that MPGN has tended to decrease in frequency with time whereas FSGS has been increasing. Although there is known to be a high frequency of infections in Peru, only 4.2% of the cases in the retrospective study were associated with infection. Furthermore, in the prospective study, only one case of hepatitis C and no cases of hepatitis B viral infection were detected, including in the 11 cases of MPGN observed. CONCLUSION: We conclude that the epidemiology of glomerular disease in Lima, Peru, is distinct from most areas of the world, but has similarities to certain regions in Africa, in that MPGN is common whereas IgA nephropathy appears to be rare. Further studies are necessary to elucidate the reasons why the patterns of glomerular disease are different from that observed in other parts of the world.

Adult↗
PubMed1999

Unintegrated HIV-1 circular 2-LTR proviral DNA as a marker of recently infected cells: relative effect of recombinant CD4, zidovudine, and saquinavir in vitro.

Unintegrated HIV-1 proviral DNA is one of the earliest detectable forms of HIV-1, and the influence of an antiretroviral drug on its appearance may reflect the efficacy of that agent in preventing infection of new cells. We characterized the dynamics of HIV-1 p24 (p24) antigen production, HIV-1 gag DNA, tandem long-terminal-repeat circular unintegrated proviral (2-LTR) HIV-1 DNA, HIV-1 tat mRNA, and cell viability in the presence of three antiretroviral agents: recombinant soluble CD4 (rsCD4), zidovudine, and saquinavir. Interference with HIV-1 entry by rsCD4 decreased p24 antigen levels modestly, decreased HIV-1 gag by twofold, and 2-LTR was detectable at the end of the culture period. Inhibition of reverse transcription by zidovudine decreased p24 antigen levels modestly, decreased HIV-1 gag by 19-fold, and inhibited detection of 2-LTR HIV-1 DNA. The protease inhibitor, saquinavir, had the greatest overall effect, with the lowest levels of p24 antigen and HIV-1 gag, and inhibition of 2-LTR. There was no detection of tat mRNA in the saquinavir-treated cultures. In addition, cell viability was significantly higher in cultures treated with saquinavir. In these experiments, 2-LTR HIV-1 DNA was indicative of the relative inhibitory effects of three antiretroviral agents acting at different steps of the HIV-1 replication cycle. We demonstrated in vitro that 2-LTR HIV-1 DNA was a useful indicator of an antiretroviral drug in preventing new cell infection and could be utilized as a dynamic marker of drug efficacy in HIV-1-infected patients.

Anti-HIV Agents↗
PubMed1998

Risk of death among chronic dialysis patients infected with hepatitis C virus.

Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis patients (10% to 40%) and is the most common cause of chronic liver disease. However, there are no studies estimating the risk for death among dialysis patients infected with HCV compared with those not infected. We conducted a prospective cohort study to estimate the risk for death among chronic dialysis patients infected with HCV compared with those not infected. In 1992, 200 patients (91%) who had been undergoing dialysis therapy for at least 6 months consented to be screened for HCV infection by enzyme immunoblot assay and polymerase chain reaction (PCR). Information about potential confounders and potential risk factors for death and HCV infection was obtained from the dialysis center database. Patient outcomes collected included death, transplantation, and loss to follow-up. The Cox proportional hazards model was used to estimate the odds of death among dialysis patients who were positive for the HCV antibody and HCV RNA compared with negative patients. Forty-four patients (22%) were HCV antibody positive. Thirty-four patients (17%) were HCV RNA positive. Patients in the HCV RNA-positive group were more likely to be younger (51.8+/-12.6 v 57.2+/-17.3 years of age), men (77% v 54%), and black (65% v 37%). None of the home hemodialysis or peritoneal dialysis patients were HCV RNA positive, whereas one of the home hemodialysis and one of the peritoneal dialysis patients were HCV antibody positive. Two patients became infected with HCV during the follow-up period. Patients who were HCV RNA positive and those who were HCV antibody positive were at increased risk for death compared with patients who were negative (adjusted relative risk [aRR]=1.78; 95% confidence interval [CI], 1.01 to 3.14; P=0.045; and aRR=1.97; 95% CI, 1.16 to 3.33; P=0.012, respectively), after adjusting for time on dialysis, race, transplantation, and age. We conclude that HCV infection increased the risk for death during the study period compared with those not infected. Further studies should assess the measures used to prevent and treat HCV infection.

Adult↗
PubMed1997

Association of hepatitis C virus infection with mortality and graft survival in kidney-pancreas transplant recipients.

BACKGROUND: Although most studies have not demonstrated decreased patient or graft survival in kidney-alone allograft recipients infected with hepatitis C virus (HCV), the impact of HCV infection on patient and graft survival in HCV-infected kidney-pancreas recipients has not been studied. METHODS: We undertook a retrospective cohort analysis of 137 kidney-pancreas transplant recipients who were transplanted between January 1989 and May 1996. HCV infection was determined by a positive polymerase chain reaction. Relative risk of death and graft failure was calculated using the Cox proportional hazards model with time-dependent covariates. Relative risks were adjusted (aRR) to control for the number of OKT3-treated rejections and cytomegalovirus status of the recipient at the time of transplantation. RESULTS: Mean length of follow-up was 30.4 months in the HCV-infected patients compared with 31.7 months in noninfected patients. Seven (5.1%) patients were infected with HCV before transplant, one (1%) relapsed after transplantation, and four (2.9%) acquired the infection after transplantation. The HCV-infected group had a 3.7-fold (95% confidence interval [CI], 1.0-13.5) increased risk of death after transplant compared with the HCV-negative group, with an aRR of 5.5 (95% CI, 1.5-20.0). Death in the HCV-infected group (n=3) was generally the result of liver failure and sepsis, whereas death for those in the uninfected group (n=11) was primarily of cardiovascular origin. Patients infected with HCV were 3.4-fold (95% CI, 1.1-10.1) more likely to develop kidney graft failure than HCV-negative patients with an aRR of 5.1 (95% CI, 1.7-15.4). The risk of pancreatic allograft failure was not significantly increased. CONCLUSIONS: We conclude that HCV infection in kidney-pancreas transplant patients results in a significantly increased risk of kidney allograft failure and death.

Adult↗
PubMed1995

Hepatitis C virus-associated glomerulonephritis.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and is associated with a variety of extrahepatic manifestations, including cryoglobulinemia and glomerulonephritis. Epidemiologic evidence suggests that HCV infection may be a major risk factor for both cryoglobulinemic and type I membranoproliferative glomerulonephritis (MPGN). Clinical symptoms and laboratory data may or may not reflect the presence of chronic liver disease. Most patients have evidence of hypocomplementemia, circulating rheumatoid factors, and cryoglobulinemia. The pathogenesis of HCV-associated MPGN is probably a result of glomerular deposition of circulating HCV and anti-HCV antibodies. Treatment with interferon-alpha has been shown to improve proteinuria, suppress viremia, and stabilize renal function. However, patients often relapse after therapy is stopped. The optimal therapy remains to be defined but may involve different dosage regimens of interferon-alpha or the combination of several antiviral agents.

Glomerulonephritis↗
PubMed1995

Hepatic ultrasonic changes in workers exposed to perchloroethylene.

OBJECTIVE: To determine if subclinical hepatotoxicity is associated with exposure to perchloroethylene at concentrations commonly experienced in the workplace, and whether surveillance with serum hepatic transaminase activity underestimates such effects. METHODS: Hepatic parenchymal echogenicity on ultrasonography and serum hepatic transaminase activity were compared in 29 community based dry cleaning operators exposed to perchloroethylene, and a control group of 29 non-exposed laundry workers. Perchloroethylene exposure was assessed by work history and air monitoring. RESULTS: Mean hepatic transaminase activities were minimally increased in dry cleaners compared with laundry workers. Increased alanine aminotransferase activities, between 1.0 and 1.5 times the normal limits, were found in five of 27 (19%) dry cleaners compared with one of 26 (4%) laundry workers. In contrast, diffuse parenchymal changes in echogenicity, as determined by hepatic ultrasonography, were increased nearly twofold in dry cleaners, occurring in 18 of 27 (67%) dry cleaners compared with 10 of 26 (39%) laundry workers (P < 0.05), and were most strongly associated with increased perchloroethylene exposure in older dry to dry or wet transfer operations (odds ratio 4.2, 95% confidence interval 1.1-15.3). Mean eight hour time weighted average perchloroethylene exposure for dry cleaners was 16 ppm, which is less than the permissible exposure limit of 100 ppm in the United States. CONCLUSIONS: It was concluded that mild to moderate hepatic parenchymal changes occur more frequently in workers exposed to perchloroethylene than in populations not exposed to chemical solvents, and that these effects are underestimated by serum hepatic transaminase activity.

Adult↗
PubMed1994

Quantitation of hepatitis C viral RNA in sera of hemodialysis patients: gender-related differences in viral load.

Hepatitis C virus (HCV) infection is common in hemodialysis patients, as determined by antibody assays and qualitative polymerase chain reaction (PCR) analysis of serum HCV RNA. To further characterize HCV infection in this population, we measured the viral load in infected hemodialysis patients by a quantitative, competitive PCR assay (QC-PCR) for HCV RNA. Hepatitis C virus RNA levels were correlated with serologic, biochemical, and demographic features of a cohort of hemodialysis patients. Sera from 208 hemodialysis patients were screened for HCV RNA (5' conserved region) by reverse transcriptase PCR (RT-PCR) and HCV-specific antibody. Forty-four patients were antibody positive (21%); among these patients, 34 (77%) were HCV RNA positive. No viremic, seronegative patients were identified. Hepatitis C virus RNA levels quantitated by QC-PCR ranged from 3 x 10(5) to 10(8) molecules of HCV RNA/mL. Male patients had significantly higher mean and median HCV RNA levels (10(7) molecules/mL) compared with female patients (3.6 x 10(6) molecules/mL and 3 x 10(6) molecules/mL, respectfully; P = 0.02). No other demographic or clinical feature of this cohort correlated with HCV RNA levels. Intravenous drug abuse was the most frequently identified risk factor (29% of seropositive patients) for infection with HCV in this population. No association between HCV RNA levels and hepatic enzyme levels (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase) was apparent. Hepatitis C virus infection is highly prevalent in our hemodialysis population, and hemodialysis patients, particularly males, have high levels of HCV in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease.

A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy.

Base Sequence↗
PubMed1992

Use of aminotransferase, hepatitis C antibody, and hepatitis C polymerase chain reaction RNA assays to establish the diagnosis of hepatitis C virus infection in a diagnostic virology laboratory.

Clinical and therapeutic decisions for hepatitis C virus (HCV) infection depend on factors that include documentation of past infection as well as identification of those who might benefit from antiviral chemotherapy with systemic interferon. To evaluate the ability of a diagnostic laboratory to accurately identify such patients, we compared results obtained with serum transaminase assays, two HCV antibody assays (enzyme immunoassay [EIA] and immunoblot), and a polymerase chain reaction (PCR)-based assay for HCV RNA using a group of consecutively submitted samples within our university-based diagnostic virology laboratory and sera from a population of random blood donors. One hundred percent of specimens with R values of greater than 3.0 in the HCV EIA were positive in the confirmatory immunoblot. However, 25% of specimens with EIA R values of between 1.0 and 3.0 were not confirmed by either recombinant immunoblot assay (RIBA) or RNA PCR assay (false-positive specimens). A significant correlation (P less than 0.01) between increasing reactivity in the RIBA and positivity in the RNA PCR assay was found. The incidence of HCV viremia, as determined by the RNA PCR assay, was 73% for confirmed seropositive specimens, 33% for seropositive specimens with indeterminate RIBA results, 12% for seronegative specimens obtained from infected patients, and 2.0% for seronegative specimens obtained from uninfected blood donors. In contrast, serum transaminase testing did not correlate with the RNA PCR assay for HCV. Use of the EIA and immunoblot assay followed by RNA PCR testing will identify most patients who are viremic with HCV.

Alanine Transaminase↗