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Biomedical subjects

K R Reddy

Publications and source records attributed to K R Reddy.

At least 19 recordsLinked to original sources
PubMed1998

Comparison of tacrolimus with microemulsion cyclosporine as primary immunosuppression in hepatitis C patients after liver transplantation.

BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.

Adult↗
PubMed1998

Re-treatment of chronic hepatitis C with consensus interferon .

A multicenter, open-label, phase 3 study was conducted in 337 patients with chronic hepatitis C virus (HCV) infection who had either not responded to previous interferon therapy or had relapsed after discontinuation of therapy with either consensus interferon (9 microg) or interferon alpha-2b (3 million U) three times a week for 24 weeks. Patients were randomized to receive a higher dose of consensus interferon (15 microg) administered subcutaneously three times a week for 24 or 48 weeks and then were observed for an additional 24 weeks. Patients who had relapsed after prior interferon therapy were more likely to have a sustained alanine aminotransferase response and HCV RNA response (as measured by reverse transcription-polymerase chain reaction with a sensitivity of < 100 copies/mL) than were patients who had not responded to prior interferon therapy. For relapsers, the sustained HCV RNA response rate was 58% (48 weeks) and 28% (24 weeks). The sustained alanine aminotransferase response for relapsers was 52% (48 weeks) and 39% (24 weeks). The sustained HCV RNA response rate among prior nonresponders was 13% (48 weeks) and 5% (24 weeks), and the sustained alanine aminotransferase response rate for nonresponders was 17% (48 weeks) and 12% (24 weeks). The administration of 15 microg of consensus interferon was well tolerated and was not associated with an increase in the incidence of side effects. These data demonstrate that re-treatment with 15 microg of consensus interferon is safe and effective therapy for patients with chronic hepatitis C who have either not responded to previous interferon therapy or relapsed after discontinuation of interferon therapy.

Adult↗
PubMed1998

Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group.

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.

Antiviral Agents↗
PubMed1998

Vegetative infection of transjugular intrahepatic portosystemic shunts.

BACKGROUND & AIMS: The occurrence of and the clinical picture of infection of transjugular intrahepatic portosystemic shunts (TIPS) has not been described previously. We describe the clinical features, associated pathogens, results of treatment of a previously unreported complication of TIPS, and primary infection of TIPS occurring after formation of the neointima. METHODS: Patients with TIPS and fever were evaluated to exclude other sources of infection. The diagnosis was based on the occurrence of fever with positive blood cultures and either a thrombus or vegetations on the stent or persistent bacteremia in a patient with a TIPS and no other detectable source of infection despite an extensive search. RESULTS: Eight patients met diagnostic criteria. Two of 8 cases occurred within 10 days of TIPS manipulation despite antibiotic administration before the procedure. The clinical features included fever (8 patients), tender hepatomegaly (5 of 8), hypoxemia (2 of 8), septic pulmonary emboli (1 of 8), septic shock (2 of 8), neutrophilia (5 of 8), and subsequent development of necrotizing fasciitis (1 of 8). Blood cultures were positive in all cases. The organisms included oral and enteric aerobic gram-negative bacteria in 7 of 8 patients and Candida in 1 patient. All 8 responded to administration of antibiotics. Two patients died of myocardial infarction and alcoholic hepatitis, respectively. CONCLUSIONS: Infective endotipsitis is an uncommon complication of TIPS. Recognition of its clinical features will facilitate diagnosis. Most patients responded to antibiotic therapy.

Adult↗
PubMed1998

Detection of anti-hepatitis C virus antibodies in patients undergoing dialysis by utilizing a hepatitis C virus 3.0 assay: correlation with hepatitis C virus RNA.

Hepatitis C virus (HCV) infection is endemic in long-term dialysis units. We assessed the performance of a recently developed HCV 3.0 assay for the detection of HCV antibodies in patients undergoing dialysis. The study evaluated 128 patients undergoing long-term maintenance hemodialysis. Anti-HCV was detected by 2.0 and 3.0 enzyme immunoassay (EIA). Results were confirmed with recombinant immunoblot assays (RIBA 2.0 and RIBA 3.0). HCV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR). Thirty-two patients (25%) were HCV EIA 2.0 positive. Of these, 1 was RIBA 2.0 negative (PCR positive), 3 were indeterminate (3 PCR positive), and 28 were positive (23 PCR positive). Thirty-five (27%) were HCV EIA 3.0 positive. One was RIBA 3.0 negative (PCR positive), 1 was indeterminate (c33c, PCR positive), and 33 were positive (27 PCR positive) by RIBA 3.0. Thus only 1 PCR-positive patient was negative with RIBA 2.0 and 3.0 assays. Two of the 3 RIBA 2.0 indeterminate samples were positive with RIBA 3.0. One remained indeterminate but was HCV RNA positive. In summary, HCV 3.0 EIA detected 4 additional viremic patients but was positive in 6 PCR-negative subjects. A high correlation of the presence of antibody to c33c with HCV RNA (28 of 34, 82%) was found, and it was found in all anti-HCV positive samples and in 1 indeterminate sample. We conclude that the HCV EIA 3.0 test with the supplemental confirmatory RIBA 3.0 test may improve the sensitivity for the detection of anti-HCV. Nevertheless, in potentially immunocompromised patients undergoing dialysis, PCR continues to be the only reliable test for detecting viremia.

Adult↗
PubMed1998

Prevalence of hepatitis C and G virus infection in chronic hemodialysis patients.

An RNA virus designated hepatitis G virus (HGV) has been recently identified in patients with acute and chronic liver disease. HGV is transfusion transmissible, it has global distribution, and it is present in the volunteer blood donor population in the United States. One hundred sixty patients undergoing maintenance hemodialysis at the University of Miami-affiliated unit were evaluated. There were 99 men and 61 women ranging in age from 22 to 80 years. Sixty percent had a history of blood transfusion, 6% had a history of drug abuse, and 9% were infected with the human immunodeficiency virus. HGV-RNA was detected by reverse-transcriptase polymerase chain reaction with amplification of two independent regions (5'-nontranslated region and NS5a coding region). Detection of digoxigenin-labeled amplification products with specific capture probes to the coding and noncoding regions was performed with the Enzymun-test DNA on an ES-300 Immunoassay System (Boehringer-Mannheim, Mannheim, Germany). Hepatitis C antibodies were measured with anti-hepatitis C virus enzyme-linked immunosorbent third-generation assays and hepatitis C virus RNA by reverse-transcriptase polymerase chain reaction. There were 32 (20%) patients with detectable HGV RNA with both primer pairs. Because of possible mutations, the HGV virus may be detectable only with one primer pair. We considered the latter as indeterminate: 12 had detectable levels to the NS5a region only, seven to the 5'-nontranslated region, and six had borderline results. Detectable and indeterminate samples were confirmed by repeat measurements in a new blood sample. Seven of 24 (29%) patients with detectable hepatitis C virus RNA had coexisting HGV with one or both HGV primer pairs (four with both and three with one). Five patients were hepatitis B surface antigen positive and HGV negative. We conclude that HGV infection is prevalent in our dialysis patients. The clinical significance of HGV infection remains to be established.

Adult↗
PubMed1997

Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation.

BACKGROUND: Orthotopic liver transplantation for end-stage hepatitis-B-virus (HBV) infection is commonly complicated by recurrence of HBV. Lamivudine, a cytosine nucleoside analogue, has been shown to suppress HBV infection. We report the development of resistance to lamivudine in three patients who underwent transplantation for end-stage liver disease secondary to hepatitis B. METHODS: Two of the patients received lamivudine for recurrent HBV infection after transplantation, whereas the third patient began treatment 1 month before transplantation in an attempt to prevent HBV recurrence after transplantation. The three patients initially responded well to treatment, but viral recurrence occurred after 9-10 months of treatment in all patients. HBV DNA was amplified from serum and sequenced through a conserved polymerase domain-the tyrosine, methionine, aspartate, aspartate (YMDD) locus. We assessed the susceptibility of HBV to lamivudine by infecting primary human hepatocytes with serum taken before the start of treatment and after recurrence in varying concentrations of lamivudine. FINDINGS: DNA sequencing showed a common mutation within the YMDD locus of the HBV polymerase gene in all patients during lamivudine treatment. In hepatocyte cultures infected with pretreatment serum, HBV DNA concentrations were reduced to less than 6% of those in control cultures by addition of lamivudine in concentrations as low as 0.03 mumol/L. By contrast, in cultures treated with serum taken after recurrence, HBV DNA concentrations did not fall below 20% of control values, even with lamivudine at 30 mumol/L. INTERPRETATION: Resistance to lamivudine has been reported in HIV patients with mutations in the YMDD locus of the polymerase gene. Our findings indicate a common mechanism of lamivudine resistance for HIV and HBV that involves similar point mutations in homologous domains of the viral polymerases.

Antiviral Agents↗
PubMed1997

'Domino' liver transplantation combined with multivisceral transplantation.

Transplantation of the liver contemporaneously with another organ from the same donor is thought to confer an immunologic advantage. The latter is particularly desirable in intestinal transplantation because of the propensity of the intestinal graft to early and late rejections and because in some cases it may facilitate the operation. In clinical practice, shortage of liver grafts constrains liver transplantation to cases in which there is coexisting end stage liver disease.

Adolescent↗
PubMed1997

Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group.

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

Adult↗
PubMed1997

Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study.

BACKGROUND & AIMS: Cirrhotic patients with a prolonged prothrombin time (PT) are known to have low levels of factor VII. Because the current modalities to correct this problem are not ideal, recombinant factor VIIa (rFVIIa) may be useful in correcting the prolonged PT observed in the coagulopathy of cirrhosis. The aim of this study was to evaluate the effectiveness of rFVIIa in nonbleeding volunteer patients with the coagulopathy of cirrhosis. METHODS: A preliminary, single-center, dose-escalation trial was performed. Cirrhotic patients with a PT of > 2 seconds above the upper limit of the reference value received an intramuscular injection of vitamin K. Ten patients whose PT did not correct to within 2 seconds above the control of the upper limit of the reference value were given three successive dosages of rFVIIa (5, 20, and 80 micrograms/kg) during a 3-week period. RESULTS: The mean PT transiently corrected to normal in all three dosage groups. No adverse effects were noted. There was no evidence of the induction of disseminated intravascular coagulation. CONCLUSIONS: This preliminary trial shows rFVIIa to be effective in transiently reversing the prolonged PT in a select group of nonbleeding cirrhotic patients. These preliminary observations support conducting a large-scale efficacy trial.

Adult↗
PubMed1996

Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy. Collaborative Study Group.

OBJECTIVE: To study 1) the geographic distribution and clinical significance of hepatitis C virus (HCV) genotypes in the United States and 2) the influence of HCV genotypes on response to interferon therapy. DESIGN: Hepatitis C virus genotype was determined in 179 stored serum samples obtained from patients who were positive for antibody to HCV and for HCV RNA by using polymerase chain reaction. SETTING: Tertiary referral centers in four geographic regions of the United States. PATIENTS: Patients who visited medical centers in the Midwest (50 patients), Northeast (42 patients), Southeast (35 patients), and West (52 patients). MEASUREMENTS: Chaotropic lysis and isopropanol precipitation were used to extract RNA from serum. Polymerase chain reaction was done on the NS5 region and was followed by automated direct sequencing and genotyping of desalted amplification products. RESULTS: 104 patients (58%) had subtype 1a; 38 (21%) had subtype 1b; 4 (2%) had subtype 2a; 23 (13%) had subtype 2b; 8 (5%) had subtype 3a; and 2 (1%) had subtype 4a. Examination of the known risk factors for acquiring HCV showed no association between genotype and mode of acquisition (blood transfusion, injection drug use, employment at a health care facility) or histologic findings at presentation (mild active hepatitis, moderately active hepatitis, or cirrhosis). Sixty-eight percent of patients with genotype 1a, 80% of patients with genotype 1b, and 37% of patients with genotype 2a or 2b had severe hepatitis. Thirteen of 46 (28%) patients with genotype 1a and 4 of 15 (26%) patients with genotype 1b had a complete biochemical response after 6 months of interferon therapy. In contrast, 10 of 14 (71%) patients with genotype 2a or 2b had a complete response to interferon therapy. Five of 39 (13%) patients with genotype 1a, 1 of 14 (7%) patients with genotype 1b, and 2 of 11 (18%) patients with genotype 2a or 2b had a sustained biochemical response. CONCLUSIONS: In the United States, HCV genotypes 1a and 1b are the predominant genotypes in patients with chronic hepatitis C. Genotype is not correlated with mode of virus acquisition or with histologic findings at presentation. Patients with HCV genotype 1a or 1b had more severe liver disease and lower rates of response to interferon therapy than did patients with HCV genotype 2a or 2b. These findings may have implications for predicting outcome and selecting patients for interferon treatment.

Adult↗
PubMed1996

The role of laparoscopy in the diagnosis of cirrhosis.

BACKGROUND: A definitive diagnosis of cirrhosis is important in the prognosis and management of patients with chronic liver disease. The diagnosis of cirrhosis is made either by histologic examination of a biopsy specimen or upon visualization of a diffusely nodular and firm surface of the liver at laparotomy or laparoscopy. A liver biopsy, however, may not demonstrate the histologic features of cirrhosis in some cirrhotic patients. Our goal in this study was to compare the accuracy of liver descriptions made during laparoscopy with liver histology found by laparoscopic biopsy in patients with chronic liver disease. METHODS: A retrospective review of paired laparoscopy and histology reports was performed on 434 consecutive patients who underwent laparoscopy between 1992 and 1994. (M:F ratio, 1.3:1; mean age, 48 +/- 14 years). ETIOLOGY: 52% hepatitis C, 8% hepatitis B, 8% fatty liver, 4% primary biliary cirrhosis, 3% autoimmune hepatitis, and 25% miscellaneous (cancer patients were excluded). RESULTS: One hundred sixty-nine patients had laparoscopic evidence of cirrhosis; 115 were confirmed by histology, representing a 32% sampling error. Two of 265 patients with histologic evidence of cirrhosis (0.8%) had no macroscopic evidence of cirrhosis at laparoscopy. CONCLUSIONS: (1) There was a 32% histologic sampling error among patients documented to have cirrhosis by laparoscopy. (2) Using laparoscopy as a gold standard, the sensitivity of liver biopsy was 68% and the specificity was 99%.

Adult↗
PubMed1996

Prognostic assays in multiple myeloma: correlated with flow cytometry.

DNA ploidy of plasma cells in bone marrow has been indicated to play a role in treatment response of multiple myeloma. Therefore, a prospective study was done to test this correlation. Univariate DNA flow cytometry was done on 13 proved multiple myeloma patients. Patients aged below 50 years showed hypodiploidy, irrespective of 'S' phase population, where as all patients above 50 years had diploidy or hyperdiploidy, except for one patient. Early stage patients (I & II) with less than 25% plasma cells in bone marrow were all aneuploids. Patients belonging to advanced clinical stage with more than 60% plasma cells in bone marrow with aneuploidy, especially hyperdiploidy (DI > 1.15), carried a poor prognosis. It was difficult to correlate the 'S' phase fraction with other parameters from the present data. Further study with BrdU labelling to determine the proliferative status of the 'S' phase cells is needed.

Adult↗