Correlation of HCV-RNA levels in serum and liver of patients with chronic hepatitis C.
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Blood↗
Biomedical subjects
K R Reddy
Publications and source records attributed to K R Reddy.
Correlation of HCV-RNA levels in serum and liver of patients with chronic hepatitis C.
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Chronic Disease↗
Absence of anti-LKM-1 antibody in hepatitis C viral infection in the United States of America.
Several studies from Europe have observed a relationship between hepatitis C virus infection and anti-liver/kidney microsome-1 (anti-LKM-1) positive chronic hepatitis. It has been suggested that hepatitis C may induce an autoimmune phenomenon that leads to the development of a specific type (type II anti-LKM-1 positive) autoimmune chronic hepatitis. We evaluated 204 sera from patients with well-documented hepatitis C infection from two centres in the United States of America and compared them with sera from 428 French patients from three centres. We evaluated the serological prevalence of anti-smooth muscle antibodies, anti-nuclear antibodies, anti-liver cytosol antibodies, and anti-mitochondrial antibodies subtype anti-M2 in patients with chronic hepatitis C. The two groups were matched in their ages, gender, mode of transmission of hepatitis C infection and severity of liver disease. Anti-LKM-1 was not observed in the patients from the USA at a time when it was noted in 3.7% of French patients. There were no differences, however, in the expression of other auto-antibodies, which were often in low titres. Absence of anti-LKM-1 in USA sera in comparison with French sera suggests that there may be differences in induction of anti-LKM-1 related to environmental and/or host genetic factors, and/or genomic variation in the hepatitis C virus.
Age Factors↗
Identification of hepatitis C virus by immunoelectron microscopy.
Sequencing of the hepatitis C virus (HCV) has provided a better understanding of the natural history, immunology, and epidemiology of this virus. However, the morphology of HCV has not been definitively characterized. In this study, through a sequence of concentration processes, virus-like particles were isolated from human serum and liver tissue, visualized by transmission electron microscopy and identified as hepatitis C virion by immunoelectron microscopy. Spherical flavi-like virus particles, approximately 70 nm in diameter, were observed in the fraction with 1.04-1.12 g ml-1 sucrose density and bound to immunogold particles with monoclonal antibodies (mAb) against hepatitis C. The nucleocapsid of the particles, which were 50 nm in diameter, appeared to be icosahedral in structure and surrounded by an envelope covered with surface projections. A 'tadpole' form of particles was also observed. The findings indicate that the low buoyant density in sucrose and the morphological features of the hepatitis C virion are consistent with the characteristics of flaviviruses and pestiviruses.
Animals↗
Hepatitis C virus in alcoholic patients with and without clinically apparent liver disease.
A high prevalence of antibodies to the hepatitis C virus (anti-HCV) has been demonstrated among patients with alcoholic liver disease, whereas the prevalence of HCV viremia in these patients remains uncertain. The aims of this study were to determine the prevalence of anti-HCV in alcoholic patients both with and without clinically apparent liver disease and to determine the presence of HCV RNA in those patients who tested positive for anti-HCV by RIBA II (Chiron Corporation, Emeryville, CA). One hundred male patients consecutively admitted to an alcoholic rehabilitation program were included. Group 1 was comprised of 40 patients with clinically apparent liver disease. Group 2 was comprised of 60 patients without clinically apparent liver disease. Anti-HCV was performed by a second-generation ELISA assay and confirmed by RIBA II. HCV RNA was performed by Quantiplex assay (Chiron Corporation) and a nested reverse transcriptase-polymerase chain reaction. No significant differences were found between the two groups with regards to age, quantity and duration of alcohol intake, or accepted risk factors for HCV. The overall prevalence of anti-HCV in our patients was 23%, with 43% of these in group 1 and 10% in group 2. HCV RNA tested positive in 94% of the anti-HCV-positive patients in group 1 and in 67% of the anti-HCV-positive patients in group 2. These data suggest that HCV infection is an important cofactor in the pathogenesis of liver disease among alcoholic patients.
Adult↗
Canities and vitiligo complicating interferon therapy for hepatitis C.
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Alopecia↗
Diagnostic laparoscopy: a 5-year experience in a hepatology training program.
Diagnostic laparoscopy continues to have a role in the evaluation and diagnosis of acute and chronic liver diseases, primary and metastatic liver tumors, and peritoneal diseases. We retrospectively reviewed the records of 1794 diagnostic laparoscopies performed at our institution from 1987 to 1992 to identify the indications, results, and safety of this procedure in our training program. A definitive diagnosis was made in 91% of cases with biopsy performed in 93%. Chronic liver disease was evaluated in 890 patients, and a diagnosis was made in 98%. Four hundred thirty-seven patients were evaluated for suspected primary or metastatic carcinoma, and a diagnosis was made in 85%. Ascites was evaluated in 73 patients, and a diagnosis was made in 82%. One-hundred sixty-four patients were evaluated for abnormal liver function tests, and a diagnosis was made in 91%. HIV-related liver function test abnormalities were evaluated in 67 patients, and a diagnosis was made in 81%. One hundred sixty-three patients underwent diagnostic laparoscopy for the evaluation of hepatomegaly, splenomegaly, unexplained portal hypertension, fever of unknown origin, and cholestasis, and a diagnosis was made in 74% of cases. Eight major complications (including abdominal viscus perforation, hemobilia, splenic laceration, bleeding) and thirty-one minor complications were seen. Our findings confirm that diagnostic laparoscopy is a safe and valuable procedure in the evaluation of chronic liver disease.
Chronic Disease↗
Procollagen-III peptide and chronic viral C hepatitis.
UNLABELLED: Chronic hepatitis develops in at least half of persons acutely infected with hepatitis C virus (HCV). Ten to 25% of these patients will develop cirrhosis. Serum procollagen-III peptide (PIIIP) may be of value in predicting the development of chronic active fibrogenic liver disease. It has been reported that in chronic viral C hepatitis, the levels of hepatitis C virus-RNA (HCV-RNA) correlate directly with the severity of hepatic histology and inversely with response to interferon therapy. OBJECTIVES: The aims of this study were to correlate the level of PIIIP with HCV-RNA concentrations, ALT values, and histological severity in patients with chronic viral C hepatitis. METHODS: Eighty-six patients with chronic C hepatitis were divided into three groups: group I (n = 34), mild chronic active hepatitis, group II (n = 25), moderate to severe chronic active hepatitis, and group III (n = 27), cirrhosis. HCV-RNA was measured by Quantiplex, and PIIIP was measured by radioimmunoassay-gnostic assay. RESULTS: Mean +/- SD level of ALT in group I was 114 +/- 48 U/L, group II was 169 +/- 115 U/L, and group III was 160 +/- 94 U/L. The mean +/- SD level of HCV-RNA in group I was 110 +/- 130 x 10(5) Eq/ml, in group II was 140 +/- 140 x 10(5) Eq/ml, and in group III was 70 +/- 80 x 105 Eq/ml. The mean +/- SD level of PIIIP in group I was 0.6 +/- 0.2 U/ml, in group II was 0.9 +/- 0.4 U/ml, and in group III was 1.2 +/- 0.6. There was a significant difference in the levels of PIIIP among the three groups (p = 0.0001). There was no correlation among ALT, HCV-RNA, and PIIIP in any of the three groups. CONCLUSIONS: PIIIP peptide determinations in patients with chronic viral C hepatitis are reflective of histological severity and may provide relatively noninvasive means of following disease progression.
Alanine Transaminase↗
Hepatotoxicity of antimicrobial, antifungal, and antiparasitic agents.
Several antibiotics are known to be hepatotoxic. Apart from subtle, reversible, and often inconsequential abnormalities, cholestasis is the predominant presentation that has a protracted and disabling course. Hepatitis, like illness, is characteristic of some drugs, and chronic liver disease may evolve. It is important to recognize if a patient has an adverse reaction to a drug because continuing use of the drug in the face of hepatitis can have disastrous consequences. Chronic liver disease may ensue and progress onto cirrhosis; this has typically been seen following use of isoniazid and nitrofurantoin. Cholestatic liver disease can progress into a chronic form of a ductopenic state; this is particularly seen after antibiotic-related cholestasis.
Anti-Bacterial Agents↗
A phase I study of chemoembolization with cisplatin and lipiodol for primary and metastatic liver cancer.
Twenty patients with either unresectable primary hepatocellular carcinoma or hepatic metastases were entered into a chemoembolization program with cisplatin and lipiodol; 19 patients were evaluable for response. Doses of cisplatin ranged from 40 to 100 mg/m2. Toxicity was tolerable and reversible and included abdominal pain, transient elevation in serum creatinine, serum bilirubin, and serum transaminases. Less common side effects include fever, ascites or pleural effusion, and hiccups. Two of four patients with ocular melanoma had partial responses. Duration of response was 10 and 11 months. Among 8 patients with unresectable hepatoma, 2 patients had partial response for 10+ and 13 months, 2 had minor response for 2 months and 4+ months, 1 patient had stable disease for 5+ months, and 3 patients failed to respond. Of the six colon cancer patients treated, one had a partial response in the liver, but developed progressive nodal disease, and another patient had a partial response for 3 months. Chemoembolization of the liver with cisplatin and lipiodol is feasible and doses of cisplatin at least 100 mg/m2 are tolerable. Antitumor activity in metastatic ocular melanoma is encouraging but requires further study.
Adult↗
Detection of hepatitis C virus RNA in hemodialysis patients.
The clinical significance of the high prevalence of antibodies to hepatitis C virus (HCV) in dialysis patients remains undefined. In order to assess the relationship between seropositivity and potential infectivity, 63 patients undergoing maintenance hemodialysis were evaluated between April and May 1990. The mean duration of maintenance hemodialysis was 45 mo (range, 13 to 144). Eighty-two percent (52 of 63) had received blood transfusions, and 16% (10 of 63) had a history of iv drug abuse. Serum samples were analyzed by HCV-cDNA polymerase chain reaction; antibodies to HCV structural (core) and nonstructural regions NS3 and NS4 were determined by enzyme immunoassay. Specimens repeatedly reactive for anti-HCV and HCV-RNA-positive samples were tested by HCV MATRIX dot immunoblot assay and HBV-DNA PCR. Twenty-five percent (16 of 63) were anti-HCV-positive. Of the 16 anti-HCV-positive patients, HCV-RNA was detected in 5 (31%) with the NS3 primers and in 12 (75%) with 5'-noncoding primers. Among the anti-HCV-negative patients, HCV-RNA was detected in 2 (4.3%) of 47 patients. Eleven of the 18 patients with HCV infection (anti-HCV and/or HCV-RNA-positive) had evidence of additional present or past viral infections (human immunodeficiency virus and/or hepatitis B virus). In summary, HCV-RNA is present in at least 75% of anti-HCV-positive patients, suggesting that they may be infectious. The detection of HCV-RNA in anti-HCV-negative patients may indicate early or chronic HCV infection not detected by current antibody assays or the inability of these patients to mount or sustain a significant antibody response.
Adult↗
Indeterminate hepatitis C.
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Hepacivirus↗
Further characterization of the redox and spectroscopic properties of Azotobacter vinelandii ferritin.
Bacterial ferritin from Azotobacter vinelandii (AVBF) has many properties in common with and a number of properties distinct from the more thoroughly studied animal ferritins. The most notable differences are the high phosphate content of the mineral core and the presence of heme (12 per AVBF) in AVBF. In both ferritin types, redox reactions are essential to the iron release and deposition function of the ferritins. The heme reduction potential in apo AVBF is pH independent as are both the heme and core reduction potential in holo AVBF. pH measurements confirm the pH independence for heme reduction in apo AVBF; however, they establish the conflicting result that 1.7 +/- 0.2 protons per iron atom are taken up during core reduction. These results are interpreted as a two-step reduction process consisting of a pH independent reduction of heme in holo AVBF followed by a pH dependent reduction of the mineral core. Detailed spectroscopic studies have been undertaken to determine if heme-core interactions are detectable during the redox reactions of AVBF. Optical spectroscopy of the heme groups in apo AVBF demonstrate that all twelve are identical and undergo uniform and rapid reduction. EPR spectroscopy establishes the presence of both low-symmetry, g = 4.3, Fe3+ from the mineral core and low-spin heme with g values of 2.87, 2.32, and 1.46 in holo and identical g values for the low-spin heme in apo AVBF. EPR integration of the heme groups in both apo and holo gave values of 13.2 +/- 1.3 heme spins per AVBF at 4.2, 10, 25, 35, and 45 K. No heme perturbations were detected in holo or apo AVBF by Resonance Raman and circular dichroism spectroscopy. Both reduced and oxidized apo AVBF gave normal fluorescence emission at 330-340 nm when excited at 279 nm. These spectroscopic, redox, and reactivity results provide more detailed properties of AVBF for comparison with other bacterial and animal ferritins.
Azotobacter vinelandii↗
Enhancement of neutrophil-mediated injury to bovine pulmonary endothelial cells by Pasteurella haemolytica leukotoxin.
In this study, we used an in vitro coculture system to determine which virulence factor from Pasteurella haemolytica A1 was responsible for augmenting bovine polymorphonuclear neutrophil (PMN)-mediated killing of bovine pulmonary artery endothelial cells (BPAEC). A 51Cr release cytotoxicity assay was used as a measure of BPAEC killing. The mechanisms associated with this BPAEC killing were also studied. Our results demonstrated that the leukotoxin and not the lipopolysaccharide from P. haemolytica was responsible for augmenting the PMN-mediated killing of BPAEC. Furthermore, this augmented killing was related to the stimulation of PMNs by the leukotoxin. Killing of BPAEC by leukotoxin-stimulated PMNs was diminished in the presence of the H2O2 inactivator, catalase. The membrane-permeant H2O2, hydroxyl radical (HO.) scavenger 1,3-dimethyl-2 thiourea, and the HO. scavenger dimethyl sulfoxide but not the myeloperoxidase inhibitor sodium azide attenuated this BPAEC killing. Pretreatment of BPAEC with a 21-aminosteroid (U74500A), a potent iron chelator-antioxidant, provided the most effective protection against BPAEC killing induced by leukotoxin-stimulated PMNs. These data were compatible with the concept that the H2O2 generated by leukotoxin-stimulated PMNs interacts with intracellular iron in the endothelial cell to form highly reactive HO.. We suggest that HO. may be a key factor in BPAEC killing. Furthermore, since the elastase-specific inhibitor N-methoxy-succinyl-Ala-Ala-Pro-Val-chloromethyl ketone (CMK) also attenuated BPAEC killing and both CMK and 1,3-dimethyl-2 thiourea functioned additively in protecting against BPAEC killing, we conclude that both HO. and elastase may jointly contribute to BPAEC killing induced by leukotoxin-stimulated PMNs. This study broadens our understanding of how leukotoxin-stimulated PMNs injure lung endothelial cells and provides new insight into the pathogenesis of bovine pneumonic pasteurellosis.
Amino Acid Sequence↗
Detection of hepatitis C virus antibody by first and second generation assays and polymerase chain reaction in patients with autoimmune chronic active hepatitis types I, II, and III.
In this study we have attempted to classify a group of North American patients with autoimmune chronic hepatitis into types I, II, and III according to the class of autoantibody present in serum, and determine the prevalence and significance of antibody to hepatitis C virus (anti-HCV). A total of 62 patients (type I, 51; type II, 3; type III, 8) were tested with first-generation enzyme-linked immunosorbent assay (ELISA)-1. Seropositive patients were assessed by second-generation recombinant immunoblot assay (RIBA)-2 and polymerase chain reaction (PCR). Our results demonstrate that 12 (19%) of the 62 patients with autoimmune hepatitis were anti-HCV ELISA-1 positive (type I, 9; type II, 1; type III, 2). Only one patient with type II autoimmune hepatitis was reactive by RIBA-2 and PCR. Eight of the 12 seropositive patients entered remission after corticosteroid therapy and seven of them became seronegative by ELISA-1. The RIBA-2 and PCR reactive patient did not respond to immunosuppressive therapy and remained seropositive. We conclude that there is a low prevalence of anti-HCV antibody in autoimmune hepatitis. Results based only on ELISA-1 anti-HCV testing can be misleading, and second-generation testing is necessary to recognize the presence of HCV infection. The fact that the only RIBA-2 reactive patient had type II autoimmune hepatitis may suggest a role for HCV infection in the pathogenesis of this condition. Nevertheless, corticosteroid therapy remains effective in those patients who are ELISA-1 seropositive, but RIBA-2 and PCR nonreactive.
Adolescent↗
Budd-Chiari syndrome associated with the hypereosinophilic syndrome.
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Adult↗
Viral pathogenesis of hepatocellular carcinoma in the United States.
Chronic hepatitis B virus infection is closely associated with the development of hepatocellular carcinoma, which is a major cause of cancer death worldwide. Recent studies have implicated hepatitis C virus infection as a major pathogenic agent of HBsAg-negative hepatocellular carcinoma. The significance of hepatitis C virus and hepatitis B virus infections in the occurrence of HBsAg-negative hepatocellular carcinoma has not been well established in the United States. We studied 91 HBsAg-negative American patients with hepatocellular carcinoma for evidence of hepatitis C virus or hepatitis B virus infection. These patients had no other predisposing factors to hepatocellular carcinoma. A sensitive polymerase chain reaction was employed to detect hepatitis C virus RNA and hepatitis B virus DNA in serum and liver. Three sets of hepatitis C virus and hepatitis B virus primers were used to optimize the detection of viral genomes. Hepatitis C virus antibodies were measured with second-generation immunoassays. Twenty-six (29%) of these patients carried low levels of hepatitis B virus DNA in either serum, liver/tumor tissue or both. On the basis of the results from serological and polymerase chain reaction analyses of serum and liver, we found that 53 of 91 patients (58%) exhibited evidence of hepatitis C virus infection. When data were combined, 14 patients (15%) had evidence of hepatitis B virus/hepatitis C virus coinfection, whereas 12 (13%) were infected with hepatitis B virus alone and 39 (43%) had hepatitis C virus only. Twenty-six (29%) had no markers of hepatitis B virus or hepatitis C virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗