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Biomedical subjects

L J Jeffers

Publications and source records attributed to L J Jeffers.

At least 19 recordsLinked to original sources
PubMed1999

Persistence of hepatitis C virus in a human megakaryoblastic leukaemia cell line.

Thrombocytopenia is a frequent clinical finding in patients with hepatitis C virus (HCV) infection. Platelets from patients with HCV infection have been identified as carriers of HCV RNA in our previous studies. The present study was designed to further investigate the possibility of HCV replication in megakaryoblasts from which platelets are eventually released. A megakaryoblastic cell line (MEG-01), established from a chronic myelogenous leukaemia patient 13 years ago, was used for this study. The MEG-01 cells were inoculated with fresh serum from a patient with HCV infection and renamed MEG-01-I cells. Surprisingly, both MEG-01 and MEG-01-I were positive by HCV reverse transcription-polymerase chain reaction (RT-PCR) for the existence of HCV RNA and minus-strand HCV RNA, regardless of inoculation. This was further confirmed by in situ RT-PCR. The HCV antigens, such as core, envelope, and non-structural (NS)3 and NS4, were also present in both cell lines, as identified by Western blotting and indirect immunofluorescence staining. In addition, virus-like particles were observed by electron microscopy in the MEG-01 cell line as well as in the MEG-01-I cell line. These findings indicate that the megakaryoblasts are vulnerable to HCV infection and that replication of HCV can occur in these cells. This may help us to better understand the pathogenesis of thrombocytopenia in patients with HCV infection. The MEG-01 cell line, which may have been continuously shedding HCV for years, should be a useful model for experimental research into HCV.

Fluorescent Antibody Technique↗
PubMed1999

A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer.

Thirty patients with primary hepatocellular carcinoma or liver metastases were entered into a program of chemoembolization with cisplatin, lipiodol, and escalating doses of thiotepa. Doses of cisplatin were 100/m2, and thiotepa doses ranged from 9 mg/m2 to 24 mg/m2. Two of three patients with ocular melanoma had partial responses in the liver metastases for 3+ and 16 months. In patients with either hepatocellular carcinoma (15 patients) or primary cholangiocarcinoma of the liver (three patients), there were two partial responses, for 22 and 33 months. Five patients had minor responses: four with a 40% reduction in tumor and one with a mixed response. There were four early deaths, which involved sepsis in two patients, respiratory failure in one, and acute myocardial infarction in one. Otherwise, toxicity was tolerable and reversible and included abdominal pain and transient elevation of serum creatinine, bilirubin, and transaminases. Less common toxicities included ototoxicity and peripheral neuropathy. Chemoembolization of the liver with cisplatin, thiotepa, and lipiodol can produce responses, but toxicity can be significant. The recommended starting phase II dose for future studies is thiotepa 24 mg/m2 and cisplatin 100 mg/m2.

Adult↗
PubMed1999

Hepatitis C and alcohol.

BACKGROUND: Alcohol abuse and hepatitis C virus (HCV) infection frequently coexist in patients with chronic liver disease. It is widely believed that alcohol and HCV act synergistically in these patients to promote the development and progression of liver damage. METHODS: A review of the relevant medical literature, identified by computer assisted literature search, was conducted. RESULTS: It has been established that alcohol consumption is associated with the accelerated progression of liver injury, higher frequency of cirrhosis, and higher incidence of hepatocellular carcinoma. Alcohol abuse is also associated with decreased response to interferon treatment, and there are reports to suggest that patients with HCV cirrhosis, who abuse alcohol, have higher mortality than those who do not. Abstinence may reverse some of these deleterious effects of alcohol, and may even improve the ultimate response to treatment. The mechanism for the synergistic effect of alcohol and HCV is not fully understood, but has been attributed to alcohol's effect on viral replication, or to its effect on the immune system, hepatic iron content, or hepatic regeneration. CONCLUSIONS: Alcohol has a deleterious effect on HCV associated liver disease. It is recommended that patients with HCV infection abstain from alcohol consumption.

Alcoholism↗
PubMed1998

Small-diameter (2 mm) laparoscopy in the evaluation of liver disease.

BACKGROUND: Percutaneous liver biopsy fails to demonstrate cirrhosis in approximately 32% of cases when compared with laparoscopy with liver biopsy. The aim of this study is to determine the usefulness of small-diameter (2 mm) laparoscopes compared with larger laparoscopes. METHODS: Patients undergoing diagnostic laparoscopy for various liver diseases were evaluated with small-diameter (2 mm) laparoscopes either alone or in combination with a 5 or 10 mm laparoscope. RESULTS: Twenty patients were enrolled in this study. Small-diameter laparoscopes provided appropriate visualization of the abdominal organs and proper guidance to liver biopsy in 9 cases. In the remaining 11 cases a larger laparoscope was used for the following reasons: short length of the trocar/introducer in a morbidly obese patient (1), liver mass located in the anterosuperior aspect of the liver precluding good visualization with forward lenses (1), and inability to properly visualize the anterosuperior aspect of the liver (9). No complications were noted with the use of the small-diameter laparoscopes alone. CONCLUSION: There is a need for an oblique-viewing minilaparoscope that allows visualization comparable to the larger laparoscopes.

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↗
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

Hepatitis C virus RNA quantification in right and left lobes of the liver in patients with chronic hepatitis C.

Quantification of hepatitis C virus RNA in liver tissue is likely to be useful in the study of the natural history, pathogenesis, progression and treatment of hepatitis C virus-associated liver disease. Quantitative measurements of hepatitis C virus RNA in liver biopsy samples using the branched DNA (bDNA) signal amplification assay were carried out. The aims of this study were threefold: first, to assess the level of hepatitis C virus RNA in biopsy samples from the right and left lobes of the liver; second, to evaluate the correlation between hepatitis C virus RNA levels in serum and liver; and third, to investigate the relationship between serum and liver hepatitis C virus RNA levels and the severity of hepatic histology in non-cirrhotic patients with chronic hepatitis C. There was a strong correlation (r = 0.92, P < 0.01) between hepatitis C virus RNA levels in the right and left lobes of the liver as well as a strong correlation between hepatitis C virus RNA levels in liver and serum (r = 0.82, P < 0.01). However, there was no significant correlation between the severity of hepatic histology and levels of hepatitis C virus RNA in serum and liver among patients with chronic active hepatitis classified according to Knodell's hepatic activity index (KI). Our results indicate that hepatitis C virus RNA quantification from a single liver biopsy is representative of both lobes in patients with chronic hepatitis, and suggest that serum hepatitis C virus RNA levels are a meaningful reflection of hepatitis C virus RNA levels in the liver.

Adult↗
PubMed1995

Hepatic iron concentration as a predictor of response to interferon alfa therapy in chronic hepatitis C.

BACKGROUND/AIMS: It has been reported that hepatic iron concentration (HIC) may influence response to therapy in chronic viral hepatitis. The aim of this study was to determine the relationship between HIC and response to interferon alfa therapy in patients with chronic hepatitis C. METHODS: HIC was measured in liver biopsy specimens from 58 patients with chronic hepatitis C treated at three centers. Three patients had mild chronic hepatitis C, 35 had moderate to severe chronic hepatitis C, and 20 had active cirrhosis. Serum ferritin levels were measured in 51 of these 58 patients. Response to therapy was defined as normalization of alanine aminotransferase levels at the end of treatment. RESULTS: Twenty-four patients (41%) responded to therapy. HICs were generally within the normal range (< 1500 micrograms/g). The mean HIC in nonresponders (860 +/- 100 micrograms/g; range, 116-2296 micrograms/g) was significantly higher than in responders (548 +/- 85 micrograms/g; range, 29-1870 micrograms/g) (P < 0.05). Eighty-eight percent of patients with an HIC of > 1100 micrograms/g and 87% of patients with an elevated serum ferritin concentration did not respond to interferon alfa therapy. CONCLUSIONS: HIC seems to influence response to interferon alfa therapy among patients with chronic hepatitis C. A subgroup of patients with chronic hepatitis C has been identified for which an HIC of > 1100 micrograms/g predicted nonresponse in 88% of patients.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗