Biomedical subjects

S M Banks

Publications and source records attributed to S M Banks.

At least 19 recordsLinked to original sources

PubMed1996

Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial.

OBJECTIVE: To determine whether human endotoxemia is associated with a loss of the physiologic beat-to-beat variability of heart rate. DESIGN: Prospective, randomized, crossover, single-blind study. SETTING: Clinical research center in a federal, nonuniversity hospital. SUBJECTS: Healthy volunteers. INTERVENTIONS: Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen. MEASUREMENTS AND MAIN RESULTS: Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs. Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy). Endotoxin administration was associated with loss of variability by all measures. This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin-related symptoms. CONCLUSIONS: Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy. Changes in approximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis. This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems.

Adult↗

PubMed1996

Role of endotoxemia in cardiovascular dysfunction and lethality: virulent and nonvirulent Escherichia coli challenges in a canine model of septic shock.

We investigated whether the severity of septic shock is determined by virulence factors associated with or the levels of endotoxemia produced by two Escherichia coli strains. Canines were challenged intraperitoneally with an E. coli strain (O6:H1:K2) that has virulence factors associated with human disease or with an equal dose of a nonvirulent strain (O86:H8) that lacks these factors. Both strains were administered in viable, heat-killed, and purified endotoxin forms. Median survival times with the virulent strain compared with the nonvirulent strain were shorter with viable bacteria (5 x 10(10) CFU/kg) (144 h versus > 672 h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(9) CFU/kg) ( > 676 h versus 26 h; P = 0.03), and similar with purified endotoxin (15 mg/kg) (28 h versus 48 h; P = 0.71). However, whether the challenge contained viable bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain produced less endotoxemia (P = 0.001). Hence, the changing outcomes with differing forms of the two strains cannot be attributed solely to endotoxin levels. The viable virulent strain caused less endotoxemia but more harm, and this does not appear to be explained by a more potent endotoxin or other heat-stable component. This study suggests that circulating endotoxin levels per se are less important in the outcome of septic shock than virulence factors associated with E. coli strains. Furthermore, the data call into question the significance of the endotoxin concentration in the blood in predicting the severity of shock and the lethality of gram-negative infections.

Animals↗

PubMed1996

Serial measures of total body oxygen consumption in an awake canine model of septic shock.

We examined serial changes in total body oxygen consumption (Vo2) in a permanently tracheotomized canine sepsis model. On Day 0, beagles had an Escherichia coli-infected (septic) or sterile (control) clot surgically placed in the peritoneum. During the 21-d study, 10 of the 16 septic animals and none of the six control animals died (p = 0.02). After clot placement septic versus control animals had decreased mean arterial blood pressure (mm Hg; Day 1: 106 versus 128, p = 0.055; Day 2: 95 versus 125, p = 0.004, respectively) and left ventricular ejection fraction (Day 1: 0.44 versus 0.69, p = 0.0006; Day 2: 0.33 versus 0.57, p = 0.0001, respectively). Despite significant lethality and cardiovascular dysfunction, in the septic group on Days 1 and 2, septic versus control animals had no significant differences in mean metabolic cart measured (Vo2DIR, ml/kg/min; Day 1: 11.9 versus 12.4, p = 0.81; Day 2: 14.2 versus 13.5, p = 0.72, respectively) and intravascular catheter calculated (Vo2INDIR, ml/kg/min; Day 1: 11.2 versus 11.2, p = 0.99; Day 2: 12.8 versus 15.4, p = 0.49, respectively). On Day 1 in septic and control animals, volume infusion produced increases (p < 0.001) in oxygen delivery (Do2). In septic and control animals these changes in Do2 were similar and were associated with similar increases in Vo2DIR (p = 0.001), and Vo2INDIR (p = 0.001). In fact, at all time points studied (baseline, Day 1, 2, and 21), both before and after volume infusion, levels of Do2, Vo2DIR, and Vo2INDIR did not differ between septic and control animals, nor did they differ between septic survivors and nonsurvivors. Because levels of Vo2DIR and Vo2INDIR were similar in both groups, we pooled data from septic and control animals. Throughout the study, Vo2 showed a moderate association with Vo2INDIR (r = 0.55, p = 0.003), but mean Vo2DIR was lower at baseline (p = 0.001) and on Day 21 (p = 0.07) and greater on Day 2 (p < 0.01). In summary, our techniques, which detected small changes in both Vo2DIR and Vo2INDIR occurring with volume infusion, did not demonstrate differences in these parameters comparing control and septic animals. These results in euvolemic septic animals suggest that total body Vo2 may not reflect pathogenetic mechanisms during sepsis and septic shock. Furthermore, these results suggest that although the level of total body Vo2 may reflect the effects of therapeutic interventions such as volume loading, it should not itself serve as a therapeutic target.

Animals↗

PubMed1996

A comparison of the Johnson Intervention with four other methods of referral to outpatient treatment.

The Johnson Intervention is a therapeutic technique in which members of the person's social network confront him or her about the damage the drinking or drug use has caused and the action they will take if treatment is refused. It is highly effective in engaging and retaining clients in inpatient treatment, but, since initial evaluations, two trends have emerged in the field. First, there has been an increase in the use of outpatient treatment and, second, a number of variations of the Johnson Intervention have been developed. The purpose of this study was to compare the effectiveness of the Johnson Intervention with four other methods of referral to outpatient treatment. The other methods included two naturally occurring types of referral (coerced and non-coerced) and two less intense and less costly variations of the Intervention (Unrehearsed and Unsupervised). Effectiveness was determined by both entry into and completion of treatment. A retrospective study was conducted on a sample of 331 cases drawn from an alcohol and other drug treatment agency. Those who had undergone the Johnson Intervention were more likely to enter treatment than those in any of the four other groups. Of those that entered treatment, the Johnson Intervention and the coerced referral groups were equally likely to complete treatment, and both groups were more likely to complete treatment than those in the other three types of referral. Although the Johnson Intervention was the most effective, the variations did show some measure of success and can be viewed as part of an Intervention continuum.

Adult↗

PubMed1995

Effects of recombinant dimeric TNF receptor on human inflammatory responses following intravenous endotoxin administration.

Effects of dimeric TNF receptor (p80) Fc (TNFR:Fc) on acute phase responses were evaluated in 18 volunteers given endotoxin (4 ng/kg i.v.). Subjects were randomized to receive either placebo (n = 6), low dose TNFR:Fc (10 mg/m2 i.v., n = 6), or high dose TNFR:Fc (60 mg/m2 i.v., n = 6). TNFR:Fc blocked plasma TNF bioactivity (p = 0.001) and increased, in a dose-ordered fashion, TNF immunoactivity (p < 0.001). TNFR:Fc decreased secondary cytokine levels including IL-1 beta (p = 0.007), IL-8 (p < 0.001), IL-1 receptor antagonist (p < 0.001), granulocyte-CSF (p = 0.03), and growth regulated peptide-alpha (p = 0.001) but not macrophage inflammatory protein-1 alpha or IL-10. Low dose, but not high dose, TNFR:Fc blunted or delayed the release of epinephrine and cortisol (p < or = 0.026). Despite the absence of plasma TNF bioactivity, high dose TNFR:Fc was less immunosuppressive than low dose TNFR:Fc as measured by cytokine and stress hormone responses. Endotoxin-related symptoms were not altered by TNFR:Fc and the febrile response was delayed but not diminished (p = 0.004). Increases in cardiac index (72 +/- 19%) and heart rate (60 +/- 10%) and decreases in systemic vascular resistance index (47 +/- 7%) were unaltered by TNFR:Fc. These data suggest that the inflammatory response to endotoxin can escape from high levels of circulating TNF-blocking activity and redundant pathways, independent of circulating TNF, can sustain inflammation and clinical responses caused by acute endotoxemia.

Animals↗

PubMed1995

The effects of end point overdispersions on the validity of single-dose tumorigenicity assays.

Overdispersion can be found in tumor incidence and tumor latency end point values obtained by the conventional assays that are being used to assess the tumorigenicity of neoplastic cells growing in tissue culture. Failure to account for such wide variations in end point data can lead to incorrect assessments of the neoplastic cell tumorigenic phenotype and misinterpretations of data relating genetic functions to tumor-forming capacity. This problem suggests the need for more detailed analyses of the relationships that exist between tumor cell dose and the parameters being used to measure tumorigenicity.

Animals↗

PubMed1995

New strategies for combatting sepsis: the magic bullets missed the mark ... but the search continues.

Despite the high expectations of scientists and industry, multiple clinical trials of anti-endotoxin- and anti-cytokine-based therapies for sepsis have failed to demonstrate benefit. Indeed, in some cases, the agents used were actually harmful to patients. In retrospect, perhaps the therapeutic premises on which these therapies were based were flawed. In the future, a better understanding of sepsis should lead to the development of accurate laboratory and clinical predictors that will identify when, and which, patients can benefit from a given therapy. Much has been learned from the efforts of industry and academia and, hopefully, the search for new therapies for this lethal syndrome will continue.

Animals↗

PubMed1995

The effects of message framing on mammography utilization.

This experiment compared the effectiveness of gain-versus loss-framed messages to persuade women to obtain mammography screening. One hundred and thirty-three women 40 years and older and not adhering to current guidelines for obtaining mammography screening were assigned randomly to view either gain-framed (emphasizing the benefits of obtaining mammography) or loss-framed (emphasizing the risks of not obtaining mammography) persuasive videos that were factually equivalent. Attitudes and beliefs were measured before and immediately following the intervention. Mammography utilization was assessed 6 and 12 months later. Consistent with predictions based on prospect theory, women who viewed the loss-framed message were more likely to have obtained a mammogram within 12 months of the intervention. These findings suggest that loss-framed messages may have an advantage in the promotion of detection behaviors such as mammography.

Adult↗

PubMed1995

Hemodynamic effects of dopamine, norepinephrine, and fluids in a dog model of sepsis.

To study how sepsis affects hemodynamic responses to catecholamines and fluids, either Escherichia coli-infected (septic, n = 8) or sterile (controls, n = 6) fibrin clots were implanted intraperitoneally into 2-yr-old beagles. Hemodynamics were measured at each of four doses of dopamine (0, 5, 10, and 20 micrograms.kg-1.min-1) and norepinephrine (0, 10, 20, and 40 micrograms.min-1), before and after infusion of fluid (Ringer 40 ml.kg-1). Septic animals had lower mean arterial pressure (MAP, P = 0.04), stroke volume index (SVI, P = 0.0001), and left ventricular (LV) ejection fraction (LVEF) (P = 0.0001) than controls. During this time, increasing doses of dopamine and norepinephrine produced corresponding increases (P < 0.001) in LVEF, SVI, and MAP. However, during sepsis, the ability of dopamine to increase MAP diminished, while its ability to increase LVEF and SVI was maintained. Conversely, the ability of norepinephrine to increase LVEF and SVI diminished, but its ability to increase MAP was maintained. During sepsis, fluids alone increased (P < 0.05) MAP, LVEF, SVI, and cardiac index (CI). Fluids with catecholamines also significantly increased (P < 0.05) MAP with only minimal increases in LVEF, SVI, and CI. These data demonstrate that during sepsis without catecholamines, fluids improve cardiac performance and systemic pressures, but with catecholamines, fluids have minimal effects on cardiac performance and augment MAP. Furthermore, during sepsis dopamine is more effective than norepinephrine in increasing LV performance, but norepinephrine is more effective than dopamine in increasing systemic pressures.

Animals↗

PubMed1995

Therapeutic trial of reconstituted human high-density lipoprotein in a canine model of gram-negative septic shock.

In a controlled, randomized trial, the authors investigated the effects of reconstituted human high-density lipoprotein (R-HDL) on survival, endotoxemia, cytokine production and pathophysiologic and metabolic events in an animal model of gram-negative septic shock. At 0.5, 8 and 16 hr after implantation of a clot infected with Escherichia coli, canines received intravenous R-HDL (n = 13), control lipid (n = 7) or human serum albumin (HSA, n = 7) divided into three doses (0.3, 0.1 and 0.1 g/kg, respectively) at an hourly rate of 0.1 g/kg. All animals were treated with antibiotics and fluids. Animals treated with R-HDL had lower levels of circulating endotoxin and tumor necrosis factor and a smaller decrease in white blood cell counts than did animals treated with lipids and HSA (all P < .05). The survival times of lipid- and HSA-treated animals were similar (P = .3) and were significantly greater than those of R-HDL-treated animals (P = .02). During the first 6 hr after clot implantation, R-HDL-treated animals had significantly greater abnormalities in liver function test findings compared with lipid- and HSA-treated animals (all P < .05). For the first 24 hr, R-HDL-treated animals had significant increases in HDL levels; however, there were no significant relationships between these levels and the constituents of HDL (apolipoprotein AI and phosphatidylcholine) or liver function abnormalities and survival times (all r < .2, P > .3). In normal animals, administration of R-HDL (in similar doses) caused transient elevation of liver enzymes; in animals given sterile clot i.p., R-HDL caused seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Continuous arteriovenous hemofiltration does not improve survival in a canine model of septic shock.

BACKGROUND: We examined whether or not continuous arteriovenous hemofiltration (CAVH), in the absence of renal failure, would improve either hemodynamic abnormalities or survival in a canine model of septic shock. STUDY DESIGN: Escherichia coli 0111, as an intraperitoneal clot, was surgically implanted into 21 one- to two-year-old purpose-bred beagles. The dogs were randomized to no CAVH (control group, n = 7), sham CAVH (extracorporeal circulation without hemofiltration, n = 7), or true CAVH (hemofiltration with removal of 600 mL/hour of ultrafiltrate, n = 7). Hemofiltration began one hour after clot implantation and continued for six hours. All dogs received antibiotics and had serial hemodynamic and laboratory evaluations. RESULTS: During the first seven hours of the study, all dogs displayed a progressive, significant decrease in mean arterial pressure, cardiac index, left ventricular ejection fraction, and serum pH (all p < 0.05). Two of seven dogs in the control group, one of seven dogs in the sham CAVH group, and one of seven dogs in the true CAVH group survived seven days after clot implantation. True CAVH, which included fluid replacement with lactated Ringer's solution, significantly increased serum lactate and decreased serum bicarbonate levels after six hours (both p < 0.05). However, pH did not differ between the three treatment groups (p > 0.20). Continuous arteriovenous hemofiltration therapy had no significant effect on cardiovascular abnormalities or survival. CONCLUSIONS: The results of this study suggest that CAVH would be unlikely to provide benefit to patients with gram-negative septic shock, in the absence of renal failure.

Animals↗

PubMed1994

Therapy of chronic hepatitis B with a 6-month course of ribavirin.

Ribavirin is a nucleoside analogue with broad spectrum antiviral activity that has been shown to inhibit viral replication in the woodchuck model of hepatitis B virus infection. We studied the effect of ribavirin on viral replication in 18 patients with chronic hepatitis B who were positive for hepatitis B e antigen. Patients were randomized to receive a 24-week course of oral ribavirin at a dose of either 800, 1000, or 1200 mg/kg per day. All patients completed 24 weeks of treatment and an additional 24 weeks of follow up without significant side effects except for mild, reversible hemolytic anemia. Response to ribavirin was similar among all three dosage groups (p > 0.5); hence the data were pooled and analyzed together. Mean hepatitis B virus DNA levels decreased from 162.7 (95% confidence interval, 106 to 219) pg/ml before treatment to its lowest level of 114.3 (95% confidence interval, 53 to 175) pg/ml at week 20 (p < 0.05). Two patients became negative for HBV DNA and lost hepatitis B e antigen. Mean serum alanine aminotransferase activity decreased markedly from 131.1 (95% confidence interval, 84 to 178) U/l before treatment to 62.4 (95% confidence interval, 48 to 77) U/l at the end of 24 weeks of ribavirin (p < 0.05) and became normal in four patients (22%). Aminotransferase levels returned to baseline within 4 weeks once ribavirin was discontinued, while HBV DNA concentrations remained below baseline even at the end of 24 weeks of follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Distinct functional activities in canine septic shock of monoclonal antibodies specific for the O polysaccharide and core regions of Escherichia coli lipopolysaccharide.

Monoclonal antibodies (MAbs) specific for O polysaccharide or core oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an E. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantly reduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial pressure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone, survival was enhanced by O-specific MAb (4/5) compared with core-specific MAb (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but survival was prolonged in antibiotic-treated animals also receiving O-specific MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08 vs. controls). These data support the complex role of LPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS.

Animals↗

PubMed1994

Characterization and frequency distribution of sperm acrosome reaction among normal and infertile men.

We studied the acrosome reaction (AR) in human spermatozoa from 58 normal fertile men and 232 infertile patients. The median AR in the normal population was 17%; AR was > 9% in 83% of the subjects studied and only 2% of fertile individuals had a failed AR (< 5%). We calculated the within person variability using multiple specimens from each subject; the 95% confidence interval for each subject was 4 AR units above and 4 AR units below his mean value. In contrast, the median AR for the infertile population was 3%. AR values were below the normal range (< 5%) in 60% of the patients and only 26% of the patients had AR values > 9%. Because patients entered the study sequentially, without regard to the aetiology of infertility, the patient population comprised a wide variety of subjects ranging from individuals with good to extremely poor semen quality. There was a progressively greater number of individuals with a failed AR as semen quality deteriorated (P < 0.01). However, among patients with good count, motility and morphology, 20% unexpectedly had a failed AR, and among patients with severely impaired semen quality, 29% had a positive AR. We also analysed the relationship of AR values with other semen measurements. The frequency of acrosomal reactions was significantly correlated (Spearman, P < 0.001) with morphology (r = 0.509), concentration (r = 0.524), progression (r = 0.416) and percentage motility (r = 0.356), but not with the percentage of sperm moving at a curvilinear velocity of < or = 40 microns/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

PubMed1994

Acrosome reaction inducibility predicts fertilization success at in-vitro fertilization.

We prospectively studied the ability of acrosome reaction (AR) inducibility to predict fertilization success in a group of 232 infertile patients presenting sequentially for in-vitro fertilization (IVF). The median percentage of eggs fertilized for the overall patient population was 25% (interquartile range 5-58%), with one to 29 oocytes available for insemination (median, five oocytes). The median percentage of eggs fertilized at IVF increased as the percentage of spermatozoa able to undergo AR became greater: spermatozoa with a failed AR (< or = 5%) fertilized only 12% of eggs, while spermatozoa with AR values > 9% fertilized 50% of eggs. The assay had a specificity of 0.75, a sensitivity of 0.55 and an odds ratio of 2.9; thus, AR-positive patients are 2.9 times more likely to achieve fertilization than patients with a failed AR. Receiver operator characteristic (ROC) curves were constructed for AR, sperm concentration and percentage of normal forms in semen. All three parameters proved to be potentially useful in predicting the occurrence of fertilization, although AR and morphology appeared to be better than sperm concentration by ROC analysis. Patients were divided into four clearly defined subgroups according to their traditional semen characteristics, including morphology. The median percentage of eggs fertilized decreased as traditional semen characteristics deteriorated, from a median of 46% for patients with excellent sperm concentration, motility and morphology, to a median of 29% for patients with suboptimal semen quality and a median of 0% for patients with severely impaired semen.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

PubMed1994

Cardiopulmonary effects of granulocyte colony-stimulating factor in a canine model of bacterial sepsis.

We investigated the effects of recombinant granulocyte colony-stimulating factor (G-CSF) in a canine model of septic shock. Awake 2-yr-old beagles were studied before and after intraperitoneal placement of an Escherichia coli-infected clot. Nine days before and until 3 days after clot placement, animals received daily high-dose (G-CSF (5 microgram/kg body wt; n = 17), low-dose G-CSF (0.1 microgram/kg body wt; n = 17), or a control protein (5 micrograms/kg body wt; n = 20). Survival rate was greater (P < 0.04, Wilcoxon test) in the high-dose G-CSF group (14/17) than in the low-dose G-CSF (10/17) and control (12/20) groups. High-dose G-CSF improved cardiovascular function, as evidenced by increased left ventricular ejection fraction (day 1 after clot; P < 0.001) and mean arterial pressure (day 2; P < 0.02) compared with low-dose G-CSF and control groups. High-dose G-CSF increased (P < 0.001) mean peripheral neutrophils before (-3 days) and after (2 h to 4 days) clot and produced a more rapid (P < 0.001) rise (day 2) and fall (day 4) in mean alveolar neutrophil numbers compared with the low-dose G-CSF and control groups. High-dose G-CSF decreased mean serum endotoxin (2-8 h; P < 0.002) and tumor necrosis factor (2 h; P < 0.02) levels and lowered blood bacteria counts (2-6 h; P < 0.04) compared with the low-dose G-CSF and control groups. Thus, in this canine model, G-CSF sufficient to increase peripheral neutrophils before and during peritonitis and septic shock enhances host defense, reduces cytokine (tumor necrosis factor) levels, and improves cardiovascular function and survival.

Animals↗

PubMed1993

A controlled trial of HA-1A in a canine model of gram-negative septic shock.

OBJECTIVE: To investigate the therapeutic efficacy and microbiological and physiological effects of a human IgM monoclonal antibody (HA-1A) directed against the lipid A component of endotoxin in a canine model of sepsis that simulates the cardiovascular abnormalities of human septic shock. DESIGN: Blinded, placebo-controlled 28-day trial. INTERVENTIONS: Purpose-bred beagles were implanted with an intraperitoneal clot infected with Escherichia coli O111:B4. At clot placement, animals received HA-1A (10 mg.kg-1), control human IgM antibody (10 mg.kg-1), or control human serum albumin intravenously. All animals were given antibiotic and fluid therapy. MEASURES: Survival and microbiological and physiological events. RESULTS: Only two (15%) of 13 animals in the HA-1A group, compared with eight (57%) of 14 control animals (combined control human IgM antibody and control human serum albumin groups) (P = .05), survived 28 days. At 24 hours, the HA-1A group had lower mean arterial pressure (P = .04) and cardiac index (P = .004) and higher lactate levels (P = .05) compared with the combined-controls group. In addition, these parameters in the HA-1A group were significantly more predictive of death. The HA-1A and combined-controls groups had similar significant increases in the level of endotoxemia and bacteremia. Studies of toxic effects showed no harmful effects of control human IgM antibody in infected animals or HA-1A in non-infected animals. CONCLUSION: In a canine model of E coli sepsis, HA-1A did not alter levels of bacteremia or endotoxemia and actually decreased survival. If these data are relevant to human septic shock, HA-1A therapy should be limited until the conditions under which this monoclonal antibody has beneficial or deleterious effects are more completely defined.

Animals↗

PubMed1993

Clinical and serological differentiation of autoimmune and hepatitis C virus-related chronic hepatitis.

Recent reports have focused on the difficulty in differentiating autoimmune hepatitis from chronic hepatitis C due to the high prevalence of anti-HCV in autoimmune hepatitis. The aim of this study was to identify clinical, biochemical, and serological variables that would help distinguish these two diseases. Pretreatment clinical and biochemical variables were compared from 17 patients with steroid-responsive autoimmune chronic active hepatitis and 62 patients with chronic hepatitis C. Serum samples from these patients were tested for autoantibodies and for anti-HCV by first- and second-generation ELISA, recombinant immunoblot assay, and HCV RNA by polymerase chain reaction. Patients with autoimmune hepatitis were more likely to be symptomatic (94% vs 47%, P < 0.005) and jaundiced (76% vs 0%, P < 0.005) at the time of referral. Anti-HCV was found in 53% of patients with autoimmune hepatitis, but only two were positive by immunoblot assay and only one of these had detectable HCV RNA. Antinuclear antibody (ANA) was detected in 21% of patients with chronic hepatitis C, although usually at a lower titer than in autoimmune hepatitis (geometric mean titer = 1:160 vs 1:500, P < 0.003). Patients with chronic hepatitis C who were ANA positive were older than those who were ANA negative, although there were no other differences in clinical or biochemical features between these groups. In particular, there was no difference in response rate to antiviral therapy. Thus, autoantibodies are frequently found in chronic hepatitis C, especially in older subjects, but appear to be clinically insignificant. Anti-HCV is frequently present in autoimmune hepatitis but is rarely confirmed by tests of higher specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗