Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model.

AIM: Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model. MATERIALS AND METHODS: In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 104.5 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment. RESULTS: In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns. CONCLUSIONS: Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.

A phase I clinical trial assessing the safety, tolerability, and pharmacokinetics of inhaled ethanol in humans as a potential treatment for respiratory tract infections.

Background: Current treatments for respiratory infections are severely limited. Ethanol's unique properties including antimicrobial, immunomodulatory, and surfactant-like activity make it a promising candidate treatment for respiratory infections if it can be delivered safely to the airway by inhalation. Here, we explore the safety, tolerability, and pharmacokinetics of inhaled ethanol in a phase I clinical trial. Methods: The study was conducted as a single-centre, open-label clinical trial in 18 healthy adult volunteers, six with no significant medical comorbidities, four with stable asthma, four with stable cystic fibrosis, and four active smokers. A dose-escalating design was used, with participants receiving three dosing cycles of 40, 60%, and then 80% ethanol v/v in water, 2 h apart, in a single visit. Ethanol was nebulised using a standard jet nebuliser, delivered through a novel closed-circuit reservoir system, and inhaled nasally for 10 min, then orally for 30 min. Safety assessments included adverse events and vital sign monitoring, blood alcohol concentrations, clinical examination, spirometry, electrocardiogram, and blood tests. Results: No serious adverse events were recorded. The maximum blood alcohol concentration observed was 0.011% immediately following 80% ethanol dosing. Breath alcohol concentrations were high (median 0.26%) following dosing suggesting high tissue levels were achieved. Small transient increases in heart rate, blood pressure, and blood neutrophil levels were observed, with these normalising after dosing, with no other significant safety concerns. Of 18 participants, 15 completed all dosing cycles with three not completing all cycles due to tolerability. The closed-circuit reservoir system significantly reduced fugitive aerosol loss during dosing. Conclusion: These data support the safety of inhaled ethanol at concentrations up to 80%, supporting its further investigation as a treatment for respiratory infections.Clinical trial registration: identifier ACTRN12621000067875.

The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans. METHODS: A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074). FINDINGS: Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 µg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups. INTERPRETATION: Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis. FUNDING: Cystic Fibrosis Foundation.

Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis.

BACKGROUND: Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes. METHODS: We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated. RESULTS: Eighty-eight episodes (3 months to 6 years old) of P. aeruginosa infection were studied. Eradication was successful in 84.1% of episodes. Median activity of NE was significantly reduced post-eradication from 9.15 to 3.4 nM (p = 0.008) but persisted in 33 subjects. High post-eradication NE levels were associated with an increased risk for P. aeruginosa infection in the next annual visit (odds ratio=1.7, 95% confidence interval 1.1-2.7, p = 0.014). Post-eradication NE levels (difference, 0.8; 95% confidence interval, 0.1-1.5) and baseline bronchiectasis computed tomography (CT) score (difference, 0.4; 95% confidence interval, 0.1-0.8) were the best predictors of bronchiectasis progression within 1 year (backward stepwise linear regression model, R2= 0.608, P<0.001), independent of eradication. CONCLUSION: In children with CF, NE activity may persist following successful P. aeruginosa eradication and is significantly associated with bronchiectasis progression. Evaluating strategies to diminish neutrophilic inflammation is essential for improving long-term outcomes.

Role of Tris-CaEDTA as an adjuvant with nebulised tobramycin in cystic fibrosis patients with Pseudomonas aeruginosa lung infections: A randomised controlled trial.

BACKGROUND: We tested if disrupting iron utilisation by P. aeruginosa by adding the Tris-buffered chelating agent CaEDTA to nebulised tobramycin would enhance bacterial clearance and improve lung function in CF patients. METHODS: In this double-blind, randomised controlled trial, 26 episodes (25 patients) with P. aeruginosa infection admitted to two CF centres for treatment of an acute pulmonary exacerbation were randomly assigned to receive either 75 mg CaEDTA in Tris-buffered saline or placebo (Tris-buffered saline) nebulised in combination with 250 mg tobramycin twice daily for six weeks followed with four week safety follow-up. Primary endpoints were safety, tolerability, and bacterial density of P. aeruginosa. A secondary endpoint was lung function. RESULTS: The study drug was well tolerated with adverse events comparable in both groups. The mean (SD) reduction in sputum P. aeruginosa count (log10 CFU/g) in the CaEDTA vs placebo group was 2·05 (2·57) vs 0·82 (2·71) at two weeks relative to admission (p = 0·39). The mean improvement in ppFEV1 was 16 vs 5 (p = 0·16); 11 vs 2 (p = 0·28); and 6 vs 2 percentage points (p = 0·47) at two, six, and ten weeks in CaEDTA and placebo groups, respectively. CONCLUSIONS: In this pilot study in CF patients, an increase in the reduction of sputum density of P. aeruginosa and an increase in ppFEV1 was observed in the group of patients who received Tris-CaEDTA added to inhaled tobramycin compared to the group who received inhaled tobramycin alone, although these differences were not statistically significant. The treatment was also shown to be safe.

Exercise-induced hypoxia secondary to an atrial septal defect and cor triatriatum dexter.

A 14-year-old boy presented to us with a diagnosis of severe asthma and oxygen desaturation of 76% on a 6-minute-walk test. A contrast echocardiogram revealed echocontrast in the left and right atria simultaneously. A secundum atrial septal defect and partial cor triatriatum dexter were diagnosed, and the atrial defect was closed by cardiac catheterisation.

Modulation of gut barrier function in patients with obstructive jaundice using probiotic LP299v.

OBJECTIVES: This study aimed to determine the effect of LP229v on intestinal permeability and tumour necrosis factor (TNF) p55 receptor concentrations in patients with obstructive jaundice undergoing biliary drainage. PATIENTS AND METHODS: Patients undergoing biliary drainage were recruited and randomized into three groups to receive Lactobacillus plantarum 299v (LP299v), inactivated LP299v (placebo) or water. These were administered daily at noon until 7 days after biliary drainage. Intestinal permeability was measured using the lactulose/mannitol (L/M) dual sugar absorption test on admission, the day before biliary drainage and on days 1 and 7 after biliary drainage. Blood and urine were collected to determine the L/M ratio and the TNF p55 receptor levels at each time point. RESULTS: A total of 25 patients were recruited; 12 had choledocholithiasis and nine had a periampullary tumour. Open surgical biliary drainage was performed in nine patients, endoscopic retrograde cholangiopancreatography in 12 and percutaneous transhepatic cholangiography in two. Five patients received LP299v, five received placebo and seven, water. The median L/M ratio was 0.035 (0.018-0.065) at baseline. No difference existed between the groups on admission, before drainage and on day 7 after drainage (P=0.59, 0.175 and 0.61, respectively). The L/M ratio was lower in the LP299v group on day 1 after drainage [0.01 (0.01) vs. 0.18 (0.03-0.3) and 0.11 (0.07-0.14); P=0.37]. Although the TNF p55 receptor levels were lower on day 1 after drainage in the LP299v group (15.3 vs. 30.9 vs. 82.7 ng/ml; P=0.43), the concentration at the four time points was similar (P=0.24, 0.96, 0.43 and 0.68). CONCLUSION: Pretreatment with probiotic LP299v improves intestinal permeability after biliary drainage and attenuates the inflammatory response. However, a larger multicentre trial is required to determine the effect on clinical outcome.

Cytokine response to portal endotoxaemia and neutrophil stimulation in obstructive jaundice.

INTRODUCTION: An exaggerated proinflammatory response to endotoxaemia can occur in obstructive jaundice. The aims of this study were to determine the hepatic proinflammatory and anti-inflammatory cytokine response to endotoxaemia in experimental biliary obstruction and to determine the source of interleukin-6 (IL-6) using immunohistochemistry. METHODOLOGY: Male Wistar rats were randomized into three groups: bile duct ligation (BDL), sham operation, and control groups. They were weighed before surgery and after 1 week. On day 8, hepatic perfusion was performed with endotoxin (Escherichia coli 0111:B4). Serial samples of blood, effluent, and influent perfusate were analyzed for proinflammatory and anti-inflammatory cytokines. Ultrastructural assessment of sections of the liver was performed. RESULTS: BDL animals lost weight in the first week compared with the sham and the control animals that gained weight. Liver function tests were elevated in the BDL group. Effluent biochemistry did not reveal liver injury as a result of perfusion. Ultrastructurally, there was no evidence of liver injury, with only active Kupffer cells, preservation of liver architecture, and minimal liver injury being detected. Serum tumor necrosis factor-α was not detected in any group before perfusion; however, serum IL-6 was higher in the BDL group. Portal endotoxaemia resulted in an increase in tumor necrosis factor-α, IL-6, and IL-10 in the BDL group. Fluorescence immunohistochemistry demonstrated IL-6 in the sinusoidal spaces and the cytoplasm of Kupffer cells. CONCLUSION: There is an exaggerated proinflammatory and anti-inflammatory cytokine response to portal endotoxaemia in animals with jaundice compared with the sham group.

Preoperative symptoms of irritable bowel syndrome predict poor outcome after laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the accepted treatment for symptomatic cholelithiasis. This study examines the effect LC has on quality of life (QOL) and gastrointestinal (GI) symptoms and determines whether patients with symptoms of irritable bowel syndrome (IBS) gain the same benefit as those without. METHODS: A total of 158 patients who underwent LC for symptomatic gallstones were recruited to this prospective observational study. IBS Manning scores were calculated and QOL was measured using the Gastrointestinal Quality of Life Index (GIQLI) preoperatively, at 6 weeks, 3 months, and 2 years postoperatively. Linear regression analysis was used to identify preoperative symptoms that predict outcome. RESULTS: One hundred twelve patients had sufficient data sets for inclusion. Patient's GIQLI scores were calculated for the four time points in the study. The mean preoperative score was 88.8 ± 1.3 (61.7% of 144, the highest score possible) and improved 6 weeks after surgery to 105.5 ± 1.3 (p < 0.001). This improvement was maintained at 3 months, but at 2 years analysis showed regression toward the baseline of 7.6 ± 2.3 (p = 0.003) points. There was a negative correlation of -5.2 ± 1.29 (p < 0.001) points between each Manning symptom and QOL scores. The largest effect was seen in patients describing loose bowel movement with the onset of pain. Patients with this symptom had a -17.3 ± 4.6 (p < 0.001) lower global QOL score. CONCLUSIONS: Patients with symptoms of IBS indicated by the Manning criteria show less improvement in quality of life after laparoscopic cholecystectomy for gallstones.

Long-term results of percutaneous transhepatic cholangiographic drainage for palliation of malignant biliary obstruction.

INTRODUCTION: Percutaneous stenting is established in the palliation of malignant biliary obstruction. We examined the indications, success rate, complications, and long-term postoperative course of patients undergoing this procedure. METHODS: All patients undergoing percutaneous transhepatic cholangiography (PTC) and metal stenting over a 12-month period in a tertiary referral center were studied. Data regarding diagnosis, number and type of procedures, complications, and survival were collected from multidisciplinary case notes and general practitioner records. RESULTS: There were 21 patients of median age 70 (mean, 71; range, 54-93), 56.5% (11) had pancreatic cancer and 33% (7) cholangiocarcinoma. The mean number of PTC procedures was 2.43 and mean length of stay in hospital 20.66 days (range, 3-99). Serum bilirubin fell post drainage from 397 to 226 (µmol/L; p < 0.001) on discharge, however, in 19% (4) there was no significant reduction. Complications included cholangitis (19%) and acute pancreatitis (10%). Mortality was high and 9 patients (43%) died within 30 days, of whom 2 died in the hospital (1 from ascending cholangitis and another from pneumonia). The median time between discharge and death was 25 days (mean, 59.1 days) and no patient was alive after 193 days. CONCLUSIONS: The prognosis following PTC stenting of malignant biliary obstruction is extremely poor despite adequate drainage. The procedure can lead to significant morbidity and a lengthy hospital stay. Patient selection is therefore of paramount importance and an expedient treatment protocol and early return home recommended.

Abdominal abscess due to retained gallstones 5 years after laparoscopic cholecystectomy.

A 76-year-old female patient with diabetes presented with pyrexia and a recurrent painful right sided loin swelling. One year previously she had undergone radiological drainage of a large right sided loin abscess. At index presentation she was investigated both radiologically and endoscopically and a source for the abscess was not found. On this presentation, a computed tomography scan confirmed a large retroperitoneal abscess pointing through the lateral abdominal wall musculature. Surgical drainage was undertaken whereby the abscess was drained and several large gallstones extruded through the incision. The patient subsequently recuperated and the wound has healed successfully by second intention. Five years previously the patient had undergone an "uncomplicated" laparoscopic cholecystectomy. This case highlights the catastrophic late effects of dropped gallstones during laparoscopic cholecystectomy.

Adherence to hepatitis C treatment in recovering heroin users maintained on methadone.

OBJECTIVES: Injection drug users are often denied hepatitis C (HCV) treatment due to concerns about adherence, despite limited data about the impact of such common issues as psychiatric illness and intercurrent drug use. We sought to define the impact of these and other potential adherence barriers in a real-world sample of recovering drug users. METHODS: We conducted a prospective observational study of 71 methadone-maintained patients who received interferon and ribavirin combination therapy in a community-based clinic with expertise in treating addictive disorders. Adherence measures were conducted with monthly interview, medication counts, and urine toxicology testing. RESULTS: Overall, 48 (68%) were adherent, and adherent patients were significantly more likely to achieve a sustained virologic response (42 vs. 4% in nonadherent patients). Patients with and without a prior psychiatric history were similarly adherent (64 vs. 72%, respectively, P>0.5), and the initiation of new psychiatric medications during HCV treatment was associated with improved adherence overall (P=0.02) and in patients that did not report a preexisting psychiatric diagnosis (P=0.04). Trend towards reduced adherence in patients without a period of abstinence was seen before initiating HCV treatment, 46 vs. 72% of those who had been abstinent for at least 1 month (P=0.10). Although occasional drug users were similarly adherent to those who were completely abstinent, patients who relapsed to regular drug use showed a significantly lower level of adherence (P=0.03). CONCLUSIONS: We conclude that the majority of methadone-maintained drug users can adhere to HCV treatment, even those with psychiatric illness and relatively limited pretreatment drug abstinence. Lack of pre-HCV treatment drug abstinence and regular drug use during HCV treatment may be relative barriers to medication adherence, but the initiation of psychiatric medications during HCV treatment may be a helpful intervention. This report provides further evidence for an individualized approach to HCV treatment that does not categorically exclude patients with potential barriers such as mental illness and limited drug abstinence.

Cannabis use improves retention and virological outcomes in patients treated for hepatitis C.

OBJECTIVES: Despite the widespread use of polypharmacy, the management of hepatitis C virus (HCV) treatment-related side-effects is often incomplete, and many patients turn to cannabis for symptom relief. Unfortunately, there are few data about cannabis use on treatment outcomes, leaving clinicians without the data needed to inform recommendations. METHODS: To define the impact of cannabis use during HCV treatment, we conducted a prospective observational study of standard interferon and ribavirin treatment in 71 recovering substance users, of whom 22 (31%) used cannabis and 49 (69%) did not. RESULTS: Seventeen of the 71 study patients (24%) discontinued therapy early, one cannabis user (5%) and 16 non-users (33%) (P=0.01). Overall, 37 patients (52%) were end-of-treatment responders, 14 (64%) cannabis users and 23 (47%) non-users (P=0.21). A total of 21 out of 71 (30%) had a sustained virological response: 12 of the 22 cannabis users (54%) and nine of the 49 non-users (18%) (P=0.009), corresponding to a post-treatment virological relapse rate of 14% in the cannabis users and 61% in the non-users (P=0.009). Overall, 48 (68%) were adherent, 29 (59%) non-users and 19 (86%) cannabis users (P=0.03). Although cannabis users were no more likely than non-users to take at least 80% of the prescribed interferon or ribavirin, they were significantly more likely to remain on HCV treatment for at least 80% of the projected treatment duration, 95 versus 67% (P=0.01). CONCLUSIONS: Our results suggest that modest cannabis use may offer symptomatic and virological benefit to some patients undergoing HCV treatment by helping them maintain adherence to the challenging medication regimen.

The impact of barriers to hepatitis C virus treatment in recovering heroin users maintained on methadone.

Although most cases of hepatitis C virus (HCV) infection are associated with injection drug use, there are few data regarding the impact of putative barriers such as psychiatric disease and intercurrent drug use on HCV treatment outcomes. To define the impact of characteristics often cited as reasons for withholding HCV treatment, we studied HCV treatment in a real world sample of 76 recovering heroin users maintained on methadone. Overall, 21 (28%) had a sustained virological response and 18 (24%) discontinued treatment early. Although there was a modest decrement in response rates in patients reporting a preexisting psychiatric history (p = .01), neither intercurrent drug use nor short duration of pretreatment drug abstinence led to significant reductions in virological outcomes (p = .09 and p = .18, respectively.) We conclude that injection drug users can be safely and effectively treated for HCV despite multiple barriers to treatment when they are treated in a setting that can address their special needs.

Diagnosis of cystic fibrosis after newborn screening: the Australasian experience--twenty years and five million babies later: a consensus statement from the Australasian Paediatric Respiratory Group.

Newborn screening for cystic fibrosis has been used in Australia and New Zealand for over 20 years. In that time, considerable experience has been developed regarding the early diagnosis of cystic fibrosis after newborn screening. To date, there has not been a consensus on the process of screening and clinical evaluation leading to the diagnosis of cystic fibrosis in infants, many of whom are not symptomatic at time of notification of the screening result. The aim of this paper is to provide some consensus on the important issues of a cystic fibrosis diagnosis arising from newborn screening, based on the experience gained in Australia and New Zealand over the last 20 years.

A new asthma spacer device to improve compliance in children: a pilot study.

OBJECTIVE: This pilot study was designed to compare the acceptance, ease of use, and effects on compliance between currently used spacer devices and the Funhaler--a new small volume spacer device designed to improve adherence to asthma medication in children. METHODOLOGY: A matched questionnaire-based survey was conducted by two interviews of each caregiver by the same person. A total of 32 children were randomly recruited from seven clinics spanning widely differing socioeconomic and geographical areas of Perth, Western Australia. Preschool children taking regular inhaled asthma medication using an existing low volume spacer device and aged between 1.5 and 6 years, took part in the pilot study. Parents completed two matched questionnaires. The first questionnaire was completed at the beginning of the study and the second after 2 weeks' use of the Funhaler spacer. Data collected related primarily to ease of use of the devices, child and parental compliance, and treatment attitudes. During the study, parents were also called at random on one occasion to ascertain whether they had attempted to medicate their child the previous day. RESULTS: Using the Funhaler incentive spacer device, parents reported significantly more success at medicating their children (22/30 always successful) in comparison to using their existing spacer device (3/30). Parental adherence to prescribed frequency and the delivery technique of children were also improved. The children also showed improved satisfaction and willingness to use the device and parents' attitude towards medicating their children was improved with the Funhaler spacer device. CONCLUSIONS: Use of a novel, incentive spacer device (Funhaler) appeared to be associated with increased success and fewer problems in medicating children, improved child and parental adherence, and a more positive attitude towards treatment, suggesting that more extensive long-term efficacy trials with the device are warranted.

The utility of indirect predictors of hepatitis C viremia.

OBJECTIVE: Although the majority of injection drug users (IDUs) have been exposed to hepatitis C (HCV), only 60-85% remain chronically viremic and at risk for HCV-induced progressive liver damage or transmitting HCV to others. Access to direct viral testing to establish the presence or absence of viremia is limited due to its expense. This study of 500 current and former IDUs examines the utility of demographic and biochemical features as a means of indirectly predicting HCV viremia. METHODS: Retrospective chart and laboratory review. RESULTS: Overall, 409 (81.8%) were viremic at the time of presentation. HCV viremia did not correlate with the presence of active drug or alcohol use, drug of abuse, duration of drug use, or length of injecting career, but was more common in males and African-Americans. An elevated ALT, found in 36% of patients, was the best biochemical predictor: 95.6% of these patients were viremic. Other predictors of viremia included thrombocytopenia, hypoalbuminemia, elevated GGT, and total bilirubin level, with a stepwise increase in viremia seen as the number of abnormal biochemical predictors increased. The absence of HCV viremia was more difficult to predict. Viremia was found in 66.3% of those lacking all biochemical predictors and even in 43.8% of those in the lowest 10th percentile of ALT. CONCLUSION: Although indirect demographic and laboratory parameters may be used to help predict viremia in 40% of HCV-exposed IDUs, they are inadequate substitutes for direct viral testing and instead should be used only as an adjunct to education and referrals in high-risk patients.