A Risk Score Model for Locoregional Recurrence Following Upfront Surgery for Pancreatic Adenocarcinoma: Implications for Adjuvant Therapy.

AIMS: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF. MATERIALS AND METHODS: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF. RESULTS: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001). CONCLUSION: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.

CD8 encephalitis with CSF EBV viraemia and HIV drug resistance, a case series.

INTRODUCTION: CD8 encephalitis is a relatively recently described condition in the setting of HIV infection. It is becoming increasingly recognised in recent years though is still likely underdiagnosed. METHODS: We present three cases of encephalitis in HIV-positive black African females initially presenting with neurological pathology. Two cases concern recent presentations of patients attending HIV services at a large tertiary referral hospital and the third case involves a retrospective analysis of an archived case. RESULTS AND DISCUSSION: MRI brain demonstrated periventricular white matter changes in 2 cases and a cerebellar lesion in the third case. CSF examination revealed lymphocytosis and elevated protein levels. CSF HIV viral load analysis showed viral escape along with new antiretroviral drug resistance mutations. CSF flow cytometry studies demonstrated a reversed CD4:CD8 ratio with a high CD8+ cells percentage. All patients had EBV DNA detected in their CSF. Brain biopsy in two patients confirmed CD8 encephalitis and also revealed isolated cells demonstrating EBV positivity by in-situ hybridization using EBER (Epstein-Barr virus-encoded small RNAs). Treatment with steroids and ART optimisation led to significant clinical and radiological improvements in all cases. DISCUSSION: CD8 encephalitis should be considered as a cause of neurological symptoms and confusion in the HIV-positive patient, particularly if poor ART adherence or viral resistance are suspected. Brain biopsy should be considered in HIV-positive patients with encephalopathy of uncertain cause. Early treatment with high-dose corticosteroids when suspecting this diagnosis is essential for a favourable outcome. The prognosis is variable but can be favourable even following severe encephalopathy. The presence of new INSTI mutations in the CSF but absent peripherally in two INSTI-era patients is a novel finding for this case series in the context of CD8 encephalitis. The role played by EBV in this disease remains unclear and warrants further investigation.

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population-level analysis.

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause-specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI: 1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Intravascular large B-cell lymphoma presenting clinically as rapidly progressive dementia.

BACKGROUND: In patients presenting with rapidly progressive dementia, prion disease may enter the differential diagnosis. The commonest malignancies masquerading as prion disease are primary CNS lymphoma and intravascular large B-cell lymphoma, both rare and difficult to diagnose without brain biopsy. CASE PRESENTATION: This 82-year-old lady with a past history of hypertension, presented with rapidly progressive cognitive impairment and ataxia. The possibility of sCJD was raised. Brain biopsy was carried out. Western blot for prion protein was negative. Brain biopsy showed intravascular large B-cell lymphoma. She died shortly afterwards. CONCLUSION: The clinical presentation of intravascular large B-cell lymphoma is diverse. Patients may present as in this case with dementia, seizures, and myoclonus leading to a clinical diagnosis of sCJD. The diagnosis here was made at biopsy but is made at autopsy in over 50% of cases.

Limited impact of awareness-raising campaigns on hepatitis C testing practices among general practitioners.

The global hepatitis strategy calls for increased effort to diagnose those infected, with a target of 90% diagnosed by 2030. Scotland's Action Plan on Hepatitis C included awareness-raising campaigns, undertaken during 2008-2011, to promote testing by general practitioners. We examined hepatitis C virus (HCV) testing practice among general practitioners before and following these campaigns. Scottish general practitioners were surveyed, using Dillman's method, in 2007 and 2013; response rates were 69% and 60%, respectively. Most respondents offer testing when presented with a risk history (86% in 2007, 88% in 2013) but only one-fifth actively sought out risk factors (19% in 2007, 21% in 2013). Testing was reportedly always/almost always/usually offered to people who inject drugs (84% in 2007, 87% in 2013). Significant improvements in the offer of testing were reported in patients with abnormal LFTs (41% in 2007, 65% in 2013, P<.001) and who had received medical/dental treatment in high prevalence countries (14% in 2007, 24% in 2013, P=.001). In 2013, 25% of respondents had undertaken HCV-related continued professional development. This group was significantly more likely to actively seek out risk factors (P=.009) but only significantly more likely to offer a test to patients who had received medical/dental treatment in high prevalence countries (P=.001). Our findings suggest that government-led awareness raising campaigns have limited impact on general practitioners' testing practices. If the majority of the HCV-infected population are to be diagnosed, practitioner-based or physician-centred interventions should be considered alongside educational initiatives targeted at professionals.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.

Identifying former injecting drug users infected with hepatitis C: an evaluation of a general practice-based case-finding intervention.

BACKGROUND: In Scotland, a general practice-based case-finding initiative, to diagnose and refer hepatitis C virus (HCV) chronically infected former injecting drug users (IDUs), was evaluated. METHODS: Testing was offered in eight Glasgow general practices in areas of high deprivation and high HCV and IDU prevalence to attendees aged 30-54 years with a history of IDU. Test uptake and diagnosis rates were compared with those in eight demographically similar control practices. RESULTS: Of 422 eligible intervention practice attendees, 218 (52%) were offered an HCV test and, of these, 121 (56%) accepted. Poor venous access in 13 individuals prevented testing. Of 105 tested, 70% (74/105) were antibody positive of which 58% (43/74) were RNA positive by PCR. Of 43 chronically infected individuals identified in intervention practices, 22 (51%) had attended specialist care within 30 months of the study, while 9 (21%) had defaulted. In control practices, 8 (22%) of 36 individuals tested were antibody positive. Test uptake and case yield were approximately 3 and 10 times higher in intervention compared with control practices, respectively. CONCLUSIONS: Targeted case-finding in primary care demonstrated higher test uptake and diagnosis rates; however, to optimize diagnosis and referral of chronically infected individuals, alternative means of testing (e.g. dried blood spots) and retention in specialist care (e.g. outreach services) must be explored.

Hepatitis B prevention, diagnosis, treatment and care: a review.

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B (CHB) infection is associated with an increased risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). The likelihood of developing CHB is related to the age at which infection is acquired; the risk being lowest in adults and >90% in neonates whose mothers are hepatitis B e antigen positive. Treatment of CHB infection aims to clear HBV DNA and prevent the development of complications. There are currently seven drugs available for the treatment of CHB: five nucleos(t)ide analogues and two interferon-based therapies. Long-term treatment is often required, and the decision to treat is based on clinical assessment including the phase of CHB infection and the presence and extent of liver damage. A safe and effective HBV vaccine has been available since the early 1980s. Vaccination plays a central role in HBV prevention strategies worldwide, and a decline in the incidence and prevalence of HBV infection following the introduction of universal HBV vaccination programmes has been observed in many countries including the USA and parts of South East Asia and Europe. Post-exposure prophylaxis (PEP) with HBV vaccine +/- hepatitis B immunoglobulin is highly effective in preventing mother to child transmission and in preventing transmission following sharps injuries, sexual contact and other exposures to infected blood and body fluids. Transmission of HBV in the health care setting has become an increasingly rare event in developed nations. However, it remains a significant risk in developing countries reflecting the higher prevalence of CHB, limited access to HBV vaccination and PEP and a lack of adherence to standard infection control precautions.

Investigation of the peak action wavelength of light-activated gene transduction.

Light-activated gene transduction (LAGT) is an approach to localize gene therapy via preactivation of cells with UV light, which facilitates transduction by recombinant adeno-associated virus vectors. Previous studies demonstrated that UVC induces LAGT secondary to pyrimidine dimer formation, whereas UVA induces LAGT secondary to reactive-oxygen species (ROS) generation. However, the empirical UVB boundary of these UV effects is unknown. Thus, we aimed to define the action spectra for UV-induced LAGT independent of DNA damage and determine an optimal wavelength to maximize safety and efficacy. UV at 288, 311 and 320 nm produced significant dose-dependent LAGT effects, of which the maximum (800-fold) was observed with 4 kJ m⁻² at 311 nm. Consistent with its robust cytotoxicity, 288 nm produced significantly high levels of DNA damage at all doses tested, whereas 311, 320 and 330 nm did not generate pyrimidine dimers and produced low levels of DNA damage detected by comet assay. Although 288 nm failed to induce ROS, the other wavelengths were effective, with the maximum (10-fold) effect observed with 30 kJ m⁻² at 311 nm. An in vivo pilot study assessing 311 nm-induced LAGT of rabbit articular chondrocytes demonstrated a significant 6.6-fold (P<0.05) increase in transduction with insignificant cytotoxicity. In conclusion, 311 nm was found to be the optimal wavelength for LAGT on the basis of its superior efficacy at the peak dose and its broad safety range that is remarkably wider than the other UV wavelengths tested.

Evaluation of a general practice based hepatitis C virus screening intervention.

BACKGROUND: In 2003 an estimated 37,500 of Scotland's population was chronically infected with HCV; 44% were undiagnosed former injecting drug users (IDU)--a priority group for antiviral therapy. AIM: To evaluate a hepatitis C virus (HCV) screening intervention. DESIGN: Outcome measures among two similar General Practice populations in an area of high HCV and drug use prevalence, one of which was exposed to an HCV screening intervention, were compared. METHODS: Thirty to fifty four year old attendees of the intervention practice were opportunistically offered testing and counselling, where clinically appropriate, (November 2003-April 2004). OUTCOMES: HCV test uptake, case detection, referral and treatment administration rates. RESULTS: Of 584 eligible attendees, 421 (72%) were offered and 117 (28%) accepted testing in the intervention practice; no testing was undertaken in the comparison practice. Prevalences of HCV antibody were 13% (15/117), 75% (3/4) and 91% (10/11) among all tested persons, current IDUs and former IDUs respectively. For 4/15 (27%) evidence of binge drinking following the receipt of their positive result, was available. Of the 11 referred to specialist care because they were HCV RNA positive, nine attended at least one appointment. Two received treatment: one had achieved a sustained viral response as of February 2008. CONCLUSION: While non targeted HCV screening in the general practice setting can detect infected former IDU, the low diagnostic yield among non IDUs limited the effectiveness of the intervention. A more targeted approach for identifying former IDUs is recommended. Additionally, the low uptake of treatment among chronically infected persons four years after diagnosis demonstrates the difficulties in clinically managing such individuals. Strategies, including support for those with a history of problem alcohol use, to improve treatment uptake are required.

Heritable T-cell malignancy models established in a zebrafish phenotypic screen.

T-cell neoplasias are common in pediatric oncology, and include acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL). These cancers have worse prognoses than their B-cell counterparts, and their treatments carry significant morbidity. Although many pediatric malignancies have characteristic translocations, most T-lymphocyte-derived diseases lack cytogenetic hallmarks. Lacking these informative lesions, insight into their molecular pathogenesis is less complete. Although dysregulation of the NOTCH1 pathway occurs in a substantial fraction of cases, many other genetic lesions of T-cell malignancy have not yet been determined. To address this deficiency, we pioneered a phenotype-driven forward-genetic screen in zebrafish (Danio rerio). Using transgenic fish with T-lymphocyte-specific expression of enhanced green fluorescent protein (EGFP), we performed chemical mutagenesis, screened animals for GFP(+) tumors, and identified multiple lines with a heritable predisposition to T-cell malignancy. In each line, the patterns of infiltration and morphological appearance resembled human T-ALL and T-LBL. T-cell receptor analyses confirmed their clonality. Malignancies were transplantable and contained leukemia-initiating cells, like their human correlates. In summary, we have identified multiple zebrafish mutants that recapitulate human T-cell neoplasia and show heritable transmission. These vertebrate models provide new genetic platforms for the study of these important human cancers.

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland.

We investigated trends in first-time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population-based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991-2006. We identified new cases of HCC through record-linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first-time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI): 0.9-11.6%, P=0.021). The adjusted relative risk of HCC was greater for males (hazard ratio=2.7, 95% CI: 1.7-4.2), for those aged 60 years or older (hazard ratio=2.7, 95% CI: 1.9-4.1) compared with 50-59 years, and for those with a previous alcohol-related hospital admission (hazard ratio=2.5, 95% CI: 1.7-3.7). The risk of individuals diagnosed with HCV developing HCC was greatly increased compared with the general Scottish population (standardised incidence ratio=127, 95% CI: 102-156). Owing to the advancing age of the Scottish HCV-diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system.

Comparison of deaths related to Hepatitis C and AIDS in Scotland.

In resource-rich countries, the incidence of and mortality from AIDS has fallen dramatically since the introduction of combination antiretroviral therapy. In contrast, developed countries have observed increases in the public health burden associated with the hepatitis C virus (HCV). We compared past and current trends in mortality related to HCV sequelae and HIV/AIDS in Scotland by linking death records with national databases of persons diagnosed with HCV and HIV/AIDS. AIDS-related deaths increased rapidly during the late-1980s to mid-1990s and declined dramatically after 1996. Deaths related to HCV (i.e., viral hepatitis, liver cancer, alcoholic liver disease, or non-alcoholic liver disease) surpassed the number of AIDS-related deaths in 1998 and increased at an average annual rate of 10.5% (95% confidence interval = 7-14%) during 1996-2005. The leading underlying cause of HCV-related deaths was alcoholic liver disease (50% of deaths during 2001-2005). This study highlights the increasing public health burden, vis-à-vis mortality, of HCV, when compared with HIV/AIDS in developed countries. Increased diagnosis and treatment of eligible HCV-infected individuals will be required if we wish to mitigate the future impact of HCV morbidity and mortality.

Preoperative shuttle walking testing and outcome after oesophagogastrectomy.

BACKGROUND: Objective assessment of cardiorespiratory reserve has been recommended before major surgery to identify patients with impaired oxygen delivery who may be at increased operative risk. Access to formal cardiopulmonary exercise (CPX) testing is limited outside larger centres. Following a previous audit of morbidity and mortality after oesophagectomy, we decided to add a simpler form of exercise test to our preoperative screen and review the outcomes. METHODS: Fifty-one patients who had surgical resection of an oesophageal cancer in our unit between April 2002 and April 2005 carried out an incremental shuttle walk exercise test before operation. Thirty-day outcome data were collected for each patient. RESULTS: Overall mortality in the group was 10%. No patient who walked 350 m or more died within 30 days. Five of the eight patients who could not achieve this distance died and two others remained in the critical care unit at 30 days. CONCLUSION: Preoperative shuttle walk testing using a standard protocol appears to be a sensitive indicator of operative risk in this group of patients. The apparent threshold value of 350 m is consistent with previously reported measures of functional capacity obtained using formal CPX testing.

Severe illness and death among injecting drug users in Scotland: a case-control study.

Between April and September 2000, 60 injecting drug users in Scotland died or were hospitalized with severe illness. Laboratory investigations suggested that Clostridium novyi and other bacteria were important aetiological agents. To determine associated environmental/behavioural factors a case-control study was undertaken with 19 'definite' and 32 'probable' cases in Glasgow, Scotland. For every deceased case (n=19), up to three proxy individuals were interviewed. Three controls were identified for each case. Multivariate logistic regression analyses compared (i) all cases and controls; (ii) definite cases and matched controls; (iii) probable cases and matched controls. In all three analyses injecting into muscle or skin and injecting most of the time with a filter used by someone else were the variables most strongly associated with illness. Comparing only muscle-injecting cases and controls, cases were significantly more likely to have injected larger amounts of heroin per average injection than were controls. The findings make an important epidemiological contribution to the understanding of the public health and clinical implications of the contamination of illicit drugs by histotoxic clostridia.

Hepatitis C: What lies ahead and can we afford it?

Hepatitis C is a chronic disease with a slow and variable progression over 20-50 years and it is an important public health problem for the 21st century. This paper describes the information required to estimate what lies ahead in terms of morbidity, mortality and the implications for the health service in Scotland and summarises work undertaken in other countries. There will be an increasing number of people with severe liver disease in the next 10-20 years and we need to invest now in primary prevention and effective treatment strategies to reduce the burden of disease in the future.

A(1) adenosine receptor agonists: medicinal chemistry and therapeutic potential.

Adenosine receptors are widely distributed in the body and modulate numerous physiological processes. Four receptor subtypes (termed A(1), A(2A), A(2B) and A(3)) have been identified based on their pharmacological profile and cloning. Activation of the A(1) adenosine receptors produces a number of effects including a reduction in heart rate and atrial contractility, the attenuation of the stimulatory actions of catecholamines on the heart as well as a reduction of lipolysis in adipose tissue. As a result, A(1)AR agonists have been targeted as anti-arrhythmic and cardioprotective agents. This review discusses the synthesis, structure-activity relationships and therapeutic potential of A(1)AR agonists.

Evaluation of a local anaesthesia regimen following mastectomy.

Breast surgery can be emotionally distressing and physically painful. Acute pain following surgery is often related mainly to the axillary surgery and is aggravated by arm and shoulder movement. We conducted a prospective double-blind, randomised, placebo-controlled trial to determine the influence of local anaesthetic irrigation of axillary wound drains on postoperative pain during the first 24 h following a modified Patey mastectomy (mastectomy with complete axillary node clearance). The treatment group received bupivacaine irrigation through the axillary wound drain 4-hourly for 24 h postoperatively. Controls received irrigation with normal saline. Morphine via a patient controlled analgesia pump was used for postoperative analgesia. Morphine consumption, visual analogue and verbal rating pain scores were recorded. There were no statistical differences in morphine requirements or pain scores between the two groups, nor were there differences in anti-emetic or supplemental analgesic consumption. Bupivacaine irrigation used in this manner does not appear to offer an effective contribution to postoperative analgesia.

Hepatitis C virus among childbearing women in Scotland: prevalence, deprivation, and diagnosis.

OBJECTIVES: (A) To examine the prevalence and demographic characteristics of hepatitis C virus (HCV) infection among childbearing women in Scotland; and (B) to determine the extent of maternal HCV infection diagnosed prior to birth. METHODS: (A) Residual dried blood spot samples from routine neonatal screening, collected throughout Scotland during March-October 2000, were unlinked from identifiers and tested anonymously for HCV antibodies; and (B) electronic record linkage of Scotland's databases of births and diagnosed HCV infections was performed. RESULTS: (A) Of 30,259 samples, 121 were enzyme linked immunosorbent assay repeat reactive and 88 of these were confirmed as anti-HCV positive in the recombinant immunoblot assay, representing a seroprevalence of 0.29-0.40%. HCV seroprevalence was high among 25-29 year olds (0.4-0.57%), in high deprivation areas (0.92-1.07%), and in Greater Glasgow (0.83-0.96%) and Grampian (0.38-0.62%). Adjusted relative risk for HCV infection was highest among residents in high deprivation areas of Glasgow (7.2 (95% confidence interval 2.0-25.5)). (B) Of 121 HCV infections found among women at delivery, 24% and 46% were estimated to have been diagnosed prior to pregnancy and birth, respectively. CONCLUSIONS: HCV prevalence among Scottish childbearing women is consistent with that expected from injecting drug use. Based on reported rates of mother to child transmission, 8-11 paediatric infections are expected per annum. Diagnosis in only 24% of infected women prior to pregnancy indicates the extent to which HCV goes unrecognised in the injecting community. The current HCV screening approach-to test only those with a history of injecting drug use (or other risk factors for infection)-identifies approximately a quarter of previously undetected infections among pregnant women.