Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

BACKGROUND AND AIM: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. METHOD: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. RESULTS: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. CONCLUSION: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.

Serum interleukin-4 is elevated in clinical drug-induced liver injury.

BACKGROUND: Drug-induced liver injury (DILI) remains a challenging diagnosis due to an absence of specific biomarkers. DILI due to volatile anaesthetics (VA-DILI) is characterised by trifluoroacetyl and CYP2E1 antibodies, but may not be seen for weeks after injury. Interleukin-4 (IL-4) may be involved in the production of these antibodies and may serve as a clinically useful early biomarker of VA-DILI. AIM: To prospectively compare serum IL-4 levels between patients who develop VA-DILI and controls following exposure to the volatile anaesthetic. METHODS: A nested case-control study of patients exposed to VA during surgery was conducted. Thirteen DILI cases were identified from the original cohort, and 26 controls were matched according to age, sex and VA agent. Serum samples were collected before and 48-96 h after VA exposure, and analysed for IL-4 using quantitative enzyme-linked immunosorbent assay techniques. RESULTS: There was a statistically significant difference in serum IL-4 in post-VA samples between DILI cases and controls (control: 0.030 pg/mL, IQR: 0.030 - 0.030 pg/mL vs DILI: 0.044 pg/mL, IQR: 0.030 - 0.061 pg/mL; p = 0.039). A greater proportion of DILI cases had post-VA IL-4 levels above the assay lower limit of detection compared to controls (control: 23% vs DILI: 69%; p = 0.013). CONCLUSION: IL-4 is a potential biomarker of DILI. Clinical diagnosis and understanding of DILI disease mechanisms may be improved by further investigation of novel biomarkers, and this IL-4 signal in serum is important as proof of concept for prospective study designs.

Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study.

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Perinatal outcomes following mid trimester detection of isolated short foetal femur length.

BACKGROUND: Short foetal femur length (FL) is a normal variant but may also be a marker for disorders such as skeletal dysplasia, Trisomy 21 (T21), Turners syndrome, congenital infection (TORCH) and foetal growth restriction (FGR). AIM: Our aim was to review outcomes in our population following a diagnosis of isolated short FL (FL <5th centile) when detected at the time of mid trimester foetal anomaly scan (FAS). METHODS: All women within NHS Tayside who attended for routine mid trimester foetal anomaly scan at 18-21 weeks gestation (Range = 18+2-21+3 weeks) between November 2011 and June 2016 were included. Those who had an isolated FL <5th centile were identified using Viewpoint. Data relating to perinatal and childhood outcomes were obtained from local databases. RESULTS: 72 women were identified. The median maternal age was 30 years (range = 17-45 years). 39/72 (54.2%) women were primigravid. 41/72 (56.9%) women had Down's syndrome screening (DSS). 12/72 (16.7%) women were offered TORCH screens, none of which were positive for recent or current infection. Invasive testing was performed in 8/72 (11%) women; 1 had previously had first trimester chorionic villus sampling (CVS) for raised maternal age. 7 women had amniocentesis (1 prior to FAS for increased DSS risk). All those that had invasive testing had normal foetal karyotype. Median gestational age at delivery was 38 weeks (range = 26-41 weeks). 10/72 (13.9%) had genetic testing after birth, 6 were performed shortly after birth due to dysmorphic features. 4/72 (5.5%) had Trisomy 21 and 3 of these had VSD that had not been identified antenatally. For those with T21, 3 mothers had declined DSS and 1 had a low risk DSS result. Fifty out of seventy two (69.4%) babies had constitutionally short femurs. 13/72 (18%) had FGR and 3/72 (4.2%) had skeletal dysplasia. One baby had William's syndrome, one had Klinefelter syndrome and two had genetic deletions of uncertain significance. CONCLUSIONS: Knowledge of outcomes will enable better counselling for women with isolated short foetal femur. In our local population, more than two-thirds of the babies with isolated short femur will be normal. Women must, however, be informed of the potential for foetal aneuploidy and foetal skeletal dysplasia. In view of this, women should be offered invasive testing and follow-up ultrasound scans to assess the foetal skeleton. Furthermore isolated short foetal femur is a marker for FGR and all women with isolated short femur should be offered serial ultrasound scans to assess foetal growth and well-being in the third trimester.

Impact of viral hepatitis aetiology on survival outcomes in hepatocellular carcinoma: A large multicentre cohort study.

While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.

The changing place of liver biopsy in clinical practice: an audit of an Australian tertiary hospital.

Liver biopsy is an important tool in hepatology, with a role now generally limited to cases of diagnostic uncertainty. A retrospective audit performed at the Royal Melbourne Hospital aimed to identify the indications for liver biopsy and its impact on management. Ten per cent (20/195) of biopsies lacked a strong clinical indication, with hepatology involvement in only 8/20. We recommend prior hepatologist assessment to minimise unnecessary biopsies.

Epidemiology of hepatitis B-associated hepatocellular carcinoma in Victoria.

BACKGROUND: Chronic hepatitis B (HBV) and cirrhosis are major risk factors for hepatocellular carcinoma (HCC). The proportion and characteristics of cases with cirrhosis are not well documented. AIM: Our aim was to compare demographic, viral and tumour characteristics of HBV-associated HCC in an Australian cohort, in patients with and without cirrhosis. METHODS: Existing HCC databases at six Melbourne teaching hospitals were reviewed for cases associated with HBV. Patient demographics, HBV viral characteristics, presence of cirrhosis, serum alpha-fetoprotein and tumour size were assessed. Mode of diagnosis was recorded through surveillance or symptoms, and treatment was either palliative, percutaneous or surgical. RESULTS: We identified 197 cases of HBV-related HCC. The mean age was 57.9 ± 12.9 years; 83% were male, and 55.3% and 35.3% were of Asian and European descent respectively. Of 168 patient with available data, 146 (87%) had cirrhosis versus 22 (13%) without. Patients with cirrhosis tended to be older (median 60 vs 52 years, P = 0.078). Asian patients were more likely to have HCC without cirrhosis than Europeans (17% vs 6%, P = 0.04). There were no other differences identified between cirrhotic and non-cirrhotic patients. Thirty-four per cent of patients had tumours greater than 5 cm at diagnosis, and 47% were diagnosed after presenting with symptoms. Twelve patients with HBV-HCC were outside current screening guidelines. CONCLUSION: Most patients in Melbourne with HBV-associated HCC have cirrhosis. HCC characteristics in non-cirrhotic and cirrhotic patients were similar. The large number of patients detected through symptoms and with large tumours reinforces the need for vigilance in screening.

Type 2 diabetes does not worsen prognosis in hepatocellular carcinoma.

INTRODUCTION: Type 2 diabetes (T2DM) is associated with liver inflammation and carcinogenesis. The prevalence of T2DM among patients with liver cirrhosis and hepatocellular carcinoma is increasing. However, the effect of T2DM on the natural history of hepatocellular carcinoma is not known. AIM: To examine the effect of T2DM on hepatocellular carcinoma (HCC) survival in treated and untreated disease. METHODS: Retrospective analysis was performed on HCC cases diagnosed during 2000-2005, and prospectively during 2006-August 2007. Demographics, HCC staging, response to treatment, and survival were collected. A comparison was made between patients with T2DM and without T2DM. RESULTS: One hundred and thirty-five patients were recruited in total; 58 (43%) had T2DM. Seventy (37 diabetic) patients were treated with percutaneous radiological therapies, with 168 treatments given. Treatment was determined by AASLD guidelines and patient tolerance, there was no randomisation. There was no significant difference in survival between diabetic and nondiabetic patients. There was a nonsignificant trend towards greater survival in diabetic patients (overall median survival diabetics 21 mths vs nondiabetics 5 mths, P=0.355). CONCLUSIONS: T2DM does not negatively impact on the natural history of treated or untreated HCC.

[First exchange of experiences concerning the H1N1 pandemic in Germany 2009/2010: report on a workshop held March 22-23, 2010, in Berlin]. / Erster Erfahrungsaustausch zur H1N1-Pandemie in Deutschland 2009/2010: Bericht über einen Workshop am 22. und 23. März 2010 in Berlin.

In April 2009 the first pandemic of the 21st century developed within a few weeks starting from Mexico. Its first wave reached Germany in autumn 2009 and was responsible for 1.8-3.5 million additional medical consultations. For the public health sector, this pandemic was one of the largest challenges of the last few decades. As a contribution to broader evaluations on national and international level, the Robert Koch Institute invited representatives from different professions involved in the pandemic response to participate in a workshop on 22-23 March 2010. This workshop was structured in short presentations, group work, and plenary discussions. Main experiences were that (a) pandemic preparedness was helpful, (b) the early warning systems were reliable, (c) vaccines were available within a few months, however, in limited amounts. Need for improvement was discussed for (a) effectiveness of vaccination logistics, (b) mechanisms for the reimbursement of the cost of vaccination, (c) availability of surveillance and monitoring systems, (d) integration of physicians in decision-making processes and health education, and (e) proactive communication strategies. Investments in the above mentioned areas can help to improve public health protection in the future.

Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis.

HFE-associated hereditary haemochromatosis is a recessive, iron-overload disorder that affects about one in 200 north Europeans and that can be easily prevented. However, genetic screening for this disease is controversial, and so we assessed whether such screening was suitable for communities. Cheek-brush screening for the Cys282Tyr HFE mutation was offered to individuals in the workplace. Outcomes were assessed by questionnaires before and after testing. 11,307 individuals were screened. We recorded no increase in anxiety in individuals who were homozygous for the Cys282Tyr mutation or non-homozygous. Self-reported tiredness before testing was significantly higher in homozygous participants than in non-homozygous participants (chi2 test, p=0.029). Of the 47 homozygous individuals identified, 46 have taken steps to treat or prevent iron accumulation. Population genetic screening for HFE-associated hereditary haemochromatosis can be practicable and acceptable.

Health protection--a strategy and a national agency.

The Chief Medical Officer for England has published a strategy for health protection and announced the formation of a new body, the Health Protection Agency, to deal with the threats to health from infectious disease, chemicals, toxins and radiation hazards. This reflects international recognition of the need to combat threats to health from the likes of tuberculosis, HIV, influenza, anti-microbial resistance, chemical accidents and bio-terrorism, and the risks to health associated with increased movements of people, animals and goods, climate change and industrialisation. The strategy will strengthen surveillance and response linking contributions from clinical specialities with public health, microbiology, toxicology and radiation science within the health protection family. The Agency will be formed by combining a number of national and specialist public bodies and personnel delivering local protection services. The strategy represents a unique opportunity to strengthen local and national structures and develop a world-class health protection service. Detailed plans are being developed by the Department of Health with a variety of stakeholders for the launch of the Agency in 2003. A number of challenges will have to be met including developing and training the workforce in health protection, providing career structures for public health scientists and nurses, strengthening electronic communications and developing health protection networks within broader public health structures. Health protection should now be recognised as a sub-speciality of public health.

Biliary epithelial trefoil peptide expression is increased in biliary diseases.

AIMS: Maintenance of the cellular integrity of the biliary epithelium may involve the production of mucins and mucin-associated peptides. In the luminal gastrointestinal tract, mucins and the mucin-associated trefoil peptides (TFF) are integral to cytoprotection and cellular repair of the mucosa. METHODS AND RESULTS: Samples of normal and diseased human liver tissue were examined using histological and immunohistochemical techniques, for the expression of TFF and mucins. Bile ducts were classified as small, medium or large depending upon the number of biliary epithelial cells. TFF expression was demonstrated in biliary epithelial cells of both normal and diseased liver tissue. TFF expression was greatest in the large bile ducts. In normal liver tissue, expression of at least one TFF was demonstrated in 2-7% of small bile ducts, 5-31% of medium bile ducts and 31-85% of large bile ducts. Seventy-seven percent of large bile ducts secreted mucins and all three TFF concurrently, compared with 3% of medium bile ducts and no small bile ducts. Biliary disease resulted in an increased expression of TFF1 and TFF3 in the medium bile ducts. CONCLUSIONS: The biliary epithelial cells in normal and diseased human liver tissue express TFF, particularly in the larger bile ducts. TFF expression may be up-regulated or induced in biliary diseases as a response to injury, as is seen in epithelial damage elsewhere in the gastrointestinal tract.

Assessing the impact of national anti-HIV sexual health campaigns: trends in the transmission of HIV and other sexually transmitted infections in England.

OBJECTIVE: To assess the impact of the sexual component of AIDS and HIV campaigns on transmission of HIV and other sexually transmitted infections (STIs). DESIGN: Comparison of time series data. SETTING: England, 1971-1999. OUTCOME MEASURES: HIV transmission and diagnoses among men who have sex with men (MSMs), rates of attendances and specific STI diagnoses (per 100 000 total population) at genitourinary medicine (GUM) clinics. RESULTS: Awareness of AIDS and campaigns in 1983-4 among homosexual men coincided with substantial declines in transmission of HIV and diagnoses of syphilis among MSMs. During general population campaigns in 1986-7 new GUM clinic attendances requiring treatment fell by 117/10(5) in men and 42/10(5) in women. Rates for gonorrhoea fell by 81/10(5) and 43/10(5) and genital herpes by 6/10(5) and 4/10(5), respectively. Previous rises in genital wart rates were interrupted, while rates of attendances not requiring treatment (the "worried well") increased by 47/10(5) and 58/10(5) for men and women, respectively. Since 1987 diagnoses of HIV among MSMs have not declined, averaging 1300-1400 annually. Following a period of unchanging rates there have been substantial increases in GUM attendances requiring treatment, notably for gonorrhoea, syphilis, and viral STIs since 1995. CONCLUSIONS: Self help initiatives and awareness among homosexual men in 1983-4 contributed significantly to a fall in HIV transmission among MSMs, and the general campaigns of 1986-7 were associated with similar effects on all STI transmission. Both effects seem to have occurred through changing sexual behaviour, and probably contributed to the UK's low national HIV prevalence. Bacterial STI incidence has increased significantly since 1995 and there is no evidence that recent prevention initiatives have reduced HIV transmission among MSMs, hence sexual health initiatives need to be comprehensively reinvigorated in England.

Duck hepatitis B virus replication in primary bile duct epithelial cells.

Primary cultures of intrahepatic bile duct epithelial (IBDE) cells isolated from duckling livers were successfully grown for studies of duck hepatitis B virus (DHBV). The primary IBDE cells were characterized by immunohistochemistry using CAM 5.2, a cytokeratin marker which was shown to react specifically to IBDE cells in duck liver tissue sections and in primary cultures of total duck liver cells. Immunofluorescence assay using anti-duck albumin, a marker for hepatocytes, revealed that these IBDE cultures did not appear to contain hepatocytes. A striking feature of these cultures was the duct-like structures present within each cell colony of multilayered IBDE cells. Normal duck serum in the growth medium was found to be essential for the development of these cells into duct-like structures. When the primary cultures of duck IBDE cells were acutely infected with DHBV, dual-labeled confocal microscopy using a combination of anti-DHBV core proteins and CAM 5.2 or a combination of anti-pre-S1 proteins and CAM 5.2 revealed that the IBDE cell colonies contained DHBV proteins. Immunoblot analysis of these cells showed that the DHBV pre-S1 and core proteins were similar to their counterparts in infected primary duck hepatocyte cultures. Southern blot analysis of infected IBDE preparations using a digoxigenin-labeled positive-sense DHBV riboprobe revealed the presence of hepadnavirus covalently closed circular (CCC) DNA, minus-sense single-stranded (SS) DNA, double-stranded linear DNA, and relaxed circular DNA. The presence of minus-sense SS DNA in the acutely infected IBDE cultures is indicative of DHBV reverse transcriptase activity, while the establishment of a pool of viral CCC DNA reveals the ability of these cells to maintain persistent infection. Taken collectively, the results from this study demonstrated that primary duck IBDE cells supported hepadnavirus replication as shown by the de novo synthesis of DHBV proteins and DNA replicative intermediates.

Effect of omeprazole-induced achlorhydria on trefoil peptide expression in the rat stomach.

BACKGROUND: Omeprazole is an inhibitor of the H+K+ ATPase of the gastric parietal cell, which is used clinically to suppress gastric acid secretion. It has also been found to inhibit gastric mucin production; however, its effects on the synthesis and secretion of the trefoil peptides, which are also expressed by mucus cells, and which play a key role in cytoprotection and epithelial repair, are unknown. METHODS: Rats (n=8) were given either omeprazole (30 mg/kg per day; p.o.) or inert carrier for 1 week, and the effects on synthesis and peptide expression of the gastric trefoil peptides, TFF1/pS2 and TFF2/SP, were compared. RESULTS: As expected, omeprazole treatment abolished H+ ion production with a mean gastric juice pH of 7.2 compared with 2.4 for controls. The omeprazole group had elevated total protein levels of 35-fold and TFF1/pS2 peptide levels elevated fourfold, respectively, but not TFF2/SP peptide in gastric juice, suggesting that the increased pH reduced the viscosity of adherent mucus, thereby increasing gastric juice concentrations by dissolution of adherent TFF1/pS2 and increased secretion. Concomitant with increased TFF1/pS2 secretion was a fall in predominantly antral mucosal trefoil peptide concentrations. In contrast to trefoil secretory rates, the steady-state synthesis of both TFF1/pS2 and TFF2/SP was unchanged after omeprazole treatment, implying both a large cellular pool of processed peptide and rapid secretion. CONCLUSION: The increase in the concentration of TFF1/pS2 in gastric secretions during chronic omeprazole-induced achlorhydria may be important in preventing tissue injury and promoting repair in response to an increased luminal bacterial population.

Variant Creutzfeldt-Jakob disease in UK children: a national surveillance study.

BACKGROUND: Variant Creutzfeldt-Jakob Disease (vCJD) was first reported in 1996; the youngest patient developed symptoms at 16 years of age. We have done 3 years of prospective active surveillance for progressive intellectual and neurological deterioration (PIND) in UK children, and have searched for vCJD among the children who were reported. METHODS: Since May, 1997, there has been active surveillance for patients younger than 16 years old with PIND by means of a monthly card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical'details of cases of PIND are obtained from reporting paediatricians by telephone interview or site visit, and an expert group of paediatric neurologists then classifies the cases. FINDINGS: After 3 years, 885 patients with suspected PIND have been reported. Among them were two fatal cases of definite vCJD and one case of probable vCJD; all were reported in 1999. One girl was age 12 years at onset--the youngest ever case of vCJD. No other children with the clinical features of vCJD were identified. The expert group has discussed 655 cases, of which 360 have a confirmed underlying cause, being categorised into 88 known neurodegenerative diseases. INTERPRETATION: That this prospective active surveillance in the UK has found few children with suspected vCJD is relatively reassuring. However, 3 years is a short time to survey a disease with an unknown incubation period. Since one probable and two definite cases of vCJD were reported to the study in 1999, there is concern that more childhood cases may appear.

National assessment of PID diagnosis, treatment and management in general practice: England and Wales.

A questionnaire based audit was used to evaluate the diagnosis and management of suspected pelvic inflammatory disease (PID) cases by general practitioners (GPs) in England and Wales. Responses were compared against a clinical management 'gold standard' devised by an independent group of GPs and specialists. Two hundred and ninety-seven (38%) of the 781 questionnaires were returned. Only 21 (7%) had all 'gold standard' sections correct. Diagnostic quality was significantly higher when the clinician was female compared with male (odds ratio [OR]=2.34; 95% confidence limits [CL]=1.19-4.63) and diagnostic quality increased with increasing socioeconomic deprivation. This is the first evaluation of the diagnosis and management of PID by GPs in England and Wales. The unusually poor response rate to a Medical Research Council General Practice Research Framework (MRC GPRF) study may reflect low disease awareness and sub-optimal management. This represents a fundamental obstacle to effective intervention and surveillance. Effective intervention will only be possible if diagnostic practice and management are improved substantially.

Strategic options for antenatal screening for syphilis in the United Kingdom: a cost effectiveness analysis.

OBJECTIVE: Antenatal screening for syphilis is well established in the United Kingdom. The prevalence of syphilis is now very low, prompting the question as to whether this screening programme is still necessary. This paper aims at identifying possible screening strategy options for the programme and comparing their effectiveness and cost effectiveness. METHODS: The cost of the screening programme in the United Kingdom was estimated. This was based on the cost of screening tests, treatment, and follow up of infected women and their infants. This information was obtained from laboratories, antenatal clinics, and genitourinary medicine clinics. Epidemiological data from a survey of women treated for syphilis in pregnancy were analysed to identify groups at increased risk of syphilis. Strategic options for the screening programme were then identified. The effectiveness, number needed to treat, and cost effectiveness of these options were compared. RESULTS: Antenatal screening in the United Kingdom detected at least 40 pregnant women who need treatment for syphilis every year. This means that 18602 women are screened for every woman detected who needs treatment for syphilis. The marginal annual cost of this screening programme in the United Kingdom is 672366 pounds sterling. This is equivalent to 90p per woman screened, or 16670 pounds sterling to detect one woman who needs treatment for syphilis. The screening programme could be targeted geographically at pregnant women in the Thames regions. This option has the potential to save 482185 pounds sterling. Other strategic options are to target pregnant women in non-white ethnic groups, or those born outside the United Kingdom. These targeted options would each detect between 70% and 77% of women needing treatment for syphilis. These options could potentially save 592938 pounds sterling and 562691 pounds sterling respectively. CONCLUSIONS: Targeting or stopping the screening programme would save relatively little money. Although selectively screening groups by country of birth or by ethnic group could detect at least 70% of cases, this would be politically and practically difficult. Targeting by region would facts and the changing international epidemiology of syphilis lead us to recommend that the current universal antenatal screening for syphilis should continue.