Availability of Alcohol on an Online Third-Party Delivery Platform Across London Boroughs, England: Exploratory Cross-Sectional Study.

BACKGROUND: Higher availability of alcohol is associated with higher levels of alcohol consumption and harm. Alcohol is increasingly accessible online, with rapid delivery often offered by a third-party driver. Remote delivery and online availability are important from a public health perspective, but to date, relatively little research has explored the availability of alcohol offered by online platforms. OBJECTIVE: This cross-sectional exploratory study describes the availability of alcohol on the third-party platform Deliveroo within London, England. METHODS: We extracted the number of outlets offering alcohol on Deliveroo for each London borough and converted these into crude rates per 1000 population (18-64 years). Outlets were grouped as outlets exclusively selling alcohol, off-licenses, and premium. We calculated Pearson correlation coefficients to explore the association between borough's crude rate of outlets per 1000 population and average Indices of Multiple Deprivation (IMD) 2019 scores. We extracted the number of outlets also selling tobacco or e-cigarettes and used non-Deliveroo drivers. We searched addresses of the top 20 outlets delivering to the most boroughs by outlet type (60 total) to determine their associated premise. RESULTS: We identified 4277 total Deliveroo-based outlets offering alcohol across London, including outlets delivering in multiple boroughs. The crude rate of outlets per 1000 population aged 18-64 years was 0.73 and ranged from 0.22 to 2.29 per borough. Most outlets exclusively sold alcohol (3086/4277, 72.2%), followed by off-licenses (770/4277, 18.0%) and premium (421/4277, 9.8%). The majority of outlets exclusively selling alcohol sold tobacco or e-cigarettes (2951/3086, 95.6%) as did off-licenses to a lesser extent (588/770, 76.4%). Most outlets exclusively offering alcohol used drivers not employed by Deliveroo (2887/3086, 93.6%), and the inverse was true for premium outlets (50/421, 11.9%) and off-licenses (73/770, 9.5%). There were 1049 unique outlets, of which 396 (37.8%) were exclusively offering alcohol-these outlets tended to deliver across multiple boroughs unlike off-licenses and premium outlets. Of outlets with confirmed addresses, self-storage units were listed as the associated premise for 85% (17/20) of outlets exclusively offering alcohol, 11% (2/19) of off-licenses, and 12% (2/17) of premium outlets. We found no significant relationship between borough IMD scores and crude rate of outlets per 1000 population overall (P=.87) or by any outlet type: exclusively alcohol (P=.41), off-license (P=.58), and premium (P=.18). CONCLUSIONS: London-based Deliveroo outlets offering alcohol are common and are sometimes operating from self-storage units that have policies prohibiting alcohol storage. This and the potential for increased alcohol accessibility online have implications for public health given the relationship between alcohol's availability and consumption or harm. There is a need to ensure that regulations for delivery are adequate for protecting children and vulnerable adults. The Licensing Act 2003 may require modernization in the digital age. Future research must explore a relationship between online alcohol availability and deprivation.

The relationship between the price and demand of alcohol, tobacco, unhealthy food, sugar-sweetened beverages, and gambling: an umbrella review of systematic reviews.

BACKGROUND: The WHO highlight alcohol, tobacco, unhealthy food, and sugar-sweetened beverage (SSB) taxes as one of the most effective policies for preventing and reducing the burden of non-communicable diseases. This umbrella review aimed to identify and summarise evidence from systematic reviews that report the relationship between price and demand or price and disease/death for alcohol, tobacco, unhealthy food, and SSBs. Given the recent recognition as gambling as a public health problem, we also included gambling. METHODS: The protocol for this umbrella review was pre-registered (PROSPERO CRD42023447429). Seven electronic databases were searched between 2000-2023. Eligible systematic reviews were those published in any country, including adults or children, and which quantitatively examined the relationship between alcohol, tobacco, gambling, unhealthy food, or SSB price/tax and demand (sales/consumption) or disease/death. Two researchers undertook screening, eligibility, data extraction, and risk of bias assessment using the ROBIS tool. RESULTS: We identified 50 reviews from 5,185 records, of which 31 reported on unhealthy food or SSBs, nine reported on tobacco, nine on alcohol, and one on multiple outcomes (alcohol, tobacco, unhealthy food, and SSBs). We did not identify any reviews on gambling. Higher prices were consistently associated with lower demand, notwithstanding variation in the size of effect across commodities or populations. Reductions in demand were large enough to be considered meaningful for policy. CONCLUSIONS: Increases in the price of alcohol, tobacco, unhealthy food, and SSBs are consistently associated with decreases in demand. Moreover, increasing taxes can be expected to increase tax revenue. There may be potential in joining up approaches to taxation across the harm-causing commodities.

Preventing liver disease with policy measures to tackle alcohol consumption and obesity: The HEPAHEALTH II study.

BACKGROUND & AIMS: Chronic liver disease (CLD) causes 1.8% of all deaths in Europe, many of them from liver cancer. We estimated the impact of several policy interventions in France, the Netherlands, and Romania. METHODS: We used a validated microsimulation model to assess seven different policy scenarios in 2022-2030: a minimum unit price (MUP) of alcohol of €0.70 or €1, a volumetric alcohol tax, a sugar-sweetened beverage (SSB) tax, food marketing restrictions, plus two different combinations of these policies compared against current policies (the 'inaction' scenario). RESULTS: All policies reduced the burden of CLD and liver cancer. The largest impact was observed for a MUP of €1, which by 2030 would reduce the cumulative incidence of CLD by between 7.1% to 7.3% in France, the Netherlands, and Romania compared with inaction. For liver cancer, the corresponding reductions in cumulative incidence were between 4.8% to 5.8%. Implementing a package containing a MUP of €0.70, a volumetric alcohol tax, and an SSB tax would reduce the cumulative incidence of CLD by between 4.29% to 4.71% and of liver cancer by between 3.47% to 3.95% in France, the Netherlands, and Romania. The total predicted reduction in healthcare costs by 2030 was greatest with the €1 MUP scenario, with a reduction for liver cancer costs of €8.18M and €612.49M in the Netherlands and France, respectively. CONCLUSIONS: Policy measures tackling primary risk factors for CLD and liver cancer, such as the implementation of a MUP of €1 and/or a MUP of €0.70 plus SSB tax could markedly reduce the number of Europeans with CLD or liver cancer. IMPACT AND IMPLICATIONS: Policymakers must be aware that alcohol and obesity are the two leading risk factors for chronic liver disease and liver cancer in Europe and both are expected to increase in the future if no policy interventions are made. This study assessed the potential of different public health policy measures to mitigate the impact of alcohol consumption and obesity on the general population in three European countries: France, the Netherlands, and Romania. The findings support introducing a €1 minimum unit price for alcohol to reduce the burden of chronic liver disease. In addition, the study shows the importance of targeting multiple drivers of alcohol consumption and obesogenic products simultaneously via a harmonized fiscal policy framework, to complement efforts being made within health systems. These findings should encourage policymakers to introduce such policy measures across Europe to reduce the burden of liver disease. The modeling methods used in this study can assist in structuring similar modeling in other regions to expand on this study's findings.

The prevalence and clustering of alcohol consumption, gambling, smoking, and excess weight in an English adult population.

BACKGROUND: The aim of this study was to examine the prevalence and clustering of four health risks (increasing-/higher-risk drinking, current smoking, overweight/obesity, and at-risk gambling), and to examine variation across sociodemographic groups in the English adult population. METHODS: We analysed data from the 2012, 2015, 2016, and 2018 Health Survey for England (n = 20,698). Prevalence odds ratios (POR) were calculated to examine the clustering of risks. We undertook a multinomial multilevel regression model to examine sociodemographic variation in the clustering of health risks. RESULTS: Overall, 23.8% of the adult English population had two or more co-occurring health risks. The most prevalent was increasing-/higher-risk drinking and overweight/obesity (17.2%). Alcohol consumption and smoking were strongly clustered, particularly higher-risk drinking and smoking (POR = 2.68; 95% CI = 2.31, 3.11; prevalence = 1.7%). Higher-risk drinking and at-risk gambling were also clustered (POR = 2.66; 95% CI = 1.76, 4.01), albeit with a very low prevalence (0.2%). Prevalence of multiple risks was higher among men for all risk combinations except smoking and obesity. The odds of multiple risks were highest for men and women aged 35-64 years. Unemployed men and women with lower educational qualifications had a higher odds of multiple risks. The relationship between deprivation and multiple risks depended on the definition of multiple risks, with the clearest socioeconomic gradients seen for the highest risk health behaviours. CONCLUSION: An understanding of the prevalence, clustering, and risk factors for multiple health risks can help inform effective prevention and treatment approaches and may support the design and use of multiple behaviour change interventions.

Unacceptable failures: the final report of the Lancet Commission into liver disease in the UK.

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government.

A comparison of gender-linked population cancer risks between alcohol and tobacco: how many cigarettes are there in a bottle of wine?

BACKGROUND: In contrast to our knowledge about the number of cancers attributed to smoking, the number of cancers attributed to alcohol is poorly understood by the public. We estimate the increase in absolute risk of cancer (number of cases per 1000) attributed to moderate levels of alcohol, and compare these to the absolute risk of cancer attributed to low levels of smoking, creating a 'cigarette-equivalent of population cancer harm'. METHODS: Alcohol and tobacco attributable fractions were subtracted from lifetime general population risks of developing alcohol- and smoking-related cancers, to estimate the lifetime cancer risk in alcohol-abstaining non-smokers. This was multiplied by the relative risk of drinking ten units of alcohol or smoking ten cigarettes per week, and increasing levels of consumption. RESULTS: One bottle of wine per week is associated with an increased absolute lifetime cancer risk for non-smokers of 1.0% (men) and 1.4% (women). The overall absolute increase in cancer risk for one bottle of wine per week equals that of five (men) or ten cigarettes per week (women). Gender differences result from levels of moderate drinking leading to a 0.8% absolute risk of breast cancer in female non-smokers. CONCLUSIONS: One bottle of wine per week is associated with an increased absolute lifetime risk of alcohol-related cancers in women, driven by breast cancer, equivalent to the increased absolute cancer risk associated with ten cigarettes per week. These findings can help communicate that moderate levels of drinking are an important public health risk for women. The risks for men, equivalent to five cigarettes per week, are also of note.

Gathering momentum for the way ahead: fifth report of the Lancet Standing Commission on Liver Disease in the UK.

This report presents further evidence on the escalating alcohol consumption in the UK and the burden of liver disease associated with this major risk factor, as well as the effects on hospital and primary care. We reiterate the need for fiscal regulation by the UK Government if overall alcohol consumption is to be reduced sufficiently to improve health outcomes. We also draw attention to the effects of drastic cuts in public services for alcohol treatment, the repeated failures of voluntary agreements with the drinks industry, and the influence of the industry through its lobbying activities. We continue to press for reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place, and the introduction of minimum unit pricing in England, targeted at the heaviest drinkers. Results from the introduction of minimum unit pricing in Scotland, with results from Wales to follow, are likely to seriously expose the weakness of England's position. The increasing prevalence of obesity-related liver disease, the rising number of people diagnosed with type 2 diabetes and its complications, and increasing number of cases of end-stage liver disease and primary liver cancers from non-alcoholic fatty liver disease make apparent the need for an obesity strategy for adults. We also discuss the important effects of obesity and alcohol on disease progression, and the increased risk of the ten most common cancers (including breast and colon cancers). A new in-depth analysis of the UK National Health Service (NHS) and total societal costs shows the extraordinarily large expenditures that could be saved or redeployed elsewhere in the NHS. Excellent results have been reported for new antiviral drugs for hepatitis C virus infection, making elimination of chronic infection a real possibility ahead of the WHO 2030 target. However, the extent of unidentified cases remains a problem, and will also apply when new curative drugs for hepatitis B virus become available. We also describe efforts to improve standards of hospital care for liver disease with better understanding of current service deficiencies and a new accreditation process for hospitals providing liver services. New commissioning arrangements for primary and community care represent progress, in terms of effective screening of high-risk subjects and the early detection of liver disease.

Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies.

The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, identifying public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the World Health Organization European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse, with variations in the exact composition of diseases and the trends in risk factors which drive them. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across most European countries. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity, and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease.

The alcohol harm paradox: using a national survey to explore how alcohol may disproportionately impact health in deprived individuals.

BACKGROUND: Internationally, studies show that similar levels of alcohol consumption in deprived communities (vs. more affluent) result in higher levels of alcohol-related ill health. Hypotheses to explain this alcohol harm paradox include deprived drinkers: suffering greater combined health challenges (e.g. smoking, obesity) which exacerbate effects of alcohol harms; exhibiting more harmful consumption patterns (e.g. bingeing); having a history of more harmful consumption; and disproportionately under-reporting consumption. We use a bespoke national survey to assess each of these hypotheses. METHODS: A national telephone survey designed to test this alcohol harm paradox was undertaken (May 2013 to April 2014) with English adults (n = 6015). Deprivation was assigned by area of residence. Questions examined factors including: current and historic drinking patterns; combined health challenges (smoking, diet, exercise and body mass); and under-reported consumption (enhanced questioning on atypical/special occasion drinking). For each factor, analyses examined differences between deprived and more affluent individuals controlled for total alcohol consumption. RESULTS: Independent of total consumption, deprived drinkers were more likely to smoke, be overweight and report poor diet and exercise. Consequently, deprived increased risk drinkers (male >168-400 g, female >112-280 g alcohol/week) were >10 times more likely than non-deprived counterparts to drink in a behavioural syndrome combining smoking, excess weight and poor diet/exercise. Differences by deprivation were significant but less marked in higher risk drinkers (male >400 g, female >280 g alcohol/week). Current binge drinking was associated with deprivation independently of total consumption and a history of bingeing was also associated with deprivation in lower and increased risk drinkers. CONCLUSIONS: Deprived increased/higher drinkers are more likely than affluent counterparts to consume alcohol as part of a suite of health challenging behaviours including smoking, excess weight and poor diet/exercise. Together these can have multiplicative effects on risks of wholly (e.g. alcoholic liver disease) and partly (e.g. cancers) alcohol-related conditions. More binge drinking in deprived individuals will also increase risks of injury and heart disease despite total alcohol consumption not differing from affluent counterparts. Public health messages on how smoking, poor diet/exercise and bingeing escalate health risks associated with alcohol are needed, especially in deprived communities, as their absence will contribute to health inequalities.

Alcohol and liver disease in Europe--Simple measures have the potential to prevent tens of thousands of premature deaths.

In the World Health Organisation European Region, more than 2,370,000 years of life are lost from liver disease before the age of 50; more than lung cancer, trachea, bronchus, oesophageal, stomach, colon, rectum and pancreatic cancer combined. Between 60-80% of these deaths are alcohol related, a disease for which no pharmaceutical therapy has yet been shown to improve long-term survival. The toxicity of alcohol is dose related at an individual level, and is dose related at a population level; overall liver mortality is largely determined by population alcohol consumption. Trends in alcohol consumption correlate closely with trends in overall liver mortality, with 3-5-fold decreases or increases in liver mortality in different European countries over the last few decades. The evidence base for alcohol control measures aimed at reducing population alcohol consumption has been subjected to rigorous evaluation; most recently by the Organisation for Economic Co-Operation and Development (OECD). Effective alcohol policy measures reduce alcohol mortality, including mortality from liver disease. The most effective and cost effective measures have been summarised by the OECD and the World Health Organisation: regular incremental above inflation tax increases, a minimum price for alcohol, effective protection of children from alcohol marketing and low level interventions from clinicians. Simple, cheap and effective changes to alcohol policy by European Institutions and member states have the potential to dramatically reduce liver mortality in Europe.

Hepatocyte expression of the senescence marker p21 is linked to fibrosis and an adverse liver-related outcome in alcohol-related liver disease.

BACKGROUND AND AIM: Alcohol-related liver disease (ALD) remains a leading cause of liver-related morbidity and mortality. Age, fibrosis stage, MELD score and continued alcohol consumption predict outcome in everyday clinical practice. In previous studies increased hepatocyte nuclear area and hepatocyte expression of p21, both markers of senescence, were associated with increased fibrosis stage and a poor outcome in non-alcohol-related fatty liver disease, while increased hepatocyte nuclear area was related to liver dysfunction in ALD cirrhosis. This study, therefore, investigated the pattern of hepatocyte cell cycle phase distribution and hepatocyte p21 expression in relation to outcome in ALD. METHODS: Liver sections from two cohorts were studied. The first comprised 42 patients across the full spectrum of ALD. The second cohort comprised 77 patients with ALD cirrhosis. Immunohistochemistry assessed hepatocyte expression of cell cycle phase markers and p21. Regenerating liver (n=12) and "normal" liver sections (n=5) served as positive and negative controls, respectively. RESULTS: In the first cohort there was little cell cycle progression beyond G1/S phase and increased hepatocyte p21 expression (p<0.0001), which correlated independently with fibrosis stage (p=0.005) and an adverse liver-related outcome (p=0.03). In the second cohort, both hepatocyte p21 expression (p<0.001) and MELD score (p=0.006) were associated independently with an adverse liver-related outcome; this association was stronger with hepatocyte p21 expression (AUROC 0.74; p=0.0002) than with MELD score (AUROC 0.59; p=0.13). Further, hepatocyte p21 expression co-localised with increased hepatic stellate cell activation. CONCLUSIONS: The findings are consistent with impaired cell cycle progression beyond the G1/S phase in ALD. The striking independent associations between increased hepatocyte p21 expression and both fibrosis stage and an adverse liver-related outcome in both cohorts suggests hepatocyte senescence plays an important role in ALD. Measuring hepatocyte p21 expression is simple and cheap and in this series was a useful measure of long-term prognosis in ALD.

Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries.

The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries.

Priority actions for the non-communicable disease crisis.

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US$9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.

Direct measurement of porto-systemic gradient in a failing Fontan circulation.

We describe the case history of a 42-year-old man with cardiac cirrhosis, portal hypertension, and life-threatening variceal bleeding after Fontan revision surgery. Direct pressure measurements in the portal vein, though high, demonstrated only a modest portosystemic gradient (PSG), 9 mm Hg. A transjugular intrahepatic portosystemic shunt procedure was performed. This reduced the PSG (3 mm Hg). His bleeding was controlled. The patient's histopathological findings were identical to that previously documented in Fontan patients, raising the question of whether these subdiaphragmatic hemodynamics are representative of the broader failing Fontan population.

Alcohol-related cirrhosis--early abstinence is a key factor in prognosis, even in the most severe cases.

AIMS: To determine the effect of pathological severity of cirrhosis on survival in patients with alcohol-related cirrhosis. DESIGN: Liver biopsies from 100 patients were scored for Laennec score of severity of cirrhosis, and medical notes were reviewed to determine various clinical factors, including drinking status. Up-to-date mortality data were obtained using the National Health Service Strategic Tracing Service. SETTING: Southampton General Hospital between 1 January 1995 and 31 December 2000. PARTICIPANTS: A total of 100 consecutive patients with biopsy proven alcohol-induced liver cirrhosis. MEASUREMENTS: Laennec score of severity of cirrhosis and mortality. FINDINGS: Most surprisingly, the severity of cirrhosis on biopsy had little impact on survival; indeed, early death was more likely in patients with the least severe cirrhosis. Abstinence from alcohol at 1 month after diagnosis of cirrhosis was the more important factor determining survival with a 7-year survival of 72% for the abstinent patients versus 44% for the patients continuing to drink. CONCLUSIONS: It is never too late to stop drinking, even with the most severe degrees of cirrhosis on biopsy. Early drinking status is the most important factor determining long-term survival in alcohol-related cirrhosis.

Hepatic changes in the failing Fontan circulation.

BACKGROUND: The failing Fontan circulation is associated with hepatic impairment. The nature of this liver injury is poorly defined. OBJECTIVE: To establish the gross and histological liver changes of patients with Fontan circulation relative to clinical, biochemical and haemodynamic findings. METHODS: Patients were retrospectively assessed for extracardiac Fontan conversion between September 2003 and June 2005, according to an established clinical protocol. Twelve patients, mean age 24.6 (range 15.8-43.4) years were identified. The mean duration since the initial Fontan procedure was 14.1 (range 6.9-26.4) years. RESULTS: Zonal enhancement of the liver (4/12) on CT was more common in patients with lower hepatic vein pressures (p = 0.007), and in those with absent cardiac cirrhosis on histological examination (p = 0.033). Gastro-oesophageal varices (4/12) were more common in patients with higher hepatic vein pressure (21 (6.3) vs 12.2 (2.2) mm Hg, p = 0.013) and associated with more advanced cirrhosis (p = 0.037). The extent of cirrhosis (7/12) was positively correlated with the hepatic vein pressure (r = 0.83, p = 0.003). A significant positive correlation was found between the Fontan duration and the degree of hepatic fibrosis (r = 0.75, p = 0.013), as well as presence of broad scars (r = 0.71, p = 0.021). Protein-losing enteropathy (5/12) occurred more frequently in patients with longer Fontan duration (11.7 (3.2) vs 17.9 (6.1) years, p = 0.038). CONCLUSIONS: Liver injury, which can be extensive in this patient group, is related to Fontan duration and hepatic vein pressures. CT scan assists non-invasive assessment. Cardiac cirrhosis with the risk of developing gastro-oesophageal varices and regenerative liver nodules, a precursor to hepatocellular carcinoma, is common in this patient group.

Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease.

Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by prominent cellular infiltrates in the bowel wall. Chemokines are chemotactic cytokines that are able to promote leukocyte migration to areas of inflammation and are also able to initiate cell activation events. They have recently been implicated in the pathophysiology of many disease states. The aim of this study was to detail the degree and distribution of specific chemokines, interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, -2, and -3, and macrophage inflammatory protein (MIP)-1alpha and -1beta, in IBD mucosa. Thirty-nine patients were included, ten controls, 20 ulcerative colitis (UC), and nine Crohn's disease (CD), with a range of disease activity. Colonic mucosal biopsies were collected from UC, CD, and control patients and embedded in glycol methacrylate. Two-micrometre-thick sections were cut and stained using immunohistochemistry for chemokine protein expression. Sections were analysed using a light microscope. Expression of all types of chemokine protein was detected in colonic mucosa from both control and IBD patients. Patterns of staining between IBD patients and controls differed significantly, but CD and UC patients demonstrated similar patterns of staining. Individual chemokine expression was found to be significantly up-regulated in IBD when patients were compared with the non-diseased group in all areas of the mucosal sections. Up-regulated chemokine expression correlated with increasing activity of the disease. It is concluded that human colonic chemokine expression is non-selectively up-regulated in IBD. The results supported the hypothesis that the degree of local inflammation and tissue damage in UC and CD is dependent on local expression of specific chemokines within IBD tissues.