Nick Sheron

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

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

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.

Increased Plasma Tumor Necrosis Factor in Severe Alcoholic Hepatitis

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.

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

STUDY OBJECTIVE To determine whether elevated tumor necrosis factor levels contribute to the clinical manifestations and complications of severe acute alcoholic hepatitis and to evaluate the relation between tumor necrosis factor and plasma levels of endotoxin and interleukin-1 beta. DESIGN Prospective, controlled study. SETTING The liver unit of a university teaching hospital. PATIENTS We studied 21 patients with acute severe alcoholic hepatitis. There were four control groups: patients with inactive alcoholic cirrhosis, alcoholic persons without liver disease, patients with impaired renal function, and normal subjects. MEASUREMENTS AND MAIN RESULTS With one exception, patients with alcoholic hepatitis had higher tumor necrosis factor levels (mean, 26.3 ng/L; 95% CI, 21.7 to 30.9) than normal subjects (6.4 ng/L; CI, 5.4 to 7.4). Patients who subsequently died had a higher tumor necrosis factor level (34.7 ng/L; CI, 27.8 to 41.6) than survivors (16.6 ng/L; CI, 14.0 to 19.2). In patients with alcoholic hepatitis, tumor necrosis factor levels correlated positively with serum bilirubin (r = 0.74; P = 0.0009) and serum creatinine (r = 0.81; P = 0.0003). Patients with alcoholic hepatitis had higher tumor necrosis factor levels than patients with inactive alcoholic cirrhosis (11.1 ng/L; CI, 8.9 to 13.3) and severely alcoholic persons without liver disease (6.4 ng/L; CI, 5.0 to 7.8). Patients with abnormal renal function had lower tumor necrosis factor levels (14.1 ng/L; CI, 5.4 to 22.8) than patients with alcoholic hepatitis. Serial samples obtained during a 1-week period from patients with alcoholic hepatitis showed no significant change in tumor necrosis factor when patients who died were compared with survivors. No correlation was found between tumor necrosis factor and plasma endotoxin. Levels of interleukin-1 beta did not exceed 20 ng/L. CONCLUSIONS Elevations in tumor necrosis factor in alcoholic hepatitis are most marked in severe cases, suggesting that tumor necrosis factor plays a role in the pathogenesis.

Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis.

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)‐1α and ‐1β, in IBD mucosa. Thirty‐nine patients were included, ten controls, 20 ulcerative colitis (UC), and nine Crohns 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. Copyright

Hepatic changes in the failing Fontan circulation

Liver disease in the UK stands out as the one glaring exception to the vast improvements made during the past 30 years in health and life expectancy for chronic disorders such as stroke, heart disease, and many cancers. Mortality rates have increased 400% since 1970, and in people younger than 65 years have risen by almost five-times. Liver disease constitutes the third commonest cause of premature death in the UK and the rate of increase of liver disease is substantially higher in the UK than other countries in western Europe. More than 1 million admissions to hospital per year are the result of alcohol-related disorders, and both the number of admissions and the increase in mortality closely parallel the rise in alcohol consumption in the UK during the past three decades. The aim of this Commission is to provide the strongest evidence base through involvement of experts from a wide cross-section of disciplines, making firm recommendations to reduce the unacceptable premature mortality and disease burden from avoidable causes and to improve the standard of care for patients with liver disease in hospital. From the substantial number of recommendations given in our Commission, we selected those that will have the greatest effect and that need urgent implementation. Although the recommendations are based mostly on data from England, they have wider application to the UK as a whole, and are in accord with the present strategy for health-care policy by the Scottish Health Boards, the Health Department of Wales, and the Department of Health and Social Services in Northern Ireland.

Increased production of tumour necrosis factor alpha in chronic hepatitis B virus infection

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.

Hepatic fibrosis and cirrhosis in the Fontan circulation: a detailed morphological study

Plasma tumour necrosis factor alpha (TNF) and in-vitro TNF production by peripheral blood mononuclear cells (PBMC) were studied in 22 HBsAg seropositive patients and compared with 23 normal and 10 disease controls. Plasma TNF and unstimulated TNF production correlated (Rs = 0.55, p = 0.012) and were significantly elevated in HBsAg and HBeAg seropositive patients (p less than 0.001, p = 0.006) compared with normal controls. TNF production was also elevated in these patients when PBMC were stimulated with interferon-gamma (p less than 0.05) or LPS (p = 0.035). Plasma TNF and TNF production in HBsAg anti-HBe seropositive subjects were not elevated. TNF production in unstimulated cells correlated with serum HBV DNA level (R = 0.53, p = 0.02) but not with serum aspartate transaminase (AST) or histological activity. It is concluded that PBMC are activated to produce TNF both spontaneously and in response to second stimuli in chronic hepatitis B virus infection and that this activity is related to the presence of viral replication.

Drinking patterns, dependency and life-time drinking history in alcohol-related liver disease

Aims: To describe the histological features of the liver in patients with a Fontan circulation. Methods: Specimens from liver biopsies carried out as part of preoperative assessment prior to extracardiac cavopulmonary conversion of an older style Fontan were examined and scored semi-quantitatively for pertinent histological features. To support the use of the scoring, biopsy specimens were also ranked by eye for severity to allow correlation with assigned scores. Results: Liver biopsy specimens from 18 patients with a Fontan circulation were assessed. All specimens showed sinusoidal fibrosis. In 17 cases there was at least fibrous spur formation, with 14 showing bridging fibrosis and 2 showing frank cirrhosis. In 17 cases at least some of the dense or sinusoidal fibrosis was orcein positive, although a larger proportion of the dense fibrous bands were orcein positive compared with the sinusoidal component. All specimens showed marked sinusoidal dilatation, and 14 showed bile ductular proliferation; 1 showed minimal iron deposition, and 1 showed mild lobular lymphocytic inflammation. There was no cholestasis or evidence of hepatocellular damage. Similar appearances were observed in 2 patients with severe tricuspid regurgitation. Discussion: The histological features of the liver in patients with a Fontan circulation are similar to those described in cardiac sclerosis. Sinusoidal dilatation and sinusoidal fibrosis are marked in the Fontan series. The presence of a significant amount of orcein negative sinusoidal fibrosis suggests there may be a remediable component, although the dense fibrous bands are predominantly orcein positive, suggesting chronicity and permanence. No inflammation or hepatocellular damage is evident, suggesting that fibrosis may be mediated by a non-inflammatory mechanism.

Concentrations of interleukin 6 and tumour necrosis factor in serum and stools of children with Shigella dysenteriae 1 infection.

AIMS To examine the hypothesis that increases in UK liver deaths are a result of episodic or binge drinking as opposed to regular harmful drinking. DESIGN A prospective survey of consecutive in-patients and out-patients. SETTING The liver unit of a teaching hospital in the South of England. PARTICIPANTS A total of 234 consecutive in-patients and out-patients between October 2007 and March 2008. MEASUREMENTS Face-to-face interviews, Alcohol Use Disorders Identification Test, 7-day drinking diary, Severity of Alcohol Dependence Questionnaire, Lifetime Drinking History and liver assessment. FINDINGS Of the 234 subjects, 106 had alcohol as a major contributing factor (alcoholic liver disease: ALD), 80 of whom had evidence of cirrhosis or progressive fibrosis. Of these subjects, 57 (71%) drank on a daily basis; only 10 subjects (13%) drank on fewer than 4 days of the week--of these, five had stopped drinking recently and four had cut down. In ALD patients two life-time drinking patterns accounted for 82% of subjects, increasing from youth (51%), and a variable drinking pattern (31%). ALD patients had significantly more drinking days and units/drinking day than non-ALD patients from the age of 20 years onwards. CONCLUSIONS Increases in UK liver deaths are a result of daily or near-daily heavy drinking, not episodic or binge drinking, and this regular drinking pattern is often discernable at an early age.