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This systematic review and meta-analysis determined the impact of structured exercise training, and the influence of associated weight loss, on intrahepatic triglyceride (IHTG) in individuals with non-alcoholic fatty liver disease (NAFLD). It also examined its effect on hepatic insulin sensitivity in individuals with or at increased risk of NAFLD. Analyses were restricted to studies using magnetic resonance spectroscopy or liver biopsy for the measurement of IHTG and isotope-labelled glucose tracer for assessment of hepatic insulin sensitivity. Pooling data from 17 studies (373 exercising participants), exercise training for one to 24 weeks (mode: 12 weeks) elicits an absolute reduction in IHTG of 3.31% (95% CI: -4.41 to -2.22%). Exercise reduces IHTG independent of significant weight change (-2.16 [-2.87 to -1.44]%), but benefits are substantially greater when weight loss occurs (-4.87 [-6.64 to -3.11]%). Furthermore, meta-regression identified a positive association between percentage weight loss and absolute reduction in IHTG (β = 0.99 [0.62 to 1.36], P 0.001). Pooling of six studies (94 participants) suggests that exercise training also improves basal hepatic insulin sensitivity (mean change in hepatic insulin sensitivity index: 0.13 [0.05 to 0.21] mg m

Despite their common use the occurrence and consequences of abnormal liver tests remain unclear.To estimate the prevalence and mortality associated with abnormal liver tests in people aged 75 years and above.A cohort study on 13,276 people aged 75 years and above, registered with general practices, with a valid measurement of one or more liver test, calculating the prevalence of abnormal aspartate transaminase (AST), alkaline phosphatase (ALP) or bilirubin. Hazard ratios (HRs) were calculated for all-cause and cause-specific mortality comparing elderly patients with abnormal liver tests to elderly patients with normal liver tests.At least one abnormal liver test was found in 2175 subjects (16.1%, 95% CI [15.4%, 16.7%]). The prevalence of a single abnormal liver test was 3.3% (95% CI [3.0%, 3.7%]) for AST, 9.2% (95% CI [8.8%, 9.7%]) for ALP and 5.4% (95% CI [5.1%, 5.9%]) for bilirubin. Abnormal AST, ALP and bilirubin were associated with increased risks of all-cause mortality; adjusted HRs, 1.27(95% CI [1.09, 1.47]), 1.47(95% CI [1.35, 1.61]) and 1.15(95% CI [1.02, 1.30]), respectively. Abnormal AST and ALP were associated with sevenfold and sixfold increased risk of death from liver disease, respectively. Two or more abnormal liver tests were associated with 2-fold and 17-fold increased risk of death from cancer and liver disease, respectively. Of the causes examined, absolute mortality rates were highest for cardiovascular disease in subjects with and without abnormal liver tests.Abnormal liver tests occur commonly in elderly people and are associated with a modest increase in all-cause mortality. There was a strong association with liver disease; however, the majority of deaths were not due to this cause.

We lack population-based estimates of the rate of decompensation in people with compensated cirrhosis as well as estimates of the manner in which the disease progresses once identified.To determine the rate of decompensation and clinical progression of disease in patients with cirrhosis based upon clinical symptoms recorded electronically in general practice data.Using Cox proportional hazards regression, we modelled the rate of decompensation for patients from the UK General Practice Research Database with a diagnosis of cirrhosis between 1987 and 2002. We determined the clinical progression in the first year following diagnosis and subsequently categorizing patients through time according to a simple clinical staging system agreed at the Baveno IV consensus conference.The rate of decompensation in patients with compensated cirrhosis was found to be 11% overall. The rate of decompensation was higher in the first year (at 31% compared with 7.3% afterwards) and in patients with an alcoholic aetiology. Patients with compensated cirrhosis had a 1-year probability of proceeding directly to death of 7% compared with 20% in patients with decompensated cirrhosis.Using data recorded in general practice records, it is possible to determine the rate of decompensation and the clinical progression of disease in people with cirrhosis.

Reports that up to 26% of subjects with psoriasis develop cirrhosis have led to a recommendation of serial liver biopsies after each cumulative dose of 1500 mg of methotrexate.To evaluate the progression of liver injury in patients with psoriasis and the impact of monitoring by liver biopsy on their management.One hundred and twenty-one liver biopsies from 66 subjects (aged 11-79 years) with psoriasis, receiving a median cumulative dose of 3206 mg of methotrexate over a period of 280.5 weeks, were evaluated.The assessment of advanced fibrosis according to the Ishak system (or= 4) correlated perfectly with that of the Scheuer system (or= 3) and poorly with that of the Roenigk scale (or= 3b) (r2 = 1.0 and 0.31, respectively). Two of 24 pre-treatment biopsies showed advanced fibrosis and both subjects were heavy drinkers. The cumulative probabilities of advanced fibrosis (Ishakor= 4) were 0%, 2.6%, 2.6%, 8.2% and 8.2% at cumulative doses of 1500, 3000, 4500, 5000 and 6000 mg, respectively. None of the subjects developed cirrhosis during follow-up or discontinued therapy on the basis of liver biopsy findings.Advanced hepatic fibrosis with low-dose methotrexate therapy is much less frequent than previously reported. Pre-treatment or monitoring liver biopsies in accordance with the current guidelines have little impact on patient management.

Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation. The role of functional polymorphisms at positions -627 and -1117 in the IL-10 gene as candidate susceptibility loci in inflammatory bowel disease and their importance in determining disease extent were evaluated in 159 patients with ulcerative colitis (83 left-sided; 76 extensive), 90 patients with Crohn's disease (22 small bowel; 29 large bowel; 39 both), and 227 controls. Genotyping was performed either by PCR-RFLP assays (-627 site) or SSCP analysis (-1117 site). An excess of -627A allele was observed in patients with left-sided colitis (52%) compared with controls (33%; P = 0.004) suggesting that IL-10 may influence the extent of the disease. These results were not replicated in a newly recruited group (N = 100) of patients with UC. We conclude that polymorphisms at -627 and -1117 sites in the IL-10 gene do not contribute to the susceptibility to IBD or determining the extent of the disease in our population.

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is increased by immunosuppressive treatment with azathioprine, 6-mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments. The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow-up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population-based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2-3-fold, may be compatible with both sets of data. Studies of the risks associated with immuno- suppression are less satisfactory, with smaller numbers of patients and relatively short follow-up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant-related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long-term safety, but post-marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine. Population-wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.

A 62-year-old male presented with variceal haemorrhage. Investigation demonstrated a fistula between the left gastric artery and portal vein with a porto-systemic gradient of 35 mm Hg. Variceal bleeding was controlled by a transcatheter embolisation of the fistula, but the patient died of septicaemia three weeks later. The second patient, a 42-year-old male who presented with variceal bleeding was shown to have diffuse arterio-venous fistulae involving the right lobe of the liver with a portosystemic gradient of 25 mm Hg. In this case the variceal bleeding was successfully controlled by insertion of a transjugular intrahepatic portosystemic shunt (TIPS). The pathogenesis of portal hypertension in arterioportal fistulae and the role of interventional radiological techniques in the management of variceal bleeding in these patients is discussed.

Evaluation of swallowing following stroke has previously concentrated on the oropharyngeal phase. We have studied whether there is esophageal dysmotility during the early phase following stroke in patients with no clinical evidence of oropharyngeal dysfunction. Twenty-five patients with a clinical diagnosis of stroke, and CT scan confirmation, without swallowing abnormalities at bedside evaluation were studied. Each subject had two esophageal manometric studies, one between days 3-5 after the stroke and the second during the third week after the stroke. Mean percentage (+/-SE) of completed peristaltic events increased from 57.8 +/- 5.9 (days 3-5) to 77.3 +/- 3.9 (week 3) (P = 0.005). Mean propagation of peristalsis (+/-SE) between 10 and 5 cm above the lower esophageal sphincter increased from 2.9 +/- 0.2 cm/sec (days 3-5) to 3.7 +/- 0.3 cm/sec (week 3) (P = 0.003). We have demonstrated subclinical peristaltic dysfunction in the smooth muscle segment of the esophagus in stroke patients with relatively preserved oropharyngeal function.

Introduction Methotrexate (MTX) is an effective and widely used immunosuppressant; however, long-term therapy has been associated with steatosis, progressive hepatic fibrosis and cirrhosis. Given the similarity of the histopathological features of methotrexate-associated chronic liver disease (MTX-CLD), non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), we hypothesised that these diseases may share a common pathogenesis. Method We analysed the diagnostic records of all individuals who have been listed for liver transplantation in the USA and reported to the Organ Procurement and Transplantation Network (OPTN) during the period 1 October 1987 and 22 May 2009 to identify those whose liver disease was deemed to have been, wholly or partly, caused by methotrexate (MTX-CLD). We compared the demographic, clinical and laboratory characteristics of adult individuals with MTX-CLD with those listed for ALD and NAFLD. Results Among 148 639 unique listings for liver transplantation, we identified 105 individuals with MTX-CLD, and these were compared with individuals listed for ALD (n=17 592) and NAFLD (n=3259). Concurrent liver disease among individuals with MTX-CLD included ALD in 4.8%, NAFLD in 7.7%, hepatocellular carcinoma in 2.9%, hepatitis C infection in 1% and other drug-induced liver disease in 1%. Compared to the ALD group, those with MTX-CLD were older (median age 57 vs 51 years, p 2 , p 2 , p Conclusion This is the largest analysis of end-stage MTX-CLD reported to date, demonstrating that it is a rare form of cirrhosis that has a distinct risk factor profile from those of ALD and, to a lesser extent, NAFLD. The severity of MTX hepatotoxicity may be potentiated by host (ethnicity) and environmental (diabetes, obesity) factors, ultimately leading to decompensated disease. A common pathogenic process may underlie MTX-CLD, ALD and NAFLD.

Introduction Alcoholic hepatitis (AH) is considered a distinct clinical entity in the spectrum of alcoholic liver disease (ALD) with a high short-term mortality. Hence, a number of scoring systems have been developed to assess severity of AH and identify the subgroup of subjects with particularly poor outcome, and suitable for specific treatments or clinical trials. Ability of these models to predict long-term survival is unknown. Methods Aims: To assess the utility of different published scoring systems in assessing short-term (30 and 90 days) and long-term (6 and 12 months) mortality in patients with AH. Methods We identified patients with liver biopsy evidence of AH from the histology database: 2004–2007. Clinical and histological data were collected from all the electronic records system and from patient notes. The Child Pugh (CP) score, Maddrey discriminant function (mDF), Glasgow AH score (GAHS), Lille model, age, bilirubin, INR, creatinine (ABIC) score, Model of End Stage Liver Disease (MELD) (including its modifications), and UK End-Stage Liver Disease (UKELD) scores were calculated. We evaluated at 30 days, 90 days, 6 months and 1-year outcome. Prognostic utility of the various scores were determined by generating a receiver operating characteristic curve (ROC curve). Results Of 140 subjects who had transjugular liver biopsy in the study period, 44 had histological evidence of AH. In this subgroup cumulative 30-day mortality was 11.4% (5/44), 90-day mortality was 13.9% (6/43), 6-month mortality was 21.9% (9/41) and 1-year mortality was 26.8% (11/41). Abstract 058 gives the area under ROC curve (AUROC) and 95% CI for the various scoring systems for predicting short and long-term mortality. Abstinence from alcohol (in the first 3 months after diagnosis of AH) was significantly associated with survival at 1 year (p Conclusion Most scoring systems with the exception of the C-P score appear to be similar in predicting the short-term (30 and 90 days) survival in patients with AH, but were uniformly poor at predicting survival beyond 6 months. Abstinence from drinking within the first 3 months is a better predictor of survival at 1 year.