Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure.

BACKGROUND: Chronic hepatitis C (CHC) is associated with systemic insulin resistance, yet there are limited data on the tissue-specific contribution in vivo to this adverse metabolic phenotype, and the effect of HCV cure. METHODS: We examined tissue-specific insulin sensitivity in a cohort study involving 13 patients with CHC compared to 12 BMI-matched healthy control subjects. All subjects underwent a two-step clamp incorporating the use of stable isotopes to measure carbohydrate and lipid flux (hepatic and global insulin sensitivity) with concomitant subcutaneous adipose tissue microdialysis and biopsy (subcutaneous adipose tissue insulin sensitivity). Investigations were repeated in seven patients with CHC following antiviral therapy with a documented sustained virological response. RESULTS: Adipose tissue was more insulin resistant in patients with CHC compared to healthy controls, as evidence by elevated glycerol production rate and impaired insulin-mediated suppression of both circulating nonesterified fatty acids (NEFA) and adipose interstitial fluid glycerol release during the hyperinsulinaemic euglycaemic clamp. Hepatic and muscle insulin sensitivity were similar between patients with CHC and controls. Following viral eradication, hepatic insulin sensitivity improved as demonstrated by a reduction in endogenous glucose production rate. In addition, circulating NEFA decreased with sustained virological response (SVR) and insulin was more effective at suppressing adipose tissue interstitial glycerol release with a parallel increase in the expression of insulin signalling cascade genes in adipose tissue consistent with enhanced adipose tissue insulin sensitivity. CONCLUSION: Chronic hepatitis C patients have profound subcutaneous adipose tissue insulin resistance in comparison with BMI-matched controls. For the first time, we have demonstrated that viral eradication improves global, hepatic and adipose tissue insulin sensitivity.

Economic modelling of early transjugular intrahepatic portosystemic shunt insertion for acute variceal haemorrhage.

INTRODUCTION: Early insertion of transjugular intrahepatic portosystemic shunt (TIPS) in high-risk patients with acute variceal haemorrhage reduces rebleeding and mortality. However, the economic benefit of utilizing this approach remains unclear. We evaluated the economic implications of introducing early TIPS into routine algorithms for the management of variceal bleeding. METHODS: Consecutive patients admitted in 2009 with variceal haemorrhage to two liver units and eligible for early TIPS insertion were identified retrospectively. The costs of a 12-month follow-up from index bleeding admission were calculated--the actual cost of follow-up and rebleeding in this cohort was compared with the theoretical 12-month follow-up costs of instead inserting an early TIPS at index admission. Our findings were subjected to a sensitivity analysis to assess the cost effectiveness of early TIPS insertion compared with standard care. RESULTS: In 2009, 78 patients were admitted to our units with variceal haemorrhage; 27 patients (35%) were eligible for early TIPS insertion. The actual cost of a 12-month follow-up was £138 473.50. Early TIPS insertion, assuming a 3.2% rebleeding rate, would save £534.70 per patient per year (P<0.0001). On sensitivity analysis, early TIPS dominated standard care up to an early TIPS rebleeding rate of 6% and remained cost-effective up to a rebleeding rate of 12%. CONCLUSION: Early TIPS insertion for high-risk patients with acute variceal bleeding is a cost-efficient intervention. This has important implications for the introduction of early TIPS as standard care and the organization of interventional radiology services.

Endoscopic mucosal resection of colorectal polyps in typical UK hospitals.

AIM: To evaluate the outcomes of endoscopic mucosal resection (EMR) for colorectal polyps, with particular regard to procedural complications and recurrence rate, in typical United Kingdom (UK) hospitals that perform an average of about 25 colonic EMRs per year. METHODS: A total of 239 colorectal polyps (≥ 10 mm) resected from 199 patients referred to Rochdale Infirmary, Salford Royal Hospital and Royal Oldham Hospital for EMR between January 2003 and January 2009 were studied. RESULTS: The mean size of polyps resected was 19.6 ± 12.4 mm (range 10-80 mm). The overall major complication rate was 2.1%. Complications were less frequent with non-adenomas compared with the other groups (Pearson's χ(2) test, P < 0.0001). Resections of larger-sized polyps were more likely to result in complications (unpaired t-test, P = 0.021). Recurrence was associated with histology, with carcinoma-in-situ more likely to recur compared with low-grade dysplasia [hazard ratio (HR) 186.7, 95% confidence interval (95% CI): 8.81-3953.02, P = 0.001]. Distal lesions were also more likely to recur compared with right-sided and transverse colon lesions (HR 5.93, 95% CI: 1.35-26.18, P = 0.019). CONCLUSION: EMR for colorectal polyps can be performed safely and effectively in typical UK hospitals. Stricter follow-up is required for histologically advanced lesions due to increased recurrence risk.