Norma C. McAvoy

Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed

Current therapy for preventing the first variceal bleed includes beta‐blocker and variceal band ligation (VBL). VBL has lower bleeding rates, with no differences in survival, whereas beta‐blocker therapy can be limited by side effects. Carvedilol, a non‐cardioselective vasodilating beta‐blocker, is more effective in reducing portal pressure than propranolol; however, there have been no clinical studies assessing the efficacy of carvedilol in primary prophylaxis. The goal of this study was to compare carvedilol and VBL for the prevention of the first variceal bleed in a randomized controlled multicenter trial. One hundred fifty‐two cirrhotic patients from five different centers with grade II or larger esophageal varices were randomized to either carvedilol 12.5 mg once daily or VBL performed every 2 weeks until eradication using a multibander device. Seventy‐seven patients were randomized to carvedilol and 75 to VBL. Baseline characteristics did not differ between the groups (alcoholic liver disease, 73%; median Child‐Pugh score, 8; median age, 54 years; median follow‐up, 20 months). On intention‐to‐treat analysis, carvedilol had lower rates of the first variceal bleed (10% versus 23%; relative hazard 0.41; 95% confidence interval 0.19‐0.96 [P = 0.04]), with no significant differences in overall mortality (35% versus 37%, P = 0.71), and bleeding‐related mortality (3% versus 1%, P = 0.26). Six patients in the VBL group bled as a result of banding ulcers. Per‐protocol analysis revealed no significant differences in the outcomes. Conclusion: Carvedilol is effective in preventing the first variceal bleed. Carvedilol is an option for primary prophylaxis in patients with high‐risk esophageal varices. (HEPATOLOGY 2009.)

Bleeding ectopic varices in cirrhosis: the role of transjugular intrahepatic portosystemic stent shunts

Aliment Pharmacol Ther 28, 294–303

Prevalence of coronary artery calcification in patients undergoing assessment for orthotopic liver transplantation.

Patients with advanced liver disease are at increased risk of cardiovascular events, especially following orthotopic liver transplantation (OLT). Coronary artery calcification (CAC) is a novel and independent predictor of cardiovascular risk, but its prevalence and utility in patients with cirrhosis are unknown. The aim of this study was to define the prevalence of CAC and its association with markers of disease severity and standard measures of cardiovascular risk in a large cohort of patients undergoing OLT assessment. A single‐center, prospective, observational study of 147 consecutive patients undergoing assessment for OLT was performed. CAC scores were derived with the Agatston method from thoracic computed tomography scans and correlated with cardiovascular risk factors and measures of liver disease severity. There were 101 patients (66 males) with a mean age of 53.2 years; 46 patients were excluded because the CAC score was not reported. The median CAC score was 40 HU (range, 0‐3533). Correlations were identified between the CAC score and age (r = 0.477; P < 0.001), male sex (r = 0.262; P = 0.008), family history of cardiovascular disease (r = 0.208; P = 0.036), Framingham risk score (r = 0.621; P < 0.001), Model for End‐Stage Liver Disease score (r = 0.221; P = 0.027), systolic blood pressure (r = 0.285; P = 0.004), diastolic blood pressure (r = 0.267; P = 0.007), cytomegalovirus status (r = 0.278; P = 0.005), fasting glucose (r = 0.330; P = 0.001), number of coronary vessels involved (r = 0.899; P < 0.001), and components of the metabolic syndrome (r = 0.226; P = 0.026). After multivariate analysis, age, systolic blood pressure, fasting glucose, number of features of metabolic syndrome, and number of vessels involved remained significantly associated with CAC. In conclusion, this study identified a high prevalence of occult coronary artery disease in patients undergoing OLT assessment and identified a strong relationship between CAC scores and a limited number of specific cardiovascular risk factors. The usefulness of these factors in predicting perioperative and postoperative cardiovascular events in patients undergoing OLT requires prospective evaluation. Liver Transpl 14:1725–1731, 2008.

Increased Whole-Body and Sustained Liver Cortisol Regeneration by 11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Men With Type 2 Diabetes Provides a Target for Enzyme Inhibition

OBJECTIVE The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11β-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[2H]4cortisol (40%) and cortisol (60%) at 1.74 mg/h. Adrenal cortisol secretion was suppressed with dexamethasone. Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution. RESULTS In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[2H]3cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P < 0.05), splanchnic 9,12,12-[2H]3cortisol production was not reduced (29 ± 6 vs. 29 ± 6 nmol/min), and cortisol appearance in the hepatic vein after oral cortisone was unchanged. CONCLUSIONS Whole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects.

Human thrombin for the treatment of gastric and ectopic varices

AIM To evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic varices. METHODS Retrospective observational study in a Tertiary Referral Centre. Between January 1999-October 2005, we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic varices. Patient details including age, gender and aetiology of liver disease/segmental portal hypertension were documented. The thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection needle. All patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was recorded. Initial haemostasis rates, rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin therapy. The duration of follow up was also listed. The study was conducted according to the United Kingdom research ethics guidelines. RESULTS Thirty-seven patients were included. 33 patients (89%) had thrombin (250 U/mL) for gastric varices, 2 (5.4%) for duodenal varices, 1 for rectal varices and 1 for gastric and rectal varices. (1) Gastric varices, an average of 15.2 mL of thrombin was used per patient. Re-bleeding occurred in 4 patients (10.8%), managed in 2 by a transjugular intrahepatic portosystemic shunt (TIPSS) (one unsuccessfully who died) and in other 2 by a distal splenorenal shunt; (2) Duodenal varices (or type 2 isolated gastric varices), an average of 12.5 mL was used per patient over 2-3 endoscopy sessions. Re-bleeding occurred in one patient, which was treated by TIPSS; and (3) Rectal varices, an average of 18.3 mL was used per patient over 3 endoscopy sessions. No re-bleeding occurred in this group. CONCLUSION Human thrombin is a safe, easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices.

Review: Non-alcoholic fatty liver disease: natural history, pathogenesis and treatment

Non-alcoholic fatty liver disease (NAFLD) is the term used to describe the alcohol-like liver injury that occurs in the absence of alcohol abuse. It embraces a range of histological abnormalities including simple steatosis or fatty liver, non-alcoholic steatohepatitis (NASH) and NAFLD induced cirrhosis. The predominant risk factor for NAFLD appears to be insulin resistance. Simple steatosis and NASH are generally asymptomatic and it is only the development of cirrhosis that has clinical consequence. At present, therapy in NAFLD concentrates on managing risk factors but in the future clinical trials may provide robust evidence for the use of insulin sensitising agents and other potential therapies.

Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis

With advancing liver disease and the development of portal hypertension, there are major alterations in somatic and visceral blood flow. Using phase‐contrast magnetic resonance angiography, we characterised alterations in blood flow within the hepatic, splanchnic and extra‐splanchnic circulations of patients with established liver cirrhosis.

EUS-assisted thrombin injection for ectopic bleeding varices—a case report and review of the literature

Ectopic varices (EV) represent dilated porto-systemic collaterals located at sites other than the gastro-oesophageal junction. They mainly develop in cirrhotic patients following oesophageal variceal band ligation and more rarely secondary to abdominal surgical procedures or to abdominal venous thrombosis secondary to inflammation.1 Bleeding from EV is unusual and represents <5% of all variceal bleeds. Norton et al .2 reviewed 169 cases of bleeding from EV; 26% were from ileostomy varices in primary sclerosing cholangitis patients, 17% in the duodenum, 17% in the jejunum or ileum, 14% in the colon, 8% in the rectum, 9% in the peritoneum. Duodenal varices most commonly complicate portal or splenic vein thrombosis.2 A 49-year-old male was diagnosed with coeliac disease 3 years prior to presentation. He was receiving iron supplements for severe iron deficiency anaemia; however, several investigations including, repeated upper and lower gastrointestinal (GI) endoscopies failed to identify a cause. Prior to transfer to our Unit, he was admitted to his regional hospital with melaena and a Hb of 66 g/l. An upper gastrointestinal endoscopy (UGIE) identified a polypoid mass in the second part of the duodenum (D2). Biopsies were taken but resulted in profuse bleeding requiring 6 U of red cell concentrate (RCC). A repeat endoscopy in our hospital showed a ‘C shaped’ non-bleeding polypoid lesion at the junction of D2/3 which was characterized further by endoscopic ultrasound (EUS); this was a vascular lesion at D2/3; the splenic vein was dilated and tortuous …

Randomised clinical study: comparison of acceptability, patient tolerance, cardiac stress and endoscopic views in transnasal and transoral endoscopy under local anaesthetic.

Transnasal endoscopy (TNE) with ultrathin endoscopes has been advocated as an attractive alternative, for diagnostic upper endoscopy.

The cirrhosis epidemic in the UK: evaluating the causes in a European context

‘Epidemic’ is defined as the occurrence of many cases of a disease within an area, whereas ‘pandemic’ is used to emphasize its occurrence over a wide geographical area. This article reviews the epidemiology of cirrhosis in Europe and particularly within Britain, illustrating the different mortality trends in different countries. The rapid rise in mortality rate in Scotland is discussed and potential explanations explored. The major causes of cirrhosis that are increasing, namely alcohol abuse, hepatitis C and nonalcoholic fatty liver disease, are reviewed. Hepatitis B, of course, remains a major cause of cirrhosis worldwide but is not responsible for the recent increased deaths from cirrhosis discussed in this article. The burden of this disease, which largely consists of variceal hemorrhage, hepatocellular carcinoma and orthotopic liver transplantation, are also discussed.