Tailoring follow-up endoscopy in patients with severe oesophagitis.

Objective: We aimed to investigate the clinical utility of follow-up oesophagogastroduodenoscopy (OGD2) in patients with severe oesophagitis (Los Angeles grades C or D) through evaluating the yield of Barrett's oesophagus (BO), cancer, dysplasia and strictures. Second, we aimed to determine if the Clinical Frailty Scale (CFS) may be used to identify patients to undergo OGD2s. Design/method: Patients in NHS Lothian with an index OGD (OGD1) diagnosis of severe oesophagitis between 1 January 2014 and 31 December 2015 were identified. Univariate analysis identified factors associated with grade. Patients were stratified by frailty and a diagnosis of stricture, cancer, dysplasia and BO. Results: In total 964 patients were diagnosed with severe oesophagitis, 61.7% grade C and 38.3% grade D. The diagnostic yield of new pathology at OGD2 was 13.2% (n=51), new strictures (2.3%), dysplasia (0.5%), cancer (0.3%) and BO (10.1%). A total of 140 patients had clinical frailty (CFS score ≥5), 88.6% of which were deceased at review (median of 76 months). In total 16.4% of frail patients underwent OGD2s and five new pathologies were diagnosed, none of which were significantly associated with grade. Among non-frail patients at OGD2, BO was the only pathology more common (p=0.010) in patients with grade D. Rates of cancer, dysplasia and strictures did not vary significantly between grades. Conclusion: Our data demonstrate that OGD2s in patients with severe oesophagitis may be tailored according to clinical frailty and only be offered to non-frail patients. In non-frail patients OGD2s have similar pick-up rates of sinister pathology in both grades of severe oesophagitis.

Thrombin Is an Effective and Safe Therapy in the Management of Bleeding Gastric Varices. A Real-World Experience.

Variceal haemorrhage is a severe complication of liver disease with high mortality. Human recombinant thrombin has gained popularity in the management of variceal haemorrhage. We report on the use of thrombin for gastric and ectopic varices at a regional tertiary care centre. This was a retrospective observational study. Patients with portal hypertension who received endoscopic injection of recombinant thrombin were identified and data collected on haemostasis and rebleeding rates, complications and mortality. Patients were grouped by indication for thrombin injection: gastric/oesophageal/ectopic varices and endoscopic band ligation (EBL)-induced ulceration. 155 patients (96M/59F, mean age 58.3 years) received endoscopic thrombin injection. Mean volume of thrombin injected at index endoscopy was 9.5 ml/2375IU. Initial haemostasis was achieved in 144 patients (92.9%). Rebleeding occurred in a total of 53 patients (36.8%) divided as follows: early rebleeding (<5 days from index endoscopy)-26 patients (18%); rebleeding within 30 days-42 patients (29.1%); delayed rebleeding (> 30 days)-11 patients (7.6%). There was statistically significant difference in rate of initial haemostasis between Child-Pugh A/B patients vs Child-Pugh C (p = 0.046). There was no significant difference in rebleeding rates between different indication groups (p = 0.78), by presence of cirrhosis or by Child-Pugh Score. All-cause mortality at 6 weeks was 18.7%; 1-year mortality 37.4% (median follow-up 48 months). There was no significant difference in mortality between groups (p = 0.37). No significant adverse events or complications were reported. Thrombin is effective and safe for gastric varices and other portal-hypertension-related bleeding including oesophageal varices, ulcers secondary to EBL and ectopic varices.

Cardiac and pulmonary issues in LT assessment candidates.

With the incidence of liver disease increasing worldwide, a growing number of patients are being referred for assessment for liver transplant (LT). Unfortunately, the donor pool is not expanding at the same rate, which consequentially results in increasing demand on a finite resource. It is therefore imperative that the candidate who undergoes an LT gets maximal benefit with a resultant maximal increase in life expectancy. This article addresses some of the main cardiac and pulmonary issues that may occur in LT assessment candidates.

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.

Increased whole-body and sustained liver cortisol regeneration by 11beta-hydroxysteroid dehydrogenase type 1 in obese men with type 2 diabetes provides a target for enzyme inhibition.

OBJECTIVE: The cortisol-regenerating enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11ß-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11ß-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11ß-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11ß-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-[(2)H](4)cortisol (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 11ß-HSD1 activity using tracer dilution. RESULTS: In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[(2)H](3)cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P < 0.05), splanchnic 9,12,12-[(2)H](3)cortisol 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 11ß-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11ß-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11ß-HSD1 are likely to be most effective in obese type 2 diabetic subjects.

Gastrointestinal bleeding: Endoscopic cyanoacrylate therapy for gastric variceal bleeding.

Bleeding from gastric varices is relatively common and can be life threatening. The optimal treatment strategy for gastric variceal hemorrhage is controversial. Both interventional radiology and endoscopic therapies require a high level of clinical expertise. Which type of therapy is best? A recent study compared endoscopic cyanoacrylate glue injection with the insertion of a transjuglar intrahepatic portosystemic shunt.

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

UNLABELLED: 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.

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.

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.

The use of transjugular intrahepatic portosystemic stent shunt in the management of acute oesophageal variceal haemorrhage.

Variceal haemorrhage is a common and serious complication of portal hypertension. Endoscopic therapy is successful in the majority in controlling bleeding but in those who continue to bleed transjugular intrahepatic portosystemic stent shunt is highly effective in achieving haemostasis, although the evidence base that this is associated with improved survival is limited. This review discusses initial management and then the particular role of transjugular intrahepatic portosystemic stent shunt. A management algorithm is proposed. The timing of intervention is emphasized and the importance of admission to specialized centres. Regional protocols are probably essential for the latter to be organized effectively.