No abstract

These updated guidelines on the management of variceal haemorrhage have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines which this document supersedes were written in 2000 and have undergone extensive revision by 13 members of the Guidelines Development Group (GDG). The GDG comprises elected members of the BSG liver section, representation from British Association for the Study of the Liver (BASL) and Liver QuEST, a nursing representative and a patient representative. The quality of evidence and grading of recommendations was appraised using the AGREE II tool.The nature of variceal haemorrhage in cirrhotic patients with its complex range of complications makes rigid guidelines inappropriate. These guidelines deal specifically with the management of varices in patients with cirrhosis under the following subheadings: (1) primary prophylaxis; (2) acute variceal haemorrhage; (3) secondary prophylaxis of variceal haemorrhage; and (4) gastric varices. They are not designed to deal with (1) the management of the underlying liver disease; (2) the management of variceal haemorrhage in children; or (3) variceal haemorrhage from other aetiological conditions.

There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirtyone livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring retransplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.

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 betablocker 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. T he most serious complication of portal hypertension is variceal hemorrhage. The annual incidence of esophageal varices in patients with cirrhosis is approximately 5%, 1 and a third of these will bleed. 2,3 Current therapy with propranolol results in a reduction in the first variceal bleed and mortality compared with placebo. 4,5 There have been two recent metaanalyses with 16 trials studied in total. 6,7 The one showed variceal band ligation (VBL) to be more effective than beta-blockers in primary prevention of variceal hemorrhage, although there was no difference in survival. 7 The other showed similar overall results, although when trials with unclear bias control and follow-up less than 20 months were excluded, the difference in bleeding was not present. 6 Carvedilol is a potent non-cardioselective betablocker, with weak vasodilating properties due to alpha-1 blockade. 8 A fall in both intrahepatic and portocollateral resistance contributes to the enhanced effects on portal pressure reduction through blockade of alpha-1 receptors as has been shown with prazosin. 9-11 A reduction in the hepatic venous pressure gradient (HVPG) of 8%-43% was observed with carvedilol in nine published hemodynamic studies involving 158 patients. [12][13][14][15][16][17][18][19][20] Carvedilol was also found to have a greater portal hypotensive effect than propranolol in randomized controlled hemodynamic studies. 15,17

BackgroundRare diseases can lead to a significant reduction in quality of life for patients and their families. Ensuring the patients voice is central to clinical decision making is key to delivering, evaluating and understanding the efficacy of therapeutic interventions. Patient reported outcome measures (PROMs) are used to capture the patient’s views about their health status and facilitate our understanding of the impact of these diseases and their treatments on patient’s quality of life and symptoms.Main textThis review explores some of the current issues around the utilisation of PROMs in rare diseases, including small patient populations and dearth of valid PROMs. Difficulties in validating new or current PROMs for use in clinical trials and research are discussed. The review highlights potential solutions for some of the issues outlined in the review and the implementation of PROMs in research and clinical practice are discussed.ConclusionPatient input throughout the development of PROMs including qualitative research is essential to ensure that outcomes that matter to people living with rare disease are appropriately captured. Given the large number of rare diseases, small numbers of patients living with each condition and the cost of instrument development, creative and pragmatic solutions to PROM development and use may be necessary. Solutions include qualitative interviews, modern psychometrics and resources such as item banking and computer adaptive testing. Use of PROMs in rare disease research and clinical practice offers the potential to improve patient care and clinical outcomes.

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato-biliary complications. The implications for renal function have not been explored previously. The aims of this single-center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity-risk-matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m 2 ). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post-transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post-transplant renal dysfunction.Key words: Acute kidney injury, chronic kidney disease, donation after cardiac death, ischemia reperfusion injury, transplantation Abbreviations: AKI, acute kidney injury; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval. DBD, donation after brain death; DCD, donation after cardiac death; eGFR, estimated glomerular filtration rate; FFP, fresh frozen plasma; INR, international normalised ratio; IQR, inter-quartile range; MELD, model for end-stage liver disease; NASH, non-alcoholic steatohepatitis; OR, odds ratio; PRS, propensity risk score; RCC, red cell concentrate; SD, standard deviation; UKELD, UK score for patients with end-stage liver disease.

Frailty is associated with increased mortality both before and after liver transplantation (LT). There are no standardized exercise programs, in particular home‐based exercise programs (HBEPs), for patients awaiting LT. The aim was to investigate the feasibility of such a program in patients awaiting LT. Patients were randomly selected from the Birmingham LT waiting list and provided with a 12‐week HBEP, including average daily step (ADS) targets and twice‐weekly resistance exercises. Feasibility was based on patient eligibility (≥66% of waiting list), target recruitment (≥90% of n = 20), safety (no related serious adverse events), and adherence (≥66% adherence to 6‐week HBEP). Measures of aerobic (incremental shuttle walk test [ISWT], ADS), functional capacity (short physical performance battery test [SPPBT]), and health‐related quality of life (EuroQol 5‐Dimension 5‐Level (EQ‐5D‐5L) and hospital anxiety and depression score [HADS]) were taken at baseline and at 6 and 12 weeks. 18 patients (50% male; median age, 55 years) were recruited. All domains of the study feasibility criteria were met. ISWT improved after 6 weeks (50 m; P ≤ 0.01) and 12 weeks (210 m; P ≤ 0.01), despite withdrawal of the telephone health calls. Similarly, improvements were seen in ADS (2700/day; P ≤ 0.01) and the SPPBT (2.5; P = 0.02) after 12 weeks. There was no difference in HADS (median difference [MD] –3; P = 0.69), but EQ‐5D‐5L after 12 weeks (17.5%; P = 0.04). In conclusion, a 12‐week HBEP, incorporating both easy‐to‐apply resistance and aerobic exercises, is safe and feasible in patients awaiting LT. Measures of aerobic and functional capacity demonstrate trends toward improvement that warrant further investigation in a randomized controlled trial.

No abstract