Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review

Prehabilitation improves surgical outcomes in patients undergoing surgery. However, patients preparing for orthotopic liver transplantation (OLT) are physically “frail” and suffer from comorbidities that generally hamper physical activity. This systematic review aims to evaluate the physical effects, safety and feasibility of prehabilitation in OLT candidates. Relevant articles were searched, in Embase, Web of Science, Cochrane, Medline and Google Scholar, to December 2021. Studies reporting on specified preoperative exercise programs, including adult OLT candidates with end-stage liver disease, with a model for end-stage liver disease (MELD) score ≥12 or Child-Pugh classification B/C, were included. This resulted in 563 potentially eligible studies, out of which eight were selected for inclusion, consisting of 1,094 patients (male sex 68%; mean age 51–61 years; mean MELD score 12-21). Six of the included studies were classified as low-quality by the GRADE system, and three studies had high risk for ineffectiveness of the training program according to the i-CONTENT tool. Significant improvement was observed in VO2 peak, 6-minute walking distance, hand grip strength, liver frailty index and quality of life. Feasibility ranged from an adherence of 38%–90% in unsupervised-to &gt;94% in supervised programs. No serious adverse events were reported. In conclusion, prehabilitation in patients awaiting OLT appears to improve aerobic capacity, and seems feasible and safe. However, larger clinical trials are required to accurately examine the preoperative and postoperative effects of prehabilitation in this specific patient population.</p

Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review

Prehabilitation improves surgical outcomes in patients undergoing surgery. However, patients preparing for orthotopic liver transplantation (OLT) are physically “frail” and suffer from comorbidities that generally hamper physical activity. This systematic review aims to evaluate the physical effects, safety and feasibility of prehabilitation in OLT candidates. Relevant articles were searched, in Embase, Web of Science, Cochrane, Medline and Google Scholar, to December 2021. Studies reporting on specified preoperative exercise programs, including adult OLT candidates with end-stage liver disease, with a model for end-stage liver disease (MELD) score ≥12 or Child-Pugh classification B/C, were included. This resulted in 563 potentially eligible studies, out of which eight were selected for inclusion, consisting of 1,094 patients (male sex 68%; mean age 51–61 years; mean MELD score 12-21). Six of the included studies were classified as low-quality by the GRADE system, and three studies had high risk for ineffectiveness of the training program according to the i-CONTENT tool. Significant improvement was observed in VO2 peak, 6-minute walking distance, hand grip strength, liver frailty index and quality of life. Feasibility ranged from an adherence of 38%–90% in unsupervised-to >94% in supervised programs. No serious adverse events were reported. In conclusion, prehabilitation in patients awaiting OLT appears to improve aerobic capacity, and seems feasible and safe. However, larger clinical trials are required to accurately examine the preoperative and postoperative effects of prehabilitation in this specific patient population

‘Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation’:study protocol of a non-randomised clinical trial

Introduction Patients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is associated with poor pre-OLT, peri-OLT and post-OLT outcomes. However, frailty in these patients may be reversable with adequate exercise and nutritional interventions. Methods and analysis Non-randomised clinical trial evaluating the effect of a home-based bimodal lifestyle programme in unfit patients with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/ kg/min and/or VO2 at peak exercise ≤18 mL/kg/min listed for OLT at the University Medical Center Groningen (UMCG). The programme is patient tailored and comprises high-intensity interval and endurance training, and functional exercises three times per week, combined with nutritional support. Patients will go through two training periods, each lasting 6 weeks. The primary outcome of this study is the impact of the programme on patients’ aerobic fitness after the first study period. Secondary outcomes include aerobic capacity after the second study period, changes in sarcopenia, anthropometry, functional mobility, perceived quality of life and fatigue, incidence of hepatic encephalopathy and microbiome composition. Moreover, number and reasons of intercurrent hospitalisations during the study and postoperative outcomes up to 12 months post OLT will be recorded. Finally, feasibility of the programme will be assessed by monitoring the participation rate and reasons for non-participation, number and severity of adverse events, and dropout rate and reasons for dropout. Ethics and dissemination This study was approved by the Medical Research Ethics Committee of the UMCG (registration number NL83612.042.23, August 2023) and is registered in the Clinicaltrials.gov register (NCT05853484). Good Clinical Practice guidelines and the principles of the Declaration of Helsinki will be applied. Results of this study will be submitted for presentation at (inter)national congresses and publication in peer-reviewed journals.</p

Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review

Prehabilitation improves surgical outcomes in patients undergoing surgery. However, patients preparing for orthotopic liver transplantation (OLT) are physically “frail” and suffer from comorbidities that generally hamper physical activity. This systematic review aims to evaluate the physical effects, safety and feasibility of prehabilitation in OLT candidates. Relevant articles were searched, in Embase, Web of Science, Cochrane, Medline and Google Scholar, to December 2021. Studies reporting on specified preoperative exercise programs, including adult OLT candidates with end-stage liver disease, with a model for end-stage liver disease (MELD) score ≥12 or Child-Pugh classification B/C, were included. This resulted in 563 potentially eligible studies, out of which eight were selected for inclusion, consisting of 1,094 patients (male sex 68%; mean age 51–61 years; mean MELD score 12-21). Six of the included studies were classified as low-quality by the GRADE system, and three studies had high risk for ineffectiveness of the training program according to the i-CONTENT tool. Significant improvement was observed in VO2 peak, 6-minute walking distance, hand grip strength, liver frailty index and quality of life. Feasibility ranged from an adherence of 38%–90% in unsupervised-to >94% in supervised programs. No serious adverse events were reported. In conclusion, prehabilitation in patients awaiting OLT appears to improve aerobic capacity, and seems feasible and safe. However, larger clinical trials are required to accurately examine the preoperative and postoperative effects of prehabilitation in this specific patient population

Laxative treatment with polyethylene glycol does not affect lipid absorption in rats

Item does not contain fulltextOBJECTIVES: Polyethylene glycol (PEG) is a frequently used laxative agent. It is unknown, however, whether PEG affects the absorptive capacity of the intestine. Reduced lipid (dietary fat and cholesterol) absorption induced by long-term PEG treatment could negatively affect growth in children. We tested whether PEG accelerates gastrointestinal transit and alters lipid absorption and plasma lipid levels. METHODS: Wistar rats were administered drinking water with or without PEG (7%) for 2 weeks. We studied whole gut transit time by recording the first appearance of red feces after intragastric carmine red administration. We measured plasma concentrations of cholesterol and triglycerides, dietary fat absorption by 48-hour fat balance and by plasma appearance of intragastrically administered stable-isotope labeled fats, and cholesterol absorption with a dual stable isotope technique. RESULTS: PEG decreased whole gut transit time by 20% (P=0.028) without causing diarrhea. PEG treatment did neither affects overall dietary fat balance nor fat uptake kinetics, cholesterol absorption, or plasma lipid concentrations. CONCLUSIONS: PEG does not affect lipid absorption nor steady-state plasma lipid levels in rats, although it accelerates the gastrointestinal transit

Study protocol for a multicentre nationwide prospective cohort study to investigate the natural course and clinical outcome in benign liver tumours and cysts in the Netherlands: the BELIVER study

Introduction Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease. Methods and analysis A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course. Ethics and dissemination The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal. Study registration NL8231 - 10 December 2019; Netherlands Trial Register

Variation in the management of benign liver tumors: A European survey and case vignette study

Background: Management of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), is multidisciplinary and subject to practice variation. We aimed to evaluate variation in clinical management of FNH and HCA in Europe. Methods: We distributed an online survey (November 2021–March 2022) among 294 European experts. The survey included questions on local practice and included eight clinical vignettes. The clinical vignettes focused on FNH or HCA management in the setting of sex, lifestyle modification, and pregnancy. Results: The response rate was 32% and respondents included surgeons (38%), gastroenterologists/hepatologists (25%), radiologists (32%), and pathologists (1.6%) from ten European countries. We observed practice variation with regard to lifestyle modification and imaging follow-up in patients with FNH, and with regard to the management of HCA >5 cm before and during pregnancy. Finally, the management of HCA >5 cm after lifestyle modification deviated from EASL guideline recommendations. Conclusion: Our survey illustrates variability in FNH and HCA management in Europe. Several areas were identified for future research and guideline recommendations, including FNH follow-up and the management of HCA >5 cm. We propose the organization of Delphi consensus meetings to prioritize areas of research and update current guidelines to optimize management for all patients with benign liver tumors

Incidence and prevalence of primary biliary cholangitis in the Netherlands – A nationwide cohort study

Background &amp; Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001). Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences. Impact and implications:: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population