Bioartificial liver: its pros and cons

Both the large variety of liver functions for maintaining body homeostasis and the proven effectivity of whole liver transplantation in the therapy of acute liver failure (ALF), are important reasons to presume that cell-free liver support systems will not be able to adequately support the failing liver. Accordingly, bioartificial liver (BAL) systems have shown their efficacy in experimental ALF models in small and large animals, and have shown to be suitable and safe in phase 1 studies in humans with ALF. However, the optimal BAL system is still under development. Important issues are the source of the cellular component and the configuration of the BAL system with regard to cell attachment, mass transfer characteristics and oxygenation at site. The deficiency of all BAL systems to excrete bile effectively is another important topic for improvement. The great challenge for the future is to develop a well-functioning and safe human hepatic cell line which can replace the widely used porcine (xenogeneic) hepatocytes. Theoretically, a combination of a cell-free liver support system and a BAL system might be optimal for the treatment of ALF patients in the near futur

MARS treatment in posthepatectomy liver failure

Posthepatactomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver failure patients. This paper describes the initial experience in the Netherlands using the MARS liver assist device in five patients with PHLF. In all patients, improvement of biochemical parameters was observed during MARS treatments along with clinical improvement in three patients. One patient survived. No clear guidelines for MARS treatment and prognostic factors for outcome after MARS treatment with regard to this patient group are available. In this paper, a MARS treatment regimen for PHLF is suggest based on literature and our experienc

Assessment of the AMC-bioartificial liver in the anhepatic pig

Background. The anhepatic pig model was used to evaluate a bioartificial liver developed in our institution (AMC-BAL). The bioartificial liver is based on oxygenated plasma perfusion of porcine hepatocytes attached to a polyester matrix. Methods. Pigs (n=15) underwent total hepatectomy with restoration of caval continuity using a polyethylene, three-way prosthesis. In group 1, pigs received limited intensive care under continuation of general anesthesia (n=5). Group II pigs (n=5) underwent, in addition, extracorporeal plasma perfusion of an AMC-BAL without hepatocytes (device control group). In group III (n=5), plasma perfusion occurred with an AMC-BAL loaded with autologous hepatocytes. Groups II and III were connected to the extracorporeal system 24 hr after hepatectomy, for a period of 24 hr. The main outcome parameters were as follows: survival time, liver enzymes (aspartate aminotransferase, alanine aminotransferase), blood ammonia, and total/direct bilirubin. Results. Survival (mean +/- SD) of the anhepatic pigs was significantly increased in the BAL-treated group (group III: 65+/-15 hr), as compared with the control groups (group I: 46+/-6 hr and group II: 43+/-14 hr). Mean blood ammonia levels during BAL treatment were significantly lower in the BAL-treated group in comparison with both control groups (P=0.02). Total and direct bilirubin levels gradually increased after hepatectomy and reached maximum values of 1.98 mg/dl and 1.50 mg/dl, respectively, showing no differences between the three groups. Conclusions. (1) Treatment of anhepatic pigs with the AMC-BAL containing autologous hepatocytes significantly increases survival time, which is associated with a significant decrease in blood ammonia. 2) Anhepatic pigs demonstrate increasing direct bilirubin levels as a result of extrahepatic bilirubin conjugatio

Anderhalvelijnszorg voor knie- en heupartrose

Om het aantal verwijzingen naar tweedelijnszorg orthopedie terug te dringen zijn in Nederland diverse anderhalvelijnszorgpilotprojecten voor knie- en heupartrose opgezet. In een aantal van deze projecten leveren orthopeden consulten in de huisartsenpraktijk. Uit een evaluatie van 3 van deze pilotprojecten blijkt dat ze de multidisciplinaire communicatie en de toegankelijkheid van de zorg verbeterden. Bovendien vergrootten ze de kennis en vaardigheden van zorgverleners. Deze vorm van zorg had ook gevolgen voor het aantal verwijzingen naar fysiotherapie en de tweede lijn

Evaluation of intermediate care for knee and hip osteoarthritis: a mixed-methods study

Background: To evaluate intermediate care for knee and hip osteoarthritis (KHOA) in the general practice that incorporate specialist services into general practice to prevent unnecessary referrals to hospitals. Methods: We used a mixed methods approach including semi-structured interviews, patient experience questionnaires and data from medical records from three intermediate care projects. Semi-structured interviews were conducted with patients, general practitioners (GPs), orthopaedists and a healthcare manager in intermediate care. Satisfaction of patients who received intermediate care (n = 100) was collected using questionnaires. Referral data and healthcare consumption from medical records were collected retrospectively from KHOA patients before (n = 96) and after (n = 208) the implementation of intermediate care. Results: GPs and orthopaedists in intermediate care experienced more intensive collaboration compared to regular care. This led to a perceived increase in GPs’ knowledge enabling better selection of referrals to orthopaedics and less healthcare consumption. Orthopaedists felt a higher workload and limited access to diagnostic facilities. Patients were satisfied and experienced better access to specialists’ knowledge in a trusted environment compared to regular care. Referrals to physiotherapy increased significantly after the implementation of intermediate care (absolute difference = 15%; 95% CI = 7.19 to 22.8), but not significantly to orthopaedics (absolute difference = 5.9%; 95% CI = -6.18 to 17.9). Conclusions: Orthopaedists and GPs perceived the benefits of an intensified collaboration in intermediate care. Intermediate care may contribute to high quality of care through more physiotherapy referrals. Further research with longer follow-up is needed to confirm these findings and give more insight in referrals and healthcare consumption

Evidence for Galalpha(1-3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems

BACKGROUND/AIMS: To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting porcine hepatocytes. Xenogeneic BAL systems may suffer from hyperacute rejection similar to whole-organ xenotransplants. Hyperacute rejection is mediated by antibodies directed against Galalpha(1-3)Gal, a carbohydrate structure present on most mammalian cells. Galalpha(1-3)Gal is produced by the enzyme alpha1,3-galactosyltansferase (alphaGal-T). Conflicting data have been published concerning Galalpha(1-3)Gal expression on hepatocytes in intact porcine liver. We investigated whether isolated porcine hepatocytes express Galalpha(1-3)Gal. METHODS: Immunofluorescence, flow cytometry, RT-PCR and enzyme activity assays were performed on freshly isolated and cultured porcine hepatocytes and liver biopsies. Anti-Galalpha(1-3)Gal antibodies were measured in plasma from patients treated with BAL by ELISA. RESULTS: Isolated porcine hepatocytes express (alphaGal-T) at low levels and Galalpha(1-3)Gal is present in low quantities on these cells, in contrast to hepatocytes in situ. Furthermore, IgG and IgM anti-Galalpha(1-3)Gal are depleted from the plasma of ALF patients during BAL treatment. CONCLUSIONS: Isolation and culture of porcine hepatocytes induce Galalpha(1-3)Gal expression, which may elicit immunological responses potentially compromising BAL functionalit

Evaluation of intermediate care for knee and hip osteoarthritis

Background: To evaluate intermediate care for knee and hip osteoarthritis (KHOA) in the general practice that incorporate specialist services into general practice to prevent unnecessary referrals to hospitals. Methods: We used a mixed methods approach including semi-structured interviews, patient experience questionnaires and data from medical records from three intermediate care projects. Semi-structured interviews were conducted with patients, general practitioners (GPs), orthopaedists and a healthcare manager in intermediate care. Satisfaction of patients who received intermediate care (n = 100) was collected using questionnaires. Referral data and healthcare consumption from medical records were collected retrospectively from KHOA patients before (n = 96) and after (n = 208) the implementation of intermediate care. Results: GPs and orthopaedists in intermediate care experienced more intensive collaboration compared to regular care. This led to a perceived increase in GPs’ knowledge enabling better selection of referrals to orthopaedics and less healthcare consumption. Orthopaedists felt a higher workload and limited access to diagnostic facilities. Patients were satisfied and experienced better access to specialists’ knowledge in a trusted environment compared to regular care. Referrals to physiotherapy increased significantly after the implementation of intermediate care (absolute difference = 15%; 95% CI = 7.19 to 22.8), but not significantly to orthopaedics (absolute difference = 5.9%; 95% CI = -6.18 to 17.9). Conclusions: Orthopaedists and GPs perceived the benefits of an intensified collaboration in intermediate care. Intermediate care may contribute to high quality of care through more physiotherapy referrals. Further research with longer follow-up is needed to confirm these findings and give more insight in referrals and healthcare consumption.</p

Quality indicators for knee and hip osteoarthritis care: a systematic review

To provide an overview of quality indicators (QIs) for knee and hip osteoarthritis (KHOA) care and to highlight differences in healthcare settings. A database search was conducted in MEDLINE (PubMed), EMBASE, CINAHL, Web of Science, Cochrane CENTRAL and Google Scholar, OpenGrey and Prospective Trial Register, up to March 2020. Studies developing or adapting existing QI(s) for patients with osteoarthritis were eligible for inclusion. Included studies were categorised into healthcare settings. QIs from included studies were categorised into structure, process and outcome of care. Within these categories, QIs were grouped into themes (eg, physical therapy). A narrative synthesis was used to describe differences and similarities between healthcare settings. We included 20 studies with a total of 196 QIs mostly related to the process of care in different healthcare settings. Few studies included patients’ perspectives. Rigorous methods for evidence synthesis to develop QIs were rarely used. Narrative analysis showed differences in QIs between healthcare settings with regard to exercise therapy, weight counselling, referral to laboratory tests and ‘do not do’ QIs. Differences within the same healthcare setting were identified on radiographic assessment. The heterogeneity in QIs emphasise the necessity to carefully select QIs for KHOA depending on the healthcare setting. This review provides an overview of QIs outlined to their healthcare settings to support healthcare providers and policy makers in selecting the contextually appropriate QIs to validly monitor the quality of KHOA care. We strongly recommend to review QIs against the most recent guidelines before implementing them into practice

Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 X 109 viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 It by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatmen