Portal Embolisation as Treatment of Severe Portal Hypertension Due to Idiopathic Intrahepatic Arterioportal Fistula:A Case Report

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension. Treatment is usually aimed at restoring the normal portal hemodynamics by obliterating the shunt. This report describes a case of idiopathic IAPF with severe portal hypertension complicated by portal enteropathy with vomiting, gastrointestinal hemorrhage and sepsis. The patient was successfully treated with portal embolization.</p

Selected liver grafts from donation after circulatory death can be safely used for retransplantation – a multicenter retrospective study

Due to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD-reLT with three DBD-reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD-reLT were compared with 63 matched DBD-reLTs. Donors in the DCD-reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m2, P-value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD-reLT was significantly higher (38.1% vs. 12.7%, P-value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT

Circulatory microRNAs as potential biomarkers for fatty liver disease: the Rotterdam study

Background: Fatty liver disease (FLD) is the most common cause of liver dysfunction in developed countries. There is great interest in developing clinically valid and minimally invasive biomarkers to enhance early diagnosis of FLD. Aim: To investigate the potential of circulatory microRNAs (miRNAs) as biomarkers of FLD at the population level. Methods: Plasma levels of 2083 miRNAs were measured by RNA sequencing in 1999 participants from the prospective population-based Rotterdam Study cohort. The Hounsfield Unit (HU) attenuation of liver was measured using non-enhanced computed tomography (CT) scan. Logistic and linear regression models adjusting for potential confounders were used to examine the association of circulatory miRNAs with liver enzymes (n = 1991) and CT-based FLD (n = 954). Moreover, the association of miRNAs with hepatic steatosis and liver fibrosis was assessed longitudinally in individuals who underwent abdominal ultrasound (n = 1211) and transient elastography (n = 777) after a median follow-up of >6 years. Results: Cross-sectional analysis showed 61 miRNAs significantly associated with serum gamma-glutamyl transferase and/or alkaline phosphatase levels (Bonferroni-corrected P < 8.46 × 10−5). Moreover, 17 miRNAs were significantly associated with CT-based FLD (P < 8.46 × 10−5); 14 were among miRNAs associated with liver enzymes. Longitudinal analysis showed that 4 of these 14 miRNAs (miR-193a-5p, miR-122-5p, miR-378d and miR-187-3p) were significantly associated with hepatic steatosis (P < 3.57 × 10−3) and three (miR-193a-5p, miR-122-5p and miR-193b-3p) were nominally associated with liver fibrosis (P < 0.05). Nine of the 14 identified miRNAs were involved in pathways underlying liver diseases. Conclusions: Plasma levels of several miRNAs can be used as biomarkers of FLD, laying the groundwork for future clinical applications

Somatic calreticulin mutations in patients with Budd-Chiari syndrome and portal vein thrombosis

Carta a l'editorWe studied the role of the recently identified CALR mutations in 141 patients with Budd-Chiari Syndrome (BCS) or portal vein thrombosis (PVT) in a large multinational cohort. A CALR mutation was present in one of the 141 patients (0.7%). This patient was previously diagnosed with primary myelofibrosis. This results in CALR positivity in one out of 44 (2.3%) patients with myeloproliferative neoplasm (MPN), and in one of 11 (9.1%) JAK2V617F negative patients diagnosed with MPN. We suggest that analysis of CALR mutations should be performed in JAK2V617F negative BCS and PVT patients..

Immunosuppressive drug withdrawal late after liver transplantation improves the lipid profile and reduces infections

BACKGROUND: Treatment with immunosuppressive drugs (IS) after transplantation is accompanied by severe side effects. A limited number of studies have investigated the effect of IS withdrawal on IS-related comorbidities after liver transplantation (LTx) and the results are contradictory. PATIENTS AND METHODS: We determined in a retrospective case-control study the clinical effects of complete IS withdrawal in operationally tolerant (TOL) LTx recipients who discontinued IS 10.8 ± 5.1 years after LTx (n = 13) compared with a completely matched control (CTRL) group with a regular IS regimen (n = 22). TOL recipients have been IS and rejection free for 4.0 ± 2.8 years. RESULTS: IS withdrawal in TOL recipients resulted in lower low-density lipoprotein levels (P = 0.027), whereas this was not observed in the CTRL group. Furthermore, persistent infections in individual recipients were resolved successfully by IS withdrawal. TOL recipients also had significantly fewer de novo infections after IS withdrawal (TOL pre vs. post withdrawal P = 0.0247) compared with recipients continued on IS during the same follow-up period (post withdrawal TOL vs. CTRL P = 0.044). Unfortunately, no improvement in kidney function, and lower rates of de novo occurrences of diabetes, hypertension, cardiovascular diseases, and malignancies were observed in the TOL group after IS withdrawal compared with the CTRL group during the same follow-up time period. CONCLUSION: IS withdrawal late after LTx reduces infection rates and low-density lipoprotein levels, but other IS-related side effects persist late after LTx. An accurate tolerance immune profile enabling identification of tolerant LTx recipients eligible for safe IS withdrawal earlier after transplantation is needed to prevent the development of irreversible IS-related side effects

Donor hepatectomy time influences ischemia-reperfusion injury of the biliary tree in donation after circulatory death liver transplantation

Background: Donor hepatectomy time is associated with graft survival after liver transplantation. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation. Methods: First, bile duct biopsies of livers included in (pre)clinical machine perfusion research were analyzed. Secondly, of the same livers, bile samples were collected during normothermic machine perfusion. Lastly, a nationwide retrospective cohort study was performed including 273 adult patients undergoing donation after circulatory death liver transplantation between January 1, 2002 and January 1, 2017. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. Cox proportiona

Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation: a nationwide retrospective cohort study

With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes. From a national cohort of adult liver transplant recipients (1996–2016), all recipients transplanted with a liver from a DM donor (n = 69) were matched 1:2 with recipients of livers from non-DM donors (n = 138). The primary end-point included early post-transplant outcome, such as the incidence of primary nonfunction (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analy

Medication-Related Problems in Liver Transplant Recipients in the Outpatient Setting: A Dutch Cohort Study

Background: After liver transplantation (LTx), adherence to immunosuppressive medication and avoidance of contra-indicated drugs is essential for long-term survival. This study aimed to investigate the prevalence, types and severity of medication-related problems (MRPs) and interventions initiated by a clinical pharmacist (CP) in a cohort of LTx recipients in the outpatient setting. Method: This study was a retrospective, observational study in LTx recipients that visited the outpatient clinic for an annual check-up. A 20-minutes consultation with a CP consisted of medication reconciliation and consultation about medication, adherence, and adverse drug reactions (ADRs). Discrepancies between actual and intended drug use, and MRPs were identified and the severity of MRPs was assessed. Potential interventions were discussed with the patient and the treating physician and evaluated after one year. Results: The CP counseled 64 LTx recipients and found 96 discrepancies in 37 patients. Most discrepancies (60.4%, n = 58) concerned missing medications. In total, 98 MRPs were identified in 53 patients (median 2; range 1-5 per patient), with a total of 113 interventions. Most frequent MRPs were: ADRs (22.4%, n = 22), nonadherence (19.3%, n = 19), unnecessary drugs (16.3%, n = 16) and undertreatment (12.2%, n = 12). Interventions most frequently proposed included optimization of dosage regimen (21.2%, n = 24), individualized recommendation regarding compliance (16.8%, n = 19) and drug discontinuation (12.4%, n = 14). After one year, 15 of the 19 patients (79%) experienced no longer compliance issues and 27 of the 29 patients (93%) used no drugs with indication issues anymore. Conclusion: The CP in an outpatient monitoring program for LTx recipients can signal relevant discrepancies and MRPs. This leads to interventions that are accepted by both the patients and the physicians, with a positive effect after one year