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Introduction and aim. The prevalence and incidence of chronic liver disease is increasing resulting, in substantial direct and indirect medical costs. Overuse of investigations, treatments and procedures contribute to rising health care costs and can expose patients to unnecessary harm and delay in receiving care. The Choosing Wisely Canada (CWC) campaign has encouraged professional societies to develop statements that are directly actionable by their members in an effort to promote higher-value health care that will lead to downstream effect on how other practitioners make decisions.Material and methods. The Canadian Association for the Study of the Liver (CASL) established its Choosing Wisely top five list of recommendations using the framework put forward by CWC. CASL convened a task force that developed a list of draft recommendations and shared this with CASL membership electronically with eventual ranking of the top five recommendations by consensus at Canadian Digestives Disease Week (CDDW) 2017. Following revisions, the CASL Executive Committee endorsed the final list, which was disseminated online by CWC (July 2017).Results. The top five recommendations physicians and patients should question include: 1) Don’t order serum ammonia to diagnose or manage hepatic encephalopathy (HE). 2) Don’t routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures. 3) Don’t order HFE genotyping based on serum ferritin values alone to diagnose hereditary hemochromatosis. 4) Don’t perform computed tomography (CT) or magnetic resonance imaging (MRI) routinely to monitor benign focal liver lesions. 5) Don’t repeat hepatitis C viral load testing in an individual who has established chronic infection, outside of anti-viral treatment.Conclusion. The Choosing Wisely recommendations will foster patient-physician discussions, reduce unnecessary treatment and testing, avert adverse effects from testing and treatment along with reducing medical expenditure in hepatology.

Introduction: Radiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepa-tocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death. Material and methods: We conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes. Results: 219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001). Conclusion: Incremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.

BACKGROUND: The literature regarding post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients (LTRs) is limited.

Background. We evaluated patient characteristics of live donor liver transplant (LDLT) recipients undergoing a fast-track protocol without intensive care unit (ICU) admission versus LDLT patients receiving posttransplant ICU care. Methods. Of the 153 LDLT recipients, 46 patients were included in our fast-track protocol without ICU admission. Both, fast-tracked patients and ICU-admitted patients were compared regarding donor and patient characteristics, perioperative characteristics, and postoperative outcomes and complications. In a subgroup analysis, we compared fast-tracked patients with patients who were admitted in the ICU for less than 24 hours. Results. Fast-tracked versus ICU patients had a lower model for end-stage liver disease score (13 ± 4 vs 18 ± 7; P < 0.0001), lower preoperative bilirubin levels (51 ± 50 μmol/L vs 119.4 ± 137.3 μmol/L; P < 0.001), required fewer units of packed red blood cells (1.7 ± 1.78 vs 4.4 ± 4; P < 0.0001), and less fresh-frozen plasma (2.7 ± 2 vs 5.8 ± 5; P < 0.0001) during transplantation. Regarding postoperative outcomes, fast-tracked patients presented fewer bacterial infections within 30 days (6.5% [3] vs 29% [28]; P = 0.002), no episodes of pneumonia (0% vs 11.3% [11]; P = 0.02), and less biliary complications within the first year (6% [3] vs 26% [25]; P = 0.001). Also, fast-tracked patients had a shorter posttransplant hospital stay (10.8 ± 5 vs 21.3 ± 29; P = 0.002). In the subgroup analysis, fast-tracked vs ICU patients admitted for less than 24 hours had lower requirements of packed red blood cells (1.7 ± 1.78 vs 3.9 ± 4; P = 0.001) and fresh-frozen plasma (2.7 ± 2 vs 5.8 ± 4.5; P = 0.0001). Conclusions. Fast-track of selected patients after LDLT is safe and feasible. An objective score to perioperatively select LDLT recipients amenable to fast track is yet to be determined.

Introduction. Hepatitis C (HCV) continues to be the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for recurrent HCV in Genotype 1 (G1) LT recipients have been disappointing (30-40%). Experience with triple therapy using protease inhibitors (PI) boceprevir (BOC), telaprevir (TVR) in these patients has been limited.Material and methods. This national multicenter retrospective study included 76 patients (64 male, mean age 57 ± 6 years), treated for G1 HCV recurrence with either BOC (n = 41) or TVR (n = 35), who were non-responders or relapsers (n = 54), treatment naïve (n = 22) or had fibrosing cholestatic HCV (n = 3). 53 patients were on cyclosporine, 22 on tacrolimus and one patient on prednisone alone.Results. On treatment virologic response was observed in 84% (64/76), 83% in BOC and 85% in TVR group. A higher week 4 response after starting triple therapy (RVR) was noted in TVR group 25/35 (81%) as compared to BOC group 26/41 (63%); p value = 0.02. The end of treatment response was 78% and 75% in BOC and TVR group, respectively. SVR 12 weeks after treatment discontinuation was observed in 59.5% (22/37); 58.3% in the BOC group and 61.5% in TVR group. Treatment was discontinued early in 23 patients (serious adverse effects n = 19, treatment failure n = 4). Infections occurred in 5 patients with 2 deaths (all in BOC). Anemia was the most common side effect (n = 55, 72%) requiring erythropoietin and RBV dose reduction. In the BOC group, cyclosporine dose reduction was 2.2 ± 1.0 fold and 8.6 ± 2.4 fold with tacrolimus. In TVR group, dose reduction was 3.0 ± 1.4 with cyclosporine and 12 ± 5.7 fold with tacrolimus. Conclusions. PI-based triple therapy appears more effective in producing HCV-RNA clearance than dual therapy. Tolerability is a serious issue and drug-drug interactions are manageable with close monitoring.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) given in combination with a nucleos(t)ide analogue has reduced the rate of recurrent hepatitis B virus (HBV) infection following liver transplantation (LT); however, the most effective protocol remains unclear.

BACKGROUND: Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy.

Approximately 400 liver transplants are performed in Canada every year and close to 6000 per year in the United States. Forty per cent to 45% of all liver transplants are performed for patients with underlying hepatitis C virus (HCV)-related liver disease. These patients have a different natural history, new complication risks and different treatment efficacy than nontransplant HCV patients. Every effort must be made to identify those patients at highest risk for progressive liver disease post-transplant. Recurrent HCV is an Achilles’ heel to transplant hepatology. The true natural history of this disease is only starting to unravel and many questions remain unanswered on the optimal management of these patients after liver transplantation. The present report summarizes the literature and ongoing research needs that are specific to HCV-related liver transplantation.

BACKGROUND: Immunocompromised individuals are more susceptible to complications produced by influenza infection. As a result, solid-organ transplant (SOT) recipients were targeted as a priority group to receive AS03-adjuvanted H1N1 influenza vaccine during 2009.

Background. The Molecular Adsorbent Recirculating System (MARS) has been shown to clear albumin-bound toxins from patients with liver failure but might cause bleeding complications potentially obscuring survival benefits. We hypothesized that monitoring clotting parameters and bed-side thromboelastography allows to reduce bleeding complications. Methods. Retrospective analysis of 25 MARS sessions during which clotting parameters were monitored by a standardized protocol. Results. During MARS therapy median INR increased significantly from 1.7 to 1.9 platelet count and fibrinogen content decreased significantly from 57 fL−1 to 42 fL−1 and 2.1 g/L to 1.5 g/L. Nine relevant complications occurred: the MARS system clotted 6 times 3 times we observed hemorrhages. Absent thrombocytopenia and elevated plasma fibrinogen predicted clotting of the MARS system (ROC 0.94 and 0.82). Fibrinolysis, detected by thromboelastography, uniquely predicted bleeding events. Conclusion. Bed-side thromboelastography and close monitoring of coagulation parameters can predict and, therefore, help prevent bleeding complications during MARS therapy.

The seismic potential of faults depends on the local mineralogy and can change upon mineral reactions. We conducted friction experiments on serpentinite, carbonate and carbonated serpentinite fault gouges at temperatures from 400°C to 630°C, under 100 MPa effective normal stress and fluid saturated conditions. Pure serpentinite fault gouges exhibited unstable slip with significant strain‐hardening. Carbonate‐bearing serpentinite fault gouges showed stable sliding at temperatures <500°C, but displayed unstable stick‐slip behavior and strong strain weakening at temperatures ≥500°C. Microstructural analyses revealed localization and the formation of olivine and pyroxene from devolatilization reactions at temperatures ≥500°C. The degree of devolatilization increased near major slip planes and was enhanced by higher temperature and carbonate content, as shown by three‐dimensional micro‐computer tomography analyses. Nano‐scale transmission electron microscopy analyses revealed the absence of hydrous and carbonate phases along major slip planes. We attribute the strong weakening and unstable slip behavior in carbonated serpentinite fault gouges to the formation of nano‐sized anhydrous phases of olivine and pyroxene along the slip plane. Our results indicate that serpentinized fault zones may experience seismic event nucleation at temperatures approaching the thermodynamic stability limit of serpentine. This suggests that the absence of seismic events cannot exclusively be attributed to serpentinization. The formation of carbonates, through replacive and additive carbonation, can explain aseismic deformation in transform faults, but at elevated temperatures, devolatilization reactions in carbonated serpentinites cause strong localization and strain weakening, accompanied by laboratory seismicity. Plain Language Summary: Carbonated serpentinite fault gouges are common along tectonic interfaces and significantly impact how these areas deform. These fault rocks contain a mix of water‐ and carbon dioxide‐bearing minerals and their frictional behavior varies based on their mineralogical composition. In our experiments, we studied pure serpentinite and carbonated serpentinite fault gouges. We found stick‐slip behavior in pure serpentinites, which means earthquakes can nucleate. Presence of carbonates can prevent the nucleation of earthquakes. At temperatures of 500°C or higher, olivine and pyroxene minerals form due to devolatilization reactions, causing the rocks to weaken and slip unstably. Key Points: Serpentinite fault gouges deform by frictional sliding at temperatures close to their stability limitAseismic behavior of ultramafic fault zones may be due to carbonation rather than serpentinization aloneDevolatilization in carbonated serpentinite fault gouges causes localization and promotes strain weakening [ABSTRACT FROM AUTHOR]

A new method to determine fluid flux at high pressures and temperatures has been developed and used to study serpentinites at subduction zone conditions. Drill cores of a natural antigorite‐serpentinite with a strong foliation were used in multi‐anvil experiments in the range of 2–5 GPa and 450–800°C. Fluids released upon dehydration are fixed by the formation of brucite in an adjacent fluid sink. The amount and distribution of brucite serves as a proxy for fluid flow. In our specific setup the sample reacted with the surrounding fluid sink to form an additional layer of olivine, which has the potential to limit fluid flux within our experiments. For conditions prior to serpentine dehydration we used Al(OH)3 as fluid source. Fluid in this experiment did not migrate through the serpentinite, indicating that serpentine has a low diffusivity. The experiments also show that small deviatoric stresses have an influence on the fluid flux and can cause an anisotropic fluid flux. Comparison between the time scales of the determined fluid flux with fluid production rates indicates fluid pressure buildup during dehydration reactions. Adjacent less permeable layers can inhibit fluid flux and cause fluid pressure buildup even at conditions when an interconnected pore space formed. Plain Language Summary: Subduction zones are regions where tectonic plates are recycled into the Earth's interior. Prior to subduction, the plates experienced extensive chemical interaction with the ocean water, forming hydrous minerals. Serpentine is an important hydrous mineral that can transport significant amounts of water into the Earth's interior. During subduction both pressure and temperature increase whereby hydrous minerals break down and release their water. The fluid migrates into the overlying mantle wedge, where it accounts for hydration as well as melting processes. The global flux balances would require this process to be very effective. However, it was so far not possible to measure the fluid flux at the subduction zone conditions in laboratories. In this study, we present a new method to determine the fluid flux prior and during dehydration. We found that prior to dehydration, the fluid flux in serpentinites is small. During dehydration the rocks ability to let fluids pass through increases. However, adjacent rocks with a low ability for fluid transport can further inhibit a fluid flux at these conditions. Generally, our experimental setup can be used for any system that immobilizes migrating fluids by hydration reactions. Key Points: A new method to determine fluid flux at high pressure and temperature conditions is developedSlow fluid migration in serpentinites promotes brittle fracturing in subduction zonesFast fluid migration upon dehydration of serpentinites promotes large‐scale fluid flux, if not inhibited by adjacent less permeable layers [ABSTRACT FROM AUTHOR]