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Background and Aims: The gut microbiome‐related metabolites betaine and trimethylamine N‐oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end‐stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child‐Pugh‐Turcotte (CPT) classification and Model for End‐stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p <.001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p =.44). After liver transplantation (n = 13), betaine decreased (p =.017; p =.36 vs. PREVEND population), whereas TMAO levels tended to increase (p =.085) to higher levels than in the PREVEND population (p =.003). Betaine levels were positively associated with the CPT stage and MELD score (both p <.001). The association with the MELD score remained in the fully adjusted analysis (p <.001). The association of TMAO with the MELD score did not reach significance (p =.11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p =.78 and p =.44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation. [ABSTRACT FROM AUTHOR]

Background and aimsPatients with acute liver failure have high rates of infections, likely from defects in immune function. Whether infections are independently associated with poor outcomes is unclear. We hypothesized that patients with acute liver injury who developed infections were at increased risk of adverse outcomes.MethodsWe conducted a retrospective analysis of 150 critically ill adult patients admitted with acute liver dysfunction at a single academic institution between 2005 and 2011. We excluded patients with immunocompromised states, patients with chronic liver disease and patients who died or were discharged within 48 h of admission. Our primary endpoint was a 30-day event-free survival, with events defined as either death or liver transplantation. Our secondary endpoint was length of stay. Univariate and multivariate analyses were performed to determine associations between presence of infection and our primary and secondary endpoints.ResultsOf our cohort of 150 patients, 62 (41%) were infected and 88 (59%) were not infected. Of the infected patients, 45% died or underwent transplantation, compared to 22% for the non-infected patients (P = 0.003). Univariate and multivariate analyses demonstrated that infections in patients with acute liver dysfunction were an independent predictor of poor outcome (i.e. death or transplantation). In addition, specific types of infection, including pneumonia, independently led to a 48% increase in length of stay (P = 0.002).ConclusionsInfections in patients with acute liver dysfunction are associated with increased risk of death or transplant and increased hospital length of stay.

In the face of a critical organ shortage in the Western world, various strategies are employed to expand the donor pool for orthotopic liver transplantation (OLT). Among them is the transplantation of organs from extended criteria donors, a valuable source of liver allografts, however, characterized by potential risks for post‐OLT complications and inferior outcomes. In recent years, machine perfusion (MP) of the explanted donor liver as well as regional perfusion techniques has witnessed significant advancements. Here, we aim to discuss different modes of dynamic organ preservation in OLT. These include hypothermic and normothermic MP, hypothermic oxygenated machine perfusion (HOPE), controlled oxygenated rewarming as well as regional perfusion protocols. Over recent years, multiple feasibility trials have demonstrated the clinical prospects of MP. In the context of OLT using organs from extended criteria donors, MP has numerous advantages compared to conventional cold storage, some of which include the preservation and reconditioning of borderline transplantable organs and the viability assessment of high‐risk donor allografts. This review aims to address the topic of liver allograft MP, highlighting particularly the current trends in clinical applications and future perspectives. Furthermore, different approaches of liver storage and reconditioning are reviewed in the context of ongoing research. [ABSTRACT FROM AUTHOR]

Background & Aims Occult hepatitis B virus infection ( OBI) in patients undergoing liver transplantation ( LT) is a suspected source of de novo hepatitis B virus ( HBV) infection after LT. This study aimed to investigate the prevalence of OBI in liver transplant recipients with alcoholic cirrhosis and demonstrate the association between OBI and de novo HBV infection after LT in these patients. Methods Forty-three patients with alcoholic cirrhosis who were negative for HBsAg before LT were recruited in this retrospective study. DNA was extracted from paraffin-embedded native liver tissues and quantified for HBV DNA by real-time PCR. Correlation between de novo HBV infection after LT (positive HBsAg and/or detectable HBV DNA in serum) and detection of intrahepatic HBV DNA before LT was analysed. Results Detectable HBV DNA in the explanted liver was found in 41.9% (18/43) of the patients and was thus defined as OBI, which was correlated with the presence of serum hepatitis B core antibody ( P = 0.008). De novo HBV infection occurred in 18.6% (8/43) of the recipients at a median of 10 months after LT. The rate of de novo HBV infection was 38.9% (7/18) in patients with OBI, compared with 4% (1/25) in patients without OBI ( P = 0.004). Furthermore, de novo HBV infection was inversely correlated with the presence of hepatitis B surface antibody in recipients with OBI ( P = 0.026). Conclusion With a prevalence of 41.9% in liver transplant recipients with alcoholic cirrhosis, OBI in the native liver can predict de novo HBV infection after LT. [ABSTRACT FROM AUTHOR]

Background Primary sclerosing cholangitis ( PSC) is a chronic inflammatory disease of the bile ducts, frequently necessitating orthotopic liver transplantation ( OLT), often accompanied by inflammatory bowel disease ( IBD). Matrix metalloproteinases ( MMPs) are associated with fibrotic diseases caused by the involvement in tissue remodelling. Aim To evaluate the contribution of MMP-2 and -9 promoter polymorphisms to disease severity in PSC, as assessed by death or need for OLT. Methods Matrix metalloproteinase-2 (−1306 C/T) and -9 (−1562 C/T) gene promoter polymorphisms were analyzed in 132 PSC patients. Follow-up was from onset PSC until death, OLT or end of follow-up. Results Twenty-year cumulative incidence ( CI) of death or OLT for PSC patients with MMP-2 CT genotype was 86.5% compared to 52.8% for CC genotype ( P = 0.030) and reached 100% at 11.3 years for TT genotype. In patients with IBD, CIs were similar: 20-years CI of death or OLT for MMP-2 CT genotype was 86.0% compared to 49.0% for CC genotype and 100% at 11.3 years for TT genotype. Patients without IBD showed a similar trend in 20 years CI for MMP-2 CT (77.8%) compared to CC (57.8%) and CI for TT genotype reached 100% at 9.3 years. Multivariate analysis showed, along with age at diagnosis, a stepwise increase in hazard ratio for MMP-2 T-allele polymorphism for death or OLT. MMP-9 genotype was not associated with disease severity in PSC. Conclusion Matrix metalloproteinase-2 C to T-1306 gene promoter polymorphism in PSC is an independent risk factor for disease severity as reflected by the need for OLT or disease progression leading to mortality. [ABSTRACT FROM AUTHOR]

Traditionally, perioperative bleeding complications were a major concern during orthotopic liver transplantation, but a tremendous decline in transfusion requirements has been reported over the last decade. In recent years, there has been an increasing awareness towards perioperative thrombotic complications, including liver vessel thrombosis, and systemic venous and arterial thromboembolic events. Whereas a number of these thrombotic complications were previously categorized as surgical complications, increasing clinical and laboratory evidence suggest a role for the haemostatic system in thrombotic complications occurring during and after transplantation. High levels of the platelet adhesive protein von Willebrand factor with low levels of its regulator ADAMTS13, an increased potential to generate thrombin, and temporary hypofibrinolysis are all indicative of increased haemostatic potential after transplantation. Clinical evidence for a role of the haemostatic system in post-operative thromboses includes a higher thrombotic risk in patients with various acquired thrombotic risk factors. Although data on efficacy of anticoagulant therapy after liver transplantation are scarce, one study has shown a significant decrease in the risk for late hepatic artery thrombosis by antithrombotic therapy with aspirin. These findings suggest that antihaemostatic therapy in prevention or treatment of thromboembolic complications after liver transplantation may be relevant. Studies on efficacy and safety of these interventions are required as many of the thrombotic complications have a pronounced negative impact on graft and patient survival. [ABSTRACT FROM AUTHOR]

Orthotopic liver transplantation (OLT) remains the definitive treatment for hepatitis C (HCV). Although HCV is the number one indication for OLT in the USA, health-related quality of life (HRQOL) scores are consistently lower for HCV patients when compared with all OLT indications. HCV is unique in that 95% of transplanted patients experience virological recurrence of HCV hepatitis. Despite few physical manifestations of disease at the time of HCV recurrence, patients report an impaired quality of life and functional status compared with OLT recipients without recurrence. Studies show that patient knowledge of the diagnosis of recurrent HCV alone can negatively impact HRQOL. This suggests that patients perceive themselves as unwell and have significant changes in their mental and physical health despite the absence of disease-related complications. Multiple studies show that patients with HCV recurrence report significantly higher scores for depression, anxiety and psychological distress. However, only a limited number of studies have investigated the influence of gender, HCV genotype, or HCV antiviral treatment on the HRQOL of OLT recipients with HCV recurrence. This review article describes what is currently known about the impact of recurrent HCV on HRQOL specifically after OLT. Understanding modifiable factors on HRQOL after HCV recurrence in OLT patients can greatly aid in tailoring multidimensional interventions to improve patient HRQOL. [ABSTRACT FROM AUTHOR]