Fontan-Associated Liver Disease: A Review.

Fontan-associated liver disease (FALD) is a chronic complication of the Fontan procedure, a palliative surgery for patients with congenital heart disease that results in a single-ventricle circulation. The success of the Fontan procedure has led to a growing population of post-Fontan patients living well into adulthood. For this population, FALD is a major cause of morbidity and mortality. It encompasses a spectrum of hepatic abnormalities, ranging from mild fibrosis to cirrhosis and hepatocellular carcinoma. The pathophysiology of FALD is multifactorial, involving hemodynamic and inflammatory factors. The diagnosis and monitoring of FALD present many challenges. Conventional noninvasive tests that use liver stiffness as a surrogate marker of fibrosis are unreliable in FALD, where liver stiffness is also a result of congestion due to the Fontan circulation. Even invasive tissue sampling is inconsistent due to the patchy distribution of fibrosis. FALD is also associated with both benign and malignant liver lesions, which may exhibit similar imaging features. There is therefore a need for validated diagnostic and surveillance protocols to address these challenges. The definitive treatment of end-stage FALD is also a subject of controversy. Both isolated heart transplantation and combined heart-liver transplantation have been employed, with the latter becoming increasingly preferred in the US. This article reviews the current literature on the epidemiology, pathophysiology, diagnosis, and management of FALD, and highlights knowledge gaps that require further research.

The Effect of Statin Therapy on Mortality in Adult Patients with Liver Cirrhosis: An Evidence-Based Case Report.

BACKGROUND: Liver cirrhosis causes over one million deaths annually worldwide, but its prognosis varies depending on the presence of complications and decompensating events. Reduction of portal pressure is associated with a reduced risk of mortality in cirrhotic patients. Statin therapy has successfully reduced portal pressure in previous studies, but its effects on overall mortality are unclear. This report aims to determine whether statin therapy significantly affects mortality in patients with liver cirrhosis. METHODS: A comprehensive literature search was conducted using five electronic databases: PubMed, Scopus, Embase, Ovid MEDLINE, and Web of Science. Meta-analyses, randomized controlled trials (RCTs), and cohort studies were selected based on pre-set inclusion and exclusion criteria. The quality of selected studies was evaluated using critical appraisal tools developed by the Center for Evidence-Based Medicine. RESULTS: One meta-analysis, one RCT, and one retrospective cohort study were included in this report. The meta-analysis and cohort study were of good quality and reported significantly reduced mortality with statin therapy in cirrhosis patients. However, the RCT had poor validity and did not report a statistically significant difference in mortality between the intervention and control groups. The survival benefits of statins may be limited to Child-Pugh A and B patients only, but this requires confirmation in a larger population of Child-Pugh C patients. CONCLUSION: Statins potentially reduce mortality in patients with liver cirrhosis, but more evidence is required before they can be widely recommended in clinical practice for this indication.

The prognostic value of neutrophil-to-lymphocyte ratio across all stages of coronary artery disease.

The natural history of coronary heart disease (CAD) commonly begins with atherosclerosis, progressing to chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and eventually, heart failure. Despite advancements in preventive and therapeutic strategies, there is room for further cardiovascular risk reduction. Recently, inflammation has emerged as a potential therapeutic target. The neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker which predicts poor prognosis in several conditions such as metabolic syndrome, sepsis, malignancy and CAD. In atherosclerosis, a high NLR predicts plaque vulnerability and severe stenosis. This is consistent with observations in CCS, where an elevated NLR predicts long-term major adverse cardiac events (MACEs). In ACS patients, high NLR levels are associated with larger infarct sizes and poor long-term outcomes. Possible reasons for this include failure of fibrinolysis, ischemia-reperfusion injury and in-stent restenosis, all of which are associated with raised NLR levels. Following myocardial infarction, an elevated NLR correlates with pathological cardiac remodeling which propagates chronic heart failure. Finally, in heart failure patients, an elevated NLR predicts long-term MACEs, mortality, and poor left ventricular assist device and transplant outcomes. Further studies must evaluate whether the addition of NLR to current risk-stratification models can better identify high-risk CAD patients.

Prognostic value of platelet to lymphocyte ratio in predicting survival of patients with metastatic castration-resistant prostate cancer receiving abiraterone acetate: An evidence-based case report and review of literature.

Platelet to lymphocyte ratio (PLR) is a candidate prognostic marker for metastatic castration-resistant prostate cancer patients receiving abiraterone acetate and evidence demonstrates that a high PLR is associated with poor survival. More studies are required to verify current findings and establish a definite cutoff point.

Tissue oxygen saturation assessment of microvascular perfusion in adults with Fontan palliation and comparator groups using vascular optical spectrophotometry: a pilot study.

OBJECTIVE: The Fontan operation greatly improves survival for single ventricle congenital heart disease patients but creates a physiology that leads to long-term multi-organ dysfunction. A non-invasive screening tool that can identify impending decline is sought. The objective of this pilot study was to assess the microcirculation in Fontan-palliated patients by measuring tissue oxygen saturation (StO2) in superficial and deeper tissues. APPROACH: Three patient cohorts were studied: Fontan group (n = 8) and two patient control groups, liver disease group (n = 8) and tetralogy of Fallot group (n = 9). 22 healthy controls were also examined. Superficial and deeper StO2 was measured at the forearm, thenar eminence, index and ring fingers of both arms using the LEA O2C spectrophotometry device. MAIN RESULTS: Superficial StO2 was reduced in Fontan patients compared to healthy controls (p  = 0.002) and tetralogy patients (p  = 0.016), but not compared to the liver group (p  = 0.313). Deeper StO2 was similar between groups (p  = 0.112). The gap between deeper and superficial StO2 was raised in Fontan patients compared to healthy controls (p  = 0.001) and tetralogy patients (p  = 0.037), but not compared to the liver group (p  = 0.504). There was no clinically relevant difference in StO2 between the left and right arms, and the variation in StO2 according to measurement site was similar between the four groups. SIGNIFICANCE: Vascular optical spectrophotometry is a feasible non-invasive measure of micro-circulatory function that can easily be performed in the clinic setting and may have utility in patients with Fontan circulations. Further, we provide important normal range data in the healthy control population which can be used to design future studies.

The Immunogenicity and Safety of CYD-Tetravalent Dengue Vaccine (CYD-TDV) in Children and Adolescents: A Systematic Review.

AIM: to assess the immunogenicity and safety of CYD-tetravalent dengue vaccine (CYD-TDV) in children. METHODS: comprehensive literature searches were conducted on various databases. Randomized-controlled trials on children with CYD-TDV as intervention were selected based on inclusion and exclusion criteria. Data extracted from selected trials included safety of vaccine and immunogenicity in terms of Geometric Mean Titres (GMT) of antibodies. RESULTS:   six clinical trials were selected based on preset criteria. GMT values were obtained using 50% Plaque Reduction Neutralization Test (PRNT) and safety was semi-quantitatively assessed based on adverse effects. Additional data processing was done to obtain a better understanding on the trends among the studies. The results showed that the groups vaccinated with CYD-TDV showed higher immunogenicity against dengue virus antigens than the control groups. Safety results were satisfactory in all trials, and most severe side effects were unrelated to the vaccine. CONCLUSION: CYD-TDV is both effective and safe for patients in endemic regions. This gives promise for further development and large-scale research on this vaccine to assess its efficacy in decreasing dengue prevalence, and its pervasive implementation in endemic countries, such as Indonesia.