Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Impact of secondary sepsis on mortality in adult intensive care unit patients.

RATIONALE: Septic patients admitted to the intensive care unit (ICU) suffer from immune dysregulation, potentially leading to a secondary sepsis episode. This study aims to (i) assess the secondary sepsis rate, (ii) compare the second with the first episodes in terms of demographics, clinical and laboratory characteristics, and outcomes, and iii) evaluate the outcome of secondary sepsis. METHODS: A single-center, retrospective study (2014-2017) was conducted in a Greek ICU, including consecutive cases of adult patients admitted to the ICU for at least 48 h with a principal admission diagnosis of sepsis and stayed for at least 48 h. We searched for a secondary episode of sepsis following the primary-one. We performed survival analyses with Cox proportional hazard, Fine-Gray, and multistate models. RESULTS: In this study, 121 patients that fulfilled the eligibility criteria were included. The secondary sepsis group included 28 (23.1 %) patients, with episode onset, median (interquartile range), 9.5 (7.7-16.2) days after ICU admission, who had less frequently had a medical admission diagnosis, a microbiologically confirmed first episode, and the C-reactive protein was lower. The overall ICU mortality of the cohort was 44.6 %. The group that developed secondary sepsis had higher mortality, but significance was lost in Cox regression [Hazard ratio (95 % CI) 0.59(0.31-1.16)]. However, after multistate modeling adjustment, the attributable mortality was estimated at 43.9 % (95 %CI ± 14.8 %). CONCLUSION: Secondary sepsis was evident in a quarter of the study participants and may be associated with an increased risk of death.

Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece); Performance Evaluation in Hospital Setting with Real Time RT-PCR.

INTRODUCTION: Rapid antigen tests (RATs) are convenient for SARS-CoV-2 detection because they are simpler and faster than nucleic acid amplification tests (NAATs). This study aimed to assess the accuracy of a locally manufactured test; Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece) in a clinical setting and during mass screening. METHODS: Nasopharyngeal samples from 624 individuals were analyzed. The results of the rapid test were compared to real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). At the end of the test's procedure, positive test strips were scanned in an S-Flow reader in order to roughly estimate the antigen concentration. RESULTS: The lower limit of detection of the test was 468.75 genome copies/mL. The PROGNOSIS rapid test displayed a sensitivity of 85.5% (141/165) (95%CI: 79.1-90.5) and a specificity of 99.8% (458/459) (95%CI: 98.8-100.0%). The general inter-rater agreement was 0.89 (95%CI: 85.1-93.3). The regression analysis between the S-flow reader measurements (viral antigen) and the viral load of the positive samples demonstrated a weak correlation (R2 = 0.288, p < 0.001). CONCLUSION: The Rapid Test Ag 2019-nCoV demonstrated sufficient sensitivity, excellent specificity and could be available to be used with low overall cost. Thus, it could be used as point of care test, but also for mass screening for rapid detection of infected persons (e.g., for travelers).

Combination of thrombolytic and immunosuppressive therapy for coronavirus disease 2019: A case report.

In a proportion of patients, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multisystem syndrome characterized by hyperinflammation, acute respiratory distress syndrome (ARDS), and hypercoagulability. A 68-year-old man with coronavirus disease 2019 (COVID-19) was admitted to the intensive care unit with respiratory failure, cytokine release syndrome (CRS), and skin ischemia - microthrombosis. Specific coagulation and inflammatory markers (D-dimer, ferritin, and C-reactive protein), along with the clinical picture, triggered the trial of recombinant tissue plasminogen activator (rt-PA) and tocilizumab. This was followed by resolution of the skin ischemia and CRS, while respiratory parameters improved. No major complications associated with rt-PA or tocilizumab occurred. The combination of rt-PA with targeted anti-inflammatory treatment could be a new therapeutic option for patients with COVID-19, ARDS, hyperinflammation, and increased blood viscosity.