MedNexus
2022年 · 第02卷第01期
MedNexus
End-stage liver disease (ESLD) refers to the terminal stage of liver disease caused by various types of chronic liver damage. It is characterized by severely impaired liver function and hepatic decompensation. ESLD can present as acute decompensation of liver cirrhosis (ADC), acute-on-chronic liver failure (ACLF), chronic liver failure (CLF), and advanced hepatocellular carcinoma (HCC). ESLD is frequently accompanied by various complications and life-threatening clinical issues, including infection (such as pneumonia or spontaneous bacterial peritonitis), hepatic encephalopathy (HE), hepatorenal syndrome (HRS), and esophageal varices with bleeding.[
Each year, viral hepatitis and its complications affect millions of patients and cause one-and-a-half million deaths. To deal with this immense public health burden, international organizations have, as part of their sustainable development goals, set up the plan "Elimination of Hepatitis by 2030," which has been ratified by most countries. The plan’s aims include the prevention of different hepatitis viruses and the treatment of existing patients. However, a mid-term analysis revealed that lest novel maneuvers are adopted, some of the plan’s objectives may not be attained. While new infections seem to be contained by vaccines and other public health measures, the persistent reservoir of chronic hepatitis viruses -hepatitis B virus (HBV) and hepatitis C virus (HCV) - may not be properly addressed. Although antiviral therapy against chronic HCV infection is promising, chronic-HBV-infected persons may not be properly handled. There are about 296 million chronic hepatitis B (CHB) patients in the world, and only 10% of them are aware of their infection. Thus, the undetected CHB patients should be found, and a proper approach should be devised to address this issue, especially in developing countries that harbor the main bulk of CHB patients. In addition, there is no finite therapy for CHB patients, and the safety and efficacy of the existing drugs are also questionable. This indicates the need for novel drugs for CHB patients. In light of this, this study aimed to offer measures that could discover the millions of undetected patients and address the need for developing innovative drugs for CHB patients and thus substantiate the "Elimination of Hepatitis by 2030" plan.
Splenectomy has been reported to improve liver function as well as hypersplenism, but it is still controversial whether splenectomy will further damage the immune function of patients with liver cirrhosis. This study aims to evaluate the impact of splenectomy on the risk of infection in patients with liver cirrhosis.
A total of 4355 patients with liver cirrhosis admitted to the First Affiliated Hospital of Nanjing Medical University from October 1, 2016 to September 30, 2020 were enrolled. The patients were first divided into the splenectomy group (SG) and the non-splenectomy group (NSG). After standardization, patients were further divided according to the stage of cirrhosis. Infection rates in different stages were calculated, respectively. Laboratory results and infection sites of patients with cirrhosis were analyzed in combination with clinical data. Continuous variables conforming to normal distribution were presented as mean ± standard deviation, compared by sample t test or paired sample t test. Non-normal variables were presented as the median (interquartile range) and compared by Mann-Whitney U test or Wilcoxon signed rank test.
Five hundred and two patients received splenectomy and 3853 patients did not. Bacterial infection was diagnosed in 497 of the 4355 (11.41%) hospitalizations of patients with cirrhosis. The infection rate of the compensated cirrhosis SG was higher than that of the NSG (8.06% vs. 5.18%, P < 0.05). However, the infection rate in the SG with decompensated cirrhosis was lower than that in the NSG (11.35% vs. 22.22%, P < 0.001). The peak level of leukocytes did not differ significantly between the SG with compensated liver cirrhosis and the NSG [11.97 (7.65) × 109/L vs. 12.19 (14.04) × 109/L, P > 0. 05]. The peak value of leukocytes in SG suffering from decompensated liver cirrhosis was significantly higher than that in NSG [12.29 (11.52) × 109/L vs. 6.37 (8.90) × 109/L, P = 0.004]. Patients with decompensated liver cirrhosis had a significantly higher rate of abdominal infection than patients with compensated liver cirrhosis, and splenectomy itself did not affect the sites of infection.
Splenectomy increases the risk of infection for patients with compensated liver cirrhosis, but significantly decreases the risk in patients with decompensated liver cirrhosis.
Bacterial infections are common in patients with decompensated cirrhosis, largely owing to bacterial translocation and cirrhosis-associated immune dysfunction. This study aims to determine the reliability for classifying infections in patients with decompensated cirrhosis based on the Centers for Disease Control and Prevention (CDC) criteria.
The patients with decompensated cirrhosis with suspicious infection in a registered prospective cohort of cirrhosis from May 1, 2014 to February 25, 2015 in the ward of First Affiliated Hospital of Zhejiang University were retrospectively identified. Agreement assessment was conducted focusing on site of infection, the possibility of infection, and pathogens of infection on both system level and specific diagnosis level. A subgroup analysis was performed based on with/without acute-on-chronic liver failure (ACLF).
A total of 402 infectious episodes among 351 patients were enrolled for consistency analysis. The overall agreement for site of infection was 94% (378/402) (k= 0.90, 95% CI 0.86-0.94) on system level and 86% (346/402) (k= 0.84, 95% CI 0.80-0.88) on specific diagnosis level. On possibility of infection, the overall agreement was 81% (306/378) (weighted k= 0.71, 95% CI 0.65-0.77), with 84% (224/267) (weighted k= 0.75, 95% CI 0.63-0.87) in patients with ACLF and 80% (70/88) (weighted k= 0.68, 95% CI 0.60-0.76) in patients without ACLF, respectively. On pathogens of infection, the overall agreement was 72% (60/83) (k = 0.70, 95% CI 0.60-0.80) among most frequent infections.
The agreement for classifying infections in patients with decompensated cirrhosis based on CDC criteria is acceptable overall, suggesting that it can be a useful tool for clinical management in patients with decompensated cirrhosis with suspicious infections.
About 75% of patients infected with human immunodeficiency virus (HIV) live in sub-Saharan Africa. In Kenya, about 1.5 million Kenyans are living with HIV, of whom almost 100,000 are children and adolescents. Highly active antiretroviral therapy (HAART) has converted HIV infection to a chronic illness with its attendant complications. Kidney disease is a common complication of HIV infection and its treatment. Kidney disease in HIV-infected persons can be asymptomatic, insidious onset and may lack specific clinical features. It can only be detected on active screening. The urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) using serum creatinine are not sensitive in identification of early kidney injury. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been used as marker of early kidney injury.
This cross-sectional study used uNGAL and serum creatinine to determine the prevalence of kidney dysfunction in HIV-infected children and adolescents with HAART at Gertrude’s Children’s Hospital, Nairobi, Kenya, from March 2016 to February 2017. Urine samples were assayed for uNGAL using the Bio Porto® enzyme-linked immunosorbent assay. Serum creatinine was assayed using the Jaffe reaction in the Cobas® 6000 biochemistry analyzer and eGFR calculated using the Schwartz formula. Scatter plot of eGFR against log uNGAL levles was performed by Statistical Package for Social Sciences and Pearson correlation coefficeint between log uNGAL levles and eGFR was analyzed.
Ninety-three patients were recruited. Their mean age was 11.8 ± 3.6 years and the median duration on HAART was 72.6 months. Males were 47 (50.5%). The prevalence of kidney dysfunction using uNGAL was 15.1% (95% CI 7.6%-22.5%) and 5.4% (95% CI 1.8 %-12.1%) by eGFR. The mean eGFR was 131 ± 25 mL·min-1·1.73 m-2 and median uNGAL was 10 ng/mL. For every one ng/mL increase in uNGAL value above the normal value, eGFR decreases by 4.8 mL·min-1·1.73 m-2 (P = 0.038). Patients with elevated uNGAL were older when compared with those with normal uNGAL (13.5 vs. 11.5 years).
Urinary NGAL picked up to three times more patients with kidney dysfunction than eGFR derived from serum creatinine. All the patients were asymptomatic. Older children and adolescents were more likely to manifest with kidney dysfunction. Further studies are necessary to evaluate if uNGAL can be utilized routinely to evaluate for early kidney disease in HIV-infected patients.
The pandemic of coronavirus disease 2019 has threatened humans for more than one and a half years. In particular, viral mutation like delta strain has led to third- or fourth-wave transmission among the countries in Asia, Europe, and North America. Although large-scale vaccination has been carried out in many countries, the incidence of reinfection and vaccine-past breakthrough infection is becoming an emerging challenge to humans worldwide. The related mechanisms underlying the reinfection and breakthrough infection remain unknown. In this review, we summarized the challenge and related reasons for severe acute respiratory syndrome coronavirus 2 reinfection and breakthrough infection. Simultaneously, we addressed some critical contents of the study in future.
Exosomes (exos) widely distributed in a variety of biological fluids, including blood, urine, saliva, sputum, breast milk, cerebrospinal fluid, and ascites, contain specific bioactive contents which are involved in physiological and pathological processes, such as signal molecular transfer, substance metabolism, gene regulation, and immune regulation. Macrophages are important innate immune cells which usually act as the first line of defense against infection, and can switch between different functional phenotypes in response to the changes around the microenvironment. Evidence suggests that macrophage-derived exos exert a crucial effect on infection, inflammation, regeneration, tumors, fibrosis, and other lesions in multiple human diseases. However, the role and mechanism of macrophage-derived exos in liver diseases remain to be explored. This review summarizes the current researches on the role and possible mechanism of macrophage-derived exos in liver diseases, with the purpose of providing new potential targets and directions for diagnostic biomarker and clinical treatment of liver diseases.
Liver failure is characterized by the rapid deterioration of liver function, often accompanied by ascites, coagulation dysfunction, hepatic encephalopathy, and other critical complications. Owing to the complex multifaceted pathogenesis and consequential clinical manifestations of the disease, liver failure displays poor prognosis and warrants comprehensive clinical treatment and management. Liver transplantation remains the only well-established treatment for liver failure. However, several factors including transplantation cost and low organ donation rates limit the rate of liver transplantation. The development of a suitable therapy for liver failure is a significant challenge and remains a cause of concern for the medical world. Granulocyte colony-stimulating factor (G-CSF), a member of the cytokine family of hematopoietic growth factors, is involved in the migration of hematopoietic stem cells into the damaged liver, and effectuates their dedifferentiation into hepatocytes. Liver regeneration involves a complex crosstalk of multiple cell types, including hepatocytes, endothelial cells, and inflammatory cells. Neutrophils and monocytes/macrophages that present different types of innate immune cells were found to play a crucial role in the progression of inflammation and restoration of the liver tissue. G-CSF, known as the most common used cytokine, may also affect these immune cells by combining G-CSF receptors on their surface. The immunomodulatory activity of G-CSF should be studied and described in order to ascertain its therapeutic effect on liver failure.
Since the coronavirus disease 2019 (COVID-19) began to spread, it remains pandemic worldwide. The European Medicines Agency’s human medicines committee and Food and Drug Administration have only granted a conditional marketing authorization for remdesivir to treat COVID-19. It is essential to apply other valuable treatments. Convalescent plasma (CP), donated by persons who have recovered from COVID-19, is the cellular component of blood that contains specific antibodies. Therefore, to determine the feasibility of CP for COVID-19, the effectiveness and controversy are discussed in depth here. It is suggested that CP plays a certain role in the treatment of COVID-19. As a treatment, it may have its own indications and contraindications, which need to be further discussed. Meanwhile, it is critical to establish a standard procedure for treatment from CP collection, preservation, transport, to transfusion, and conduct some large sample randomized controlled trials to confirm the transfusion dosage, appropriate time, frequency, and actively prevent adverse outcomes that may occur.
The novel coronavirus (SARS-CoV-2) infection has become a heavy burden on global health. Although the coronavirus disease 2019 (COVID-19) may adversely affect multiple organs and systems of infected patients, to the best of our knowledge, there is little investigation of the SARS-CoV-2’s impact on bone marrow. Our clinical and cytological findings in this case of severe COVID-19 infection provide novel insights into the pathogenesis of SARS-CoV-2 infection in the hematopoietic system. We recommend that physicians consider SARS-CoV-2 infection’s effect on bone marrow in patients who are slow to recover and suggest that a better understanding of the bone marrow morphology in COVID-19-infected patients is needed.
本期目次
