Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.

The consequences of COVID-19 infecting pregnant women and the potential risks of vertical transmission have become a major issue. Since little is currently known about COVID-19 in pregnancy, the understanding of COVID-19 in this particular group will be updated in time, and a comprehensive review will be useful to evaluate the impact of COVID-19 in pregnancy. Based on recently published literature and official documents, this review provides an introduction to the pathogenesis, pathology, and clinical features of COVID-19 and has focused on the current researches on clinical features, pregnancy outcomes and placental histopathological analysis from pregnant women infected with SARS-CoV-2 in comparison with SARS-CoV and MERS-CoV. These viruses trigger a cytokine storm in the body, produce a series of immune responses, and cause changes in peripheral leukocytes and immune system cells leading to pregnancy complications that may be associated with viral infections. The expression of ACE2 receptors in the vascular endothelium may explain the histological changes of placentas from pregnant women infected by SARS-CoV-2. Pregnant women with COVID-19 pneumonia show similar clinical characteristics compared with non-pregnant counterparts. Although there is no unequivocal evidence to support the fetal infection by intrauterine vertical transmission of SARS, MERS and SARS-CoV-2 so far, more and more articles began to report maternal deaths due to COVID-19. In particular, from February 26, 2020 (date of the first COVID-19 case reported in Brazil) until June 18, 2020, Brazil reported 124 maternal deaths. Therefore, pregnant women and neonates require special attention regarding the prevention, diagnosis and management of COVID-19.

Acute liver failure (ALF) is a severe liver disease caused by disruptions in the body’s immune microenvironment. In the early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes derived from the bone marrow or abdomen to replace the depleted macrophages entering the liver. These monocytes differentiate into mature macrophages, which are activated in the immune microenvironment of the liver and polarized to perform various functions. Macrophage polarization can occur in two directions: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. Controlling the ratio and direction of M1 and M2 in ALF can help reduce liver injury. However, the liver damage caused by pyroptosis should not be underestimated, as it is a caspase-dependent form of cell death. Inhibiting pyroptosis has been shown to effectively reduce liver damage induced by ALF. Furthermore, macrophage polarization and pyroptosis share common binding sites, signaling pathways, and outcomes. In the review, we describe the role of macrophage polarization and pyroptosis in the pathogenesis of ALF. Additionally, we preliminarily explore the relationship between macrophage polarization and pyroptosis, as well as their effects on ALF.

Acute liver injury (ALI) is characterized by massive hepatocyte death with high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the physiopathological processes of ALI, which can damage mitochondria and release NLRP3 inflammasome particles, causing systemic inflammatory responses. Z-DNA Binding Protein 1 (ZBP1) is a sensor that induces cell death. Here, we investigated whether ZBP1 participates in hepatocyte pyroptosis and explored the possible pathogenesis of ALI. Hepatocyte pyrotosis was induced with lipopolysaccharide (LPS) and nigericin (Nig), and the expression of Zbp1 (ZBP1) was examined by western blot analysis and RT-qPCR. Further, we transfected AML-12 (LO2 and HepG2) cell lines with Zbp1 (ZBP1) siRNA. After ZBP1 was silenced, LDH release and flow cytometry were used to measure the cell death; Western blot analysis and RT-qPCR were used to detect the marker of NLRP3 inflammasome activation and pyroptosis. We also detected the expression of mitochondrial linear rupture marker phosphoglycerate mutase family member 5 (PGAM5) using western blot analysis and reactive oxygen species (ROS) using the DCFH-DA method. The expression of ZBP1 was up-regulated in LPS/Nig-induced hepatocytes. Si-Zbp1 (Si-ZBP1) inhibited NLRP3 inflammasome activation and pyroptosis in LPS/Nig-induced hepatocytes. Moreover, ZBP1 silencing inhibited the expression of PGAM5 by reducing ROS production. ZBP1 promotes hepatocellular pyroptosis by modulating mitochondrial damage, which facilitates the extracellular release of ROS.

Background: The majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15 − 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. The clinical features and ALT flare patterns in HBeAg-positive mothers versus HBeAg-negative mothers are not fully explored. Thus, we design a cohort study to investigate the aforementioned area and generate data to assist healthcare providers in better managing mothers with hepatitis B. We aim to assess the frequency of postpartum ALT flares and predictors for such events. Method: This study is a single-center and prospective cohort study (n = 360) that consists of two groups of patients including HBsAg-positive mothers (n = 120) and healthy mothers without HBV infection (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted to prevent Mother-to-child transmission (MTCT) but discontinued at delivery if there is no further indication for the treatment. Mothers are enrolled at the gestational weeks of 12–24. After delivery, both mothers and their infants will be followed up until postpartum week 24. Clinical and laboratory data are collected every 4 weeks during the study except there are no follow-up visits at the postpartum weeks 16 and 20. The primary objective is the proportion of patients with postpartum ALT flares. The secondary objectives are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers. Discussion: The current study focuses on the incidence of postpartum ALT flares in mothers with chronic hepatitis B including subgroup analysis based on HBeAg status. The data will have several clinical implications, such as providing evidence for an appropriate monitoring schedule in CHB mothers after delivery. Further analyses on predictors of such events may assist clinicians in identifying mothers who might develop severe postpartum ALT flares. The data generated from healthy mothers have the potential to identify the patterns of ALT changes during pregnancy and postpartum, so we can gain a better understanding of the normal range of ALT in this subpopulation. Trial Registration Number at the Chinese Clinical Trial Registry: ChiCTR2200061130.