Nanodrug delivery systems for metabolic chronic liver diseases: advances and perspectives.

Nanomedicines are revolutionizing healthcare as recently demonstrated by the Pfizer/BioNTech and Moderna COVID-2019 vaccines, with billions of doses administered worldwide in a safe manner. Nonalcoholic fatty liver disease is the most common noncommunicable chronic liver disease, posing a major growing challenge to global public health. However, due to unmet diagnostic and therapeutic needs, there is great interest in the development of novel translational approaches. Nanoparticle-based approaches offer novel opportunities for efficient and specific drug delivery to liver cells, as a step toward precision medicines. In this review, the authors highlight recent advances in nanomedicines for the generation of novel diagnostic and therapeutic tools for nonalcoholic fatty liver disease and related liver diseases.

Chronic liver diseases are a growing concern for global public health since they can affect up to 25% of the global adult population. Currently, there is no effective treatment or cure for these diseases. Nanometer-sized capsules can be loaded with drugs and more accurately deliver these drugs to their sites of action. They help improve the availability of medicines to the liver and have the potential to reduce their side effects. Here, the authors discuss recent advances to explain how nanotechnology can help improve the benefits of existing medicines for liver disease therapy.

Approaches for Selective Vaccinations in Cirrhotic Patients.

Bacterial and viral infections are common in cirrhotic patients, and their occurrence is associated with the severity of liver disease. Bacterial infection may increase the probability of death by 3.75 times in patients with decompensated cirrhosis, with ranges of 30% at 1 month and 63% at 1 year after infection. We illustrate the indications and the modalities for vaccinating cirrhotic patients. This topic is important for general practitioners and specialists.

Antibody response after a booster dose of SARS-CoV-2 vaccine in liver transplant recipients and those with chronic liver diseases.

INTRODUCTION AND OBJECTIVES: Lower antibody (Ab) responses after SARS-CoV-2 vaccination have been reported in liver transplant (LT) recipients and those with chronic liver diseases (CLD). The role of a booster dose in those with poor responses to initial vaccination is not well defined. METHODS: In this prospective study, we determined antibody (Ab) response to spike protein after a booster dose in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis after they had a poor response to an initial standard regimen. RESULTS: Of the 80 patients enrolled, 45 had LT, and 35 had CLD (18 with cirrhosis). A booster dose was given at a median of 138.5 days after the completion of the standard regimen. After the booster dose, 58 (73%, 31 LT, 27 CLD) had good response (≥250 U/mL), and 22 (28%, 14 LT, and 8 CLD) had poor response (7 undetectable and 15 with low Ab levels). No patient had any serious adverse events. The antibody responses were lower in those who had undetectable Ab (80 U/mL) than those who had low levels of Ab (0.80-249 U/mL) after the standard vaccination regimen (42% vs. 87%, p=0.0001). The antibody responses after homologous and heterologous booster doses were similar. CONCLUSIONS: We have shown that a booster dose will enhance Ab responses in LT recipients and those with CLD who had poor responses after an initial vaccine regimen.

Modifications of Medical Care of Chronic Liver Diseases During COVID-19 Pandemic: Necessity or Novelty?

In late 2019, coronavirus-2 (SARS-COV 2) infection emerged in Wuhan, China and spread to all countries making the first pandemic of the 21st century. It seems that this infection will persist which is long enough to obligate modifications in both lifestyle and health care systems. Because chronic liver diseases (CLD) are prevalent all over the world, it is expected to manage patients with CLD and COVID-19. The aim of this review was to shed light on the impact of COVID-19 pandemic on the management of patients with CLD and how to give medical care to CLD patients during COVID-19 pandemic.

Human Gut Microbiome and Liver Diseases: From Correlation to Causation.

The important role of human gut microbiota in liver diseases has long been recognized as dysbiosis and the translocation of certain microbes from the gut to liver. With the development of high-throughput DNA sequencing, the complexity and integrity of the gut microbiome in the whole spectrum of liver diseases is emerging. Specific patterns of gut microbiota have been identified in liver diseases with different causes, including alcoholic, non-alcoholic, and virus induced liver diseases, or even at different stages, ranging from steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. At the same time, the mechanism of how microbiota contributes to liver diseases goes beyond the traditional function of the gut-liver axis which could lead to liver injury and inflammation. With the application of proteomics, metabolomics, and modern molecular technologies, more microbial metabolites and the complicated interaction of microbiota with host immunity come into our understanding in the liver pathogenesis. Germ-free animal models serve as a workhorse to test the function of microbiota and their derivatives in liver disease models. Here, we review the current evidence on the relationship between gut microbiota and liver diseases, and the mechanisms underlying this phenotype. In addition to original liver diseases, gut microbiota might also affect liver injury in systemic disorders involving multiple organs, as in the case of COVID-19 at a severe state. A better understanding of the gut microbial contribution to liver diseases might help us better benefit from this guest-host relationship and pave the way for novel therapies.

Liver injury in the era of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.

COVID-19 pandemic: Pathophysiology and manifestations from the gastrointestinal tract.

The pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified ß-coronavirus (SARS-CoV-2) has emerged as a dire health problem, causing a massive crisis for global health. Primary method of transmission was firstly thought to be animal to human transmission. However, it has been observed that the virus is transmitted from human to human via respiratory droplets. Interestingly, SARS-CoV-2 ribonucleic acid (RNA) has been isolated from patient stools, suggesting a possible gastrointestinal (GI) involvement. Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms with the most common being anorexia, diarrhea, nausea and vomiting. The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples. The exact incidence of digestive symptoms is a matter of debate. The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms' mechanism. Cases with solely GI symptoms have been reported in both adults and children. Viral RNA has also been detected in stool and blood samples, indicating the possibility of liver damage, which has been reported in COVID-19 patients. The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis, however data from these cases is lacking. The aim of this review is firstly, to briefly update what is known about the origin and the transmission of SARS-CoV-2, but mainly to focus on the manifestations of the GI tract and their pathophysiological background, so that physicians on the one hand, not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other, to have SARS-CoV-2 on their mind when the "gastroenteritis" type symptoms predominate.

Effect of COVID-19 on patients with compensated chronic liver diseases.

BACKGROUND AND AIM: Cytokine storm has been reported in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examine the incidence of acute on chronic liver failure (ACLF) in COVID-19 patients with pre-existing compensated chronic liver disease (CLD). METHODS: From 20 Jan 2020 to 7 Feb 2020, we studied 140 consecutive COVID-19 patients admitted to either Fuyang Second People's Hospital (FYSPH), Anhui or the Fifth Medical Center of Chinese PLA General Hospital (PLAGH) in Beijing, China. Pre-existing CLD includes those with liver cirrhosis assessed by APRI/FIB-4 score and /or ultrasound; NAFLD as identified by either ultrasound or hepatic steatosis index with significant liver fibrosis and chronic hepatitis B (CHB) or hepatitis C (CHC) infection. The diagnosis, grading of severity and clinical management of COVID-19 patients complied to the guideline and clinical protocol issued by the China National Health Commission. All patients had liver function test at least twice weekly till discharge with full recovery or death. RESULTS: In total, 3 had liver cirrhosis, 6 patients had CHB, 13 had NAFLD with significant liver fibrosis (one also had CHB). On admission, none had liver decompensation. COVID-19 disease progression was significantly less frequent in non-CLD patients (10/118 8.5%) than CLD patients (13/22 59.1%, p < 0.001). One patient with CLD had acute-on-chronic liver failure (ACLF). CONCLUSION: Disease progression is significantly higher in those COVID-19 patients with CLD as compared to those with no CLD. ACLF can also occur in patient with pre-existing compensated CLD who had severe COVID-19.

How Patients With Chronic Liver Diseases Succeed to Deal With COVID-19?

The human pathogenic coronaviruses cause infections of the respiratory tract from mild to severe ranges. Mild cases may look like the common cold, while cases with severe disease may represent severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19). Currently, COVID-19 is a rapidly emerging infection and the number of COVID-19 cases and its associated deaths are quickly growing around the world. COVID-19 infection can involve multiple body organs other than respiratory tract and lungs such as liver. It is hypothesized that COVID-19-associated liver injury can hamper the host drug metabolism and excretion. Liver involvement present with the elevation of enzymatic levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) accompanied by enhanced total bilirubin and decreased albumin levels has been reported in COVID-19 cases. One of the major concerns during COVID-19 outbreak is the population with a history of pre-existing liver disorders including viral hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis, hepatic compensated, and decompensated cirrhosis. Herein, we discussed the probable correlation between COVID-19 infection and liver damages, particularly chronic and pre-existing liver diseases during COVID-19 outbreak. Furthermore, we explained about the liver transplant recipients and post-transplant drugs used in patients with COVID-19 infection. Finally, we discussed about the therapeutic medications administered in COVID-19 patients with underlying liver injuries and their significant considerations.