COVID-19 and the liver: What do we know so far?

The coronavirus disease 2019(COVID-19) pandemic has caused unprecedented pressure on public health and healthcare. The pandemic surge and resultant lockdown have affected the standard-of-care of many medical conditions and diseases. The initial uncertainty and fear of cross transmission of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) have changed the routine management of patients with pre-existing liver diseases, hepatocellular carcinoma, and patients either listed for or received a liver transplant. COVID-19 is best described as a multisystem disease caused by SARS-CoV-2, and it can cause acute liver injury or decompensation of the pre-existing liver disease. There has been considerable research on the pathophysiology, infection transmission, and treatment of COVID-19 in the last few months. The pathogenesis of liver involvement in COVID-19 includes viral cytotoxicity, the secondary effect of immune dysregulation, hypoxia resulting from respiratory failure, ischemic damage caused by vascular endotheliitis, congestion because of right heart failure, or drug-induced liver injury. Patients with chronic liver diseases, cirrhosis, and hepatocellular carcinoma are at high risk for severe COVID-19 and mortality. The phase Ⅲ trials of recently approved vaccines for SARS-CoV-2 did not include enough patients with pre-existing liver diseases and excluded immunocompromised patients or those on immunomodulators. This article reviews the currently published research on the effect of COVID-19 on the liver and the management of patients with pre-existing liver disease, including SARS-CoV-2 vaccines.     

Tracheal papillomatosis: what do we know so far?

Tracheal papillomatosis (TP) is a benign condition characterized by papillomatous growth of the bronchial epithelium that involves the trachea. This abnormal growth is a result of infection with human papilloma virus (HPV). Two subtypes of HPV were found in most cases of TP, HPV-6 and HPV-11. TP, presents in two forms, the juvenile onset (JO) or adult onset (AO). The clinical presentation is typically nonspecific and it ranges from mild symptoms like cough to life-threatening conditions like upper airway obstruction. Treatment depends on the location of the papillomas and age of the patient and the plan of therapy is usually made on an individual basis. Treatment can range from observation with symptomatic control to specific medical therapy and multiple surgeries in case of recurrence or progressively worsening disease. The recent invention of HPV vaccine is expected to be the first step in eradicating respiratory papillomatosis.     

Liver injury induced by COVID 19 treatment – what do we know?

The severity of coronavirus disease 2019 (COVID-19) may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some medications in the management of COVID-19 patients. However, limited studies have systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some of these medications in the management of COVID-19 patients. Significantly, it was relieved after the cessation of these agents. However, to our knowledge, no studies have systematically investigated the evidence of DILI in COVID-19 patients. In this review, we discussed the association between hepatotoxicity in COVID-19 patients and the drugs used in these patients and possible mechanisms of hepatotoxicity. The currently available evidence on the association of different therapeutic agents with hepatotoxicity in COVID-19 patient was systematically reviewed.     

The emergency of molecular and transgenic lymphology: what do we (really) know so far?

Since its first sequential visualization in 1902 by Florence Sabin, the development and maintenance of the lymphatic system has intrigued scientists and clinicians worldwide. Its close ties to the vascular network, relevance in the spread and control of parasitic and cancerous diseases, and involvement in the development of other disease states manifested by lymphedema are well known. What is still not clear is how the system develops in the first place, and this limits its effective manipulation for the management of disease states. The aim of the current article is to summarize advances that have been made via genetic approaches using transgenic and knockout mice. It should be noted that studies of lymphatic vessel growth utilizing protein reagents or transgenic technology alone, in a tissue/cell culture environment, during tumor metastasis, in a lymphatic disease paradigm, or during tissue repair, have shown that various growth factors, such as platelet-derived growth factor BB (1), hepatocyte growth factor (2), fibroblast growth factor (3), and VEGF-A (4) appear to play a role. This article is a commentary on the usefulness of specific genetic engineering tools in understanding the development of the lymphatic system--with a focus on the questions that have been addressed using these tools, the extent to which the questions have actually been answered, and the questions that have subsequently been raised. It is not meant to be a discussion of protein reagents or of specific biological situations that exhibit lymphangiogenesis (see reviews 5-7).     

Favipiravir for the treatment of COVID-19 in elderly patients—what do we know after 2 years of COVID-19?

GeroScience - Since the appearance of coronavirus disease 2019 (COVID-19), numerous studies have been conducted to find effective therapeutics. Favipiravir (FVP) is one of the repurposed drugs...     

Liver injury induced by COVID 19 treatment – what do we know?

The severity of coronavirus disease 2019 (COVID-19) may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some medications in the management of COVID-19 patients. However, limited studies have systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some of these medications in the management of COVID-19 patients. Significantly, it was relieved after the cessation of these agents. However, to our knowledge, no studies have systematically investigated the evidence of DILI in COVID-19 patients. In this review, we discussed the association between hepatotoxicity in COVID-19 patients and the drugs used in these patients and possible mechanisms of hepatotoxicity. The currently available evidence on the association of different therapeutic agents with hepatotoxicity in COVID-19 patient was systematically reviewed.     

Transfusion-transmitted hepatitis E:What we know so far?

Hepatitis E virus(HEV)is a major cause of viral hepatitis globally.There is growing concern about transfusion-transmitted HEV(TT-HEV)as an emerging global health problem.HEV can potentially result in chronic infection in immunocompromised patients,leading to a higher risk of liver cirrhosis and even death.Between 0.0013%and 0.281%of asymptomatic blood donors around the world have HEV viremia,and 0.27%to 60.5%have anti-HEV immunoglobulin G.HEV is infectious even at very low blood concentrations of the virus.Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced;ribavirin may be considered as treatment.Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin.Sofosbuvir,a nucleotide analog,showed modest antiviral activity in some clinical studies but sustained viral response was not achieved.Therefore,rescue treatment remains an unmet need.The need for HEV screening of all blood donations remains controversial.Universal screening has been adopted in some countries after consideration of risk and resource availability.Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV.Future studies are needed to define the incidence of transmission through transfusion,their clinical features,outcomes and prognosis.     

Disease management: what have we learned so far?

Disease management (DM) is becoming an increasingly important tool for use in end-stage renal disease (ESRD). The goal of a DM program is to offer a continuum of care that uses guidelines and case management protocols to prevent acute care episodes, achieve improved outcomes and reduce health care costs. This article reviews the theory behind DM, describes key components of DM programs and explains the financial incentives for DM in ESRD. Of key importance in the increasing role of DM for ESRD has been the development of nationally recognized guidelines, the effects of which are now beginning to emerge. At the same time, recent studies have identified targeted opportunities for DM programs to improve outcomes and costs, including anemia management, dialysis dose, and vascular access. DM, through the use of guidelines and targeted toward these and other areas, has the potential to significantly impact the quality of care provided to ESRD patients.     

Cholangiocarcinoma and liver transplantation: What we know so far?

Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.     

Metabolic complications of protease inhibitors: what have we learned so far?

Reports of success with protease inhibitor-based HAART are appearing at the same time as reports of puzzling metabolic effects. These effects include loss of peripheral subcutaneous fat, truncal obesity, hyperlipidemia, and frank diabetes. There is no consensus on how often these problems manifest themselves. Patients taking protease inhibitors (PIs) also appear to be at higher risk of developing coronary disease, although more study is needed. Another question explored is whether PI-related complications can be reversed.     

CD123 bi-specific antibodies in development in AML: What do we know so far?

Bispecific antibodies are synthetic molecules designed to simultaneously bind two separate antigens. Given the recent success of blinatumomab in the treatment of acute lymphoblastic leukemia, there is growing interest in the use of bispecific antibodies as T-cell redirecting antibody for the treatment of cancer. In acute myeloid leukemia (AML), CD123 (also known as the interleukin receptor 3 alpha subunit) has emerged as a promising therapeutic target for bispecific antibodies. Prior attempts to target CD123 with unconjugated antibodies and antibody-drug conjugates have been mixed. However, available data from CD123-directed bispecific antibodies currently in clinical trials have been encouraging. In this review, we discuss the biology of CD123 and prior attempts to target this cell surface marker as part of anti-leukemic therapy. We then summarize and discuss the five CD123-directed bispecific antibodies currently in clinical trials for treatment of AML and provide practical insights regarding the use of these agents.     

Vasodilators in the treatment of acute heart failure: what we know, what we don’t

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebo-controlled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. Unfortunately, most of this discussion is only partially evidence based due to lack of appropriate clinical trials. In general, we believe that vasodilators should be administered early to AHF patients with normal or high blood pressure (BP) at presentation. They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients’ outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1–2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice.     

COVID-19 and the liver: What do we know after six months of the pandemic?

Despite liver injury in patients infected with severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is associated with prolonged hospitalization, and liver dysfunction is mainly described in patients with severe viral disease. How liver abnormalities may affect virus infection is still unknown. Improved understanding of host genetics, lifestyle, underlying comorbidities and adequate follow-up of patients with liver damage are critical in the new scenario of the pandemic virus.     

Liver disease in the era of COVID-19: Is the worst yet to come?

The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.