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.     

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.     

COVID-19 and liver disease: Are we missing something?

Since the coronavirus disease 2019 (COVID-19) has hit the world as a pandemic, researchers all over the world have worked on its diagnostics, prognosticating factors, etc. The present study showed liver enzymes, especially aspartate aminotransferase (AST) levels, to be high in non-survivors with raised AST/alanine aminotransferase ratio. Considering the non-specific nature of AST with its presence in organs other than liver such as muscle, heart, kidney and brain makes it difficult to interpret. Even pre-existing metabolic syndrome and non-alcoholic fatty liver disease are confounding factors for deranged liver functions detected during COVID-19 disease. Therefore, the results of the study should be taken with caution.     

Rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn?

Non-alcoholic fatty liver disease (NAFLD) prevalence has increased drastically in recent decades, affecting up to 25% of the world’s population. NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis, which can progress to fibrosis. Several molecular and metabolic changes are required for the hepatocyte to finally vary its function; hence a “multiple hit” hypothesis seems a more accurate proposal. Previous studies and current knowledge suggest that in most cases, NAFLD initiates and progresses through most of nine hallmarks of the disease, although the triggers and mechanisms for these can vary widely. The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge. Among certain requirements to be met, a good model must imitate certain aspects of the human NAFLD disorder, be reliable and reproducible, have low mortality, and be compatible with a simple and feasible method. Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease. Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding. In this review, we provide a brief introduction to NAFLD hallmarks, the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.     

COVID-19 and the liver: Are footprints still there?

The coronavirus disease 2019(COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionall...     

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.     

COVID-19 and pediatric fatty liver disease: Is there interplay?

The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with higher morbidity and mortality rates. Besides respiratory symptoms, a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while in children there is compelling but currently limited evidence. In particular, patients with COVID-19 have shown a higher risk of liver injury (mainly expressed as increased transaminase levels or hepatic steatosis). Conversely, a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver diseases. The dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19, but other different pathogenic mechanisms have also been supposed. Of note, patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection. This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients. Taking into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood, a strict monitoring of this condition is recommended. We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.     

Management of Flood syndrome: What can we do better?

Approximately 20% of cirrhotic patients with ascites develop umbilical herniation. These patients usually suffer from multisystemic complications of cirrhosis, have a significantly higher risk of infection, and require accurate surveillance– especially in the context of the coronavirus disease 2019 pandemic. The rupture of an umbilical hernia, is an uncommon, life-threatening complication of large-volume ascites and end-stage liver disease resulting in spontaneous paracentesis, also known as Flood syndrome. Flood syndrome remains a challenging condition for clinicians, as recommendations for its management are lacking, and the available evidence for the best treatment approach remains controversial. In this paper, four key questions are addressed regarding the management and prevention of Flood syndrome: (1) Which is the best treatment approach–conservative treatment or urgent surgery? (2) How can we establish the individual risk for herniation and possible hernia rupture in cirrhotic patients? (3) How can we prevent umbilical hernia ruptures? And (4) How can we manage these patients in the conditions created by the coronavirus disease 2019 pandemic?     

What lies ahead and can we afford it?

Hepatitis C is a chronic disease with a slow and variable progression over 20-50 years and it is an important public health problem for the 21st century. This paper describes the information required to estimate what lies ahead in terms of morbidity, mortality and the implications for the health service in Scotland and summarises work undertaken in other countries. There will be an increasing number of people with severe liver disease in the next 10-20 years and we need to invest now in primary prevention and effective treatment strategies to reduce the burden of disease in the future.     

Hepatic consequences of COVID-19 infection. Lapping or biting?

The outbreak of coronavirus disease 2019 (COVID-19) starting last December in China placed emphasis on liver involvement during infection. This review discusses the underlying mechanisms linking COVID-19 to liver dysfunction, according to recent available information, while waiting further studies. The manifestations of liver damage are usually mild (moderately elevated serum aspartate aminotransferase activities), and generally asymptomatic. Few patients can still develop severe liver problems, and therapeutic options can be limited. Liver dysfunction may affect about one-third of the patients, with prevalence greater in men than women, and in elderly. Mechanisms of damage are complex and include direct cholangiocyte damage and other coexisting conditions such as the use of antiviral drugs, systemic inflammatory response, respiratory distress syndrome-induced hypoxia, sepsis, and multiple organ dysfunction. During new COVID-19 infections, liver injury may be observed. If liver involvement appears during COVID-19 infection, however, attention is required. This is particularly true if patients are older or have a pre-existing history of liver diseases. During COVID-19 infection, the onset of liver damage impairs the prognosis, and hospital stay is longer.     

Cisapride: What can we learn from the rise and fall of a prokinetic?

Cisapride, the prototype serotonergic agent, evolved from a body of research that defined the key roles of serotonergic receptors in gastrointestinal motor and sensory function. Impressed by its in vitro properties and encouraged by clinical trial data, cisapride became the drug of choice for the treatment of a wide range of motility disorders and clinicians appeared impressed by its efficacy and comfortable with its side‐effect profile. Once serious cardiac events began to be reported in association with cisapride therapy, dark clouds rapidly gathered and soon enveloped the drug, leading to its widespread withdrawal from markets. What lessons can we learn from the story of cisapride? How can its brief but spectacular rise and equally sensational demise inform the development of new drugs which are so sorely needed in the management of motility and functional gastrointestinal disorders? This review explores the background to the development of cisapride, its history in clinical trials and the experience with adverse events and, in so doing, attempts to identify lessons for the future in the therapeutics of enteric neuromodulatory drugs.     

Covid-19 pandemic and asthma: What did we learn?

This review addresses some of the major lessons we have learnt regarding asthma and the covid-19 pandemic, including susceptibility to SARS-CoV-2 infection and severe covid-19, potentially protective factors, comparison to other respiratory infections, changes in healthcare behaviour from the perspective of patients and clinicians, medications to treat or prevent covid-19, and post-covid syndrome.