新型冠状病毒肺炎流行期间慢性肝病的管理

正由严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)感染所导致的新型冠状病毒肺炎(2019冠状病毒病,COVID-19)已经在全球流行[1]。截至2020年8月8日,SARS-CoV-2已经感染了全世界1 900多万人,造成70多万人死亡[2]。COVID-19患者多为成年人,可能存在慢性肝病(主要包括慢性乙型肝炎、慢性丙型肝炎、酒精性肝病及非酒精性脂肪性肝病)。     

《2021年欧洲肝病学会专家立场声明:慢性肝病、肝胆恶性肿瘤及肝移植受者COVID-19疫苗的接种》摘译

正2019年以来,严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的冠状病毒病-2019(coronavirus disease 2019,COVID-19;国内习惯称为新型冠状病毒肺炎)疫情肆虐全球。据世界卫生组织(WHO)评估,截至2021年1月,全球已有近1亿人感染SARSCoV-2。有慢性肝病(chronic liver diseases,CLD)的人群,     

肥胖与病毒感染性疾病的关系及新型冠状病毒肺炎防治思路探讨

新型冠状病毒肺炎(COVID-19)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的呼吸系统传染病,具有传染性强、潜伏期长的特点.目前,COVID-19已经扩散至全球多个国家,且感染人数仍在不断攀升.对阳性患者进行隔离和减少人群聚集是COVID-19的主要预防办法,然而针对COVID-19的特效药仍在探索...     

新型冠状病毒的人兽共患病特性研究进展

新型冠状病毒(SARS-CoV-2)目前仍在全球人群中高水平传播。已有研究显示，SARS-CoV-2来自于动物，有数十种动物对SARS-CoV-2易感(包括自然感染和实验感染),少数动物感染SARS-CoV-2后可再将病毒传播给人类，但SARS-CoV-2由动物传播到人的风险较低，由SARS-CoV-2引起的新型冠状病毒病(COVID-19)还不能称为真正意义上的人兽共患病(zoonosis)。考虑到SARS-CoV-2源于自然的属性及其在人类和动物间广泛传播和适应性突变，未来有可能出现新的SARS-CoV-2宿主，并成为引发人类再次或持续感染的传染源，未来仍需继续加强动物中SARS-Co2V-2的监测以及动物与人类之间病毒传播机制的研究。     

新型冠状病毒肺炎的肝损伤

目前,新型冠状病毒(2019-nCoV)感染导致的新型冠状病毒肺炎(COVID-19),已在我国及全球70余国家迅速蔓延,成为全世界高度关注的公共卫生事件。2019-nCoV感染后除发热和呼吸道症状外,常出现不同程度的肝损伤。综述了COVID-19相关肝损伤的临床特征、病理、致病机制及治疗策略,以期为COVID-19的防治提供临床决策参考。     

从SARS到COVID-19——血管紧张素转化酶2在冠状病毒感染致高血糖中作用的探讨

严重急性呼吸综合征(SARS)和新型冠状病毒感染(COVID-19)肺炎均为冠状病毒感染导致,病原体同源性高并具有共同受体——血管紧张素转化酶2(ACE2)。两种疾病的流行病学数据及临床资料分析显示,SARS患者血糖升高,高血糖对SARS及COVID-19进展均有负面影响。本文就ACE2在冠状病毒感染致高血糖的作用进行综述和探讨。     

新型冠状病毒肺炎和心血管疾病关系的研究进展

当前,由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发的新型冠状病毒肺炎(COVID-19)疫情在全球蔓延。SARS-CoV-2主要通过血管紧张素转换酶2(ACE2)受体感染宿主细胞,在引起呼吸系统损伤的同时,也造成急性心肌损伤和慢性心血管疾病。COVID-19患者合并心血管疾病也十分常见,对患者的预后有显著...     

新型冠状病毒肺炎患者肝功能损伤的发生机制

自2019年12月以来,新型冠状病毒肺炎(COVID-19)疫情发展迅速。随着病例资料的积累,我们发现COVID-19患者除表现出典型呼吸系统症状和体征,还出现了不同程度的肝功能异常表现。本文将结合新型冠状病毒(SARS-CoV-2)感染所致的肝功能损伤表现及相关文献进行总结和分析,提出SARS-CoV-2可能引起肝损伤的机制。     

新型冠状病毒肺炎患者消化系统受累的临床表现及其发病机制

目前新型冠状病毒肺炎(COVID-19)在全球范围内引起大流行,其是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的急性呼吸道传染病,该病毒属于β冠状病毒属,与严重急性呼吸综合征(SARS)病毒具有79%的同源性。尽管COVID-19患者的典型症状为发热、咳嗽等呼吸道感染症状,但仍有部分患者会出现消化系统表现。研究表明SARS-CoV-2受体血管紧张素转换酶2(ACE2)在胃肠道、肝脏以及胰腺细胞中表达,且在COVID-19患者粪便中检出了SARS-CoV-2 RNA,提示粪-口途径是SARS-CoV-2潜在的传播途径。本文就COVID-19患者消化系统受累的临床表现及其发病机制作一综述。     

新型冠状病毒病与心肌损伤

严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)可通过血管紧张素转换酶2(ACE2)、细胞外基质金属蛋白酶诱导子(EMMPRIN/CD147)、葡萄糖调节蛋白78(GRP78)途径感染宿主细胞,导致新型冠状病毒病(COVID-19),同时引起急性心肌损伤和心血管系统的慢性损伤。因此,在治疗新型冠状病毒病过程中应特别注意心脏的保护。本期继续特邀相关领域专家对新型冠状病毒感染及心肌损伤进行介绍,旨在加深对这方面的认识,提高防治水平。     

Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage,etiology and vaccination

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.     

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 comorbidities of hepatic diseases in a global perspective

The worldwide outbreak of coronavirus disease 2019 (COVID-19) has challenged the priorities of healthcare system in terms of different clinical management and infection transmission, particularly those related to hepatic-disease comorbidities. Epidemiological data evidenced that COVID-19 patients with altered liver function because of hepatitis infection and cholestasis have an adverse prognosis and experience worse health outcomes. COVID-19-associated liver injury is correlated with various liver diseases following a severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infection that can progress during the treatment of COVID-19 patients with or without pre-existing liver disease. SARS-CoV-2 can induce liver injury in a number of ways including direct cytopathic effect of the virus on cholangiocytes/hepatocytes, immune-mediated damage, hypoxia, and sepsis. Indeed, immediate cytopathogenic effects of SARS-CoV-2 via its potential target, the angiotensin-converting enzyme-2 receptor, which is highly expressed in hepatocytes and cholangiocytes, renders the liver as an extra-respiratory organ with increased susceptibility to pathological outcomes. But, underlying COVID-19-linked liver disease pathogenesis with abnormal liver function tests (LFTs) is incompletely understood. Hence, we collated COVID-19-associated liver injuries with increased LFTs at the nexus of pre-existing liver diseases and COVID-19, and defining a plausible pathophysiological triad of COVID-19, hepatocellular damage, and liver disease. This review summarizes recent findings of the exacerbating role of COVID-19 in pre-existing liver disease and vice versa as well as international guidelines of clinical care, management, and treatment recommendations for COVID-19 patients with liver disease.     

COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST,A Year Later

Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato-biliary manifestations in coronavirus disease 2019 (COVID-19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato-biliary manifestations in COVID-19 and discuss the similarities, contrasting features and disease-specific management across a range of hepato-biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato-biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID-19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS-CoV-2 infection of the liver. Patients with non-alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID-19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS-CoV-2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS-CoV-2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID-19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato-biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.     

Autoimmune liver diseases and SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.     

COVID-19 and liver injury: An ongoing challenge

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.     

Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection

The corona virus disease 2019(COVID-19) pandemic caused by the severe acute respiratory syndrome corona virus 2(SARS-CoV-2) has had a significant impact on the lives of millions of people,especially those with other concomitant diseases,such as chronic liver diseases.To date,seven corona viruses have been identified to infect humans.The main site of pathological action of these viruses is lung tissue.However,a substantial number of studies have proven that SARSCoV-2 shows affinity towards severa...     

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 and Indirect Liver Injury: A Narrative Synthesis of the Evidence

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.     

Management of COVID-19 patients with chronic liver diseases and liver transplants

The epidemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has increasingly attracted worldwide concern. Liver damage or dysfunction occurred in patients with COVID-19 (mainly characterized by moderately elevated serum aspartate aminotransferase levels). However, it is not yet clear whether the COVID-19-related liver injury is mainly caused by the virus infection, potentially hepatotoxic drugs, or other coexisting conditions. Progression of pre-existing chronic liver disease (CLD) may be the underlying mechanism of liver injury. Although COVID-19 patients with CLD, such as nonalcoholic fatty liver disease, liver cirrhosis, and liver cancer, have been deemed at increased risk for serious illness in many studies, little is known about the impact of CLD on the natural history and outcome of COVID-19 patients. Thereby, based on the latest evidence from case reports and case series, this paper discusses the clinical manifestations, treatment, prognosis, and management of the COVID-19 patients with different CLD. This article also reviews the effect of COVID-19 on liver transplantation patients (LT), hoping to work for future prevention, management, and control measures of COVID-19. However, due to the lack of relevant research, most of them are still limited to the theoretical stage, further study of COVID-19 and CLD needs to be improved in the future.