Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper.

The COVID-19 pandemic has presented a serious challenge to the hepatology community, particularly healthcare professionals and patients. While the rapid development of safe and effective vaccines and treatments has improved the clinical landscape, the emergence of the omicron variant has presented new challenges. Thus, it is timely that the European Association for the Study of the Liver provides a summary of the latest data on the impact of COVID-19 on the liver and issues guidance on the care of patients with chronic liver disease, hepatobiliary cancer, and previous liver transplantation, as the world continues to deal with the consequences of the COVID-19 pandemic.

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.

COVID-19 in gastroenterology: Where are we now? Current evidence on the impact of COVID-19 in gastroenterology.

BACKGROUND: The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. OBJECTIVE: At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. METHODS/RESULTS/CONCLUSION: We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

A single-center report of COVID-19 disease course and management in liver transplanted pediatric patients.

BACKGROUND: In 2019, SARS-CoV-2 causing COVID-19 emerged. Severe COVID-19 symptoms may evolve by virtue of hyperactivation of the immune system. Equally, immunocompromised patients may be at increased risk to develop COVID-19. However, treatment guidelines for children following liver transplantation are elusive. METHODS: As a liver transplantation center, we diagnosed and followed up 10 children (male/female: 8/2) with a median age of 8.5 years (IQR: 5.2-11.0), with COVID-19 post-liver transplant between March 2019 and December 2020. COVID-19 diagnosis was based on PCR test and or florid X-ray findings compatible with COVID-19 in the absence of other cause. We retrospectively collected clinical and laboratory data from electronic patient records following written consent from patients/parents. RESULTS: Nine patients were diagnosed as definitive (PCR positive) with one patient being diagnosed as probable COVID-19. Seven patients recovered without any support whereas three were admitted for non-invasive oxygenation. Lymphopenia and/or high levels of serum IL-6 were detected in four patients. Six patients mounted anti-SARS-CoV-2 antibodies at median 30 days (IQR: 26.5-119.0) following COVID-19 diagnosis. Antibiotic therapy, favipiravir, anakinra, and IVIG were used as treatment in 4,1,1 and 2 patients, respectively. Furthermore, we kept the tacrolimus with or without everolimus but stopped MMF in 2 patients. Importantly, liver allograft function was retained in all patients. CONCLUSIONS: We found that being immunocompromised did not affect disease severity nor survival. Stopping MMF yet continuing with tacrolimus was an apt treatment modality in these patients.

Equitable Access to Liver Transplant: Bridging the Gaps in the Social Determinants of Health.

The COVID-19 pandemic and social justice movement have highlighted the impact of social determinants of health (SDOH) and structural racism in the United States on both access to care and patient outcomes. With the evaluation for liver transplantation being a highly subjective process, there are multiple ways for SDOH to place vulnerable patients at a disadvantage. This policy corner focuses on three different methods to reverse the deleterious effects of SDOH-identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach.

COVID-19 in Chronic Liver Disease and Liver Transplantation: A Clinical Review.

The coronavirus disease 2019 (COVID-19) pandemic has brought challenges to clinicians caring for patients with chronic liver disease. In the past 6 months, COVID-19 has led to over 150,000 deaths in the United States and over 660,000 deaths around the world. Mounting evidence suggests that chronic liver diseases can have an adverse effect on the clinical outcomes of patients with COVID-19. We present a comprehensive review of the latest literature on preexisting liver diseases and its interrelationship with COVID-19 infection in cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, autoimmune hepatitis, and viral hepatitis B. As social distancing and telemedicine gain new footing, we synthesize recommendations from 3 major hepatology societies [American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL), and the Asian Pacific Association for the Study of Liver (APASL)] to present the best approaches for caring for patients with liver diseases as well as those requiring liver transplantation.

Management of Patients with Liver Transplant and Chronic Liver Diseases During COVID-19 Pandemic: A Brief Review.

The coronavirus associated disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has rapidly spread all around the world and became pandemic in March 2020. Data on liver transplantation and chronic liver disease during the pandemic has remained scarce, and there is little information on whether immunosuppressed patients are at higher risk of developing severe COVID-19 infection. This review provides information for health care providers who care for patients with liver transplantation and chronic liver diseases.

Prognosis and Treatment of Liver Transplant Recipients in the COVID-19 Era: A Literature Review.

Liver transplantation during the COVID-19 pandemic is challenging. Both donor and recipient issues can be influenced by the risks attributed to the pandemic. Allocation policy may need to be modified and criteria may be influenced by local infection rates and availability of medical facilities. Modifying immunosuppression (IS) protocols is controversial and is not evidence-based. In this study, we review the published literature on liver transplant recipients who were infected with COVID-19. A literature review was performed using PubMed, ScienceDirect, and WHO databases to identify relevant English-language articles published up to May 20, 2020. Fifteen articles reported 120 liver transplant recipients who were infected with COVID-19. Only 10 papers with 22 patients reported full encounter characteristics. Four papers reported 23, 17, 13, and 6 patients, respectively, but with minimal data. One paper reported the authors' own 39 patients' characteristics and demographics. The mean age was 58.2 years with 66% males. The most commonly reported presentations in descending order were fever (91%), cough (36.7%), shortness of breath (SOB) (31.8%), and diarrhea (31.8%). Liver transplant patients infected with COVID-19 were maintained on Tac (79%), mycophenolate (MMF) (48.4%), and Prednisone (29.6%) and were managed by reducing MMF in 14.3% of patients and reducing Tac in 14.3% of patients; 28.6% of patients needed ICU admission, 13.6% of patients had died, and the reported general population COVID-19 mortality rate was 3.4%. The clinical presentation of COVID-19 in liver transplant recipients may be different from the general population, with higher rates of severe disease, complications, and mortality.

The successful management of Thirty-six hepatopancreatobiliary surgeries under the intensive protective arrangements during the COVID-19 pandemic.

ackground: During the pandemic of COVID-19, the overwhelm of infected patients created an exponential surge for ICU and ward beds. As a result, a major proportion of elective surgeries was postponed. However, various emergency and urgent procedures were allowed. Due to the mortality complications of hepatopancreatobiliary issues, we decided to afford urgent procedures under intensive protective arrangements. Method and results: In our ward (liver transplant), 4 ICU beds and 16 ward beds were allocated to non-COVID-19 patients. A total of 36 hepatopancreatobiliary procedures were managed for one month. All the surgeries were afforded under personal protective equipment and other intensive protective arrangements for personnel and patients. During 6 weeks following the surgery, all patients were followed up through telemedicine and no new case of COVID-19 was detected. Conclusion: In general, it appears that intensive protections could significantly reduce the number of COVID-19 incidence among patients with co-morbidities who undergo invasive procedures.

Impact of COVID-19 on liver transplantation in Europe: alert from an early survey of European Liver and Intestine Transplantation Association and European Liver Transplant Registry.

There are scarce data on the impact of COVID-19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID-19 in liver transplant recipients and candidates in Europe. An Internet-based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety-four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS-CoV-2. Seventy-three (67%) centers selected recipients for LT in the COVID-19 pandemic, whereas 33% did not. Eighty-eight centers reported COVID-19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID-19 among LT candidates and recipients was estimated 1.05% (range 0.5-20%) and 0.34% (range 0.1-4.8%), respectively, and it was significantly higher among candidates (P < 0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large-scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID-19. These results plead for an early and pro-active screening of COVID-19 symptoms in these populations.

COVID-19 in an international European liver transplant recipient cohort.

OBJECTIVE: Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. DESIGN: We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. RESULTS: 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. CONCLUSION: In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.

Clinical characteristics and management of a liver transplanted patient admitted with SARS-CoV-2 infection.

We present here the case of a 62-year-old man, who was referred to the emergency department with fever and cough for 3 days. He underwent liver transplantation 4 years earlier due to HCV and NASH-related cirrhosis with hepatocellular carcinoma. At admission he was in reduced general conditions. Nasopharyngeal smear specimen resulted positive for SARS-CoV-2 infection. Pulmonary low-dose CT-scan revealed bilateral subpleural ground-glass infiltrates. O2 saturation was 93%. A treatment with lopinavir/ritonavir and hydroxychloroquine twice daily was started. The patient received also cefepime and remained in isolation. Seven days later imaging showed a progression of the pulmonary infiltrates. Cefepime was replaced by meropenem. During the following 3 days the fever resolved, and the general conditions of the patient significantly improved. Consequently, treatment with lopinavir/ritonavir and hydroxychloroquine was stopped. The evolution of SARS-CoV-2 interstitial pneumonia in this immunosuppressed patient was moderate to severe and liver injury was not clinically significant. Despite its limitations, this case report confirm that the liver may be only mildly affected during SARS-CoV-2 infection, also in liver transplanted patients. Further studies are needed to assess whether the outcome of SARS-CoV-2 infection is worse in immunosuppressed patients than in the general population.

Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery.

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable.

Saudi association for the study of liver diseases and transplantation position statement on liver transplantation during the COVID-19 pandemic.

The World Health Organization (WHO), on March 11th 2020, upgraded the status of the novel coronavirus disease (COVID-19) from epidemic to pandemic. Over two million individuals have been infected with SARS-CoV-2, the virus causing COVID-19, and as of April, 14th 2020, there were over 5000 confirmed cases in Saudi Arabia (SA). Many countries, including SA, have imposed major restrictions on travel, and everyday life, and the implications of these necessary changes are being felt in liver transplant (LT) centers in SA. Concerns remain that there is an increased risk for individuals over 65 years of age, with underlying medical conditions, or for those who are immunocompromised. Therefore, the Saudi Association for the Study of Liver Diseases and Transplantation (SASLT) established an urgent task force to launch a statement that can be utilized by LT centers as a guidance in the management of patients with advanced liver disease from the time of LT listing to the post-operative care of transplanted patients.