The road to pandemic recovery: Tracking COVID-19's impact on cirrhosis care and outcomes among 111,558 Veterans.

BACKGROUND AIMS: This study aimed to evaluate quarterly trends in process and health outcomes among Veterans with cirrhosis and assess the factors associated with cirrhosis outcomes before and during the COVID-19 pandemic. APPROACH RESULTS: US Veterans with cirrhosis were identified using the Veterans Health Administration Corporate Data Warehouse. Quarterly measures were evaluated from September 30, 2018, through March 31, 2022, including twice yearly screening for hepatocellular carcinoma (HCC-6), new HCC, surveillance for or treatment of esophageal varices, variceal bleeding, all-cause hospitalization, and mortality. Joinpoint analyses were used to assess the changes in trends over time. Logistic regression models were used to identify the demographic and medical factors associated with each outcome over time. Among 111,558 Veterans with cirrhosis with a mean Model for End-stage Liver Disease-Sodium of 11±5, rates of HCC-6 sharply declined from a prepandemic peak of 41%, to a nadir of 28%, and rebounded to 36% by March 2022. All-cause mortality did not significantly change over the pandemic, but new HCC diagnosis, EVST, variceal bleeding, and all-cause hospitalization significantly declined over follow-up. Quarterly HCC diagnosis declined from 0.49% to 0.38%, EVST from 50% to 41%, variceal bleeding from 0.15% to 0.11%, and hospitalization from 9% to 5%. Rurality became newly, significantly associated with nonscreening over the pandemic (aOR for HCC-6=0.80, 95% CI 0.74 to 0.86; aOR for EVST=0.95, 95% CI 0.90 to 0.997). CONCLUSIONS: The pandemic continues to impact cirrhosis care. Identifying populations at the highest risk of care disruptions may help to address ongoing areas of need.

Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study.

BACKGROUND: Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, function and mass) and negatively impact on both morbidity and mortality. There is currently limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease-specific mechanisms driving sarcopenia. Therefore, this study aims to identify potential mechanisms driving sarcopenia within chronic inflammatory disease via a multi-modal approach; in an attempt to help define potential interventions for future use. METHODS: This prospective cohort study will consist of a multi-modal assessment of sarcopenia and its underlying mechanisms. Recruitment will target three chronic inflammatory diseases: chronic liver disease (CLD) (n=50), with a subset of NAFLD (n=20), inflammatory bowel disease (IBD) (n=50) and rheumatoid arthritis (RA) (n=50) both before and after therapeutic intervention. In addition, 20 age and sex matched healthy individuals will be recruited for comparison. Participants will undergo 4 assessment visits at weeks 0, 2, 12 and 24. Visits will consist of the following assessments: blood tests, anthropometrics, functional assessment, quadriceps muscle imaging, actigraphy, quality of life questionnaires, food diary collection and muscle biopsy of the vastus lateralis (at weeks 2 and 24 only). In addition, stool and urine samples will be collected for future microbiome and metabolomics analysis. DISCUSSION: This is the first study to use a multi-modal assessment model to phenotype sarcopenia in these chronic inflammatory diseases. We hope to identify generic as well as disease-specific mechanisms driving sarcopenia. We appreciate that these cohorts do require separate standards of care treatments which limit comparison between groups. ETHICS AND DISSEMINATION: The study is approved by the Health Research Authority - West Midlands Solihull Research Ethics Service Committee Authority (REC reference: 18/WM/0167). Recruitment commenced in January 2019 and will continue until July 2021. The study was halted in March 2020 and again in January 2021 with the COVID-19 pandemic. The findings will be disseminated through peer-reviewed publications and conference presentations. All data will be stored on a secure server. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734496.

Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome.

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

Liver transplantation in Italy in the era of COVID 19: reorganizing critical care of recipients.

Transplant programs have been severely disrupted by the COVID-19 pandemic. Italy was one of the first countries with the highest number of deaths in the world due to SARS-CoV-2. Here we propose a management model for the reorganization of liver transplant (LT) activities and policies in a local intensive care unit (ICU) assigned to liver transplantation affected by restrictions on mobility and availability of donors and recipients as well as health personnel and beds. We describe the solutions implemented to continue transplantation activities throughout a given pandemic: management of donors and recipients' LT program, ICU rearrangement, healthcare personnel training and monitoring to minimize mortality rates of patients on the waiting list. Transplantation activities from February 22, 2020, the data of first known COVID-19 case in Italy's Emilia Romagna region to June 30, 2020, were compared with the corresponding period in 2019. During the 2020 study period, 38 LTs were performed, whereas 41 were performed in 2019. Patients transplanted during the COVID-19 pandemic had higher MELD and MELD-Na scores, cold ischaemia times, and hospitalization rates (p < 0.05); accordingly, they spent fewer days on the waitlist and had a lower prevalence of hepatocellular carcinoma (p < 0.05). No differences were found in the provenance area, additional MELD scores, age of donors and recipients, BMI, re-transplant rates, and post-transplant mortality. No transplanted patients contracted COVID-19, although five healthcare workers did. Ultimately, our policy allowed us to continue the ICU's operations by prioritizing patients hospitalized with higher MELD without any case of transplant infection due to COVID-19.

The impact of the COVID-19 outbreak on liver transplantation programs in Northern Italy.

In January 2020, Novel Coronavirus Disease 2019 (COVID-19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID-19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18-74) whereas mean recipient age was 55 (13-69); mean MELD score was 12 (6-24). All donors underwent screening for SARS-CoV-2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post-LT (range 3-46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement.

Lessons from SARS-CoV-2 screening in a Brazilian organ transplant unit.

Protecting immunosuppressed patients during infectious disease outbreaks is crucial. During this novel coronavirus disease 2019 pandemic, preserving "clean areas" in hospitals assisting organ transplant recipients is key to protect them and to preserve transplantation activity. Evidence suggests that asymptomatic carriers might transmit the SARS-CoV-2, challenging the implementation of transmission preventive strategies. We report a single-center experience using universal SARS-CoV-2 screening for all inpatients and newly admitted patients to an Organ Transplant Unit located in a region with significantly high community-based transmission.

Earliest cases of coronavirus disease 2019 (COVID-19) identified in solid organ transplant recipients in the United States.

With the rapidly expanding pandemic of SARS-CoV-2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID-19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID-19, including two hospitalized patients and two patients managed entirely in the outpatient setting.

Fatal outcome in a liver transplant recipient with COVID-19.

Liver injury is common in patients with COVID-19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID-19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID-19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.

Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient.

Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.