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1.
Sci Rep ; 13(1): 9308, 2023 Jun 08.
Article in English | MEDLINE | ID: covidwho-20238512

ABSTRACT

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , End Stage Liver Disease , Liver Neoplasms , Liver Transplantation , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/etiology , Liver Transplantation/adverse effects , Liver Neoplasms/epidemiology , Liver Neoplasms/surgery , Liver Neoplasms/etiology , Pandemics , COVID-19/epidemiology , COVID-19/etiology , Severity of Illness Index
2.
Nutrients ; 15(11)2023 May 23.
Article in English | MEDLINE | ID: covidwho-20243208

ABSTRACT

Childhood obesity is a global public health problem. Worldwide, 41 million children under 5 years and 340 million children and adolescents between 5 and 19 years are overweight. In addition, the recent COVID-19 epidemic has further amplified this social phenomenon. Obesity is a condition associated with various comorbidities, such as nonalcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD in obesity is intricate and involves the interaction and dysregulation of several mechanisms, such as insulin resistance, cytokine signaling, and alteration of the gut microbiota. NAFLD is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, evaluated by histological analysis. It can evolve from hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Body weight reduction through lifestyle modification remains the first-line intervention for the management of pediatric NAFLD. Indeed, studies suggest that diets low in fat and sugar and conversely rich in dietary fibers promote the improvement of metabolic parameters. This review aims to evaluate the existing relationship between obesity and NAFLD in the pediatric population and to assess the dietary patterns and nutritional supplementations that can be recommended to prevent and manage obesity and its comorbidities.


Subject(s)
COVID-19 , End Stage Liver Disease , Non-alcoholic Fatty Liver Disease , Pediatric Obesity , Adolescent , Child , Humans , Child, Preschool , Non-alcoholic Fatty Liver Disease/metabolism , Overweight/metabolism , Pediatric Obesity/metabolism , COVID-19/metabolism , Diet , Fibrosis , End Stage Liver Disease/pathology , Liver/metabolism
3.
Ann Hepatol ; 28(4): 101098, 2023.
Article in English | MEDLINE | ID: covidwho-2298249

ABSTRACT

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.


Subject(s)
COVID-19 , End Stage Liver Disease , Hepatitis, Alcoholic , Liver Transplantation , Humans , Female , Liver Transplantation/adverse effects , Living Donors , Treatment Outcome , Retrospective Studies , Severity of Illness Index , Neoplasm Recurrence, Local , Hepatitis, Alcoholic/diagnosis , Hepatitis, Alcoholic/surgery , Ethanol , Graft Survival
4.
Transplant Proc ; 55(5): 1176-1181, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2248459

ABSTRACT

BACKGROUND: COVID-19 has led to an unprecedented global health crisis. This situation caused an immediate reduction in solid organ transplantation activity. This study aimed to present the follow-up results of patients with chronic liver disease who underwent liver transplantation (LT) after a history of COVID-19 infection. METHODS: Sociodemographic characteristics and clinicopathological data of 474 patients who underwent LT at Inonu University Liver Transplant Institute between March 11, 2020 and March 17, 2022 were prospectively recorded and analyzed retrospectively. Among these, the data of 35 patients with chronic liver disease who were found to be exposed to COVID-19 infection in the pre-LT period were analyzed for this study. RESULTS: The median body mass index, Child score, and Model for end-stage liver disease/ Pediatric end-stage liver disease scores of the 35 patients were calculated as 25.1 kg/m2 (IQR: 7.4), 9 points (IQR: 4), and 16 points (IQR: 10), respectively. Graft rejection occurred in 4 patients at a median of 25 days post-transplant. Five patients underwent retransplantation at a median of 25 days post-transplant. The most common cause of retransplantation is early hepatic artery thrombosis. There were 5 deaths during postoperative follow-up. Mortality developed in 5 (14.3%) patients exposed to COVID-19 infection in the pretransplant period, whereas mortality occurred in 56 (12.8%) patients not exposed to COVID-19 infection. There was no statistically significant difference in mortality between the groups (P = .79). CONCLUSIONS: The results of this study showed that exposure to COVID-19 before LT does not affect post-transplant patients and graft survival.


Subject(s)
COVID-19 , End Stage Liver Disease , Liver Diseases , Liver Transplantation , Child , Humans , Liver Transplantation/methods , End Stage Liver Disease/diagnosis , End Stage Liver Disease/surgery , Retrospective Studies , Severity of Illness Index
5.
BMJ Open Gastroenterol ; 10(1)2023 02.
Article in English | MEDLINE | ID: covidwho-2233456

ABSTRACT

BACKGROUND: Liver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events. MATERIAL AND METHODS: In this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected. RESULTS: This study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting. CONCLUSION: This study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.


Subject(s)
COVID-19 , End Stage Liver Disease , Liver Failure, Acute , Liver Transplantation , Thrombosis , Humans , Liver Transplantation/adverse effects , COVID-19/epidemiology , Retrospective Studies , End Stage Liver Disease/epidemiology , End Stage Liver Disease/surgery , Pandemics , Severity of Illness Index , Liver Failure, Acute/etiology , Thrombosis/epidemiology , Thrombosis/etiology
6.
Hepatology ; 77(6): 2016-2029, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-2222833

ABSTRACT

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.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , End Stage Liver Disease , Esophageal and Gastric Varices , Liver Neoplasms , Veterans , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Liver Neoplasms/diagnosis , Pandemics , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/complications , End Stage Liver Disease/complications , Retrospective Studies , Gastrointestinal Hemorrhage/epidemiology , COVID-19/epidemiology , COVID-19/complications , Severity of Illness Index , Liver Cirrhosis/epidemiology , Liver Cirrhosis/therapy , Liver Cirrhosis/complications , Fibrosis
7.
BMJ Open Gastroenterol ; 10(1)2023 01.
Article in English | MEDLINE | ID: covidwho-2193728

ABSTRACT

INTRODUCTION: The global pandemic has diverted resources away from management of chronic diseases, including cirrhosis. While there is increasing knowledge on COVID-19 infection in liver cirrhosis, little is described on the impact of the pandemic on decompensated cirrhosis admissions and outcomes, which was the aim of this study. METHODS: A single-centre, retrospective study, evaluated decompensated cirrhosis admissions to a tertiary London hepatology and transplantation centre, from October 2018 to February 2021. Patients were included if they had an admission with cirrhosis decompensation defined as new-onset jaundice or ascites, infection, encephalopathy, portal hypertensive bleeding or renal dysfunction. RESULTS: The average number of admissions stayed constant between the pre-COVID-19 (October 2018-February 2020) and COVID-19 periods (March 2020-February 2021). Patients transferred in from secondary centres had consistently higher severity scores during the COVID-19 period (UK Model for End-Stage Liver Disease 58 vs 54; p=0.007, Model for End-Stage Liver Disease-Sodium 22 vs 18; p=0.006, EF-CLIF Acute Decompensation (AD) score 55.0 vs 51.0; p=0.055). Of those admitted to the intensive care without acute-on-chronic liver failure, there was a significant increase in AD scores during the COVID-19 period (58 vs 48, p=0.009). In addition, there was a trend towards increased hospital readmission rates during the COVID-19 period (29.5% vs 21.5%, p=0.067). When censored at 30 days, early mortality postdischarge was significantly higher during the COVID-19 period (p<0.001) with a median time to death of 35 days compared with 62 days pre-COVID-19. DISCUSSION: This study provides a unique perspective on the impact that the global pandemic had on decompensated cirrhosis admissions. The findings of increased early mortality and readmissions, and higher AD scores on ICU admission, highlight the need to maintain resourcing for high-level hepatology care and follow-up, in spite of other disease pressures.


Subject(s)
COVID-19 , End Stage Liver Disease , Humans , Retrospective Studies , Aftercare , Pandemics , Patient Discharge , Severity of Illness Index , COVID-19/epidemiology , COVID-19/complications , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Morbidity , Hospitals
8.
Am J Gastroenterol ; 117(10): 1706-1708, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2056479

ABSTRACT

INTRODUCTION: Many studies on alcoholic hepatitis (AH) use the International Classification of Disease (ICD) coding to identify patients. Data regarding the diagnostic accuracy of ICD codes for AH are limited. METHODS: A total of 151 patients with ICD-10 codes for AH were reviewed for the presence or absence of AH using standardized diagnostic criteria. RESULTS: Sixty-eight of the 151 patients met AH criteria, corresponding to a positive predictive value of 45%. Patients with AH experienced higher model for end-stage liver disease and mortality than those who did not ( P < 0.05). DISCUSSION: Our results suggest ICD-10 codes are not reliable for identifying AH. Studies using the ICD codes should be interpreted cautiously.


Subject(s)
End Stage Liver Disease , Hepatitis, Alcoholic , Hepatitis, Alcoholic/diagnosis , Humans , International Classification of Diseases , Predictive Value of Tests , Severity of Illness Index
9.
Rev Gastroenterol Peru ; 41(4): 227-232, 2021.
Article in English | MEDLINE | ID: covidwho-1863864

ABSTRACT

Liver transplantation is the major treatment for end-stage liver disease. Postoperative care is a great challenge to reduce morbidity and mortality in patients. In this sense, management in the liver ICU allows hemodynamic management, coagulation monitoring, renal support, electrolyte disturbances, respiratory support and early weaning from mechanical ventilation and evaluation of the liver graft. OBJECTIVE: The present study shows the results of the management of liver transplant patients in 20 years of experience in a transplant center in a low- to middle-income country. MATERIALS AND METHODS: The medical records of 273 adult patients in the ICU in the immediate postoperative liver transplant were reviewed, from March 20, 2000 to November 30, 2020, including the effect of the pandemic caused by COVID-19. Liver-kidney, retransplanted, SPLIT, and domino transplant patients were excluded. RESULTS: The most frequent etiology for LTx was NASH (35%), the mean age was 49 years, MELD Score ranged 15 - 20 (47.5%), 21 - 30 (46%) > 30 (6.2%). ICU pre transplant stay 7%, average ICU stay: 7.8 days. APACHE average admission: 14.9 points. Weaning extubation of 91.8% patients in ICU and Fast Track in 8.2%. The most frequent respiratory complication was atelectasis 56.3%, pneumonia (31.3%); AKI 1 (60.9%), and 11.1% with hemodyalisis support (AKI3). Immunosuppression: Tacrolimus (8.9%). Post-operative ICU mortality was 6.2%. CONCLUSIONS: The management of liver transplantation in the ICU is essential to achieve optimal results in patients who present advanced liver disease and require advanced life support in the immediate postoperative period and thus optimize graft survival.


Subject(s)
COVID-19 , End Stage Liver Disease , Liver Transplantation , Adult , COVID-19/epidemiology , Humans , Intensive Care Units , Length of Stay , Middle Aged , Peru , Retrospective Studies
10.
Cells ; 11(7)2022 03 24.
Article in English | MEDLINE | ID: covidwho-1785535

ABSTRACT

Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (-45%) and NAFLD (-35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.


Subject(s)
End Stage Liver Disease , Non-alcoholic Fatty Liver Disease , Sarcopenia , Humans , Muscle Fibers, Skeletal , Non-alcoholic Fatty Liver Disease/complications , Protein Biosynthesis , Sarcopenia/complications
11.
Prog Transplant ; 32(2): 148-151, 2022 06.
Article in English | MEDLINE | ID: covidwho-1785085

ABSTRACT

The ongoing burden of COVID-19 in persons with end stage liver failure necessitates the development of sound and rational policies for organ transplantation in this population. Following our initial experience with two COVID-19 recovered recipients who died shortly after transplant, we adjusted our center policies, re-evaluated outcomes, and retrospectively analyzed the clinical course of the subsequent seven COVID-19 recovered recipients. There were two early deaths and 5 successful outcomes. Both deceased patients shared common characteristics in that they had positive SARS-CoV2 PCR tests proximal to transplant (7-17 days), had acute on chronic liver failure, and suffered thromboembolic phenomena. After a careful review of clinical and virological outcome predictors, we instituted policy changes to avoid transplantation in these circumstances. We believe that our series offers useful insights into the unique challenges that confront transplant centers in the COVID-19 era and could guide future discussions regarding this important area.


Subject(s)
COVID-19 , End Stage Liver Disease , Liver Transplantation , End Stage Liver Disease/surgery , Humans , RNA, Viral , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
12.
Hepatol Commun ; 6(4): 920-930, 2022 04.
Article in English | MEDLINE | ID: covidwho-1756574

ABSTRACT

Palliative care (PC) benefits patients with serious illness including end-stage liver disease (ESLD). As part of a cluster randomized trial, hepatologists were trained to deliver primary palliative care to patients with ESLD using an online course, Palliative Care Always: Hepatology (PCA:Hep). Here we present a multimethod formative evaluation (feasibility, knowledge acquisition, self-efficacy, and practice patterns) of PCA:Hep. Feasibility was measured by completion of coursework and achieving a course grade of >80%. Knowledge acquisition was measured through assessments before and throughout the course. Pre/post-course surveys were conducted to determine self-efficacy and practice patterns. The hepatologists (n = 39) enrolled in a 12-week online course and spent 1-3 hours on the course weekly. The course was determined to be feasible as 97% successfully completed the course and 100% passed. The course was acceptable to participants; 91.7 % reported a positive course experience and satisfaction with knowledge gained (91.6%). The pre/post knowledge assessment showed an improvement of 6.0% (pre 85.9% to post 91.9%, 95% CI [2.8, 9.2], P = 0.001). Self-efficacy increased significantly (P < 0.001) in psychological symptom management, hospice, and psychosocial support. A year after training, over 80% of the hepatologists reported integrating a variety of PC skills into routine patient care. Conclusion: PCA:Hep is feasible, acceptable, and improves learner knowledge and confidence in palliative care skills. This is a viable method to teach primary PC skills to specialists caring for patients with ESLD.


Subject(s)
End Stage Liver Disease , Gastroenterologists , Gastroenterology , Hospice and Palliative Care Nursing , End Stage Liver Disease/psychology , Humans , Palliative Care/methods
13.
Am J Gastroenterol ; 117(4): 678-684, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1625363

ABSTRACT

INTRODUCTION: We evaluated the coronavirus disease 2019 (COVID-19) pandemic's impact on hepatocellular carcinoma (HCC) screening and diagnosis among patients with cirrhosis in the Veterans Health Administration. METHODS: Rates and predictors of screening and diagnosis were reviewed September 1, 2019-February 29, 2020 ("pre-COVID-19," N = 94,612) and April 1, 2020-September 30, 2020 ("post-COVID-19," N = 88,073). RESULTS: Screening and diagnosis rates declined by 44% and 13%, respectively, after the COVID-19 pandemic. Screening declined irrespective of liver disease severity, but diagnosis declined only in Model for End Stage Liver Disease-Sodium score <20 or Fibrosis-4 score <3.25. Fibrosis-4 score ≥3.25 and HCC risk ≥1.5%/year strongly predicted HCC diagnosis but only moderately predicted receipt of screening. DISCUSSION: Screening and diagnosis rates declined after the COVID-19 pandemic. Prioritizing screening for patients at greatest risk for HCC may reduce delays in diagnosis.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , End Stage Liver Disease , Liver Neoplasms , COVID-19/epidemiology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Humans , Liver Cirrhosis/epidemiology , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Pandemics , Severity of Illness Index
14.
BMJ Open Gastroenterol ; 9(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1612991

ABSTRACT

BACKGROUND AND AIMS: SARS-CoV-2 and consequent pandemic has presented unique challenges. Beyond the direct COVID-related mortality in those with liver disease, we sought to determine the effect of lockdown on people with liver disease in Scotland. The effect of lockdown on those with alcohol-related disease is of interest; and whether there were associated implications for a change in alcohol intake and consequent presentations with decompensated disease. METHODS: We performed a retrospective analysis of patients admitted to seven Scottish hospitals with a history of liver disease between 1 April and 30 April 2020 and compared across the same time in 2017, 2018 and 2019. We also repeated an intermediate assessment based on a single centre to examine for delayed effects between 1 April and 31 July 2020. RESULTS: We found that results and outcomes for patients admitted in 2020 were similar to those in previous years in terms of morbidity, mortality, and length of stay. In the Scotland-wide cohort: admission MELD (Model for End-stage Liver Disease) (16 (12-22) vs 15 (12-19); p=0.141), inpatient mortality ((10.9% vs 8.6%); p=0.499) and length of stay (8 days (4-15) vs 7 days (4-13); p=0.140). In the Edinburgh cohort: admission MELD (17 (12-23) vs 17 (13-21); p=0.805), inpatient mortality ((13.7% vs 10.1%; p=0.373) and length of stay (7 days (4-14) vs 7 days (3.5-14); p=0.525)). CONCLUSION: This assessment of immediate and medium-term lockdown impacts on those with chronic liver disease suggested a minimal effect on the presentation of decompensated liver disease to secondary care.


Subject(s)
COVID-19 , End Stage Liver Disease , Communicable Disease Control , Humans , Retrospective Studies , SARS-CoV-2 , Scotland/epidemiology , Severity of Illness Index
15.
Skelet Muscle ; 11(1): 27, 2021 12 11.
Article in English | MEDLINE | ID: covidwho-1571932

ABSTRACT

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.


Subject(s)
End Stage Liver Disease/complications , Sarcopenia/etiology , Adult , Arthritis, Rheumatoid/complications , Case-Control Studies , Female , Humans , Inflammatory Bowel Diseases/complications , Male , Non-alcoholic Fatty Liver Disease/complications , Prospective Studies
16.
Hepatology ; 74(6): 3316-3329, 2021 12.
Article in English | MEDLINE | ID: covidwho-1458999

ABSTRACT

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.


Subject(s)
Alcohol Drinking/adverse effects , COVID-19/complications , Liver Diseases, Alcoholic/etiology , Liver Transplantation/statistics & numerical data , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Cost of Illness , End Stage Liver Disease/epidemiology , End Stage Liver Disease/etiology , Female , Health Care Rationing/statistics & numerical data , Health Care Rationing/trends , Hepatitis, Alcoholic/epidemiology , Hepatitis, Alcoholic/etiology , Humans , Interrupted Time Series Analysis/methods , Liver Diseases, Alcoholic/epidemiology , Liver Diseases, Alcoholic/surgery , Liver Transplantation/trends , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/etiology , Retrospective Studies , SARS-CoV-2/genetics , Severity of Illness Index , Time Factors , United States/epidemiology , Waiting Lists
17.
Sci Rep ; 11(1): 19245, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1442808

ABSTRACT

There is a paucity of studies investigating the impact of chronic corticosteroid use for coexisting conditions in patients with Coronavirus Disease 2019 (COVID-19). Additionally, the information regarding the impact of chronic liver disease (CLD) on COVID-19 outcomes is evolving. Our study aims to investigate hospitalization outcomes of patients with COVID-19 on long term corticosteroids for coexisting conditions while also seeking to compare outcomes between such patients with a history of CLD to analyze the impact on mortality. We conducted a retrospective chart review across our 10-hospital network identifying patients on chronic corticosteroids (Prednisone ≥ 5 mg daily dose or equivalent dose of another steroid, for a duration of 30 days or more) who were hospitalized with COVID-19 from March 1, 2020 to June 30, 2020. Of these patients who met inclusion criteria, patients were then divided into groups based upon their history of CLD. Primary outcomes of the study looked to investigate the hospitalization outcomes of patients with a history of CLD and comorbid conditions requiring chronic corticosteroid use. Secondary outcomes sought to further investigate risk factors for mortality in our study sample. 837 charts were reviewed. 139 patients met inclusion criteria of which 34 patients had a history of CLD. Statistical analysis demonstrated no difference in length of hospital stay but increased ICU admission rate in the CLD group (41.2% vs 23.8%). No statistically significant difference was seen in between the CLD and non-CLD groups in term of complication rates and 28-day mortality. However, chronic corticosteroids patients were found to have higher rates of ICU admission and overall 28-day and ICU mortality in comparison to patients who were not on chronic corticosteroids prior to COVID-19 hospitalization. The larger contributor to COVID-19 severity was likely chronic corticosteroid use rather than CLD and thus chronic corticosteroid use should be limited throughout the COVID-19 pandemic especially in patients with additional speculated risk factors for COVID-19 such as CLD.


Subject(s)
Adrenal Cortex Hormones/adverse effects , COVID-19 , End Stage Liver Disease , Adrenal Cortex Hormones/therapeutic use , Aged , Aged, 80 and over , Austria/epidemiology , COVID-19/epidemiology , COVID-19/pathology , Comorbidity , Critical Care Outcomes , End Stage Liver Disease/drug therapy , Female , Humans , Male , Middle Aged , Mortality , Retrospective Studies , Risk Factors
18.
Exp Clin Transplant ; 19(11): 1232-1237, 2021 11.
Article in English | MEDLINE | ID: covidwho-1431093

ABSTRACT

Shortages of grafts for liver transplant remain a persistent problem. The use of lacerated livers for liver transplant can add an option for extended criteria donations, especially during the COVID-19 pandemic. We present the case of a successful liver transplant performed using a high-grade lacerated liver previously treated with superselective arterial embolization and packing for bleeding control. In view of the absence of guidelines for the use of lacerated livers for transplant, we also performed a review of the literature on injured liver grafts that were used for liver transplants. Meticulous care and careful selection of recipients were essential prerequisites for achieving successful outcomes.


Subject(s)
Abdominal Injuries/etiology , COVID-19 , End Stage Liver Disease/surgery , Heart Massage/adverse effects , Liver Transplantation , Liver/injuries , Liver/surgery , Myocardial Infarction/therapy , Takotsubo Cardiomyopathy/complications , Abdominal Injuries/diagnostic imaging , Abdominal Injuries/therapy , Adolescent , Adult , Clinical Decision-Making , Donor Selection , End Stage Liver Disease/diagnosis , Fatal Outcome , Female , Humans , Liver/diagnostic imaging , Liver Transplantation/adverse effects , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/etiology , Risk Assessment , Risk Factors , Takotsubo Cardiomyopathy/diagnosis , Treatment Outcome , Young Adult
19.
Hepatology ; 74(4): 1825-1844, 2021 10.
Article in English | MEDLINE | ID: covidwho-1372726

ABSTRACT

BACKGROUND AND AIMS: NASH will soon become the leading cause of liver transplantation in the United States and is also associated with increased COVID-19 mortality. Currently, there are no Food and Drug Administration-approved drugs available that slow NASH progression or address NASH liver involvement in COVID-19. Because animal models cannot fully recapitulate human NASH, we hypothesized that stem cells isolated directly from end-stage liver from patients with NASH may address current knowledge gaps in human NASH pathology. APPROACH AND RESULTS: We devised methods that allow the derivation, proliferation, hepatic differentiation, and extensive characterization of bipotent ductal organoids from irreversibly damaged liver from patients with NASH. The transcriptomes of organoids derived from NASH liver, but not healthy liver, show significant up-regulation of proinflammatory and cytochrome p450-related pathways, as well as of known liver fibrosis and tumor markers, with the degree of up-regulation being patient-specific. Functionally, NASH liver organoids exhibit reduced passaging/growth capacity and hallmarks of NASH liver, including decreased albumin production, increased free fatty acid-induced lipid accumulation, increased sensitivity to apoptotic stimuli, and increased cytochrome P450 metabolism. After hepatic differentiation, NASH liver organoids exhibit reduced ability to dedifferentiate back to the biliary state, consistent with the known reduced regenerative ability of NASH livers. Intriguingly, NASH liver organoids also show strongly increased permissiveness to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vesicular stomatitis pseudovirus as well as up-regulation of ubiquitin D, a known inhibitor of the antiviral interferon host response. CONCLUSION: Expansion of primary liver stem cells/organoids derived directly from irreversibly damaged liver from patients with NASH opens up experimental avenues for personalized disease modeling and drug development that has the potential to slow human NASH progression and to counteract NASH-related SARS-CoV-2 effects.


Subject(s)
End Stage Liver Disease/pathology , Liver/pathology , Non-alcoholic Fatty Liver Disease/pathology , Organoids/metabolism , Adult , Aged , Biopsy , COVID-19/complications , COVID-19/virology , Cell Differentiation/immunology , End Stage Liver Disease/immunology , Female , Gene Expression Profiling , Healthy Volunteers , Hepatocytes/immunology , Hepatocytes/metabolism , Humans , Induced Pluripotent Stem Cells/immunology , Induced Pluripotent Stem Cells/metabolism , Liver/cytology , Liver/immunology , Liver Regeneration , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/immunology , Non-alcoholic Fatty Liver Disease/virology , Organoids/immunology , SARS-CoV-2/immunology , Up-Regulation/immunology
20.
Liver Transpl ; 27(9): 1312-1325, 2021 09.
Article in English | MEDLINE | ID: covidwho-1336025

ABSTRACT

Over the last year, the novel coronavirus disease 2019 (COVID-19) has continued to spread across the globe, causing significant morbidity and mortality among transplantation candidates and recipients. Patients with end-stage liver disease awaiting liver transplantation and patients with a history of liver transplantation represent vulnerable populations, especially given the high rates of associated medical comorbidities in these groups and their immunosuppressed status. In addition, concerns surrounding COVID-19 risk in this patient population have affected rates of transplantation and general transplantation practices. Here, we explore what we have learned about the impact of COVID-19 on liver transplantation candidates and recipients as well as the many key knowledge gaps that remain.


Subject(s)
COVID-19 , End Stage Liver Disease , Liver Transplantation , End Stage Liver Disease/epidemiology , End Stage Liver Disease/surgery , Humans , Liver Transplantation/adverse effects , Pandemics , SARS-CoV-2
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