The impact of COVID-19 on trends in alcohol use disorder treatment in Veterans Health Administration.

BACKGROUND AND AIMS: The COVID-19 pandemic disrupted health-care provision in the United States and prompted increases in telehealth-delivery of care. This study measured alcohol use disorder (AUD) treatment trends across visit modalities before and during COVID-19. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We conducted a national, retrospective cohort study with interrupted time-series models to estimate the impact of COVID-19 on AUD treatment in the Veterans Health Administration (VHA) in the United States during pre-COVID-19 (March 2019 to February 2020) and COVID-19 (March 2020 to February 2021) periods. We analyzed monthly trends in telephone, video and in-person visits for AUD treatment and compared patient and treatment characteristics of patients receiving AUD treatment between the pre-COVID-19 and COVID-19 periods. AUD was defined using International Classification of Diseases, 10th revision (ICD-10) codes for alcohol abuse (F10.1) and alcohol dependence (F10.2), which have previously been used to study AUD in VHA. FINDINGS: The predicted percentage of VHA patients with an AUD diagnosis receiving any AUD treatment at the beginning of the pre-COVID period was 13.8% (n = 49 494). The predicted percentage decreased by 4.3% (P = 0.001) immediately at the start of the COVID-19 period due to a decline in AUD psychotherapy. Despite an increase of 0.3% per month (P = 0.026) following the start of COVID-19, the predicted percentage of VHA patients with an AUD diagnosis receiving any AUD treatment at the end of the study period remained below the pre-COVID-19 period. In February 2021, AUD psychotherapy visits were primarily delivered by video (50%, 58 748), followed by in-person (36.6%, 43 251) and telephone (13.8%, 16 299), while AUD pharmacotherapy visits were delivered by telephone (38.9%, 3623) followed by in-person (34.3%, 3193) and video (26.8%, 2498) modalities. Characteristics of VHA patients receiving AUD treatment were largely similar between pre-COVID-19 and COVID-19 periods. CONCLUSIONS: Despite increased telehealth use, the percentage of United States Veterans Health Administration patients with an alcohol use disorder (AUD) diagnosis receiving AUD treatment declined during COVID-19 (March 2020 to February 2021) mainly due to a decrease in psychotherapy.

Liver Injury in Patients Hospitalized with Coronavirus Disease 2019 Correlates with Hyperinflammatory Response and Elevated Interleukin-6.

Liver injury is commonly seen in coronavirus disease 2019 (COVID-19); however, the mechanism behind liver injury, particularly in patients with severe and critical COVID-19, remains unclear, and the clinical course is poorly described. We conducted a single-center retrospective cohort study of consecutive patients hospitalized with severe and critical COVID-19 with or without liver injury and who underwent immunologic testing (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-1ß). Liver injury was defined as peak aminotransferases ≥3 times the upper limit of normal (40 U/L) or ≥120 U/L. Patients with liver injury were compared to those who had normal aminotransferases throughout the hospital course. We studied 176 patients: 109 with liver injury and 67 controls. Patients with liver injury were more likely to be men (71.6% vs. 37.3%, P < 0.001). Peak inflammatory markers and IL-6 were higher in the liver injury group: C-reactive protein (CRP), 247 vs. 168 mg/L, P < 0.001; lactate dehydrogenase (LDH), 706 vs. 421 U/L; ferritin, 2,973 vs. 751 ng/mL, P < 0.001; IL-6, 121.0 vs. 71.8 pg/mL, P < 0.001. There was no difference in the levels of IL-8, TNF-α, and IL-1ß. The liver injury group had a longer length of stay in the hospital and more severe COVID-19 despite having less diabetes and chronic kidney disease. Conclusion: An exaggerated hyperinflammatory response (cytokine storm) characterized by significantly elevated CRP, LDH, ferritin, and IL-6 levels and increasing severity of COVID-19 appears to be associated with the occurrence of liver injury in patients with severe/critical COVID-19.

Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study.

BACKGROUND & AIMS: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. METHODS: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. RESULTS: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. CONCLUSIONS: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. LAY SUMMARY: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID-19): U.S. Multicenter Experience.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID-19 are open for study. APPROACH AND RESULTS: We conducted a multicenter study in the United States of 112 adult LT recipients with COVID-19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age- and sex-matched nontransplant patients with chronic liver disease and COVID-19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51-23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38-24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39-38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04-46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID-19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68-28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75-35.69) in LT recipients. CONCLUSIONS: Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.

Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study.

BACKGROUND: Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients. METHODS: In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course. Patients without a known hospitalisation status or mortality outcome were excluded. For comparison, data from a contemporaneous cohort of consecutive patients with SARS-CoV-2 infection who had not received a liver transplant were collected from the electronic patient records of the Oxford University Hospitals National Health Service Foundation Trust. We compared the cohorts with regard to several outcomes (including death, hospitalisation, intensive care unit [ICU] admission, requirement for intensive care, and need for invasive ventilation). A propensity score-matched analysis was done to test for an association between liver transplant and death. FINDINGS: Between March 25 and June 26, 2020, data were collected for 151 adult liver transplant recipients from 18 countries (median age 60 years [IQR 47-66], 102 [68%] men, 49 [32%] women) and 627 patients who had not undergone liver transplantation (median age 73 years [44-84], 329 [52%] men, 298 [48%] women). The groups did not differ with regard to the proportion of patients hospitalised (124 [82%] patients in the liver transplant cohort vs 474 [76%] in the comparison cohort, p=0·106), or who required intensive care (47 [31%] vs 185 [30%], p=0·837). However, ICU admission (43 [28%] vs 52 [8%], p<0·0001) and invasive ventilation (30 [20%] vs 32 [5%], p<0·0001) were more frequent in the liver transplant cohort. 28 (19%) patients in the liver transplant cohort died, compared with 167 (27%) in the comparison cohort (p=0·046). In the propensity score-matched analysis (adjusting for age, sex, creatinine concentration, obesity, hypertension, diabetes, and ethnicity), liver transplantation did not significantly increase the risk of death in patients with SARS-CoV-2 infection (absolute risk difference 1·4% [95% CI -7·7 to 10·4]). Multivariable logistic regression analysis showed that age (odds ratio 1·06 [95% CI 1·01 to 1·11] per 1 year increase), serum creatinine concentration (1·57 [1·05 to 2·36] per 1 mg/dL increase), and non-liver cancer (18·30 [1·96 to 170·75]) were associated with death among liver transplant recipients. INTERPRETATION: Liver transplantation was not independently associated with death, whereas increased age and presence of comorbidities were. Factors other than transplantation should be preferentially considered in relation to physical distancing and provision of medical care for patients with liver transplants during the COVID-19 pandemic. FUNDING: European Association for the Study of the Liver, US National Institutes of Health, UK National Institute for Health Research.