COVID­19 vaccination in liver transplant recipients (Review).

Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) infection has significantly affected immunocompromised individuals and subsequently, liver transplant recipients (LTRs). Early in the course of pandemic, this vulnerable population was prioritized for vaccination, after obtaining encouraging data about the vaccination benefits on disease severity and mortality. As the published knowledge was mainly supported from studies which were limited to the healthy population, the present review summarizes the data from the literature on coronavirus disease 2019 (COVID-19) vaccination in LTRs and the available vaccination guidelines of international societies. The COVID-19 vaccination of LTRs is strongly recommended as a safe and effective measure in order to prevent severe disease and mortality.

Seroconversion following a booster dose of COVID-19 vaccine in liver transplant recipients. A systematic review and meta-analysis.

INTRODUCTION: Although it is well established that two doses of COVID-19 vaccines are associated with reduced immune responses in liver transplant recipients [LTRs], studies regarding their immunogenicity and tolerability after a booster dose are limited. OBJECTIVES: We aimed to review the available literature data regarding antibody responses and safety of the third dose of COVID-19 vaccines in LTRs. METHODS: We searched PubMed for eligible studies. The primary outcome was to compare the rates of seroconversion after the second and third COVID-19 vaccine dose in LTRs. Meta-analysis was performed using a generalized linear mixed model (GLMM) and the Clopper and Pearson method was used to calculate the two-sided confidence intervals (CI). RESULTS:  Six prospective studies involving 596 LTRs met the inclusion criteria. The pooled rate of antibody response before the third dose was 71% (95%CI:56-83%; heterogeneity: I2=90%, p<0.001), while after the third dose was 94% (95%CI:91-96%; heterogeneity: I2=17%, p=0.31). There was no difference in antibody responses after the third dose in relation to the use, or not, of calcineurin inhibitors (p=0.44) or mammalian target of rapamycin inhibitors (p=0.33), while the pooled rate of antibody responses in those under mycophenolate mofetil (MMF) was 88% (95%CI:83-92%; heterogeneity: I2=0%, p=0.57), significantly lower (p<0.001), compared to those under MMF-free immunosuppression [pooled rate:97%, 95%CI:95-98%; heterogeneity: I2=30%, p=0.22]. No safety concerns of the booster dose were reported. CONCLUSIONS: Our meta-analysis demonstrated that the third dose of COVID-19 vaccines induced adequate humoral and cellular immune responses in LTRs, while MMF remained a negative predictor of immunological responses.

COVID-19 and liver injury in individuals with obesity.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.

Considerations for management of patients with diabetes mellitus and acute COVID-19.

Diabetes mellitus (DM) is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019 (COVID-19). On the other hand, medications used in the management of COVID-19 are potentially associated with increases in blood glucose levels and a higher incidence of infections. Accordingly, care of patients with DM and acute COVID-19 requires careful consideration of both diseases. Hyperglycemia and hypoglycemia are associated with adverse outcomes and therefore frequent measurement of blood glucose levels and a basal-bolus insulin regimen are required in most patients. Regarding the management of COVID-19, dexamethasone increases blood glucose levels and might also increase the risk for infections. On the other hand, limited data suggest that antiviral and immunomodulatory agents used in COVID-19 are not strongly associated with higher incidence of infections in this population. As knowledge evolves in this field, optimization of the management of both DM and COVID-19 will hopefully improve the outcome of these patients.

Acute hepatitis and liver injury in hospitalized patients with COVID­19 infection.

Coronavirus disease 2019 (COVID-19) is a systemic illness with an increased host inflammatory response that affects multiple extra-pulmonary organs, including the gastrointestinal tract. Abnormalities in liver biochemistry have been observed in a significant proportion of patients with COVID-19 upon admission, and this proportion increases with hospitalization. These abnormalities are typically manifested as elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, with less frequently detected elevations in the levels of cholestatic enzymes. Elevated aminotransaminase levels have been linked to an increased risk of mortality and complications, indicating the severity of COVID-19 infection. The present study evaluated the prevalence and the baseline factors associated with the development of acute hepatitis (ΑΗ), liver injury (LI) and associated patterns, as well as the presence of abnormalities in the levels of aminotransferases at discharge in the same cohort. For this purpose, 1,304 patients with confirmed COVID-19 infection were enrolled in the study. According to the results obtained, AST levels at baseline were the only independent factor for AH during hospital stay, while AST, alkaline phosphatase and ferritin levels were independent baseline factors for the development of LI. The patients with hepatocellular, compared to those with cholestatic LI, exhibited similar survival rates, as well as similarities in the development of acute kidney injury and the need for oxygen via high-flow nasal cannula and/or mechanical ventilation. In addition, age and ALT were independent risk factors for persistent abnormal values of AST and ALT at discharge.

Comparison of liver function test- and inflammation-based prognostic scores for coronavirus disease 2019: a single center study.

BACKGROUND: Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed. METHODS: 1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded. RESULTS: One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 &gt;2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P &lt; 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index &gt;36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR &gt;12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024). CONCLUSIONS: FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients' outcomes: a single-center Greek study.

Background: Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized. Methods: A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded. Results: On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003). Conclusions: Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.