ABSTRACT
Immune-mediated liver injury (ILI) following coronavirus disease 2019 (COVID-19) vaccination is not well-characterized. Therefore, we systematically reviewed the literature on ILI after COVID-19 vaccination. We searched PubMed, Cochrane, Ovid, Embase, and gray literature to include articles describing ILI following COVID-19 vaccination. Reports without confirmatory evidence from liver biopsy were excluded. Descriptive analysis, and study quality were reported as appropriate. Of the 1,048 articles found, 13 (good/fair quality; 23 patients) were included. Studies were primarily from Europe (n = 8), America (n = 2), Asia (n = 2), or Australia (n = 1). Patients were predominantly females (62.5%) of age 55.3 years (49.1-61.4), with an antecedent exposure to Moderna messenger RNA (mRNA)-1273 (47.8%), Pfizer-BioNTech BNT162b2 mRNA (39.2%), or ChAdOx1 nCoV-19 vaccine (13%). Pre-existing comorbidities (69.6%) were common, including liver disease in 26.1% and thyroid disorders in 13% of patients. About two-thirds of the patients were on concurrent medications (paracetamol, levothyroxine, statins, and non-steroidal anti-inflammatory drugs). Jaundice was the most common symptom (78.3%). Peak bilirubin, alanine aminotransferase, and alkaline phosphatase levels were 10.8 (6.8-14.8) mg/dl, 1,106.5 (757.0-1,702.5) U/L, and 229 (174.6-259.6) U/L, respectively. Histological findings were intense portal lymphoplasmacytic infiltrate with interface hepatitis. Steroids were used in 86.9% of patients, and complete response, recovering course, and death were reported in 56.5%, 39.1%, and 4.3% of patients, respectively. ILI following COVID-19 vaccination is rare. The diagnosis is established on temporal correlation, biochemical findings, and histopathology. Prognosis is excellent with corticosteroids. Causality establishment remains a challenge.
Subject(s)
COVID-19 Vaccines , COVID-19 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Female , Humans , Liver/pathology , Male , Middle Aged , RNA, Messenger , VaccinationABSTRACT
OBJECTIVES: We evaluated the magnitude and factors contributing to poor outcomes among cirrhosis patients with fungal infections (FIs). METHODS: We searched PubMed, Embase, Ovid and WOS and included articles reporting mortality in cirrhosis with FIs. We pooled the point and relative-risk (RR) estimates of mortality on random-effects meta-analysis and explored their heterogeneity (I 2 ) on subgroups, meta-regression and machine learning (ML). We assessed the study quality through New-Castle-Ottawa Scale and estimate-asymmetry through Eggers regression. (CRD42019142782). RESULTS: Of 4345, 34 studies (2134 patients) were included (good/fair/poor quality: 12/21/1). Pooled mortality of FIs was 64.1% (95% CI: 55.4-72.0, I 2 : 87%, p < .01), which was 2.1 times higher than controls (95% CI: 1.8-2.5, I 2 :89%, p < .01). Higher CTP (MD: +0.52, 95% CI: 0.27-0.77), MELD (MD: +2.75, 95% CI: 1.21-4.28), organ failures and increased hospital stay (30 vs. 19 days) were reported among cases with FIs. Patients with ACLF (76.6%, RR: 2.3) and ICU-admission (70.4%, RR: 1.6) had the highest mortality. The risk was maximum for pulmonary FIs (79.4%, RR: 1.8), followed by peritoneal FIs (68.3%, RR: 1.7) and fungemia (55%, RR: 1.7). The mortality was higher in FIs than in bacterial (RR: 1.7) or no infections (RR: 2.9). Estimate asymmetry was evident (p < 0.05). Up to 8 clusters and 5 outlier studies were identified on ML, and the estimate-heterogeneity was eliminated by excluding such studies. CONCLUSIONS: A substantially worse prognosis, poorer than bacterial infections in cirrhosis patients with FIs, indicates an unmet need for improving fungal diagnostics and therapeutics in this population. ACLF and ICU admission should be included in the host criteria for defining IFIs.