Pre-transplant multidrug-resistant infections in liver transplant recipients-epidemiology and impact on transplantation outcome.

BACKGROUND: Cirrhotic patients are highly exposed to healthcare services and antibiotics. Although pre-liver transplantation (LT) infections are directly related to the worsening of liver function, the impact of these infections on LT outcomes is still unclear. This study aimed to identify the effect of multidrug-resistant microorganism (MDRO) infections before LT on survival after LT. METHODS: Retrospective study that included patients who underwent LT between 2010 and 2019. Variables analyzed were related to patients' comorbidities, underlying diseases, time on the waiting list, antibiotic use, LT surgery, and occurrences post-LT. Multivariate analyses were performed using logistic regression, and Cox regression for survival analysis. RESULTS: A total of 865 patients were included; 351 infections were identified in 259 (30%) patients, of whom 75 (29%) had ≥1 pre-LT MDRO infection. The most common infection was spontaneous bacterial peritonitis (34%). The agent was identified in 249(71%), 53(15%) were polymicrobial. The most common microorganism was Klebsiella pneumoniae (18%); the most common MDRO was ESBL-producing Enterobacterales (16%), and carbapenem-resistant (CR) Enterobacterales (10%). Factors associated with MDRO infections before LT were previous use of therapeutic cephalosporin (p = .001) and fluoroquinolone (p = .001), SBP prophylaxis (p = .03), ACLF before LT (p = .03), and days of hospital stay pre-LT (p < .001); HCC diagnosis was protective (p = .01). Factors associated with 90-day mortality after LT were higher MELD on inclusion to the waiting list (p = .02), pre-LT MDRO infection (p = .04), dialysis after LT (p < .001), prolonged duration of LT surgery (p < .001), post-LT CR-Gram-negative bacteria infection (p < .001), and early retransplantation (p = .004). CONCLUSION: MDRO infections before LT have an important impact on survival after LT.

Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis.

BACKGROUND: Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE-associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. AIMS: To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. METHODS: Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n = 1) and anti-Sm (n = 2) were excluded. RESULTS: Moderate to high titres (>40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P = 0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4 vs. 28.5%, P = 0.44), hepatic laboratorial findings (P > 0.05). Importantly, at the final observation (follow-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared with the negative group (100 vs. 60%, P = 0.04). CONCLUSION: The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses.

Primary adrenal insufficiency due to bilateral adrenal infarction in COVID-19: a case report.

CONTEXT: Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated. CASE REPORT: A 46-year-old woman presented with abdominal pain, hypotension, skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 ug/dL, ACTH of 807 pg/mL and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone. DISCUSSION: Among 115 articles, we identified nine articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in five cases, but ACTH levels were measured in only three cases (high in one case and normal/low in other two cases). Bilateral adrenal non- or hemorrhagic infarction was identified in five reports (two had adrenal insufficiency, two had normal cortisol levels and one case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19. CONCLUSIONS: Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.

Efficacy and safety of chloroquine plus prednisone for the treatment of autoimmune hepatitis in a randomized trial.

BACKGROUND AND AIM: Standard treatment for autoimmune hepatitis (AIH) consists of predniso(lo)ne and azathioprine. However, alternative therapy is required for non- or partial responders and in cases of side effects. The aim of this study was to evaluate the treatment outcomes associated with chloroquine plus prednisone in AIH patients. METHODS: Fifty-seven patients were recruited to receive either azathioprine or chloroquine, both with prednisone, in a randomized trial. The primary end-point was complete remission, based on normalization of aminotransferase levels in the first 6 months of treatment plus maintenance for at least 18 months, with minimal or no inflammatory activity in the liver biopsy. Secondary end-points were partial and nonresponse, severe side effects, and treatment withdrawal. RESULTS: There were no differences between groups regarding clinical, serological, histological, and treatment characteristics at baseline. There were no significant differences in the biochemical response rate (67.7 vs 53.8%, P = 0.41) or the complete remission rate (32.26 vs 15.38%, P = 0.217). However, despite the long study period, the sample size was smaller than that required for a noninferiority study. The mean prednisone dose was similar in both groups. There was a nonsignificantly higher rate of adverse effects and a tendency toward improvement in glycemic and cholesterol profiles in the chloroquine group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: The combination of chloroquine and prednisone exhibited potentially beneficial effects in AIH patients (https://ClinicalTrials.gov: NCT02463331).

Hepatic Artery Thrombosis in Liver Transplantation in Adult Recipients Using Pediatric Deceased Donors.

INTRODUCTION: Routinely, pediatric donor (PD) grafts are allocated to pediatric liver transplantation (LT) recipients; however, occasionally they can be allocated for adult recipients (ARs). Some authors reported decreased patient/graft survival and higher vascular complications, such as hepatic artery thrombosis (HAT), in LT in ARs using PDs. METHODS: It is a retrospective study enrolling 1202 ARs undergoing LT using whole liver grafts during the period of January 2002 to April 2019. The patients were categorized according to donor age in 2 groups: PDs and adult donors (ADs). The variables were collected from the database including the graft to recipient weight ratio (GWRW) and the incidence of HAT and graft primary nonfunction (PNF). RESULTS: The AD group had 1152 patients, and the PD group had 50 patients. PNF occurred in 68 (5.66%) patients, and the distribution between the 2 groups were similar: 65 (5.64%) in the AD group, and 3 (6%) in the PD group (P = .915). HAT was diagnosed in 30 (2.6%) patients in the AD group and in 6 (12%) patients in the PD group. HAT was significantly higher in the PD group (P = .001). In the PD group, the GWRWs among patients diagnosed with HAT were similar (P = .152). CONCLUSION: HAT is higher in PDs, although it is a viable alternative with satisfactory results. Serial Doppler in the first week and early introduction of platelet antiaggregants and/or anticoagulants may be beneficial, albeit it is not clear if it could reduce the incidence of HAT.