SARS-CoV-2 infection in adult liver transplantation recipients: a systematic review of risk factors for mortality and immunosuppression role.

OBJECTIVE: Data on mortality, immunosuppression, and vaccination role regarding liver transplant (LT) recipients affected by COVID-19 are still under debate. This study aims to identify risk factors for mortality and the role of immunosuppression in COVID-19 LT recipients. MATERIALS AND METHODS: A systematic review of SARS-CoV-2 infection in LT recipients was performed. The primary outcomes were risk factors for mortality, the role of immunosuppression and vaccination. A meta-analysis was not performed as there was a different metric of the same outcome (mortality) and a lack of a control group in most studies. RESULTS: Overall, 1,343 LT recipients of 1,810 SOT were included, and data on mortality were available for 1,110 liver transplant recipients with SARS-CoV-2 infection. Mortality ranged between 0-37%. Risk factors of mortality were age >60 years, Mofetil (MMF) use, extra-hepatic solid tumour, Charlson Comorbidity Index, male sex, dyspnoea at diagnosis, higher baseline serum creatinine, congestive heart failure, chronic lung disease, chronic kidney disease, diabetes, BMI >30. Only 51% of 233 LT patients presented a positive response after vaccination, and older age (>65y) and MMF use were associated with lower antibodies. Tacrolimus (TAC) was identified as a protective factor for mortality. CONCLUSIONS: Liver transplant patients present additional risk factors of mortality related to immunosuppression. Immunosuppression role in the progression to severe infection and mortality may correlate with different drugs. Moreover, fully vaccinated patients have a lower risk of developing severe COVID-19. The present research suggests safely using TAC and reducing MMF use during the COVID-19 pandemic.

Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours.

OBJECTIVE: Recent studies have suggested that androgen secretion by ovarian virilizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion in women with such tumours. DESIGN AND PATIENTS: A single i.m. injection of D-Trp-6-GnRH (GnRHa), 3.75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroepiandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non-classical 21-hydroxylase deficiency were screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 50 mg twice daily for 3 weeks, starting 1 week before GnRHa administration. MEASUREMENT: Testosterone, androstenedione (A), DHEAS, 17-hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa. RESULTS: In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning, exploratory laparotomy was undertaken. A Sertoli-Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hilus cell tumour and two hyperthecoses in the four post-menopausal patients. After bilateral ovariectomy and hysterectomy in the post-menopausal woman and after unilateral ovariectomy in the premenopausal women, androgen levels were normalized. CONCLUSIONS: In virilized women, the findings of increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarian androgen-secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonadotrophin stimulation.