Retrospective assessment of fracture risk through opportunistic radiological screening in a large modern cohort of liver transplant recipients

Objective: Liver transplantation has been associated with a high prevalence of osteoporosis, although most data rely on single-center studies with limited sample size, with most of them dating back to late 1990s and early 2000s. The present thesis aims to assess the prevalence of fragility fractures and contributing factors in a large modern cohort of liver transplant recipients managed in a referral Italian Liver Transplant Center. Design and Methods: Paper and electronic medical records of 429 consecutive patients receiving liver transplantation from 1/1/2010 to 31/12/2015 were reviewed, and 366 patients were selected. Clinically obtained electronic radiological images within 6 months from the date of liver transplant surgery, such as lateral views of spine X-rays or CT abdominal scans, were opportunistically reviewed in a blinded fashion to screen for morphometric vertebral fractures. Clinical fragility fractures reported in the medical records, along with information on etiology of cirrhosis and biochemistries at the time of liver surgery were also recorded. Results: Prevalence of fragility fractures in the whole cohort was 155/366 (42.3%), with no significant differences between sexes. Of patients with fractures, most sustained vertebral fractures (145/155, 93.5%), the majority of which were mild or moderate wedges. Multiple vertebral fractures were common (41.3%). Fracture rates were similar across different etiologies of cirrhosis and were also comparable in patients with diabetes or exposed to glucocorticoids. Kidney function was significantly worse in women with fractures. Independent of age, sex, alcohol use, eGFR, etiology of liver disease, lower BMI was the only independent risk factor for fractures (adjusted OR 1,058, 95%CI 1,001-1,118, P=0.046) in this study population. Conclusions: A considerable fracture burden was shown in a large and modern cohort of liver transplant recipients. Given the remarkably high prevalence of fractures, a metabolic bone disease screening should be implemented in every patient awaiting liver transplantation.

Liver transplantation for transthyretin amyloidosis: experience of a single center in Italy

Liver transplantation is the only definitive treatment for transthyretin amyloidosis, with an excellent 5-year survival in endemic countries where the Met30 mutation is predominant. We report our experience of liver transplantation for transthyretin amyloidosis. We reviewed the clinical records of 17 transplanted patients (11 males, 6 females; age at liver transplant: 45.7±11.7 years). We had a wide spectrum of non-Met30 mutations (52.9%), with a predominance of Gln89 (23.5%). Five-year survival after transplantation was 43.8%; at multivariate analysis, both non-Met30 mutations (HR 17.3, 95% CI 1.03-291.7) and modified BMI (HR 0.50, 95% CI 0.29-0.87) showed significant and independent prognostic roles (P=0.048 and P=0.015, respectively). Five out of the 9 non-Met30 carriers received combined heart transplantation because of severe cardiomyopathy; they showed a trend towards a better prognosis vs. the 4 patients who did not receive combined heart transplantation (although not statistically significant; P=0.095). At follow-up, no significant improvement of transthyretin amyloidosis manifestations was observed. The results of liver transplantation for transthyretin amyloidosis in our population are poorer than those reported in the literature probably because of the high prevalence of non-Met30 mutations.

Indicazione e risultati dei trattamenti locoregionali nell’epatocarcinoma

La chemioembolizzazione (TACE) è uno dei trattamenti locoregionali più largamente utilizzati nel trattamento dell’epatocarcinoma (HCC). A tutt’oggi però rimangono irrisolte alcune importanti controversie sul suo impiego. Nella presente tesi sono stati analizzati alcuni dei principali oggetti di dibattito quali (1) indicazione al trattamento, (2) trattamenti multipli e schema di ritrattamento e (3) trattamento dei pazienti candidabili a trapianto di fegato. A tal fine sono stati riportati tre studi che hanno analizzato gli argomenti sopradescritti. La TACE viene comunemente eseguita nei pazienti al di fuori delle raccomandazioni delle linee guida tra cui i pazienti con nodulo singolo, i pazienti con trombosi portale e con performance status (PS) compromesso. Dallo studio 1 è emerso che la TACE può essere considerata una valida opzione terapeutica nei pazienti con HCC singolo non candidabili a trattamenti curativi, che la trombosi portale non neoplastica ed una lieve compromissione del performance status (PS-1) verosimilmente legata alla cirrosi non hanno impatto sulla sopravvivenza post-trattamento. Multipli trattamenti di chemioembolizzazione vengono frequentemente eseguiti ma non esiste a tutt’oggi un numero ottimale di ritrattamenti TACE. Dallo studio 2 è emerso che il trattamento TACE eseguito “on demand” può essere efficacemente ripetuto nei pazienti che non abbiano scompenso funzionale e non siano candidabili a trattamenti curativi anche se solo una piccola percentuale di pazienti selezionati può essere sottoposto a più cicli di trattamento. La TACE è frequentemente impiegata nei pazienti in lista per trapianto di fegato ma non c’è evidenza dell’efficacia di trattamenti ripetuti in questi pazienti. Dallo studio 3 è emerso che il numero di TACE non è significativamente associato né alla necrosi tumorale, né alla recidiva né alla sopravvivenza post-trapianto. Un tempo d’attesa prima del trapianto ≤6 mesi è invece risultato essere fattore predittivo indipendente di recidiva riflettendo la possibile maggiore aggressività tumorale in questa classe di pazienti.