First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study.

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study.

INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

Outcomes of Liver Transplant for Adults With Wilson's Disease.

Wilson's disease (WD) is a rare genetic disorder with protean manifestations. Even if liver transplantation (LT) could represent an effective therapeutic option for patients with end-stage liver disease, it has remained controversial in the presence of neuropsychiatric involvement. This study aimed to examine the frequency of adult LT for WD in Italy, focusing on the disease phenotype at the time of LT. A retrospective, observational, multicenter study was conducted across Italy exploring the frequency and characteristics of adults transplanted for WD between 2006 and 2016. A total of 29 adult WD patients underwent LT during the study period at 11 Italian LT centers (accounting for 0.4% of all LTs performed), and 27 of them were considered in this analysis (male/female, n = 9/18; age at LT, 29 years [19-60 years]; median Model for End-Stage Liver Disease score at LT, 27 [6-49]). Isolated hepatic phenotype was the indication for LT in 17 (63%) patients, whereas 2 (7%) patients underwent LT for neurological impairment on compensated liver disease. Overall 1- and 5-year patient survival was excellent (88% and 83%, respectively). Neuropsychiatric symptoms early after LT completely recovered in only a few patients. In conclusion, WD remains an uncommon, unusual indication for LT in Italy, displaying good post-LT graft and patient survival. Because isolated neuropsychiatric involvement represents a rare indication to LT, more data are needed to properly assess the value of LT for WD in this subset of patients.

Switch from intravenous or intramuscular to subcutaneous hepatitis B immunoglobulin: effect on quality of life after liver transplantation.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) therapy is available in intravenous (IV) or intra-muscular (IM) formulations. Recently, a subcutaneous (SC) formulation was introduced. This study evaluated changes in quality of life when liver transplant (LT) recipients were switched from IV or IM HBIG to the SC formulation. METHODS: This multicentre, observational study involved adults who had undergone LT at least 1 year prior to study entry. Quality of life was evaluated using the ITaLi-Q questionnaire, assessing the impact of HBIG therapy on daily activities and patient satisfaction, and the SF-36 Health Survey. Patients completed the questionnaires prior to switching from IV or IM HBIG to SC HBIG and 6 months later. RESULTS: Eighty-six patients were enrolled; before the switch, 68.6% were receiving IM HBIG and 31.4% IV HBIG. After 6 months, significant improvements in 7 of the 8 ITaLi-Q domains were found, particularly side effects, need for support to adhere to the therapy and satisfaction with the HBIG therapy. Significant improvements in several SF-36 domains were documented, including physical functioning, physical and emotional role limitations, pain, social functioning, physical and mental summary scores. CONCLUSIONS: The SC route of administration reduces side effects and their interference with daily life, ameliorates negative feelings, and increases patient autonomy.

Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study.

Several risk factors for ischaemic-type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donor's decade (<60 yo; 60-69 yo; 70-79 yo and ≥80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL. There was no difference in the incidence of overall biliary complications according to procurement technique for recipients of grafts <80 years. A higher incidence of ITBL was observed for patients receiving grafts ≥80 years and perfused through the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts, donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P = 0.008), and type-2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all independent risk factors for ITBL, while double perfusion at procurement (HR = 0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P = 0.04) were protective factors. Dual aortic and portal perfusion has the potential to reduce post-transplant ITBL incidence for recipients of octogenarian donor grafts. Larger series are needed to confirm this preliminary experience.

The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience.

BACKGROUND & AIMS: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. METHODS: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. RESULTS: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. CONCLUSIONS: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.

Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study.

BACKGROUND: In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). METHODS: All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). RESULTS: Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. CONCLUSION: An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.

Post-transplant liver graft schistosomiasis in a migrant from Sub-Saharan Africa.

We report a case of post-transplant liver graft infection with Schistosoma spp in a migrant from sub-Saharan Africa transplanted for HBV-related cirrhosis and with undiagnosed schistosomiasis pre-transplantation. The occurrence of tropical diseases in non-endemic areas warrants screening protocols for organ donors and recipients with a history of exposure in endemic areas.

The Italian compassionate use of sofosbuvir observational cohort study for the treatment of recurrent hepatitis C: clinical and virological outcomes.

Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3-F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child-Pugh class and model of end stage liver disease (MELD) scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98.3% (58/59) in patients who received a second antiviral (P < 0.01). In patients treated with sofosbuvir/ribavirin, a significant difference in SVR was observed between patients diagnosed with METAVIR F4 (211/250; 84.4%), METAVIR F3 (95/105; 90.5%) and fibrosing cholestatic hepatitis (10/10; 100%) (P = 0.049). A significant association was found between patients who worsened from Child-Pugh class A and who experienced viral relapse (4/26 vs. 8/189, P = 0.02). In patients with a baseline MELD score <15, a significant association was found between maintaining a final MELD score <15 and the achievement of SVR (187/219 vs. 6/10, P = 0.031). This real-world study indicates that sofosbuvir/ribavirin treatment for 24 weeks was effective, and the achievement of SVR was associated with a reduced probability of developing worsening liver function.

Comparison of two mineralcorticosteroids receptor antagonists for the treatment of central serous chorioretinopathy.

PURPOSE: To evaluate the effect of oral spironolactone and eplerenone, two specific antagonists of the mineralocorticoid receptor, in central serous chorioretinopathy (CSCR). METHODS: In this prospective, placebo-controlled trial, sixty patients with persistent CSCR were assigned to three treatment group. Twenty patients in Group 1 were treated with 25 mg of spironolactone (Aldactone; Pfizer) for 1 week, then increased to 50 mg for the following 3 weeks, then shifted to eplerenone 50 mg for 1 month. Twenty patients in Group 2 were treated with 25 mg of eplerenone (Inspra; Pfizer) for 1 week, then increased to 50 mg for the following 3 weeks, and then shifted to spironolactone 50 mg for 1 month. Twenty patients in Group 3 were treated with 1 placebo control tablet for 1 week, then increased to two tablets for the following 3 weeks, and then shifted to spironolactone 50 mg for 1 month. At the end of the second month, all the treatments were stopped, and the patients were followed for two additional months. Primary outcome measure was a change in BCVA at 1, 2, and 4 months. Secondary outcome was a change of >20 % in the size of SRF recorded with OCT at 1, 2, and 4 months of treatment. RESULTS: In terms of BCVA, treatment in Group 1 was effective from the first month (spironolactone, p value 0.01), and in Group 2 effective from the second month (shift to spironolactone, p value 0.004). Since the p value after the first month was 0.2 in Group 2, even with a larger sample, it would be difficult to see an efficacy of an eplerenone treatment after 1 month. As for the SRF, both in Group 1 and Group 2, both treatments were found to be equally effective after 1 month of administration (p values 0.004). At 4 months, only in Group 3, there was no statistical improvement of BCVA and SRF (p values 0.09 and 0.5). CONCLUSIONS: Spironolactone is statistically superior to eplerenone in improving BCVA of patients with CSCR, while both drugs can be considered equally effective in promoting the reabsorption of SRF.

Risk analysis of ischemic-type biliary lesions after liver transplant using octogenarian donors.

The use of octogenarian donors to increase the donor pool in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk of ischemic-type biliary lesions (ITBL). The aim of this study was to investigate retrospectively the role of a number of different pre-LT risk factors for ITBL in a selected population of recipients of octogenarian donor grafts. Between January 2003 and December 2013, 123 patients underwent transplantation at our institution with deceased donor grafts from donors of age ≥80 years. Patients were divided into 2 groups based on the presence of ITBL in the posttransplant course. Exclusion criteria were retransplantations, presence of vascular complications, and no availability of procurement liver biopsy. A total of 88 primary LTs were included, 73 (83.0%) with no posttransplant ITBLs and 15 (17.0%) with ITBLs. The median follow-up after LT was 2.1 years (range, 0.7-5.4 years). At multivariate analysis, donor hemodynamic instability (hazard ratio [HR], 7.6; P = 0.005), donor diabetes mellitus (HR, 9.5; P = 0.009), and donor age-Model for End-Stage Liver Disease (HR, 1.0; P = 0.04) were risk factors for ITBL. Transplantation of liver grafts from donors of age ≥80 years is associated with a higher risk for ITBL. However, favorable results can be achieved with accurate donor selection. Donor hemodynamic instability, a donor history of diabetes mellitus, and allocation to higher Model for End-Stage Liver Disease score recipient all increase the risk of ITBL and are associated with worse graft survival when octogenarian donors are used. Liver Transplantation 22 588-598 2016 AASLD.

ANTIANGIOGENICS IN CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH LASER IN CENTRAL SEROUS CHORIORETINOPATHY.

BACKGROUND/PURPOSE: To report characteristics and treatment outcome of choroidal neovascularization (CNV) secondary to laser photocoagulation and photodynamic therapy (PDT) in central serous chorioretinopathy. METHODS: Retrospective analysis of 12 eyes of 12 patients, who were diagnosed to have CNV secondary to laser photocoagulation or PDT for central serous chorioretinopathy. Collected data included demographic details, history of presenting illness, clinical examination details including visual acuity at presentation, and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last follow-up. Secondary outcomes included change in visual acuity at final follow-up from baseline, number of injections, treatment-free interval, and adverse events. RESULTS: This study included 12 eyes of CNV secondary to laser photocoagulation (8 eyes) and PDT (4 eyes). Mean age of study subjects was 47.6 ± 15.4 years (range 33-82) with 8 men and 4 women. Mean interval between laser photocoagulation/PDT and diagnosis of CNV was 23.9 ± 54.5 months. All subjects had unilateral CNV with classic CNV on fluorescein angiography. Eight eyes had extrafoveal CNV, and four eyes had juxtafoveal CNV. Baseline best-corrected visual acuity was 0.56 ± 0.51 (Snellen equivalent 20/60) logMAR, and final best-corrected visual acuity was 0.53 ± 0.51 (Snellen equivalent 20/60) logMAR with no significant difference (P = 0.84). All four eyes that presented with the CNV secondary to PDT group required additional PDT treatment because of poor response to antivascular endothelial growth factor therapy. At the last follow-up, only one patient in the laser group had active CNV; the remaining patients of both groups had scarred CNV. Mean follow-up duration was 22.4 ± 23.1 months. Mean number of injections was 3.16 ± 2.62. Longest treatment-free interval was 8.29 ± 11.4 months. CONCLUSION: Antivascular endothelial growth factor therapy appears to be safe and efficacious in CNVs secondary to laser photocoagulation and PDT. Choroidal neovascularizations secondary to PDT appear to be more resistant to antivascular endothelial growth factor therapy than those because of laser photocoagulation and required additional PDT.

RETINAL ASTROCYTIC HAMARTOMA: Optical Coherence Tomography Classification and Correlation With Tuberous Sclerosis Complex.

PURPOSE: To propose a classification of retinal astrocytic hamartoma based on spectral domain optical coherence tomography and correlate each class with systemic manifestations of tuberous sclerosis complex. METHODS: Retrospective chart review conducted at four international referral medical retina centers. There were 43 consecutive patients with an established diagnosis of tuberous sclerosis complex based on presence of at least 2 major or 1 major and 2 minor features of the diagnostic criteria. Clinical and spectral domain optical coherence tomography features regarding retinal astrocytic hamartoma were documented. RESULTS: The mean patient age at presentation was 16.2 years. The retinal astrocytic hamartoma was classified as Type I (n = 41), Type II (n = 25), Type III (n = 20), or Type IV (n = 12). Patients with Type II showed greater number of cutaneous fibrous plaques (odds ratio = 64.8; 92% confidence interval: 64.2-65; P < 0.001); those with Type III displayed higher incidence of subependymal giant-cell astrocytomas (odds ratio = 43.2; 95% confidence interval: 43.0-43.3; P < 0.001); and those with Type IV showed higher incidence of pulmonary lymphangiomyomatosis (odds ratio = 126; 95% confidence interval: 122-128; P < 0.001). CONCLUSION: Retinal astrocytic hamartoma can be classified into four morphologic groups, based on spectral domain optical coherence tomography. There are important systemic tuberous sclerosis complex correlations with each class.

Genetic of uveitis.

Immune-mediated uveitis may be associated with a systemic disease or may be localized to the eye. T-cell-dependent immunological events are increasingly being regarded as extremely important in the pathogenesis of uveitis. Several studies have also shown that macrophages are major effectors of tissue damage in uveitis. Uveitis phenotypes can differ substantially, and most uveitis diseases are considered polygenic with complex inheritance patterns. This review attempts to present the current state of knowledge from in vitro and in vivo research on the role of genetics in the development and clinical course of uveitis. A review of the literature in the PubMed, MEDLINE, and Cochrane databases was conducted to identify clinical trials, comparative studies, case series, and case reports describing host genetic factors as well as immune imbalance which contribute to the development of uveitis. The search was limited to primary reports published in English with human subjects from 1990 to the present, yielding 3590 manuscripts. In addition, referenced articles from the initial searches were hand searched to identify additional relevant reports. After title and abstract selection, duplicate elimination, and manual search, 55 papers were selected for analysis and reviewed by the authors for inclusion in this review. Studies have demonstrated associations between various genetic factors and the development and clinical course of intraocular inflammatory conditions. Genes involved included genes expressing interleukins, chemokines, chemokine receptors, and tumor necrosis factor and genes involved in complement system. When considering the genetics of uveitis, common threads can be identified. Genome-wide scans and other genetic methods are becoming increasingly successful in identifying genetic loci and candidate genes in many inflammatory disorders that have a uveitic component. It will be important to test these findings as uveitis-specific genetic factors. Therefore, the burgeoning understanding of the human genome promises to result in new insight into the pathogenesis of uveitis.

Two masquerade presentations of retinoblastoma.

Masquerade syndromes are disorders occurring with intraocular inflammation misdiagnosed as uveitis. The underlying causes may be benign or malignant conditions, and one of the most important diagnoses to take into consideration in children is retinoblastoma. We present two cases with uncertain early misdiagnosis whose definite diagnosis eventually was retinoblastoma.

WIDE-FIELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To describe wide-field spectral domain optical coherence tomography morphologic relationships of the vitreous, retina, and choroid in healthy and pathologic eyes. METHODS: Standardized horizontal, vertical, and two oblique (supertemporal to inferonasal and supranasal to inferotemporal) spectral domain optical coherence tomography sections were collected for each patient. For extramacular imaging, images were obtained from 8 locations: (1) nasal to the optic disk, (2) extreme nasal periphery, (3) superior to the superotemporal vascular arcade, (4) extreme superior periphery, (5) inferior to the inferotemporal vascular arcade, (6) extreme inferior periphery, (7) temporal to the macula, and (8) extreme temporal periphery. Wide-angle montage images of optical coherence tomography from equator-to-equator were composed with a montaging software. RESULTS: Wide-field spectral domain optical coherence tomography scans were obtained in 10 healthy subjects, in 7 patients with central serous chorioretinopathy, in 5 patients with wet age-related macular degenerations, in 5 patients with dry age-related macular degenerations, in 4 patients with retinitis pigmentosa, and in 1 patient with acute exudative polymorphous vitelliform maculopathy. CONCLUSION: The novel approach of montaging spectral domain optical coherence tomography images to examine relationships between the choroid, retina, and associated structures adjacent to and outside of the macula may have a number of relevant applications in the study of vitreoretinal interface, paramacular and macular pathologic features.

OUTCOMES OF TREATMENT OF CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH CENTRAL SEROUS CHORIORETINOPATHY WITH INTRAVITREAL ANTIANGIOGENIC AGENTS.

PURPOSE: To report clinical characteristics and treatment outcomes from the largest case series of choroidal neovascularization secondary to central serous chorioretinopathy. METHODS: Retrospective analysis of 46 eyes of 43 consecutive subjects. Collected data included demographic details, history of presenting illness, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were the proportion of eyes that had improved (3 or more lines), stable (within ±1 line), or decreased (3 or more lines) vision at the final visit as compared with baseline examination. Secondary efficacy outcomes included change in visual acuity at final follow-up, number of injections, treatment-free interval, and adverse events. RESULTS: Mean age was 57.56 years (range 29-79 years). Mean follow-up duration was 38.3 months ± 58.9 months. More than 3 lines of improvement in 12 eyes (26%), vision was stable (within ±1 line) in 19 eyes (41.3%), and >3 lines of loss was noted in 6 eyes (13%). Mean change in the number of lines was 1.16 ± 3.74. Mean number of anti-vascular endothelial growth factor injections during the follow-up was 4.45 ± 4.1. The longest treatment-free interval was 8.9 months ± 7.5 months. There were no adverse events noted. CONCLUSION: Anti-vascular endothelial growth factor therapy as a primary therapy for choroidal neovascularization secondary to central serous chorioretinopathy is safe and efficacious, without any serious adverse events.