Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients. A multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients

Massive hepatic angiomyolipoma in a young woman with tuberous sclerosis complex: Significant clinical improvement during tamoxifen treatment

Background/AimsIsolated liver angiomyolipomas (AMLs) occur in about 40% of TSC patients. Because of their slow growth, these tumors are often asymptomatic. Since AMLs express estrogen and progesteron receptors we suggest the possible benefits of tamoxifen for the treatment of liver AMLs.MethodsWe report the case of a 26-year-old female affected by tuberous sclerosis (TSC2) with cerebral, renal and hepatic involvement admitted to the Liver Unit for severe malnutrition, anorexia and abdominal pain. MRI showed a grossly enlarged liver, causing severe gastric compression. The liver was entirely filled with multiple nodular lesions of different sizes. Liver biopsy showed tumoral tissue with microscopic and ultrastructural features of angiomyolipoma. All liver function tests were repeatedly normal. Prior to considering the patient for partial hepatectomy, she was administered tamoxifen (20mg b.i.d).ResultsAfter 6 months of tamoxifen treatment a greatly improved quality of life and a significant weight gain were observed. After 12 months the clinical conditions further improved and the MRI showed a significant reduction of the largest lesion with a liquid central area and a diminished compression of the stomach.ConclusionsThis is to our knowledge the first report in which tamoxifen has been successfully used in a TSC patient with multiple liver angiomyolipomas

Depuration Capacity of Mussels (Mytilus galloprovincialis) in Presence of Marteilia Spp. Parasites

Bivalve molluscs are filter-feeding organisms present in the water column: during their activity, they could retain micro-organisms that are potentially dangerous to human health. For this reason, EU Regulations may require that a purification treatment be performed prior to bivalve trade. The length of the purification process could be affected by stress factors, such as parasitic infections. The purpose of this study was to determine if the presence of Marteilia spp. parasite in shellfish could modify time and efficacy of their microbiological purification treatment, in order to set up specific protocols. Lysosomal membrane stability, phagocytosis capacity, granulocyte/hyalinocyte rate and neutral lipid accumulation are biomarkers used to evaluate shellfish physiological state. These biomarkers were used to exclude any differences caused by stressor factors that could affect the purification results. Mussels were sampled from two different production areas. The presence or absence of parasites was confirmed by cytological test. Both groups of parasitized and non-parasitized mussels were contaminated with E.coli: they were then sampled for microbiological analyses and tested for biomarkers for up to 70 hours of purification. Parasitized and non-parasitized molluscs did not show any differences in levels of E. coli after 12, 24, 36, 48 and 70 hours of depuration. In relation to biomarkers, mussels seem to react to Lysosomal membrane stability in presence of Marteilia. The present study shows that the presence of Marteilia spp. does not affect the purification rate of mussels

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider, for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immune-competent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance". However, with regard to HBV and LT, outstanding issues are still on the table: (1) A standard HBV prophylaxis protocol after transplant has not yet been clearly defined; (2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs; and (3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons

Donation after Circulatory Death in Paediatric Liver Transplantation: Current Status and Future Perspectives in the Machine Perfusion Era

Efforts have been made by the transplant community to expand the deceased donor pool in paediatric liver transplantation (LT). The growing experience on donation after circulatory death (DCD) for adult LT has encouraged its use also in children, albeit in selective cases, opening new perspectives for paediatric patients. Even though there has recently been a slight increase in the number of DCD livers transplanted in children, with satisfactory graft and patient outcomes, the use of DCD grafts in paediatric recipients is still controversial due to morbid outcomes associated with DCD grafts. In this context, recent advances in the optimization of donor support by extracorporeal membrane oxygenation and in the graft preservation by liver machine perfusion could find application in order to expand the donor pool in paediatric LT. In the present study we review the current literature on DCD liver grafts transplanted in children and on the use of extracorporeal donor support and liver perfusion machines in paediatrics, with the aim of defining the current status and future perspectives of paediatric LT

Reduced lysosomal acid lipase activity in blood and platelets is associated with nonalcoholic fatty liver disease

OBJECTIVES: To investigate whether blood total lysosomal acid lipase activity (BT-LAL) levels are uniquely associated with the noncirrhotic and cirrhotic stages of nonalcoholic fatty liver disease (NAFLD) and with protection from NAFLD in metabolically/genetically predisposed subjects and a normal liver. To clarify which enzyme-carrying circulating cells are involved in reduced BT-LAL of NAFLD.METHODS: In a cross-sectional study, BT-LAL was measured by a fluorigenic method in patients with NAFLD (n = 118), alcoholic (n = 116), and hepatitis C virus-related disease (n = 49), in 103 controls with normal liver and in 58 liver transplant recipients. Intracellular platelet and leukocyte LAL was measured in 14 controls and 28 patients with NAFLD.RESULTS: Compared with controls, (i) BT-LAL and LAL in platelets, but not in leukocytes, were progressively reduced in noncirrhotic NAFLD and in nonalcoholic steatohepatitis-related cirrhosis; (ii) platelet and leukocyte counts did not differ in patients with noncirrhotic NAFLD; and (iii) BT-LAL did not differ in alcoholic and hepatitis C virus noncirrhotic patients. BT-LAL progressively increased in controls with metabolic syndrome features according to their PNPLA3 rs738409 steatosis-associated variant status (II vs IM vs MM), and their BT-LAL was higher than that of noncirrhotic NAFLD, only when carriers of the PNPLA3 unfavorable alleles were considered. Liver transplant recipients with de novo NAFLD compared with those without de novo NAFLD had lower BT-LAL.DISCUSSION: LAL in blood and platelets is progressively and uniquely reduced in NAFLD according to disease severity. High BT-LAL is associated with protection from NAFLD occurrence in subjects with metabolic and genetic predisposition. Low LAL in platelets and blood could play a pathogenetic role in NAFLD

A Keynesian perspective on the health economics of kidney transplantation would strengthen the value of the whole organ donation and transplantation service

BackgroundIn this study, the Keynesian principle “savings may be used as investments in resources” is applied to Kidney Transplantation (KT), contextualizing the whole Organs Donation and Transplantation (ODT) service as a unique healthcare entity. Our aim was to define the financial resources that may be acquired in the form of savings from the KT activity.MethodsWe analyzed registry and funding data for ODT in our region, between 2015 and 2019. Our hypotheses aimed to evaluate whether the savings would offset the Organ Donation (OD) costs, define the scope for growth, and estimate what savings could be generated by higher KT activity. To facilitate the evaluation of the resources produced by KT, we defined a coefficient generated from the combination of clinical outcomes, activity, and costs.ResultsThe ODT activity reached a peak in 2017, declining through 2018–2019. The savings matured in 2019 from the KT activity exceeded €15 million while the OD costs were less than €9 million. The regional KT activity was superior to the national average but inferior to international benchmarks. The estimated higher KT activity would produce savings between €16 and 20 million.ConclusionThe financial resources produced by KT contribute to defining a comprehensive perspective of ODT finance. The optimization of the funding process may lead to the financial self-sufficiency of the ODT service. The reproducible coefficient allows a reliable estimate of savings, subsequently enabling adequate investments and budgeting. Applying such a perspective jointly with reliable estimates would establish the basis for an in-hospital fee-for-value funding methodology for ODT

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production &gt;99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p&lt;0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted \u3b4 and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted \u3bb, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p&lt;0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide