Digestive and Liver Disease Supplements最新文献

We present the case of a 36-year-old patient with ileo-colonic stricturing Crohn's disease that recurred after surgery, did not respond to maximal medical therapy and was only partially responsive to treatment with adalimumab administered subcutaneously. The patient underwent surgery following an episode of intestinal obstruction, revealing chronic, adhesive peritonitis, with the intestinal loops fixed strongly together, and a fibrotic stricture of the pre-anastomotic ileum. The numerous adhesions were carefully separated and the stenotic tract of ileum was resected. Following the resection the patient had an early clinical relapse, which was documented by abdominal ultrasound. The patient was, therefore, treated again with adalimumab: the new cycle of treatment achieved clinical and ultrasonographic remission of the disease. Despite the previous treatment, no side-effects occurred.

The dramatic increase of transplantation activity in the last years has been related to the increase of eligible donors and to the use of “marginal grafts” from aged donors or even from hepatitis B virus (HBV) infected patients in emergencies. Hepatitis B after transplantation is related to the appearance of HBsAg in subjects originally positive (reactivation) or negative (de-novo hepatitis B, DNHB). DNHB can be influenced by: a) transmission from donors who are carriers of occult B infection (OBI); b) reactivation in recipients who are carriers of OBI; c) by HBV infection from HBsAg-positive donors. Hepatitis B immunoglobulin (HBIG) and antiviral(s) have become the standard of care after liver transplantation (LT) worldwide, changing the long-term outcome of HBsAg-positive recipients. In HBsAg-negative recipients HBIGs maintain an important role in the peri-operative and long-term period after liver transplantation for prevention of DNHB from OBI donors; in other transplants hepatitis B reactivation from OBI carriers (donors or recipients) remains an uncommon event and the role of prophylaxis is controversial. Data related to HBV infection and DNHB in solid organs and bone marrow transplantation are reviewed.

Liver transplant activity started in Spain in 1984 and has reached 16,132 interventions at 31st December 2008, with a mean activity of more than 1000 transplants during the last years. There are 25 transplant teams (1/1.85 million inhabitants), two of them paediatric. The maximum activity has been recorded at the Hospital La Fe (Valencia) with 1,557 transplants (more than 100 annually). The majority were standard deceased donor transplants. Other modalities were: 222 living donors (1.4%), 89 donors after cardiac death (0.5%), 187 split (1.1%) and 100 domino (0.6%). Combined transplants made in this period of time were 309 (1.9%): 244 liver–kidney, 15 liver–pancreas, 20 liver–intestine and 30 multi-visceral. Around 5% of transplants were performed under national priority. As Spain leads the world in organ donor rate, liver transplant activity means 6% of all the interventions performed in the world, with the largest relative activity (23–25 per million population). The analysis of the results is performed by the Spanish Liver Transplant Registry jointly managed by the National Transplant Organization and the Spanish Society of Liver Transplantation. As in other international registries, patient and graft survival have been improving across time in the different categories of basic diseases and associated risk factors.

Organ shortage limits the applicability of liver transplantation to treat end-stage liver disease, and the use of extended-criteria donors is a necessity in the current era. Donors after cardiac death (DCD) suffer irreversible cardiac arrest prior to donation and represent a potential source of additional organs if properly maintained. DCD undergo an initial period of warm ischemia that provokes cellular alterations. Experimental and clinical studies performed at our center have demonstrated that normothermic extracorporeal membrane oxygenation (NECMO) is effective at maintaining abdominal organs in DCD. NECMO helps stop and even revert some of the changes that occur during warm ischemia and offers the opportunity to evaluate graft viability prior to implantation. Nonetheless, the percentage of organs arising from DCD that are accepted for transplant remains relatively low due to the co-existence of other factors that prohibit their utilization, namely poor perfusion and hepatic steatosis. The use of dual-pump normothermic machine perfusion (NMP) in the ex vivo phase of DCD liver preservation can offer additional benefits over traditional cold storage. In experimental studies, ischemic injury and hepatocellular function are significantly improved in DCD grafts preserved with NMP. Clinical studies on the use of NMP in DCD liver transplantation are under way.

Donor–recipient matching is an important factor influencing the outcome of liver transplantation (LT), especially when, due to organ shortage, extended criteria donors (ECD) are used. Among donor risk factors, donor age has been associated with severe HCV recurrence after LT, and severe steatosis increases the risk of NAFLD after LT and impairs liver regeneration when partial liver is used. Grafts from HCV positive donors can be used (in absence of fibrosis) in HCV positive recipients; however, attention should be paid when donor age is over 50. Anti-HB core positive grafts are used in patients with HBsAg or anti-HBc patients with long term prophylaxis to prevent recurrence. The use of partial (living or cadaveric) livers is marginal in western countries but seems not to worsen prognosis. Decision whether to allocate ECD to sickest or healthiest recipients is still a matter of debate in terms of outcome and utility, therefore dedicated studies are needed.

End-stage liver diseases due to HBV are among the major indications for liver transplantation worldwide and represent a peculiar issue in Italy where they can be as high as 25%. The widespread use of long-term prophylaxis with hepatitis B immunoglobulin (HBIG), either alone or in combination with antiviral drugs in the post-liver transplant period, has significantly improved both graft and patient survival. HBIG prophylaxis is usually administered intravenously, or intramuscularly The two formulations present a peculiar difference in their pharmacokynetics: peak serum concentrations after intravenous administration are observed within 2 hours, whereas intramuscular injection of HBIG provides peak serum concentrations between day 5 and 11. However, long-term intravenous prophylaxis is expensive and time-consuming. In order to determine when and how to choose between intravenous or intramuscular route, the anhepatic phase is crucial for the potential risk of graft infection and for which a management strategy that specifically addresses the virological status and history of the patient should be adopted. During the first week post-transplantation, high-dose protocols are traditionally applied, although the ideal, patient-tailored protocols should be defined on the basis of both viral and patient-related features. After the first week post-transplantation, available evidence clearly indicates that the type of formulation has little or no effect on the prophylactic regimen, and lower doses of HBIG appear to be needed when given in combination with nucleos(t)ide analogues.

A major achievement for patients transplanted for hepatitis B virus (HBV) associated end-stage liver disease is the successful prevention of reinfection with high dose of hepatitis B immunoglobulin (HBIG). The introduction of lamivudine in combination with HBIG reduces recurrence rates to less than 5% at 5 years. Currently, this combination is the accepted standard regimen in most transplantation units. However, a major drawback of this therapy is that high-dose intravenous (IV) HBIG is very expensive. Several strategies have been explored to reduce such costs. These include withdrawal of HBIG at some time after transplantation while continuing lamivudine, vaccination of patients prior to cessation of HBIG and substitution of high-dose IV HBIG by low-dose intramuscular (IM) HBIG. It has been demonstrated that crucial pharmacokinetic parameters, including anti-HBs antibodies through levels at time of HBIG re-administration, do not differ significantly after IV and IM administration in stable hepatitis B surface antigen (HBsAg) negative patients with at least 12 months follow-up after orthotopic liver transplantation, confirming the cost-effectiveness of IM HBIG administration. Recent studies suggest that, compared with combination of HBIG plus lamivudine prophylaxis, the combination of adefovir plus lamivudine prophylaxis provides equivalent protection against HBV reinfection with better tolerability at a significantly lower cost. Nonetheless, HBIG continue to be the cornerstone of HBV recurrence prevention.

The prognosis after liver transplantation is related to the efficacy of prophylaxis of hepatitis B virus (HBV) graft re-infection. The risk of HBV re-infection is directly related to HBV viral load at the time of transplantation. HBV prophylaxis after transplantation with long-term administration of hepatitis B immunoglobulins (HBIG) or monoprophylaxis with lamivudine can significantly reduce the risk of HBV recurrence. Antivirals can control HBV replication in patients with decompensated HBV cirrhosis awaiting transplantation. However, there is a risk of HBV viral breakthrough during nucleo(t)side antiviral treatment. Efficacy of antivirals and the risk of viral resistance should be taken into account. The post-transplant combination of antiviral therapy and HBIG prophylaxis is very effective in reducing the rate of HBV re-infection to less than 10%, increasing the survival rate. The current 5-year survival after transplantation for HBV related liver disease is 85%. In patients without active viral replication at transplantation, the possibility of discontinuing HBIG prophylaxis over the long-term after transplantation with maintenance of antiviral treatment or HBV vaccination is under evaluation. In conclusion, the prophylaxis of HBV re-infection combining antiviral therapy prior to transplantation, and combination of HBIG and antiviral therapy post-transplantation is effective in reducing the rate of HBV re-infection.

The decision to allocate a given organ from a deceased (DD) or living donor (LD) to a particular recipient awaiting liver transplantation (LT) is strongly influenced by ethical and health policy issues. The liver transplant community is currently discussing several ethical principles with a view to improving the allocation process as a whole. These principles are: urgency, utility, intention-to-treat survival, transplant benefit, harm to candidates on waiting list (WL), harm to living donors, chances of re-transplantation. The potential conflict between different principles is particularly relevant for patients with hepatocellular carcinoma (HCC) for a number of reasons: (a) candidates for LT with HCC are increasing; (b) the HCC population varies considerably in prognostic terms; (c) tumor progression before LT in HCC patients may significantly impair post-LT outcome; and (d) effective alternatives to LT are often available for treating HCC patients. In this paper, we propose a model for effectively representing the potential equipoise achievable between the different ethical principles involved in LT. We considered a triangle with transplant benefit (life expectancy with LT minus that without LT) at its superior apex, and potential harm to candidates on the WL and living donor at the inferior apices. The model may be helpful in clinical decision-making regarding LT: (1) by modulating the relative prognostic weight of different ethical principles involved in the relationship between transplant benefit and harm to candidates on the WL; and (2) by simplifying the decision between DDLT and LDLT in a given geographical setting.