A combination of hepatitis B immunoglobulins (HBIg) and nucleos(t)ide analogues (NA) is currently recommended for HBV prophylaxis after liver transplantation (LT), but the optimal regimen is still controversial. Several issues concerning use of HBIg after LT still await definitive clarification, such as dosage (high vs. low); timing (ab initio vs. delayed); schedule (on demand vs. fixed-dose); route of administration (intravenous vs. intramuscular vs. subcutaneous), and duration (short-term vs. long-term vs. lifelong). Alongside efficacy, issues concerning patients' safety and adherence, costs, and resource consumption should be part of the post-transplant decision algorithm to achieve optimization of anti-HBV prophylaxis and maximization of graft and patient survival. Based on the available data, HBIg withdrawal after LT needs to be validated in the long term. On the other hand, a monthly, fixed, low-dose HBIg schedule currently seems the solution to increase the cost–benefit ratio of combination prophylaxis regimens post-transplantation.
Liver transplantation remains the ultimate cure for patients with hepatitis B virus-related end-stage liver disease. Clinical Practice Guidelines currently recommend that patients with decompensated HBV cirrhosis should be treated without delay with nucleos(t)ide analogues regardless of the patient's serum ALT, HBV DNA level, and HBeAg status. The main goal of pre-transplantation antiviral therapy is to achieve a rapid and prolonged suppression of viral replication and thus decrease the risk of hepatitis B virus reinfection of the graft. In addition, sustained negativization of serum HBV DNA may also result in clinical stabilization which can decrease the mortality rate while on the waiting list and delay or avoid liver transplantation in some cases. Clinical improvement may take from 3 to 6 months to become evident. Lamivudine and adefovir are no longer considered first-line therapy in these patients. Potent nucleos(t)ide analogues with good resistance profiles such as entecavir or tenofovir should be used instead. Preliminary data suggest that these agents are effective and have a good safety profile in patients with decompensated cirrhosis. More safety data, however, are needed, particularly in patients with severe impairment of liver function. More data are needed to determine which of the newer antiviral agents offer the best risk–benefit ratio in this challenging patient population. Although a tenofovir-based regimen may be preferred in decompensated patients with lamivudine-resistant hepatitis B virus, there are some concerns about the long-term safety of tenofovir including nephrotoxicity and metabolic bone disease.
Despite its widespread diffusion, liver transplantation (LT) still remains one of the most resource consuming surgical procedures. In times of economic constraints, the entire medical community is discussing the strategies necessary to allow a sustainable development of LT. Sustainability is the capacity to endure and, in ecology, the word describes how biological systems remain diverse and productive over time. In clinical practice, sustainability is the potential for long-term maintenance of human well-being, which has environmental, economic and social dimensions. Making LT a sustainable clinical practice entails a multidimensional, multilevel approach balancing patients' needs with those of the entire society. Consumption of resources is pivotal to a sustainable LT practice, and the strategies to adopt should focus on increasing deceased donor availability as well as on reducing current long-term graft attrition rates. It is our duty to rethink the way we are currently performing LT and our major commitment is to transfer our capacities to future generations, without wasting resources and to invest in research. This calls for urgent action to be taken at the care-provider-to-patient, social and political levels, and for networking of all professionals involved in care of liver disease patients.
In Liver Transplantation (LT) units the clinicians routinely deal with complex decision making situations that cannot always be solved with the available scientific evidence. They include selection of the best candidates for LT, minimizing mortality and drop-out rates within the waiting list (WL) and rationalizing donor–recipient matching. These topics constitute some of the current challenges in LT and they may drive a number of future research trends. Since the MELD implementation the organ allocation model has moved from a system based on length of time on the WL to a disease severity based policy, and thus to a more rational use of LT and a decrease in WL mortality. However, during the last decade several limitations of this system have been highlighted, and modifications of the MELD score have been proposed. Furthermore, patients with hepatocellular carcinoma do not fit inside the MELD system and the current strategy of prioritization based on number and size of nodules has not eliminated the drop-out risk, despite the use of locoregional ablative treatment while on the WL. A better understanding of tumour behavior, especially concerning microvascular invasion, is urgently needed to improve management of patients with hepatocellular carcinoma. Finally, the donor and recipient features maintain a complex relationship that affects outcome. The use of artificial neural network to find the most adequate recipient to each graft, may allow a more rationalized allocation policy.
Recurrent hepatitis C after liver transplantation is a rapidly evolving condition in which fibrosis deposition is accelerated, with 30% of patients developing graft cirrhosis within the first 5 years after transplantation. Antiviral therapy after transplantation achieves sustained virological response (SVR) in approximately 30% of patients, and a milder fibrosis stage at treatment seems to increase the probabilities of response to treatment. Importantly, SVR to antiviral therapy in this setting has been shown to modify the natural history of the disease, given the excellent prognosis of patients who are able to clear the virus. In this regard, an early recognition of these patients can help to start antiviral therapy in less advanced stages of the recurrence, with higher probabilities of achieving SVR. Non-invasive methods, and especially Fibroscan™, have been shown to significantly correlate with fibrosis stage and, more importantly, to permit early identification of those patients at higher risk of presenting worse outcomes. In addition, they can also confidently distinguish those patients who will present a good outcome and in which a significant number of protocol liver biopsies may be avoided.
Cirrhosis with/without hepatocellular carcinoma is the primary indication for liver transplantation (LT) in many countries. Hepatitis C virus (HCV) reinfection occurs universally resulting in HCV-graft disease with progression to cirrhosis in about one third of cases after 5 years. Graft failure secondary to recurrent HCV is now the most frequent cause of death, graft failure and need for retransplantation in these patients, with a cumulative risk of allograft failure due to recurrent disease at 10–13 years of 25–30%. The use of suboptimal quality organs, particularly from old donors, has a negative impact on disease severity and transplant outcome, which may explain the increasing rate of severe recurrent disease reported in some centers in recent years, paralleling the increasing donor age. Antiviral therapy, on the other hand, particularly among patients who achieve a sustained viral response (SVR), is associated with improved histology, reduced rate of graft decompensation and better graft and patient survival. Peginterferon (pegIFN) with ribavirin (RBV) is currently the treatment of choice, with SVR achieved in 25–40% of cases. Side effects, particularly anaemia, are extremely frequent and sometimes severe (rejection, de novo autoimmune hepatitis). Baseline factors associated with SVR include genotype non-1, donor and recipient CC IL28B polymorphism, low baseline viraemia, young donor age or mild disease severity. In turn, on-treatment factors predictive of SVR include viral kinetics and treatment adherence.
End-stage liver disease related to HCV infection is the most common indication for liver transplantation both in Europe and in USA (http://www.UNOS.org; http://www.ELTR.org). The results of liver transplantation for this indication are negatively affected by the high rate of viral recurrence which, through an accelerated rate of disease progression, significantly impairs patient and graft survival.
In western countries, about 10–25% of patients undergoing liver transplantation (LT) are HBsAg carriers. In Asia, HBV-related liver disease is the leading indication to LT. After surgery hepatitis B can develop in patients transplanted for HBV-related disease or in HBsAg-negative recipients of anti-HBc positive grafts. In the last years prophylaxis with HBIG and/or antivirals has been proposed in both conditions with excellent results. However, lack of efficacy of prophylaxis is frequently associated with the selection of HBV mutants resistant to the different drugs.
Crohn’s disease (CD) is a chronic inflammatory disease of unknown aetiology that may affect any part of the gastrointestinal tract [1]. Medical treatment includes 5-aminosalicylic acid, steroids, immunomodulators, and biologicals [2]; the choice of drug depending upon the extent and severity of the disease. The introduction of biological therapy in the late 1990s expanded the available therapeutic options, and numerous studies have shown that biological therapies are effective in inducing and maintaining clinical remission, allowing complete suspension of oral steroids in most cases [3]. Moreover, early mucosal healing induced by biological therapy is associated with fewer hospitalizations, fewer surgical interventions, and long-term clinical remission [3,4]. In Italy, two antitumour necrosis factor-alpha (TNF-α) antibodies (infliximab and adalimumab) are currently available for the treatment of patients with CD. Infliximab is a chimeric immunoglobulin G1 (IgG1) antibody administered intravenously, while adalimumab is a fully human IgG1 anti-TNF-α available for subcutaneous injection. Although no head-to-head trials comparing infliximab with adalimumab have been published to date, these two agents appear to have similar efficacy and adverse-event profiles, and so the choice depends on availability, route of delivery, patient preference, cost, and national
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.
We describe the case of a young woman with fistulising Crohn’s disease of the ileum and colon. The disease was diagnosed at the age of 19 years. About 6 years after the initial diagnosis, the patient underwent partial resection of the transverse colon because of gastro-colonic and jejunal-colonic fistulae. In March 2006, following weight loss of about 6 kg and the appearance of an entero-cutaneous fistula draining faecal material, the patient was admitted to hospital where she was treated with systemic steroids, antibiotics and total parenteral nutrition. Treatment with intravenous infliximab was attempted but was unsuccessful (the drug had to be stopped because of the development of an adverse reaction). In June 2008, the patient was referred to us for the first time. The patient smoked about 20 cigarettes/day and did not have a family history of chronic inflammatory bowel disorders. Clinical examination showed clear signs of malnutrition (height: 160 cm; weight: 39 kg; body mass index: 15.2 kg/m2), a mild state of dehydration, muscle hypotrophy, and two fistulous orifices draining faecal material in the left iliac fossa. There was widespread tenderness to palpation in all quadrants of the abdomen. Laboratory tests revealed mild anaemia, neutrophil leukocytosis, and increased levels
Perianal fistulae are a common complication of Crohn’s disease (CD) and represent 17–43% of all localizations. Fistulas arise before diagnosis at an early stage of the disease. Young age, male sex, smoking and genetic factors are disposing features [1,2]. Sometimes, mostly in patients without a previous diagnosis of IBD, it can be difficult to correctly interpret certain specific presentations of perianal disorders.
Anti-tumour necrosis factor-alpha has dramatically changed the natural history of Crohn's disease in the last decades. Adalimumab is effective in inducing and maintaining clinical remission as well as in inducing deep mucosal healing, which is a prognostic factor for further progression of the disease. Long-term treatment with adalimumab is considered safe and should be continued for at least 3 years in patients with aggressive long-standing Crohn's disease.
