Acute kidney injury and post-reperfusion syndrome in liver transplantation

In the past decades liver transplantation (LT) has become the treatment of choice for patients with end stage liver disease (ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death (DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease (CKD). Acute kidney injury (AKI) post-LT has been recently recognized as an important risk factor for the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome (PRS) that can influence recipient’s morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since pre-LT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A PubMed search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on PubMed search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRS-induced AKI, avoiding confounding factors, we have limited our study to “acute kidney injury AND DCD AND liver transplantation”. Accordingly, three out of five studies were selected for our purpose

Imaging follow-up after liver transplantation

Liver transplantation (LT) represents the best treatment for end-stage chronic liver disease, acute liver failure and early stages of hepatocellular carcinoma. Radiologists should be aware of surgical techniques to distinguish a normal appearance from pathological findings. Imaging modalities, such as ultrasound, CT and MR, provide for rapid and reliable detection of vascular and biliary complications after LT. The role of imaging in the evaluation of rejection and primary graft dysfunction is less defined. This article illustrates the main surgical anastomoses during LT, the normal appearance and complications of the liver parenchyma and vascular and biliary structures.Liver transplantation (LT) represents the best treatment for end-stage chronic liver disease, acute liver failure and early stages of hepatocellular carcinoma. Radiologists should be aware of surgical techniques to distinguish a normal appearance from pathological findings. Imaging modalities, such as ultrasound, CT and MR, provide for rapid and reliable detection of vascular and biliary complications after LT. The role of imaging in the evaluation of rejection and primary graft dysfunction is less defined. This article illustrates the main surgical anastomoses during LT, the normal appearance and complications of the liver parenchyma and vascular and biliary structures

Survival after liver transplantation in the United Kingdom and Ireland compared with the United States

<b>Background and Aim</b>: Surgical mortality in the US is widely perceived to be superior to that in the UK. However, previous comparisons of surgical outcome in the two countries have often failed to take sufficient account of case-mix or examine long-term outcome. The standardised nature of liver transplantation practice makes it uniquely placed for undertaking reliable international comparisons of surgical outcome. The objective of this study is to undertake a risk-adjusted disease-specific comparison of both short- and long-term survival of liver transplant recipients in the UK and Ireland with that in the US. <b>Design, setting and participants</b>: Multi-centre cohort study using two high quality national databases including all adults who underwent a first single organ liver transplant in the UK and Ireland (n=5,925) and the US (n=41,866) between March 1994 and March 2005. <b>Main outcome measures</b>: Post-transplant mortality during the first 90 days, 90 days-1 year and beyond the first year, adjusted for donor and recipient characteristics. <b>Results</b>: Risk-adjusted mortality in the UK and Ireland was generally higher than in the US during the first 90 days (hazard ratio 1.17 95%CI 1.07-1.29), both for patients transplanted for acute liver failure (hazard ratio 1.27 95%CI 1.01-1.60) as well as those transplanted for chronic liver disease (hazard ratio 1.18 95% CI 1.07- 1.31). Between 90 days and 1 year post-transplantation, no statistically significant differences in overall risk- adjusted mortality were noted between the two cohorts. Survivors of the first post-transplant year in the UK and Ireland had lower overall risk-adjusted mortality than those transplanted in the US (hazard ratio 0.88 95% CI 0.81- 0.96). This difference was observed among patients transplanted for chronic liver disease (hazard ratio 0.88 95%CI 0.81-0.96) but not those transplanted for acute liver failure (hazard ratio 1.02 95%CI 0.70- 1.50). <b>Conclusions</b>: Whilst risk adjusted mortality is higher in the UK and Ireland during the first 90 days following liver transplantation, it is higher in the US among those liver transplant recipients who survived the first post- transplant year. Our results are consistent with the notion that the US has superior acute peri-operative care whereas the UK appears to provide better quality chronic care following liver transplantation surgery

Liver transplantation for viral hepatitis in 2015

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release

Diminishing Use of Liver Biopsy among Liver Transplant Recipients for Hepatitis C.

Background and Aims: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality. Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy. The introduction of direct-acting antiviral agents (DAAs) has changed the management of recurrent HCV infection. This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs. Methods: A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV. The analysis included 475 adult liver transplants for hepatitis C performed at the University of California, Los Angeles from January 1, 2006 to October 1, 2015. Patients were divided into two eras, pre- and post-introduction of DAAs on December 1, 2013. Results: In the era before the introduction of DAAs, the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs. 26.9%, p < 0.001). Conclusions: The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV. Given that DAAs are well tolerated and have high efficacy, liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation

UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

Living Donor Liver Transplantation for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a major worldwide health problem, which is expected to increase steadily due to different underlying liver diseases. Surgical treatment modalities including liver transplantation (LT) or liver resection (LR) are the mainstay options for early cases of HCC. Liver transplantation for well‐selected cases provides excellent survival outcomes comparable to nonmalignant indications of LT. Living donor liver transplantation (LDLT) is an alternative option or even the sole one in the current era of organ shortage problem and in some Asian countries where deceased organ donation is markedly reduced due to various reasons. The adoption of LDLT for HCC treatment elicited many dynamic changes and debates to the dilemma of LT as a whole. In this chapter, we focus on different perspectives of LDLT for HCC, including selection criteria evolution, controversial topics, ethical considerations, operative highlights, and other points

Management of Hepatocellular Carcinoma in the Setting of Liver Cirrhosis

Cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14th most common cause of death worldwide. Hepatocellular carcinoma (HCC) consists a significant health issue worldwide, responsible for more than 1 million deaths annually. The incidence and mortality rates vary across different geographical areas. Between 60 and 90% of HCC patients already have liver cirrhosis, attributed mainly to chronic hepatitis B and C, alcohol abuse, and non-alcoholic fatty liver disease (NASH). The surgical management of HCC in the setting of liver cirrhosis with curative intent includes liver resection, ablation or microwave coagulation, and liver transplantation (LT). Liver resection in a cirrhotic liver with HCC is associated with lower survival rates compared with liver transplantation (LT), depending on the diseases’ stage but on the contrary liver resection could be potentially offered in a larger population compared to liver transplantation. One of the biggest limitations of liver resection is the risk of tumor recurrence, which is high, and it may exceed 70% 5 years after the procedure. Liver transplantation is considered the best treatment for hepatocellular carcinoma at early stages because it removes the tumor as well as the underlying cirrhotic liver

Specific issues concerning the management of patients on the waiting list and after liver transplantation

The present document is a second contribution collecting the recommendations of an expert panel of transplant hepatologists appointed by the Italian Association for the Study of the Liver (AISF) concerning the management of certain aspects of liver transplantation, including: the issue of prompt referral; the management of difficult candidates; malnutrition; living related liver transplants; hepatocellular carcinoma; and the role of direct acting antiviral agents before and after transplantation. The statements on each topic were approved by participants at the AISF Transplant Hepatology Expert Meeting organized by the Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are graded according to the GRADE grading system

Outcomes in liver transplantation: does sex matter?

A growing literature has highlighted important differences in transplant-related outcomes between men and women. In the United States there are fewer women than men on the liver transplant waitlist and women are two times less likely to receive a deceased or living-related liver transplant. Sex-based differences exist not only in waitlist but also in post-transplant outcomes, particularly in some specific liver diseases, such as hepatitis C. In the era of individualized medicine, recognition of these differences in the approach to pre and post-liver transplant care may impact short and long-term outcomes