Management of immunosuppressant agents following livertransplantation:Less is more

Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.

Guide for diagnosis and treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosisis determined by several factors; tumour extension, alpha-fetoprotein(AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient's performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound(US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography(CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC.

Laparoscopic liver resection:Experience based guidelines

Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.

Vascular complications following liver transplantation:Aliterature review of advances in 2015

Although vascular complications(VCs) following orthotopic liver transplantation(OLT) seldom occur, they are the most feared complications with a high incidence of both graft loss and mortality, as they compromise the blood flow of the transplant(either inflow or outflow). Diagnosis and therapeutic management of VCs constitute a major challenge in terms of increasing the success rate of liver transplantation. While surgical treatment used to be considered the first choice for management, advances in endovascular intervention have increased to make this a viable therapeutic option. Considering VC as a rare but a major and dreadful issue in OLT history, and in view of the continuing and rapid progress in recent years, an update on these uncommon conditions seemed necessary. In this sense, this review comprehensively discusses the important features(epidemiological, clinical, paraclinical, prognostic and therapeutic) of VCs following OLT.

Predictive roles of intraoperative blood glucose for posttransplant outcomes in liver transplantation

Diabetogenic traits in patients undergoing liver transplantation(LT) are exacerbated intraoperatively by exogenous causes, such as surgical stress, steroids,blood transfusions, and catecholamines, which leadto intraoperative hyperglycemia. In contrast to the strict glucose control performed in the intensive care unit, no systematic protocol has been developed for glucose management during LT. Intraoperative blood glucose concentrations typically exceed 200 mg/dL in LT, and extreme hyperglycemia(> 300 mg/dL) is common during the neohepatic phase. Only a few retrospective studies have examined the relationship between intraoperative hyperglycemia and posttransplant complications, with reports of infectious complications or mortality. However, no prospective studies have been conducted regarding the influence of intraoperative hyperglycemia in LT on post-transplant outcome. In addition to absolute blood glucose values,the temporal patterns in blood glucose levels during LT may serve as prognostic features. Persistent neohepatic hyperglycemia(without a decline) throughout LT is a useful indicator of early graft dysfunction. Moreover,intraoperative variability in glucose levels may predict the need for reoperation for hemorrhage after LT.Thus, there is an urgent need for guidelines for glucose control in these patients, as well as prospective studies on the impact of glucose control on various posttransplant complications. This report highlights some of the recent studies related to perioperative blood glucose management focused on LT and liver disease.

Intermediate hepatocellular carcinoma: How to choose the best treatment modality?

Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma(HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large(> 5 cm) solitary HCC should be firstly considered for liver resection(LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization(TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization(TARE)-plus percutaneous ablation] is "a priori" preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases(patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be "patient-tailored" and made by a multidisciplinary team.

Different behaviour of BK-virus infection in liver transplantrecipients

Polyomavirus BK(BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A Pub Med search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease(CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication.

Utility of liver biopsy in predicting clinical outcomes after percutaneous angioplasty for hepatic venous obstruction in liver transplant patients

AIM: To determine utility of transplant liver biopsy in evaluating efficacy of percutaneous transluminal angioplasty(PTA) for hepatic venous obstruction(HVOO). METHODS: Adult liver transplant patients treated with PTA for HVOO(2003-2013) at a single institution were reviewed for pre/post-PTA imaging findings, manometry(gradient with right atrium), presence of HVOO on prePTA and post-PTA early and late biopsy(EB and LB, < or > 60 d after PTA), and clinical outcome, defined as good(no clinical issues, non-HVOO-related death) or poor(surgical correction, recurrent HVOO, or HVOOrelated death). RESULTS: Fifteen patients meeting inclusion criteria underwent 21 PTA, 658 ± 1293 d after transplant.In procedures with pre-PTA biopsy(n = 19), no difference was seen between pre-PTA gradient in 13/19 procedures with HVOO on biopsy and 6/19 procedures without HVOO(8 ± 2.4 mm Hg vs 6.8 ± 4.3 mm Hg; P = 0.35). Post-PTA, 10/21 livers had EB(29 ± 21 d) and 9/21 livers had LB(153 ± 81 d). On clinical follow-up(392 ± 773 d), HVOO on LB resulted in poor outcomes and absence of HVOO on LB resulted good outcomes. Patients with HVOO on EB(3/7 good, 4/7 poor) and no HVOO on EB(2/3 good, 1/3 poor) had mixed outcomes. CONCLUSION: Negative liver biopsy greater than 60 d after PTA accurately identifies patients with good clinical outcomes.