An Imaging Biomarker for Assessing Hepatic Function in Patients With Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: We aimed to evaluate the potential of hepatobiliary phase magnetic resonance imaging (MRI) as parameter for assessment of hepatocellular function in patients with primary sclerosing cholangitis (PSC). METHODS: We collected data from 111 patients (83 male, 28 female; median, 44 years old), from March 2012 through March 2016, with a confirmed diagnosis of PSC who underwent MRI evaluation before and after injection (hepatobiliary phase) of a hepatocyte-specific contrast agent (gadoxetate disodium). Signal intensities were measured in each liver segment. Mean relative enhancement values were calculated and correlated with findings from liver functions tests, prognostic scoring systems (model for end-stage liver disease [MELD] score; Mayo risk score; Amsterdam-Oxford-PSC score), abnormalities detected by endoscopic retrograde cholangiopancreatography (using the Amsterdam cholangiographic classification system), and clinical endpoints (liver transplantation, cholangiocarcinoma, liver-related death). Our primary aim was to associate relative enhancement values with liver function and patient outcomes. RESULTS: Most patients had moderate-stage disease and had intermediate levels of risk (median MELD score, 8 and median Mayo score, 0.27). Clinical endpoints were reached by 21 patients (6 developed cholangiocarcinoma, 8 underwent liver transplantation, and 7 patients died). The highest levels of correlations were observed for relative enhancement 20 min after contrast injection and level of alkaline phosphatase (r = -0.636), bilirubin (r = -0.646), albumin (r = 0.538); as well as international normalized ratio (r = 0.456); MELD score (r = -0.587); Mayo risk score (r = -0.535), and Amsterdam-Oxford model score (r = -0.595) (P < .0001). Relative enhancement correlated with all clinical endpoints (all P < .05). A cutoff relative enhancement value of 0.65 identified patients with a clinical endpoint with 73.9% sensitivity 92.9% specificity (area under the receiver operating characteristic curve, 0.901; likelihood ratio, 10.34; P < .0001). CONCLUSIONS: In an analysis of 111 patients with PSC, we found MRI-measured relative enhancement, using a hepatocyte-specific contrast agent, to identify patients with clinical outcomes with 73.9% sensitivity 92.9% specificity. Long-term, multicenter studies are needed to further evaluate this marker of PSC progression.

Evaluation of living liver donors using contrast enhanced multidetector CT - The radiologists impact on donor selection.

BACKGROUND: Living donor liver transplantation (LDLT) is a valuable and legitimate treatment for patients with end-stage liver disease. Computed tomography (CT) has proven to be an important tool in the process of donor evaluation. The purpose of this study was to evaluate the significance of CT in the donor selection process. METHODS: Between May 1999 and October 2010 170 candidate donors underwent biphasic CT. We retrospectively reviewed the results of the CT and liver volumetry, and assessed reasons for rejection. RESULTS: 89 candidates underwent partial liver resection (52.4%). Based on the results of liver CT and volumetry 22 candidates were excluded as donors (31% of the cases). Reasons included fatty liver (n = 9), vascular anatomical variants (n = 4), incidental finding of hemangioma and focal nodular hyperplasia (n = 1) and small (n = 5) or large for size (n = 5) graft volume. CONCLUSION: CT based imaging of the liver in combination with dedicated software plays a key role in the process of evaluation of candidates for LDLT. It may account for up to 1/3 of the contraindications for LDLT.

The dilemma of living liver donor death: to report or not to report?

Living donor liver transplantation has become a life-saving alternative for end-stage liver disease patients who have no chance of receiving a deceased donor organ. On the basis of information available to the medical community, mortality risk for the living donor is reviewed and implications of not reporting donor deaths are discussed.

Death of a living liver donor from illicit drugs.

In children with acute hepatic failure, it has been suggested to offer living donor transplantation to all parents when a deceased donor organ can not be provided. Ethically, living related donation is coercive by its very nature, especially in emergencies. We report a 36-year-old woman who died from a drug overdose 57 days after living donor liver resection. The recipient was her 3-year-old son, who experienced acute hepatic failure as a result of acetaminophen intoxication. A deceased donor organ had not become available within 2 days after listing. Was the death of this living donor preventable or unpreventable? Certainly if the mother had decided not to take drugs, she would not have died from an overdose. One could argue that this was her personal choice, and beyond our influence. On the other hand, if we had not performed the surgery, the recipient might have died without receiving a liver transplant in time.

Adult-to-adult right lobe living donor liver transplantation: comparison of endoscopic retrograde cholangiography with standard T2-weighted magnetic resonance cholangiography for evaluation of donor biliary anatomy.

AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, postoperatively. METHODS: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (>=2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.

Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis C virus related cirrhosis.

AIM: Steroids can increase hepatitis C virus (HCV) replication. After liver transplantation (LTx), steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages. Steroids can worsen the outcome of recurrent HCV infection. Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS: Thirty patients undergoing LTx received initial steroid-free immunosuppression. Indication for LTx included 7 patients with HCV related cirrhosis. Initial immunosuppression consisted of tacrolimus 2X0.05 mg/kg.d po and mycophenolate mofetil (MMF) 2X15 mg/kg.d po. The tacrolimus dosage was adjusted to trough levels in the target range of 10-15 microg/L during the first 3 mo and 5-10 microg/L thereafter. Manifestations of acute rejection were verified histologically. RESULTS: Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years. Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient. All HCV-infected patients had HCV genotype II (1b). HCV seropositivity occurred within the first 4 mo after LTx. The virus load was not remarkably increased during the first year after LTx. Histologically, grafts had no severe recurrent hepatitis. CONCLUSION: From our experience, initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients. Furthermore, none of the HCV infected patients developed serious chronic liver diseases. It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

Histidine-tryptophan-ketoglutarate solution for organ preservation in human liver transplantation-a prospective multi-centre observation study.

Based on experimental work and clinical small studies, histidine-tryptophan-ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.

Experience with hystidine tryptophan ketoglutarate versus University Wisconsin preservation solutions in transplantation.

We present our experience with histidine tryptophan ketoglutarate (HTK) and University Wisconsin (UW) preservation solutions in liver transplantation and a review of the literature in pancreas and kidney transplantation comparing these solutions. A group of 134 liver transplantations in 123 recipients was analyzed retrospectively. Grafts procured in adults were perfused with HTK in 63 cases and with UW in 71 cases. We compared results according to preoperative, intraoperative, and postoperative parameters, as well as complications and survival. No differences regarding donor and recipient data, intraoperative fresh frozen plasma (FFP) substitution, length of intensive care unit (ICU) stay, and ischemic damage of the graft were found. The rate of complications was comparable in both groups. However, the bilirubin was higher in the UW group. The rate of biliary complications was higher in the UW group (n = 8) versus the HTK group (n = 5). HTK ischemic type biliary lesions (ITBL) were only present in the UW group. Patient and graft survival were statistically nonsignificant. The data confirm that HTK and UW, with exception of biliary complications, are considered comparable in clinical liver transplantation. The same conclusion can be taken from the literature analyzed concerning renal transplantation, and in smaller groups of pancreas transplants, similar results were published.

IHPBA concordant classification of primary liver cancer: working group report.

The working group of the International Scientific Committee of the International Hepato-Pancreato-Biliary Association(IHPBA) examined conventional staging systems and decided to establish a new staging system that depended on macroscopic findings after liver resection. The TNM/International Union Against Cancer (UICC) classification has been widely used but is too complicated. Vauthey and colleagues, and the Liver Cancer Study Group of Japan (LCSGJ) have proposed new simplified classifications. These are compared and discussed. The IHPBA working group proposed a new classification, as follows. T factor. 1. Solitary 2. No more than 2 cm 3. No vascular invasion to portal vein, hepatic vein, and bile duct T1 meets all of the above three requirements.T2 meets two of the three requirements.T3 meets one of the three requirements.T4 does not meet any requirements. Stage: I T1N0M0 II T2N0M0 III T3N0M0IV A T4N0M0 Any TN1M0 IV B Any T/N, M1 The survival curves of each stage were separated clearly (P < 0.0001). The staging system is easy to remember and easy to use. We hope this staging system will be generally used in future.

Transplantation for liver tumors: current status.

The question of liver transplantation for hepatobiliary malignancy has continued to generate controversial discussion. As shown by single-center studies and large databases, there is a clear indication for total hepatectomy and liver replacement under the premises of appropriate selection of suitable patients as well as of favorable type and stage of tumors. Future improvement of tumor-free patient survival can be expected from better understanding of tumor biology, including prevention and earlier detection of cancer, and effective multimodality treatment strategies.