Liver transplantation for hepatocellular carcinoma (HCC) in patients with cirrhosis is a radical treatment of the tumor and associated precancerous state. It is potentially curative in a proportion of patients. The outcomes of early studies of liver transplantation in this indication were initially unfavorable. Selection of transplant candidates at an early stage, in the absence of extrahepatic spread, gives better survival than surgical resection and alternative nonsurgical treatments. Transarterial chemoembolization can be used for preoperative control of the disease. Adjuvant chemotherapy may be indicated in the postoperative period for the prevention of recurrence in patients with histologic features of invasiveness in the surgical specimen. Liver transplantation as the treatment of choice for early HCC in screening programs in cirrhotic patients may become limited by graft availability as the numbers of hepatitis C-related cases increase. Resection may be indicated if the waiting time is likely to be long.

No abstract

Summary Caroli's disease (CD) or syndrome (CS) are rare inherited disorders which may cause severe, life‐threatening, cholangitis or which may lead to hepatobiliary degeneration. The typical cystic biliary anomalies are often associated to congenital hepatic fibrosis (CHF) and, less frequently, to cystic renal disease especially autosomic recessive polycystic kidney disease (ARPKD). The place of liver transplantation (LT) in the treatment of CD or CS is evaluated based on our own experience of three successfully transplanted patients, the literature review of 19 patients and the European experience with 110 patients collected in the European Liver Transplant Registry. LT should be proposed as a definitive therapeutic option once severe cholangitis or (suspicion of) malignant transformation is present. The frequently used radiological, endoscopical or surgical biliary drainage procedures carry a high morbidity and mortality rate. In case of concomitant symptomatic CHF and renal failure, combined or sequential hepatorenal transplantation should be carried out, dependant on the evolution of the hepatic and renal disease. In case of associated ARPKD, renal transplantation is often indicated early on because of the more rapid progression of the renal component of the disease.

The toxic effects and tissue uptake of both cisplatin and oxaliplatin--[(1R, 2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O']platinum--were previously shown to vary similarly according to dosing time in mice. A 4-hour infusion of cisplatin resulted in fewer side effects and allowed administration of higher doses at 16 hours than at 4 hours in patients with cancer. We hypothesized that the continuous venous infusion of oxaliplatin for 5 days would be less toxic and would deliver a higher dose to the patient if the drug were infused at a circadian rhythm-modulated rate (peak at 16 hr; schedule B) rather than at a constant rate (schedule A). We tested this hypothesis in a randomized phase I trial. We escalated the dose of oxaliplatin to the patient by 25 mg/m2 per course. Courses were repeated every 3 weeks. An external, multichannel, programmable-in-time pump was used for the infusions. Toxicity was assessable for 94 courses in 23 patients (12 patients with breast carcinoma, nine with hepatocellular carcinoma, and two with cholangiocarcinoma). The incidence of neutropenia of World Health Organization grades II-IV and the incidence of distal paresthesias were 10 or more times higher (P less than .05) with schedule A than with schedule B. In addition, vomiting was 55% higher (P = .15) with schedule A than with schedule B. Furthermore, with schedule B, the mean dose of oxaliplatin (P less than .001) and its maximum tolerated dose (P = .06) could be increased by 15% over those doses with schedule A. An objective response was achieved in two of the 12 patients with previously treated breast cancer. We recommend that the dose of oxaliplatin for phase II trials be 175 mg/m2, delivered according to the circadian rhythm-modulated rate.

Summary Background The importance of primary biliary cholangitis as an indication for liver transplantation has probably been influenced by the introduction of therapies, and changes in selection criteria and disease epidemiology. Aims To assess the time trends in liver transplantation for primary biliary cholangitis and to evaluate the characteristics of the patient population during the past three decades. Methods Patients undergoing liver transplantation from 1986 to 2015 in centres reporting to the European Liver Transplantation Registry were included. We excluded combined organ transplantations and patients <18 years. Trends were assessed using linear regression models. Results We included 112 874 patients, of whom 6029 (5.3%) had primary biliary cholangitis. After an initial increase in the first decade, the annual number of liver transplantation for primary biliary cholangitis remained stable at around 200. The proportion of liver transplantations for primary biliary cholangitis decreased from 20% in 1986 to 4% in 2015 ( P < 0.001). Primary biliary cholangitis was the only indication showing a consistent proportional decrease throughout all decades. From the first to the third decade, the age at liver transplantation increased from 54 (IQR 47‐59) to 56 years (IQR 48‐62) and the proportion of males increased from 11% to 15% (both P < 0.001). Conclusions We have found a proportional decrease in primary biliary cholangitis as indication for liver transplantation. However, despite treatment with ursodeoxycholic acid and improved disease awareness, the absolute annual number of liver transplantations has stabilised.

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case‐by‐case basis. In this report, we propose a simplified approach to this decision‐making process.

A variety of renal diseases can be associated with end-stage liver diseases requiring orthotopic liver transplantation (OLT), including cirrhosis-associated glomerulonephritis (GN), and nephropathy unrelated to the liver disease. A retrospective survey showed that nine patients undergoing liver transplantation in our centre had histologically proven GN or interstitial nephritis with renal failure and/or nephrotic-range proteinuria, and experienced severe complications post-OLT since nephrotoxic immunosuppressive drugs (CsA and FK506) could not be adequately given. Four of the nine patients died. Therefore, combined liver-kidney transplantation has been suggested as first choice treatment in such patients. From January 1990 to February 1994, in patients with end-stage liver disease referred for OLT, and who presented with unexplained renal function impairment and/or significant proteinuria, severe nephropathy was confirmed by renal biopsy in nine: four mesangiocapillary GN with immune deposits, one membranous nephropathy, two diabetic glomerulosclerosis and two interstitial nephritis. All underwent liver transplantation immediately followed by kidney transplantation. The postoperative period was uneventful, and neither death nor renal failure were recorded. Combined transplantation resulted in all patients in the normalization of renal function, and in the disappearance of proteinuria within the first postoperative month. From 6 months to 4 years post-transplant, the renal function remained within normal ranges in all patients. Routine renal transplant biopsy was performed in two patients with pre-transplant cirrhosis-associated GN, and showed no evidence of recurrence of the original nephropathy. We conclude that combined liver-kidney transplantation is an adequate therapeutic option in patients with end-stage liver disease associated with advanced kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract