Abstract: A 64-year-old man with HBV-related cirrhosis presented with a liver nodule measuring 2.8 cm revealed by a routine ultrasound and concomitant increased alpha-fetoprotein (AFP) up to 400 UI/l. Contrast-enhanced CT was suggestive of hepatocellular carcinoma (HCC) and the patient underwent laser ablation procedure. Five months later, because of raised AFP up to 1600 UI/l, ultrasonography and abdominal CT were repeated, showing an increased diameter of liver nodule, measuring 3.8 cm. The patient underwent down-staged trans-arterial chemoembolization (TACE) and then was entered into the active liver transplant (LT) list. Lamivudine was already started and the patient underwent LT showing HBV-DNA serum levels <10(3) log/copies at the time of surgery. Pathological analysis performed on the explanted liver showed, instead of the suspected HCC, hepatic yolk sac tumor with the presence of typical 'Schiller-Duval bodies'. The first 12 months of postoperative follow-up were excellent, with no evidence of tumor recurrence.

Abstract: Cholestasis, induced by liver ischemia-reperfusion injury (IRI), is characterized by dilatation of bile canaliculi and loss of microvilli. Tauroursodeoxycholic acid (TUDCA) is an anti-cholestatic agent, modulating protein kinase C (PKC) alpha pathway. PKC reduces ischemic damage in several organs, its isoform alpha modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCalpha-ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzer + 10 mm TUDCA (4 degrees C for 6 h) were reperfused (37 degrees C with O(2)) with Krebs-Ringer bicarbonate + 2.5 micromol/min of Taurocholate or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCalpha and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCalpha inhibitor Go-6976. TUDCA-treated livers showed increased bile flow (0.25+/-0.17 vs. 0.042+/-0.02 microl/min/g liver, P<0.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCalpha and ezrin expression (P=0.03 and P=0.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCalpha inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCalpha-ezrin pathway.

Abstract: BACKGROUND: Patients with hepatopulmonary syndrome (HPS) with end-stage liver disease (ESLD) have higher cardiorespiratory mortality than those without. The aims of this study were to determine whether echocardiography could distinguish patients with ESLD with and without HPS and whether the diagnosis of HPS by contrast echocardiography (CE) was altered by the performance of the test in a supine or standing position. METHODS: Subjects were recruited prospectively from patients with end-stage liver disease undergoing assessment for liver transplantation. Hepatopulmonary syndrome was diagnosed on the basis of arterial blood gas analysis, lung function testing and agitated saline contrast echocardiography in the absence of primary cardiac or pulmonary disease. Bubble contrast injections were performed supine or standing in a randomised order and read by a blinded observer. RESULTS: CE showed late right-to-left shunting in 13 of 50 consecutive patients with cirrhosis (26%). Eight patients (16%) had definite diagnoses of HPS. CE in the standing position consistently increased both the number and the size of shunts compared with supine injection. CE detected intrapulmonary shunting before a change in arterial blood gases. Standard echocardiographic parameters did not distinguish between those with and without HPS. CONCLUSION: This study suggests that screening for HPS in patients with advanced cirrhosis should be done using CE with patients in the upright position.

Abstract: BACKGROUND/AIMS: HCV-related disease recurrence progresses rapidly after liver transplantation. We hypothesised that withdrawal of immunosuppression might favourably impact on disease progression. METHODS: Weaning off immunosuppression was attempted in 34 HCV-RNA positive patients (mean age 62+/-6.4 years) transplanted 63.5+/-20.1 months earlier, under cyclosporine A monotherapy. Patients were followed for 3 years including yearly protocol liver biopsies. Primary endpoints were feasibility of weaning off immunosuppression and its impact on disease progression. Secondary endpoint was to identify predictors of an immunosuppression-free state and fibrosis progression. RESULTS: Complete and permanent immunosuppression withdrawal was achieved in 8 patients (23.4%), whereas 14 (41.2%) developed rejection within eight months despite an initial response and 12 (35.2%) rejected during tapering. After a mean follow-up 45.5+/-5.8 months weaned patients showed stabilisation/improvement of histological fibrosis (P<0.01), lower necro-inflammation (P<0.02) and improved liver function (P<0.05) compared to weaning-intolerants. Multiple logistic regression identified low blood cyclosporine A trough levels during the first post-transplant week (P=0.004) and initial steroid-free immunosuppression (P<0.008) as independent predictors of sustained weaning. Achievement of immunosoppression freedom (P=0.02) and baseline staging score (P<0.0001) were independently associated with stabilisation/improvement of histological fibrosis. CONCLUSIONS: Reconstitution of immune-competence in the host improves the natural history of HCV recurrence in the graft.

Abstract: A 37-year-old male liver transplant recipient developed hemorrhagic shock from massive rectal bleeding a few hours after a protocol liver biopsy. Conservative treatment was not possible and the patient underwent a radiological investigation of the celiac and mesenteric arterial trunks, which showed active bleeding from a branch of the middle colic artery. Embolization with Tabotamp (Ethicon, Neuchatel, CH Switzerland) particles led to successful hemostasis. We thus discuss the possible mechanisms of injury. To our knowledge, no other cases of major rectal bleeding following percutaneous liver biopsy have been reported in the literature. We emphasize the need for Doppler ultrasound assistance, in terms of either preoperative examination with or without marking or guidance. The latter is the safest and most reliable technique, given the low risk of puncture of other organs and the low probability of obtaining an inadequate sample.

Abstract: Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction. MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.

Abstract: Portal vein thrombosis (PVT) is a frequent finding in liver transplantation, the management of which depends mainly on its extent. In cases of mild to moderate PVT, a low dissection of the portal trunk, a jump graft, or direct implantation of graft portal vein into large venous collaterals or thrombectomy offer alternatives. For severe PVT anecdotal reports suggest that cavoportal hemitransposition, portal arterialization, or combined liver and intestine transplantation may be attempted, although the results to date are not satisfactory. When extensive perivenous and venous inflammatory changes reach the infrapancreatic region, liver transplantation probably should not be performed due to the high mortality rate.

Abstract: Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.