L. Toti

Glycogen Storage Disease Type Ia and VI Associated With Hepatocellular Carcinoma: Two Case Reports

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism due to intracellular enzyme deficiency resulting in abnormal storage of glycogen in tissues. GSD represents an indication for liver transplantation (OLT) when medical treatment fails to control the metabolic dysfunction and/or there is an high risk of malignant transformation of hepatocellular adenomas (HCA). Herein we have reported two cases of GSD, type Ia and type VI, which were both associated with rapidly growing HCA, and underwent OLT because of suspect changes in their radiological features. Final histological findings in the explanted liver showed the presence of hepatocellular carcinoma (HCC) in both cases. In GSD type Ia and VI, OLT is considered to be the treatment of choice when a liver neoplasm is suspected. While the association of HCC with GSD type Ia is well known, this is the first case of HCC in GSD type VI so far reported to the best of our knowledge.

TUDCA prevents cholestasis and canalicular damage induced by ischemia‐reperfusion injury in the rat, modulating PKCα–ezrin pathway

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) α pathway. PKC reduces ischemic damage in several organs, its isoform α modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCα–ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzeru2003+u200310u2003mm TUDCA (4u2003°C for 6u2003h) were reperfused (37u2003°C with O2) with Krebs–Ringer bicarbonateu2003+u20032.5u2003μmol/min of Taurocholate or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCα and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCα inhibitor Go‐6976. TUDCA‐treated livers showed increased bile flow (0.25u2003±u20030.17 vs. 0.042u2003±u20030.02u2003μl/min/g liver, Pu2003<u20030.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCα and ezrin expression (Pu2003=u20030.03 and Pu2003=u20030.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCα inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCα–ezrin pathway.

Everolimus and Enteric-Coated Mycophenolate Sodium Ab Initio after Liver Transplantation: Midterm Results

BACKGROUND AND AIMnEverolimus (EVR) use in liver transplantation (OLT) has been prescribed with calcineurin inhibitors (CNIs), steroids, and monoclonal antibodies. The aim of our study was to evaluate the safety, feasibility, and impact on renal function of EVR ab initio, in combination with enteric-coated mycophenolate sodium (EC-MPS) without the use of induction treatment, steroids, or CNIs.nnnPATIENTS AND METHODSnWe retrospective analyzed nine consecutive patients who underwent OLT at our institution. The initial dose of EVR (1.5 mg/d) was adjusted to achieve trough levels of 8 to 12 ng/mL. EC-MPS introduced at 1080 mg/d was maintained at the same dose over time.nnnRESULTSnAt a mean follow-up of 21.48 (standard deviation [SD] 1.4) months from OLT, 7/9 recipients were alive with stable graft function. The 2-year patient and graft survivals were 77%. One recipient died due to cerebral hemorrhage and one, lung failure. No clinical evidence of an acute rejection episode was observed. Mean estimated glomerular filtration rate value, according to the Modification of Diet in Renal Disease formula increased from 59.5 (SD 9.89) mL/min/1.73 m(2) at OLT to 100.2 (SD 47.5) mL/min/1.73 m(2) (P = .03) after 12 months and 98.71 (SD 33.74) mL/min/1.73 m(2) (P = .03) after 24 months follow-up.nnnCONCLUSIONnA double immunosuppression therapy with EVR and EC-MPS ab initio seemed to be efficacions and safe, representing a valid alternative to CNIs to prevent renal failure after OLT.

Switch from Twice-Daily Tacrolimus (Prograf) to Once-Daily Prolonged-Release Tacrolimus (Advagraf) in Kidney Transplantation

Advagraf is a new modified-release once-daily formulation of tacrolimus. The aim of this study was to define the efficacy and safety of switching from Prograf to Advagraf immunosuppression in kidney transplant recipients. The switched dose ratio of Prograf to Advagraf was 1:1. Forty-one patients (34 men and 7 women) were switched at 36.6 ± 16.1 months after kidney transplantation. All patients maintained stable renal function and the conversion. In 16 subjects it was possible to withdraw steroid administration after obtaining adequate Advagraf blood levels, among whom 14 remained steroid free. Adverse events, including dizziness and tinnitus, were reported in 1 patient, who was reverted to Prograf. One patient who was receiving triple therapy with low tacrolimus blood levels experienced are acute rejection episode. The switch to Advagraf was safe and efficacious in kidney transplant recipients with or without steroid administration. Moreover, interruption of steroid was possible and well tolerated after achieving adequate stable blood levels with Advagraf.

Deep Vein Thrombosis as Debut of Cytomegalovirus Infection Associated With Type II Cryoglobulinemia, With Antierythrocyte Specificity in a Kidney Transplant Recipient: A Case Report

Immunologic alterations, such as cryoglobulinemia, have been described in the acute phase of primary cytomegalovirus (CMV) infections in immunocompetent patients. There are few references about these influences of a primary CMV infection in an at-risk kidney transplant recipient (donor positive/recipient negative-D(+)/R(-)). Herein we have described the case of a 46-year-old man, who was naive for CMV and underwent renal transplantation from a CMV+ cadaveric donor, thereby at high risk for disease transmission. The immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. The recipient was not treated with CMV prophylaxis, but rather regularly screened for possible pre-emptive treatment. At 35 days after transplantation, he was admitted because of deep vein thrombosis (DVT) in the transplant ipsilateral lower limb accompanied by oliguria, fever, and epigastric pain accompanied by type II cryoglobulinemia and acute CMV infection. The direct antiglobulin test (DAT) for C3d was positive. The cryoglobulins displayed anti-red blood cell specificity, with maximum activity at 4°C. The DVT was successfully treated with locoregional thrombolysis in combination with anticoagulant therapy. The DAT improved with CMV treatment and increased steroid therapy. The urine output and renal function tests improved with resolution of the thrombosis, achieving complete recovery without sequelae. Our hypothesis was that CMV infection triggered cryoglobulinemia. The blood disorder caused hyperviscosity, inducing DVT. This case, of CMV infection showed associated cryoglobulinemia presenting with antierythrocyte specificity in a kidney transplant recipient.

Management of Spermatic Cord Liposarcoma in Renal Transplant Recipients: Case Report

Herein, we report the case of a 52-year-old man with a spermatic cord liposarcoma that developed 4 years after renal transplantation. The patient was admitted with a diagnosis of inguinal hernia. During surgical exploration, a solid mass was found arising from the spermatic cord. Histologic analysis demonstrated a well-differentiated sclerosing liposarcoma.

Longterm Survival and Cost‐Effectiveness of Immunosuppression Withdrawal After Liver Transplantation

Lifelong immunosuppression (IS) after liver transplantation is associated with severe adverse effects and increased recipients’ morbidity and mortality. Clinical operational tolerance has been reported in up to 40% in very well‐selected recipients. Longterm survival and cost savings within the Italian national health system in operational tolerant recipients is reported. Seventy‐five liver recipients were enrolled for IS withdrawal at our institution during the period from April 1998 to December 2015. The study population comprised 32 (42.7%) tolerant patients; 41 (54.7%) nontolerant patients needing uptake of IS after clinical or biopsy‐proven rejection; and 2 (2.7%) immediate nontolerant patients who developed early rejection after the first drug reduction. The primary endpoint of the study was to assess the longterm patients and graft outcome; the secondary endpoint was the assessment of cost savings in the context of IS withdrawal. The follow‐up was 95.0 months (interquartile range, 22.5‐108.5 months). IS withdrawal did not result in patient nor graft loss and resulted in a major cost savings reaching about €630,000. In conclusion, longterm IS withdrawal represents a remarkable cost savings in the health care of liver recipients without exposing them to graft loss.

Endovascular Mechanical Thromboaspiration of Right Hepatic Arterial Thrombosis After Liver Transplantation

A 56-year-old male Patient presented 27xa0days after a liver transplantation (LT) with fever and hyperbilirubinemia. He underwent CT examination resulting in a diagnosis of right hepatic artery (HA) occlusion with hepatic bilomas. Once placed a long right femoral 6F introducer at the origin of the HA, a 0.014” guidewire was advanced over the thrombus, in a segmental branch. A 4MAX (Penumbra, Alameda, USA) catheter was advanced and withdrawn under constant aspiration until complete clot removal was achieved. Follow-up CT and D-US assessments at 12xa0months demonstrated regular HA patency and bilomas reduction. Endovascular thromboaspiration is an effective strategy in cases of E-HAT after LT.