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Background: Today, women who have undergone liver transplantation enjoy better health, so they encounter more frequently the possibility of living pregnancy. Many questions about the safety of pregnancy are pending. This study analyzes pregnancy outcomes in women with a liver transplant managed at Policlinico Universitario "A.Gemelli.", Results: We identified 17 childbirths in 13 women who had undergone a liver transplant. Causes of transplant include congenital or acquired disorders. The mean age at transplant was 22 ± 9 years, mean maternal age at delivery was 33 ± 5 years, and transplant-to-pregnancy interval was 12 ± 6 years. The mean gestational week was 36.1 ± 3.5. All women had normal liver function after pregnancy. Immunosuppressive therapy before and during pregnancy included tacrolimus (n = 8), cyclosporine (n = 5) and mycophenolate mofetil (n = 1). No maternal death was registered. Maternal complications included increase of aspartate transaminase and alanine transaminase, graft deterioration requiring liver retransplantation, increase of bile acids (n = 1), itch (n = 1), and anemia (n = 1). Twelve women had a high adherence to an immunosuppressive regimen during pregnancy. A woman with poor compliance continued therapy with mycophenolic acid during pregnancy, showing preterm birth (25th week) with fetal respiratory failure. Another woman continued therapy with tacrolimus during breastfeeding without adverse effects., Conclusion: Liver transplant does not influence women's fertility; during pregnancy, we report low rates of minor graft complications and no major issues. There are no adverse effects on babies. An evaluation by a multidisciplinary team is recommended. Compliance to an immunosuppressive regimen is fundamental to ensure the stability of graft function and to prevent graft deterioration in pregnancy. Moreover, it is suggested to avoid teratogenic drugs, such as mycophenolic acid., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The increasing gap between the number of patients who could benefit from liver transplantation and the number of available donors has fueled efforts to maximize the donor pool using marginal grafts that usually were discarded for transplantation. This study included data of all patients who received decreased donor liver grafts between January 2004 and January 2013 (n = 218) with the use of a prospectively collected database. Patients with acute liver failure, retransplantation, pediatric transplantation, and split liver transplantation were excluded. Donors were classified as standard donor (SD), extended criteria donor (ECD), and overextended criteria donor (OECD). The primary endpoints of the study were early allograft primary dysfunction (PDF), primary nonfunction (PNF), and patient survival (PS), whereas incidence of major postoperative complications was the secondary endpoint. In our series we demonstrated that OECD have similar outcome in terms of survival and incidence of complication after liver transplantation as ideal grafts., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with ≥3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation., Methods: Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery., Results: We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal "tardus-parvus" waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra-hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications., Conclusions: The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Fungal infections, although less frequent than bacterial infections, represent a severe comorbidity with an exponential increase in mortality rate in liver transplantation patients. The incidence of invasive fungal infections (IFIs) after solid organ transplantation ranges from 7% to 42%, with Candida spp. and Aspergillus spp. as the most common pathogens. Fungal infections in liver transplant recipients have been associated with poor outcome and mortality rates ranging from 65% to 90% for invasive aspergillosis and 30% to 50% for invasive candidiasis. The results largely depend on early diagnosis and early initiation of specific treatment for IFIs. Therefore, the diagnosis must be prompt, preferably based on microbiological data, both cultures and biomarkers, and/or based on clinical features and known risk factors., Materials and Methods: This study evaluated the incidence of fungal infections in patients after liver transplantation in our center between January 2003 and December 2012. The retrospective analysis of 215 consecutive liver transplantation patients was undertaken to estimate incidence, risk factors, and clinical courses of IFIs in the first 3 months after liver transplantation., Results: Candidemia and invasive candidiasis microbiologically proven were found in 26 patients (12%), whereas in 6 patients (2.8%) invasive fungal infections from other non-Candida fungi developed: Aspergillus (4 cases: 2 A fumigatus, 2 A terreus), Fusarium oxysporum (1 case), and Rhodotorula rubra (1 case). Two patients with Aspergillus and the patient with Fusarium died. The patient with Rhodotorula as well as 22 of the patients with candidemia (85%) survived. All of the episodes developed during the first 3 months posttransplantation. All cases have followed a previous polymicrobial bacterial infection (especially in the biliary tract) with large use of combined antibiotic therapies., Conclusions: The rate of fungal infection was found to increase in parallel with the number of risk factors. Prophylactic strategies can decrease the risk of fungal infections. Early detection and treatment with adequate early empiric therapy is the key to obtaining a better outcome in liver transplantation patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ischemic-type biliary lesions (ITBLs) are now a discussed cause of morbidity and mortality in liver transplant recipients, even if not definitively characterized. We reviewed 13 years of donor and recipient data between April 2001 and April 2013. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, focusing on the relationship between severe macrovesicular steatosis of the graft and incidence of ITBL. A total of 445 grafts were harvested: 416 of them were transplanted at our institution, the remaining 29 were discarded by our donor team as showing more than 40% macrovesicular steatosis. Mild-moderate (20% to 40%) macrovesicular steatosis (P<.001) and cold ischemia time (P=.048) significantly increased the risk of ITBLs, also resulting in independent risk factors at multivariate analysis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate the incidence, clinical characteristics, treatment, and outcome of de novo tumors (DNT) of the upper aerodigestive tract in patients with alcoholic cirrhosis after orthotopic liver transplantation (OLT)., Methods: Among 225 consecutive OLT performed between January 2002 and January 2012, a total of 205 patients received a first liver allograft. Eleven (4.9%) patients developed DNT (lung, pancreas, bowel, esophagus, larynx, tongue, tonsil, and lymphoma). Among these, we observed 5 patients with DNT of the upper aerodigestive tract., Results: The 5 patients with DNT of the upper aerodigestive tract underwent OLT for alcoholic cirrhosis. There were 4 men and 1 woman with a mean age at transplantation of 47 years. The mean period of alcohol abuse was 90 months. The tumors occurred after a mean post-transplantation time of 39 months. The immunosuppressive regimen included Tacrolimus, mTOR, mycophenolate mofetil (MMF), and low-dose steroids. We observed 2 cases of squamous cell carcinoma of the esophagus, 1 case of tonsillar cancer, 1 case of larynx carcinoma, and 1 case of tongue carcinoma. All patients underwent surgical excision. After surgery, 4 patients received chemotherapy and 2 patients radiotherapy. At present, among the 5 patients with DNT of the upper aerodigestive tract, only 2 are alive without disease and 1 is alive with a local recurrence., Conclusion: The incidence of DNT of the upper aerodigestive tract after OLT is higher among patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of post-transplantation immunosuppression in patients exposed to alcohol before transplantation. We suggest a careful post-transplantation follow-up and more attention to improve early diagnosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Orthotopic liver transplantation (OLT) is a life-saving procedure for the treatment of many end-stage diseases, but infectious and acute rejection episodes remain major causes of morbidity and mortality. Bacterial and fungal infections can be due to intra-abdominal, biliary, respiratory, urinary, wound, central venous catheters (CVC) or unknown sources. Using the computerized database of our microbiology laboratory, we analyzed all the bacterial and fungal infections in the first three months following OLT among 151 consecutive adult recipients at single center between January 2005 and December 2011. Samples included blood, bile CVC, urine, and bronchoalveolar lavage (BAL) specimen. Culture and identification of the isolated microorganisms was done in accordance with standard microbiological procedures. Three hundred thirteen samples from the above sites showed positive results for gram-positive cocci (n = 137; 43.8%), gram-negative rods (n = 156; 49.8%), and Candida species (n = 19; 6.1%). One patient (0.3%) experienced a CVC-related infection caused by Fusarium oxysporum. Bacterial and particularly biliary tract infections seem to play major roles in morbidity and mortality in the first three months following OLT. The major contributors to patient morbidity and mortality were candidemia and/or invasive candidiasis mainly from the biliary tract and/or CVC-related infections., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Hepatic artery stenosis (HAS) is an important complication after liver transplantation. However, studies are not conclusive in terms of definition, incidence, best treatment, and timing of intervention. The aim of this study was to evaluate the incidence of SSHA that occurred in a single center over the past 12 years, pointing out diagnostic and therapeutic strategies., Methods: The incidence of HAS was reviewed in 258 liver transplant recipients between January 1999 and December 2011. All patients underwent Doppler ultrasound (DUS) at fixed times. Multidetector computed tomographic angiography (MDCTA) was performed to confirm the DUS findings., Results: HAS occurred in 23 cases (9.3%). In all cases diagnosis was performed by DUS resulting in a sensitivity of 100% and a specificity of 99.6%. Based on DUS and MDCTA data integration, in 10 cases we adopted the "wait and see" strategy, whereas 13 patients underwent interventional radiology techniques., Conclusion: DUS monitoring is efficacious in the diagnosis of HAS after liver transplantation. Interventional radiology procedures are safe and efficacious., (Copyright © 2013. Published by Elsevier Inc.)

Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major cause of morbidity in liver transplant recipients, significantly affecting the chance of survival of both patients and grafts. We retrospectively reviewed 10 years of prospectively collected donor and recipient data from April 2001 to April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, including donor and recipient data. Two hundred fifty-one grafts were harvested: 222 of them were transplanted at our institution, the remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular steatosis. Mild-moderate (20%-40%) macrovesicular steatosis (P < .001) and cold ischemia time (P = .048) significantly increased the risk of ITBL, also as an independent risk factor after multivariate analysis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: In the last years, the incidence of Candida infections in liver transplant recipients has increased with still higher morbidity and mortality. Anidulafungin, a new echinocandin that does not interfere with cytochrome p450, shows no need for dosage adjustment based upon renal or hepatic function or weight., Aim: To analyze tolerance to and microbiologic and clinical efficacy of Anidulafungin to treat Candida infections in liver transplant patients., Materials and Methods: This phase 3b, prospective, open-label, single-center study focused on liver transplant patients with a suspected and/or diagnosed Candida infection. The patients received Anidulafungin intravenously, optionally followed by oral therapy with azoles. The primary endpoint was the global response at the end of therapy; secondary endpoints were the efficacy of intravenous therapy, 90-day survival, as well as tolerance for and interaction with immunosuppresants., Results: We considered 42 consecutive liver recipients transplanted between 2009 and 2010 among whom 13 (31%) were recruited for the study and four patients were treated with Anidulafungin as empirical therapy, six as preemptive therapy, and three as targeted treatment for documented candidemia (7.1%). The immunosuppressive regimen consisted of tacrolimus and low dose of steroids. The Candida species were: C albicans (50%), C glabrata (12.5%), C parapsilosis (12.5%), C krusei (12.5%), C lusitaniae (6.2%), C tropicalis (6.2%), and multiple others (25%). The principle site of isolation was the bile (53.8%), followed by the bloodstream (23.1%), central venous catheters (15.4%), bronchoalveolar lavage (15.4%), peritoneum (7.7%), and other locations (7.7%). Two patients (15.4%) died of severe sepsis with multiple organ failure. There was no alteration of hepatic enzymes, indices of cholestasis or changes in immunosuppressant drug levels., Conclusion: Anidulafungin was an effective, safe, and well-tolerated drug. There were neither toxic effects to the grafts or adverse interactions with immunosuppresants., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Liver transplantation (OLT) is a lifesaving procedure for the treatment of many end-stage liver diseases, but infection and acute rejection episodes still remain the main causes of morbidity and mortality. Bloodstream infections (BSIs), particularly, are the major cause of mortality among these patients. BSIs in OLT, are from intra-abdominal, biliary, respiratory, urinary, wound and/or central venous catheter sources. A certain percentage are of unknown origin. Using the computerized database of our microbiology laboratory, we analyzed all BSIs in 75 consecutive adult liver transplant patients in a single center between January 2008 and July 2011. BSIs occurred in 21/75 (28%) patients. Thirteen subjects had a single; two, two episodes, and the other six patients each >4 episodes. All episodes occurred in the first 60 days following OLT; the majority (74%), in the first month. Among 44 microorganisms recovered, 52.3% were gram-negative, the most frequent being Pseudomonas aeruginosa and Klebsiella pneumoniae; 47.7% were gram-positive, the most frequent being coagulase-negative staphylococci, particularly Staphylococcus epidermidis. Overall 65.9% of the isolates were resistant to several antibiotics: 40.9% displayed the multiding-resistant and 25% the panding-resistant phenotype. There was a high incidence of gram-negative and most importantly, resistant bacteria, which required appropriate therapy. These data showed that it is imperative to promote strategies to prevention and contain antimicrobial resistance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The gap between the availability of livers from organ donors and the increased demand has led many centers to apply strategies to reduce this deficit. Splitting of cadaveric organs for use in 2 recipients; domino transplantation; and organs from living donors, non-heart-beating donors, and extended-criteria donors (ECDs) are all currently used in orthotopic liver transplantation (OLT). Fatty changes in the donor liver are a risk factor for poor function after OLT; however, the presence of steatosis, frequently present in livers from ECDs, does not exclude the use of these organs. Since January 2000 at our institution, we observed 39 steatotic grafts that were stratified istologically as follows: low steatosis, 5% to 15%; mild steatosis, 16% to 30%; moderate steatosis, 31% to 60%; and severe steatosis (>60%). Histologic techniques can enable identification of the type of fatty change as macrovesicular and microvesicular. These alterations have different effects on primary nonfunction and primary dysfunction. Fifteen grafts, all with severe or moderate, macrovesicular changes were discarded. Twenty-four fatty grafts with low to moderate steatosis were utilized for transplant. Sections from 2 liver biopsies (1 wedge in the left lobe and 1 needle in the right lobe) were stained with hematoxylin-eosin, Masson trichrome, Gomori reticulin, and oil red O. The OLT was performed only in patients with a MELD (Model for End-Stage Liver Disease) score lower than 27. The rate of primary dysfunction was 12.5%, and of primary nonfunction 8.4%. The 6-month graft survival for all fatty livers was 80%. We encourage the careful use of grafts with low to moderate steatosis in recipients without additional risks.

Enteric-coated mycophenolate sodium (EC-MPS) is a formulation of mycophenolic acid (MPA) that releases the active molecule in the intestine reducing drug-related gastrointestinal (GI) side effects. The aim of present work was to summarize the use of EC-MPS for one-way conversion from mycophenolate mofetil (MMF) due to GI side effects and for de novo administration in a stable liver transplant population. In 10 patients on MMF and low-dose calcineurin inhibitors (CNI), significant GI side effects suggested drug conversion to ameliorate subjective symptoms. In 5 patients, EC-MPS was initiated de novo together with reduction of CNI for prevention of long-term renal failure. Conversion was carried out at equivalent MMF/EC-MPS dosages. Reevaluation at 2 months after conversion showed that no episode of rejection or infection occurred, and white blood cell count, CNI levels and doses, and creatinine clearance did not vary significantly. In 70% of converted patients there was a reduction of GI symptoms, especially diarrhea. Eighty percent suspended proton pump inhibitors. The de novo-treated patients showed no significant GI side effects. In conclusion, conversion from MMF to EC-MPS demonstrated significant GI symptom relief and de novo drug administration was well tolerated.

The indications for liver transplantation among patients with post-hepatitis B virus (HBV)-related cirrhosis have changed over the past 35 years. We reviewed the long-term results of 47 patients treated with liver transplantation for HBV-related cirrhosis. Patients were classified into 3 groups according to the perioperative regimen. In the initial experience, no immunoprophylaxis was adopted (no-IP; n=5). From 1988-1996, an immunoprophylaxis scheme was adopted (HBIg; n=16). From 1997-2007, we adopted the combination of lamivudine and HBIg (LAM-HBIg; n=26). We calculated the prevalence of serological reinfection and patient survival at 1 to 20 years, using the 3 regimens. The recurrence rate was 75% in the group of untreated patients; 30% in the HBIg group; and 9% in the LAM-HBIg group. The overall survival was 67% at 5 years, and 64% at 10 and 20 years. The long-term survival for each of the 3 therapeutic approaches, namely, for the patients who did not receive any treatment, for the HBIg group, and for the LAM-HBIg group, were 20%, 50%, and 84%, respectively. We suggest to use the LAM-HBIg combination.

In liver transplantation the identification of risk factors and the risk quantification for each single case represent a field of great interest. There are donor-related and recipient-related risk factors. Donor risk index (DRI) was retrospectively calculated in 223 liver transplant cases. We did not include patients with preoperative diagnosis of hepatocarcinoma and retransplants. The cases were stratified into two classes according to the DRI (low risk, DRI<1.7, and high risk, DRI >or= 1.7). A new index, namely the organ patient index (OPI) was calculated adding the Model for End-stage Liver Disease (MELD) score to the DRI. Patients were stratified into two classes according to the OPI (low risk, OPI 2.85). The cases with low DRI (n=144) showed better survival than the cases with high DRI (n=82; P< .02). The cases with low OPI (n=173) showed better survival than cases with high OPI (n=50; P< .01). The OPI predicted outcomes better than DRI, increasing the gap in the long-term graft survival between the low- and the high-risk class. The inclusion of the MELD in the new index allowed better prediction of graft survival.

MELD and PELD scores of 255 consecutive grafts were calculated (236 adult cases and 19 pediatric cases). No correction for the etiology of liver disease was performed. Retransplants were excluded. Three categories of patients were identified: low MELD (scores <12, n = 61); intermediate MELD (scores between 12-24, n = 159); high MELD (scores > or =25, n = 35). Grafts were categorized according to donor quality: standard livers (n = 199), vs nonstandard livers (n = 56). Nonstandard livers were identified by age > or =60, or at least by two of the following conditions: severe hemodynamic instability, ultrasound evidence of steatosis, natriemia > or =155 mEq/L, ICU stay >7 days, liver trauma, protracted anoxia as cause of brain death, transaminases levels x 4. In standard livers, the 12-month graft survival (GS) for low, intermediate, and high MELD classes were 88%, 74%, and 77%, respectively. In nonstandard livers, the 12-month GS for the low, intermediate, and high MELD classes were 84%, 55%, and 44%, respectively; differences between low MELD class and both intermediate and high MELD classes were significant (P < .05). Cox regression analysis of all cases identified the following parameters as independent predictors of GS: donor status; donor age; and recipient creatinine. The highest correlation with GS was found using donor age and recipient creatinine as covariates. In standard livers no variable was able to predict GS. In nonstandard livers the MELD-PELD score was the unique variable able to predict GS. We suggest avoiding the use of nonstandard livers for patients with high MELD scores.

We described the characteristics of livers already labeled as marginal, nonstandard, or selected with extended criteria: donors of elderly age, steatosis, hemodynamic instability, long cold ischemia time, high serum Na, HbcAb-positive status, HCVAb-positive status. Recipients characteristics (gender, UNOS status, MELD score, indication for transplantation) and their best possible match to nonstandard donors were evaluated with a report of the recent guidelines and the specific algorithms to optimize recipient identification.

The University of Wisconsin solution (UW) and the Bretschneider solution (HTK) were used in 39 adult cadaveric donors: 22 perfused with UW (group 1) and 17 with HTK (group II). Donors were flushed through the aorta (UW, 5 to 6 L; HTK, 8 to 10 L) and through the portal vein (UW or HTK, 1 L). Grafts perfused with HTK showed lower levels of SGOT at postoperative day 7 than those transplanted with UW (38 +/- 19 vs 58 +/- 31, P < .05). No difference was observed in other functional and outcome parameters. No cases of primary dysfunction were observed. Six-month graft survival was 85.7% in HTK group and 80.9% in UW group (P = NS). Six unrelated deaths were observed. Five biliary complications were observed in five patients: three in the UW group and two in the HTK group. In conclusion, data fail to show major differences between the two solutions used.

The model for End-stage Liver Disease (MELD) has been adopted by the Organ Procurement and Transplantation Network (OPTN) in 2002 as the standard priority rule for the liver transplantation waiting list. We retrospectively calculated the pretransplant MELD scores of 226 consecutive adult grafts. We did not correct for hepatocellular carcinoma comorbidity or for the etiology of liver disease. Cases were categorized according to the MELD score: class I, MELD scores between 6 and 14 (low MELD, n = 116); class II, MELD score between 15 and 24 (intermediate MELD, n = 78); class III, MELD score between 25 and 42 (high MELD, n = 32). All patients were transplanted using deceased donors. Grafts were categorized also according to donor quality (standard donor vs nonstandard donor). Sorting into categories was performed before transplant by officers of the Central-South Italian Transplant Organization overregional organ procurement agencies, namely OCST. Differences in Kaplan-Meier graft survivals (GS) between low MELD class and high MELD class were statistically significant (P < .01). Among standard donors, the 6-month GS were 83%, 94%, and 63% for the low, intermediate, and high MELD subset, respectively, differences that did not reach statistical significance. Among nonstandard donors, the 6-month GS were 77%, 71%, and 38% for the low, intermediate, and high MELD classes, respectively. Differences between low MELD class and intermediate MELD class and between low MELD class and high MELD class were statistically significant (P < .01). We strongly suggest that the utilization of nonstandard organs should be avoided for patients with high MELD scores.