Continuous Renal Replacement Therapy after Liver Transplantation: Peri-Operative Associated Factors and Impact on Survival.

Continuous renal replacement therapy (CRRT) following orthotopic liver transplantation (OLT) is usually started for multifactorial reasons, with variable incidence among series. This paper presents a single-center retrospective observational study on the early use (within one week) of CRRT after consecutive cadaveric OLT from January 2008 to December 2016. Preoperative patient characteristics and intraoperative data were collected, and patients were divided into two groups (CRRT and no CRRT) to explore the factors associated with the use of CRRT. Repeated measurements of postoperative creatinine were analyzed with generalized estimating equation (GEE) models. Among 528 OLT patients, 75 (14.2%) were treated with CRRT at least once in the first week. Patients treated with CRRT showed lower survival in a Kaplan−Meier curve (log-rank p value < 0.01). Patients treated with CRRT had a more severe preoperative profile, with a significantly higher age, MELD, BUN, creatinine, and total bilirubin, as well as a longer surgery time and a higher number of transfusions of red blood cells, plasma, and platelets (all p values < 0.05). In a stepwise multiple analysis, the following characteristics remained independently associated with the use of CRRT: the MELD score OR 1.12 (95% CL: 1.07−1.16), p value < 0.001, and the preoperative value for blood urea nitrogen OR 1.016 (95% CL: 1.010−1.023), p value < 0.001. The early use of CRRT after OLT occurred at a low rate in this large cohort; however, it was associated with worse outcomes. Apart from the preoperative severity, repeated intraoperative hypotension episodes, which were likely modifiable or preventable, were associated with the increased use of CRRT and higher postoperative creatinine.

2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation.

BACKGROUND: Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). AIM: This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. METHODS: Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. RESULTS: Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4 weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. CONCLUSIONS: These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.

Immunosuppressive regimens for adult liver transplant recipients in real-life practice: consensus recommendations from an Italian Working Group.

It is a well-recognized fact that implementing new guidelines in clinical practice may be difficult; therefore the Italian Society for Organ and Tissue Transplantation (SITO) set out to define practical immunosuppression tools for the management of liver transplantation patients. In 2017, an Italian Working Group of liver transplant experts and hepatologists issued a set of consensus statements along with evidence-based recommendations on the use of everolimus after liver transplantation. This article presents the evidence- and consensus-based algorithms developed within the Italian Working Group, which are aimed towards guiding clinicians in the selection of immunosuppressive regimens for the management of adult liver transplant recipients in real-life practice. The liver transplant recipient population, typically managed in clinical practice, was divided into the following categories: (1) standard patients; (2) critically ill patients; (3) patients with a specific etiology; (4) patients with hepatocellular carcinoma; (5) and patients with de novo malignancies. The algorithms are divided into two parts, according to the time from transplantation (0-3 months and > 3 months) and are discussed here along with relevant supporting literature, when available. Ultimately, it is hoped that the evidence- and consensus-based algorithms developed within the Italian Working Group, and presented here, contribute to simplify, personalize, and optimize immunosuppression of liver transplantation recipients in clinical practice.

Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial.

BACKGROUND: Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging. METHODS: We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18-65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov, NCT01387503. FINDINGS: Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4-11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60-85). 5-year tumour event-free survival was 76·8% (95% CI 60·8-96·9) in the transplantation group versus 18·3% (7·1-47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07-0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9-97·1) in the transplantation group versus 31·2% (16·6-58·5) in the control group (HR 0·32, 95% CI 0·11-0·92; p=0·035). The most common registered grade 3-4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation). INTERPRETATION: Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria. FUNDING: Italian Ministry of Health.

Radiation exposure during transjugular intrahepatic portosystemic shunt creation in patients with complete portal vein thrombosis or portal cavernoma.

BACKGROUND: This study aims to evaluate radiation exposure in patients with complete portal vein thrombosis (CPVT) or portal cavernoma (PC) undergoing transjugular intrahepatic portosystemic shunt (TIPS) creation using real-time ultrasound guidance for portal vein targeting. MATERIALS AND METHODS: This is a single institution retrospective analysis. Between August 2009 and September 2018, TIPS was attempted in 49 patients with CPVT or PC. Radiation exposure (dose area product [DAP], air KERMA (AK) and fluoroscopy time [FT]), technical success, clinical success, complications and survival were analyzed. RESULTS: In total, 29 patients had CPVT and 20 patients had PC. 41/49 patients had cirrhosis. TIPS indications were refractory ascites (n = 25), variceal bleeding (n = 16) and other (n = 8). TIPS was successfully placed in 94% (46/49) of patients via a transjugular approach alone (n = 40), a transjugular/transhepatic approach (n = 5) and a transjugular/transsplenic approach (n = 1). Median DAP was 261 Gy * cm2 (range 29-950), median AK was 0.2 Gy (range 0.05-0.5), and median FT was 28.2 min (range 7.7-93.7). Mean portosystemic pressure gradient decreased from 16.8  ±  5.1 mmHg to 7.5  ±  3.3 mmHg (P <  0.01). There were no major procedural complications. Overall clinical success was achieved in 77% of patients (mean follow-up of 21.1 months). Encephalopathy was observed in 16 patients (34%), grade II-III encephalopathy in 7 patients (15%). TIPS revision was performed in 15 patients (32%). Overall survival rate was 75%. CONCLUSION: In our experience, the use of real-time ultrasound guidance allowed the majority of the TIPS to be performed via a transjugular approach alone with a reasonably low radiation exposure considering the high technical difficulties of the selected cohort of patients with CVPT or PC.

Recurrence of Hepatitis B Infection in Liver Transplant Patients Receiving Long-Term Hepatitis B Immunoglobulin Prophylaxis.

BACKGROUND Long-term real-world data are relatively sparse regarding recurrence of chronic hepatitis B virus (HBV) infection after liver transplantation using hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogue (NUC) prophylaxis. MATERIAL AND METHODS Data from 371 adults transplanted for HBV-related disease at 20 European centers and given HBIg for ³12 months ± NUC therapy were analyzed retrospectively. RESULTS HBIg comprised Hepatect® (iv HBIgB; n=299), subcutaneous Zutectra® (sc HBIg, n=236), and other HBIg preparations (n=130); 93.5% received NUC therapy. Mean follow-up was 6.8±3.5 years. The primary efficacy variable, freedom from HBV recurrence, occurred in 95.7% of patients (95% CI [93.1%, 97.5%]). The observed incidence of recurrence was 16/371 (4.3%) (annual rate 0.65%); 5/16 patients with recurrence had discontinued HBIg and 7/16 had anti-HBs <100 IU/l. Excluding these 7 patients, the HBV recurrence rate was 2.4%. The recurrence rate while on HBIg therapy was 1 per 2069 months. In patients who discontinued HBIg, risk of HBV recurrence versus sc HBIg users was increased by 5.2-fold (1 per 1 603 versus 1 per 8379 treatment months). The annual rate of HBV-related hepatocellular carcinoma (HCC) recurrence was 1.7%. CONCLUSIONS These results support the long-term use of HBIg with NUC therapy as an effective management strategy to minimize risk of HBV recurrence and virus-related complications after liver transplantation.

Delisting HCV-infected liver transplant candidates who improved after viral eradication: Outcome 2 years after delisting.

BACKGROUNDS & AIMS: Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. METHODS: One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. RESULTS: Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). CONCLUSIONS: Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low.

Specific issues concerning the management of patients on the waiting list and after liver transplantation.

The present document is a second contribution collecting the recommendations of an expert panel of transplant hepatologists appointed by the Italian Association for the Study of the Liver (AISF) concerning the management of certain aspects of liver transplantation, including: the issue of prompt referral; the management of difficult candidates; malnutrition; living related liver transplants; hepatocellular carcinoma; and the role of direct acting antiviral agents before and after transplantation. The statements on each topic were approved by participants at the AISF Transplant Hepatology Expert Meeting organized by the Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are graded according to the GRADE grading system.

Prevalent use of combined prophylaxis of hepatitis B after liver transplantation in Italy: results of a national survey in a large cohort.

BACKGROUND: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsAg-positive candidates and the use of hepatitis B Immunoglobulin-free schedules. METHODS: This national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 Italian centers. RESULTS: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsAg-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. Similar rates (18% of HBsAg-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. Combined prophylaxis with Hepatitis B Immunoglobulins remained prevalent among centers and was effective in 96% of HBsAg-positive recipients and in 94% of HBsAg-negative recipients of anti-HBc-positive grafts. CONCLUSIONS: Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B Immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsAg-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years.

Use of Everolimus in Liver Transplantation: Recommendations From a Working Group.

Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project, named Everolimus: the road to long-term functioning, was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: (A) renal function; (B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; (C) antiproliferative effects of EVR; and (D) management of EVR-related adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs.

Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study.

BACKGROUND & AIMS: All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. METHODS: 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015. RESULTS: The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24weeks, 27.6% and 10.3% at 48weeks, 33.3% and 19.2% at 60weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p<0.0001) and 2 points for Child-Pugh (CP) (delta-CP, p<0.0001). Three variables emerged from the most parsimonious multivariate competing risk model as predictors of inactivation for clinical improvement, namely, baseline MELD classes (MELD 16-20: HR=0.120; p=0.0005, MELD >20:HR=0.042; p<0.0001), delta MELD (HR=1.349; p<0.0001) and delta albumin (HR=0.307; p=0.0069) both assessed after 12weeks of DAA therapy. CONCLUSIONS: This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained. LAY SUMMARY: The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, "direct acting antivirals" or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5.

Right hepatic lobe living donation: a 12 years single Italian center experience.

Mini invasive techniques are taking over conventional open liver resections in the setting of left lateral segmentectomy for living liver donation, and hydride procedure are being implemented for the living related right hepatectomy. Our center routinely performs laparoscopic left lateral segmentectomy for pediatric recipient and has been the first in the Europe performing an entirely robotic right hepatectomy. Great emphasis is posed on living donor safety which is the first priority during the entire operation, then the most majority of our procedures are still conventional open right hepatectomy (RHLD), defined as removal of a portion of liver corresponding to Couinaud segments 5-8, in order to obtain a graft for adult to adult living related liver transplant. During this 10 years period some changes, herein highlighted, have occurred to our surgical techniques. This study reports the largest Italian experience with RHLD, focused on surgical technique evolution over a 10 years period. Donor safety must be the first priority in right-lobe living-related donation: the categorization of complications of living donors, specially, after this "highly sensitive" procedure, reflects the need for prompt and detailed reports.

Antiviral therapy and fibrosis progression in patients with mild-moderate hepatitis C recurrence after liver transplantation. A randomized controlled study.

BACKGROUNDS/AIMS: We evaluated the effect of antiviral therapy on fibrosis progression in patients with histological features of mild/moderate HCV disease recurrence defined by a Grading score≥4 and Staging score up to 3 (Ishak) at 1 year after liver transplantation. METHODS: Seventy-three consecutive patients with mild/moderate recurrence were randomized either to no treatment or to receive Pegilated-Interferon-alfa-2b and ribavirin for 52 weeks. Liver biopsies obtained at baseline (1 year after transplantation) and 2 years afterwards were evaluated for assessment of disease progression, defined as worsening of at least 2 staging points or progression to stage 4 or higher. RESULTS: As for these two major histological end points there were no statistically significant differences between the 2 groups (36.1% vs. 50%, p=0.34 and 36.1% vs. 38.9%, p=1). Fifteen treated patients (41%) achieved a sustained virological response which was associated with a reduced risk of fibrosis worsening for both endpoints when compared to viremic patients (p=0.04). CONCLUSIONS: Although antiviral-therapy was beneficial in preventing fibrosis progression in patients achieving a sustained virological response, the majority of the overall population of our patients with mild-moderate disease recurrence could not benefit from antiviral therapy either because they either could not be treated or did not respond to treatment (EudraCT number: 2005-005760).

Nutritional aspects in patient undergoing liver resection.

In the past two decades, hepatic surgery has achieved important technical breakthroughs resulting in a drastic reduction of the onset of complications and in an improved post-resective survival. Pre-operative nutritional status is one of the key points for the success of a liver resection. Modern surgical achievement such as the development of living-related liver donation, and the possibility to perform more laparoscopic liver resection gave us the opportunity to extend post-operative protocol focused on early intestinal feeding to tumor patients. The aims of this review were to report the current status of the knowledge regarding nutritional aspects in liver resection patients.

Transjugular liver biopsy in liver transplant patients using an 18-gauge automated core biopsy needle.

Aim of this retrospective study is to evaluate accuracy and safety of transjugular liver biopsy using an 18-gauge automated core biopsy needle, in patients underwent liver transplantation. 183 consecutively transjugular liver biopsy were performed in 115 liver transplant patients. An 18-gauge automated core needle biopsy was used in all patients. Technical success was achieved in 182 procedures (99.5%). In one patient we were not able to obtain a liver sample. The mean number of passages was 1.43 (range 1-5). Mean number of fragments was 2 (range 1-12). Mean total length of the specimens was 1.7 cm (range 0.5-3.4 cm). The specimen was adequate for diagnosis in 172 (94.5%) cases and suboptimal or inadequate in 10 (4.5%). Suboptimal or inadequate samples were associated with higher number of passages (2.0 vs. 1.4, p<0.012), higher number of fragments (4.3 vs. 1.9, p<0.0001) and decreased total length of the specimens (0.99 vs. 1.73, p<0.03). As only complication one patient (0.5%) had a large perihepatic hematoma requiring blood transfusion. In conclusion using an 18-gauge automated core needle biopsy, in most liver transplant recipients, an accurate diagnosis can be obtained with one or two passages. This is associated with a low risk of complications.

Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients with HBcAb-positive liver grafts.

We followed the efficacy of long-term lamivudine monotherapy in preventing development of de novo hepatitis B (DNHB) in a large cohort of hepatitis B surface antigen (HBsAg)-negative recipients with grafts from hepatitis B core antibody (HBcAb)-positive donors. Recipients were observed over a long follow-up. Between July 1999 and December 2008, 45 patients (median age 54, range 19-67) who were HBsAg negative before transplantation were included in the study of monoprophylaxis with lamivudine starting on post-operative day 1, and continuing for life. Mean follow-up: 37.9 months; median 32.1 months (range 2.4-117). No suspension of therapy was reported during the study. Post-transplantation, no DNHB was observed in follow-up: all 45 HBsAg-negative recipients remained HBsAg and HBV DNA negative. Thirty-four of these HBsAg-negative recipients were alive at conclusion of the study. A total of 11 patients died, five of HCV recurrence, two of hepatocellular carcinoma (HCC) recurrence, two of disseminated KSV infection, and two of multiorgan failure because of early graft dysfunction. Patient and graft survival of HBsAg-negative recipients with HBcAb-positive donor grafts (45 cases) were not significantly different from those of the HBsAg-negative recipients with HBcAb-negative donor grafts (302 cases). In our experience, lamivudine monoprophylaxis provided complete protection against HBV reactivation and showed long-term efficacy.

Efficacy and safety of fully covered self-expandable metallic stents in biliary complications after liver transplantation: a preliminary study.

After liver transplantation, the most common biliary complication is the anastomotic stricture, which is followed by biliary leakage. Studies have focused on the endoscopic treatment of biliary complications in transplanted patients with duct-to-duct reconstruction, showing a success rate of 70% to 80% after orthotopic liver transplantation and of 60% after living-related liver transplantation. Once the endoscopic approach fails, surgical treatment with a Roux-en-Y choledochojejunostomy is the sole alternative treatment. The aim of this prospective observational study was to analyze the efficacy and safety of fully covered self-expandable metallic stents for the treatment of posttransplant biliary stenosis and leaks in patients in whom conventional endoscopic retrograde cholangiopancreatography (ERCP) failed. From January 2008 to January 2009, 16 patients met the criteria of endoscopic treatment failure, and instead of surgery, a fully covered stent was placed. All patients had at least 6 months of follow-up (mean follow-up of 10 months). After removal, 14 patients showed immediate resolution of both the biliary stenosis and leak. After a mean of 10 months of follow-up, only 1 patient showed biliary stenosis recurrence. No major complications occurred in any of the patients, except for stent migration in 6 patients, although these presented with no clinical consequences. In conclusion, in patients not responding to standard endoscopic treatment, the placement of fully covered metal stents is a valid alternative to surgery. A cost analysis should be performed in order to evaluate whether to treat transplanted patients suffering from biliary complications with covered self-expandable metallic stent placement as first-line therapy.

Liver biopsy findings from healthy potential living liver donors: reasons for disqualification, silent diseases and correlation with liver injury tests.

BACKGROUND/AIMS: Liver biopsies detect silent donor disease in potential living liver donors and provide material for studies of subclinical non-alcoholic fatty liver disease (NAFLD). Our primary goal was to determine the contribution of biopsy findings to potential donor evaluation. Factors contributing to pre-clinical NAFLD and correlations between liver injury tests and histopathology have been also determined. METHODS: Patient records, laboratory tests and results of the histopathologic examination and diagnoses of 284 patients from 2001 to 2005 were retrospectively extracted from the EDIT database. Hepatic histology was correlated with liver injury tests and with general demographic characteristics in an otherwise normal healthy population. RESULTS: A minority (n=119; 42%) of biopsies from this population of 143 males/141 females (average age=36.8years; mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107; 37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16; 6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001), age (p=0.003), iron (p=0.01), and ALT (p=0.004). CONCLUSIONS: Liver biopsies provide valuable information about otherwise undetectable liver disease in potential liver donors. Obesity, age and iron, which are influenced by sex, contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles are needed to detect early NAFLD.