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Older age at the time of infection with hepatitis viruses is associated with an increased risk of liver fibrosis progression. We hypothesized that the pace of fibrosis progression may reflect changes in gene expression within the aging liver. We compared gene expression in liver specimens from 54 adult donors without evidence of fibrosis, including 36 over 40 y old and 18 between 18 and 40 y old. Chitinase 3-like 1 (CHI3L1), which encodes chitinase-like protein YKL-40/CHI3L1, was identified as the gene with the greatest age-dependent increase in expression in liver tissue. We investigated the cellular source of CHI3L1 in the liver and its function using liver tissue specimens and in vitro models. CHI3L1 expression was significantly higher in livers of patients with cirrhosis of diverse etiologies compared with controls represented by patients who underwent liver resection for hemangioma. The highest intrahepatic CHI3L1 expression was observed in cirrhosis due to hepatitis D virus, followed by hepatitis C virus, hepatitis B virus, and alcohol-induced cirrhosis. In situ hybridization of CHI3L1 messenger RNA (mRNA) identified hepatocytes as the major producers of CHI3L1 in normal liver and in cirrhotic tissue, wherein hepatocytes adjacent to fibrous septa showed higher CHI3L1 expression than did those in more distal areas. In vitro studies showed that recombinant CHI3L1 promotes proliferation and activation of primary human hepatic stellate cells (HSCs), the major drivers of liver fibrosis. These findings collectively demonstrate that CHI3L1 promotes liver fibrogenesis through a direct effect on HSCs and support a role for CHI3L1 in the increased susceptibility of aging livers to fibrosis progression.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P

In the setting of liver transplant (LT), the survival after the diagnosis of de novo malignancies (DNMs) has been poorly investigated. In this study, we assessed the impact of DNMs on survival of LT recipients as compared to corresponding LT recipients without DNM. A nested case-control study was conducted in a cohort of 2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases were 244 LT recipients who developed DNMs after LT. For each case, two controls matched for gender, age, and year at transplant were selected by incidence density sampling among cohort members without DNM. The survival probabilities were estimated using the Kaplan-Meier method. Hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. The all-cancer 10-year survival was 43% in cases versus 70% in controls (HR = 4.66; 95% CI: 3.17-6.85). Survival was impaired in cases for all the most frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98-276.74), non-Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15-20.01), head and neck (HR = 4.65; 95% CI: 1.81-11.95), and colon-rectum (HR = 3.61; 95% CI: 1.08-12.07). The survival gap was observed for both early and late mortality, although the effect was more pronounced in the first year after cancer diagnosis. No significant differences in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The survival gap herein quantified included a broad range of malignancies following LT and prompts close monitoring during the post-transplant follow-up to ensure early cancer diagnosis and to improve survival.

This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry.LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment.A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis.Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales.Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Endometrial cancer is the most common gynaecologic malignancy. Among all cancers, high body mass index (BMI) and obesity (defined as BMI >30 kg/m2) are associated with the incidence and mortality r...

To analyze whether a large uterine size was associated with increased rate of intraoperative and postoperative surgical complications in patients who underwent total laparoscopic hysterectomy (TLH) for myomatous uteri.We examined prospectively data from 461 consecutive TLHs performed by a single surgeon between August 2004 and August 2014 at the Department of Obstetrics and Gynecology, Sirai Hospital, Carbonia, and at the Department of Gynecologic Oncology, Businco Hospital, Cagliari, Italy. Demographic and surgical data were stratified by uterine weight (range 90-5500 g) into four groups:300 g; from 300 to 500 g; from 500 to 800 g; and800 g. Outcomes examined included blood loss, operative time, intraoperative and postoperative complications, and duration of hospital stay. A linear regression analysis was performed to identify whether uterine weight was an independent predictor affecting these outcomes. In addition, BMI, previous surgery with adhesiolysis, and endometriosis were tested as a predictor of surgical complications and outcomes.No significant difference was found in intraoperative and postoperative complications, as well as hospital stay, by uterine weight. Increased uterine size was significantly associated with longer operative time and increased blood loss. Beside uterine weight, prior surgery was predictive of postoperative complications. In contrast, higher BMI was not associated with increased complication rate. Independent predictors of longer operative time included previous surgery, endometriosis, and BMI.Our results showed that in experienced hands, TLH is feasible and safe also in presence of very large uteri. TLH results in a few complications and short hospital stay regardless of uterine weight.

Objective: Laparoscopic liver resection (LLR) for Hepatocellular Carcinoma (HCC) is one of the most important indications for the minimally invasive approach. Our study aims to analyze the experience of the Italian Group of Minimally Invasive Liver Surgery with laparoscopic surgical treatment of HCC, with a focus on tumor location and how it affects morbidity and mortality. Methods: 38 centers participated in this study; 372 cases of LLR for HCC were prospectively enrolled. Patients were divided into two groups according to the HCC nodule location. Group 1 favorable location and group 2 unfavorable location. Perioperative outcomes were compared between the two groups before and after a propensity score match (PS) 1:1. Results: Before PS in group 2 surgical time was longer; conversion rate was higher; postoperative transfusion and comprehensive complication index were also higher. PS was performed with a cohort of 298 patients (from 18 centers), with 66 and 232 patients with HCC in unfavorable and favorable locations, respectively. After PS matching, 62 patients from group 1 and group 2 each were compared. Operative and postoperative course were similar in patients with HCC in favorable and unfavorable LLR locations. Surgical margins were found to be identical before and after PS. Conclusions: These results show that LLR in patients with HCC can be safely performed in all segments because of the extensive experience of all surgeons from multiple centers in performing traditional open liver surgery as well as laparoscopic surgery.

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially “splittable” donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P=.009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P=.045]). The pediatric (4.5% vs 2.5% [P=.398]) and adult (9.7% to 5.2% [P20kg (HR=5.113, P=.048) in LLS, and ischemic time >8hours (HR=2.475, P=.048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with

This cohort study assessed, in Italy, the overall pattern of risk of de novo malignancies following liver transplantation (LT). The study group included 2,832 individuals who underwent LT between 1985 and 2014 in nine centers all over Italy. Person-years (PYs) at cancer risk were computed from 30 days after LT to the date of cancer diagnosis, to the date of death or to the end of follow-up. Excess cancer risk, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). During 18,642 PYs, 246 LT recipients developed 266 de novo malignancies, corresponding to a 1.8-fold higher cancer risk (95% CI: 1.6-2.0). SIRs were particularly elevated for virus-related malignancies, including Kaposi's sarcoma (SIR = 53.6, 95% CI: 30.0-88.5), non-Hodgkin lymphomas (SIR = 7.1, 95% CI: 4.8-10.1) and cervix uteri (SIR = 5.4, 95% CI: 1.1-15.8). Among virus-unrelated malignancies, elevated risks emerged for head and neck (SIR = 4.4, 95% CI: 3.1-6.2), esophagus (SIR = 6.7, 95% CI: 2.9-13.3) and adrenal gland (SIR = 22.9, 95% CI: 2.8-82.7). Borderline statistically significant elevated risks were found for lung cancer (SIR = 1.4, 95% CI: 1.0-2.1) and skin melanoma (SIR = 2.6, 95% CI: 1.0-5.3). A reduced risk emerged for prostate cancer (SIR = 0.1, 95% CI: 0.0-0.5). These findings underline the need of preventive interventions and early detection of malignancies, specifically tailored to LT recipients.

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows.

Background Total laparoscopic hysterectomy (TLH) has demonstrated to be feasible and safe in the presence of very large uteri. However, it is currently difficult to establish the upper uterine weight limit for successful performance of a laparoscopic hysterectomy. Case presentation Here we report the case of a TLH performed for a very large fibromatous uteri weighing 5320 g in a 40-year-old Caucasian woman. The surgery had no complications with an operating time of approximately 220 min. The patient was discharged from the hospital on postoperative day 3 in very good condition. To our knowledge, the present paper is the only to describe a uterus of this size removed by laparoscopic hysterectomy. Conclusions Our case demonstrates that uterine size is not a determinant for a final surgical decision to use laparoscopic hysterectomy. Therefore, if not contraindicated by the patient’s comorbidities or peculiar anatomical conditions, we believe that laparoscopic hysterectomy could be performed in the presence of large uteri without hypothetical weight limits.

The shortage of organs and the increasing median age of deceased donors for orthotopic liver transplantation stimulate transplant centres to accept grafts that otherwise would have been discarded due to severe vascular abnormalities. We encountered a donor with two arterial aneurysms and a left accessory hepatic artery: an arterial aneurysm of the common hepatic artery and a left accessory hepatic artery arising from a second aneurysm of the left gastric artery (Michels type V). A complex reconstruction was created to transplant the liver. Multiple arterial anastomosis was made and the hepatic inflow of the transplanted liver restored. Although the procedure increased the risk of hepatic artery thrombosis, one more organ supposed to be discarded was saved.

Uterine leiomyosarcoma (LMS) in some cases may disseminate through the abdominal cavity, without extra-abdominal spreading, determining a condition of abdominal sarcomatosis, which represents a peculiar situation. Only radical surgical removal offers a chance of long-term survival in such cases of LMS. Here we describe a case of diffuse abdominal sarcomatosis from uterine LMS in a 51-year-old perimenopausal woman who underwent laparoscopic radical hysterectomy, bilateral salpingo-oophorectomy, total pelvic peritonectomy, pelvic lymphadenectomy to the mesenteric inferior artery, and omentectomy. Then, given the high probability of disease recurrence, the patient underwent a close follow-up consisting of positron emission tomography (PET)/computed tomography every 3 months and diagnostic (and if necessary operative) laparoscopy every 6 months. To date, the patient had 11 laparoscopies; 5 of them were preceded by a PET indicative of the presence of disease with high metabolic activity, which was confirmed at surgery and each time completely removed laparoscopically with no evidence of residual disease. To date, 5 years from diagnosis the patient is alive and continues her follow-up. Our report brings to light the ability of laparoscopic surgery to obtain disease control in a case of LMS with abdominal dissemination. Moreover, laparoscopic surgery, as demonstrated in our case, may have an important role in the close follow-up of the disease and allow a timely and early radical surgical approach of relapses before they become extremely large and difficult to remove radically.

Occult Hepatitis B virus (o-HBV) infection has been reported in HB surface antigen (HBsAg)-negative liver donors whose risk of transmitting HBV justifies a specific prophylaxis in liver recipients. The clinical significance of o-HBV infection in HBsAg-negative recipients and their need for prophylaxis is unknown. Liver samples collected during surgery from 23 HBsAg-negative patients (9 liver donors and 14 recipients) and 20 HBsAg-positive recipients (controls) were studied by polymerase chain reaction with an independent set of primers mapping the core and surface HBV genes. Intrahepatic HBV DNA was detected as core and surface genes in all the HBsAg-positive recipients, in none of the HBsAg-negative donors and in 9/14 (64%) of the HBsAg-negative recipients (2 HCV negative, 7 HCV positive). The intrahepatic amount of HBV was significantly lower in HBsAg-negative than in HBsAg-positive livers (median values 1.36 Log10/μg DNA vs. 3.66 Logs, p

The influence of steatosis and of other donor and recipient characteristics in affecting liver performance post-orthotopic liver transplantation (OLT) was evaluated in 311 consecutive liver transplantations made in 278 patients. Donor variables considered were age, sex, blood group, cause of death, intensive care unit (ICU) days, need for vasopressors, hepatic enzymes and bilirubin, total and warm ischemia time, and macro- and microvescicular steatosis. Recipient variables considered were age, sex, blood group, biliary output, and post-OLT peak levels of hepatic enzymes. Patient and graft survival were the main outcome indicators. In the multivariate analysis, macrovescicular steatosis involving 25% or more of the hepatocytes was the only variable independently associated with shorter patient survival (p < 0.05). Five (62.5%) of the eight livers with macrovescicular steatosis involving 25% or more of the hepatocytes incurred in a delayed non-function (DNF) and one (12.5%) in a primary non-function (PRNF). The incidence of DNF and PRNF in the group with macrovescicular steatosis involving less than 25% of the liver cells was 1.6% (p < 0.001) and 2.3%, respectively. Microvescicular steatosis of any degree was not associated with a worse prognosis. Macrovescicular steatosis involving 25% or more of the hepatocytes identifies marginal livers, the use of which significantly increases the risk of graft non-function post-OLT.

Objective The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. Methods Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990–2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/103 PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2–1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. Conclusions These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

BACKGROUND: The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. METHODS: Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. RESULTS: The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (≥ 10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. CONCLUSIONS: The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.

The first Italian liver transplant center to reach the goal of 1000 procedures was Turin. The paper reports this single-center experience, highlighting the main changes that have occurred over time. From 1990 to 2002, 1000 consecutive liver transplants were performed in 910 patients, mainly cirrhotics. Surgical technique was based on the preservation of the retrohepatic vena cava of the recipient. The veno-venous bypass was used in 30 cases only and abandoned since 1997. Operating time, warm ischemia time and length of hospital stay significantly decreased over the years, while operating room extubation became routine. Immunosuppression pivoted on cyclosporine A. Management of retransplantations, marginal grafts, and of HCV-positive, HBV-positive and hepatocellular carcinoma recipients were optimized. Median follow-up of the patients was 41 months. Overall survival rates at 1, 5 and 10 years were 87%, 78% and 72% respectively. Survival rates obtained in the second half of the cases (1999-2002 period) were significantly better than those obtained in the first half (1990-1998 period) (90% vs. 83% at 1 year and 81% vs. 76% at 5 years respectively). Increasing experience in liver transplant surgery and postoperative care allowed standardization of the procedure and expansion of the activity, with parallel improvement of the results.

Liver transplantation involving living-related donors has been adopted in many centers as a way of relieving organ shortage. This study reviewed the anesthetic considerations for donor operations at our institution in relation to intraoperative blood transfusion, complications, and postoperative liver function test results. From January 1990 to May 2001, 30 living-related liver transplantations were performed at Baskent University Hospital, Ankara. The donor data used for analysis were retrospectively obtained through chart review, anesthesia records, and the computerized hospital database. Left lobectomy was performed in 19 cases, and left lateral segmentectomy in 11 cases. Intraoperatively, the average volume of intravenous fluids used was 6431±468 ml, and the average amount of blood transfused was 2.1±0.4 units. The mean postoperative hospital stay was 11.5±1.3 days. The only intraoperative complication observed in these 30 donors was severe bleeding during retrohepatic vena cava dissection in one of the cases. The postoperative complications related to anesthesia were one case each of shoulder pain, neuropraxia, and compartment syndrome. The levels of total and direct bilirubin, aspartate aminotransferase, and alanine aminotransferase peaked within the first 2 postoperative days (2.19±0.36 mg/dl, 1.02±0.18 mg/dl, 245.7±26.6 U/l, 313.5±51.9 U/l, respectively). In all 30 donors, these levels had normalized by 1 month after surgery. Maximal efforts must be applied in the anesthetic approach to minimize donor complications in living-related liver transplantation; however, this will not completely eliminate some risks to the donor.

Background. The risk of hepatic artery thrombosis after orthotopic liver transplantation is higher in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, unsafe native hepatic arteries. Aims. To assess the use of arterial conduits as alternative technique for graft revascularization. Patients. At the Liver Transplant Center of the “sGiovanni Battista” Hospital in Torino, a review has been made of 600 consecutive orthotopic liver transplantations in 545 adult patients from 1990 to 1999. Methods. In 95 orthotopic liver transplantations (15.8%) in 88 patients, the graft was supplied by infrarenal conduit, while in 505 orthotopic liver transplantations (84.2%) in 457 patients, a direct anastomosis was used. Results and conclusions. The overall incidence of hepatic artery thrombosis in our series was 3.5% ( 21 600 ): 5.3% ( 5 91 ) for conduits and 3.2% ( 16 505 ) for standard technique (p=ns, χ test). The actuarial 5-year graft survival was 67.7% for conduits and 68.6% for the standard technique; p (log rank): ns. The iliac prosthesis torsion was the only complication related to the use of infrarenal iliac conduit. The arterial conduit, performed with donor iliac artery, is an effective and safe revascularization technique in patients at high risk of arterial thrombosis.

Background: During liver transplantation, an oversized graft or active bleeding in the hepatic area can make performance of the suprahepatic caval anastomosis extremely difficult or even impossible. In other instances, a brief as possible warm ischemia is desired to provide a marginal graft with maximum chances of good functioning. Methods: In order to manage those conditions, a suture technique was devised that allows the construction of a substantial part of the suprahepatic caval anastomosis keeping the graft outside the abdomen of the recipient. Results: Over a 12-month period, the technique was applied in 7 out of 148 transplants (5%). The 7 cases presented one or more of the following conditions: significant oversize mismatch (n = 6), active bleeding in the hepatic area (n = 1), and marginal graft (n = 4). Warm ischemia time averaged 27 minutes, a value not significantly different from the mean warm ischemia time of 25 minutes recorded in the easier transplants in which the conventional technique was used ( P = 0.2467). Conclusions: This extracorporeal suture technique allows construction of the suprahepatic caval anastomosis in critical situations arising during liver transplantation and avoidance of the prolonged warm ischemia that could be expected in such cases.

Background/Aims : Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. Methods : Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA). Results : ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months ( P =0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter ( P =0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P : 0.02). In ETV responders the hepatitis activity index improved by >2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients. Conclusions : CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.

In the transplanted organ, early after reperfusion, a consistent while usually transient tissue damage is detectable which could interfere with appropriate recovery and function. In the case of transplanted human liver, a certain degree of cytolysis as well as post-hepatic cholestasis have actually been monitored early after surgery (Ericzon et al., 1990; Biasi et al., 1995). Then, studies addressed to elucidate the mechanisms underlying post-transplantation liver injury are necessary. The inflammatory process which always follows a cytolytic event generates a variety of molecules actually able to modulate not only cellular function but also its genetic program. Hence, extent and duration of flogistic reactions should be controlled for not being overwhelming tissue and organ homeostasis.

s of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48 S7 the increase of HRR. The analysis of survival benefit comparing the risk of waiting list drop-out with the mortality of the 170 transplanted patients with same HRR, showed an important benefit for LT in patients with HRR>16.3. Conclusions: In patients with MELD

206 THE UN-SUSTAINABLE MATCH IN HCV LIVER TRANSPLANT PATIENTS A.W. Avolio, S. Agnes, M.C. Lirosi, M. Salizzoni, A. Pinna, B. Gridelli, L. De Carlis, M. Colledan, G. Gerunda, U. Valente, G. Rossi, G. Ettorre, A. Risaliti, V. Mazzaferro, F. Bresadola, M. Rossi, G. Tisone, F. Zamboni, L. Lupo, O. Cuomo, F. Calise, A. Vitale, N. Nicolotti, R. Romagnoli, A. Cucchetti, S. Gruttadauria, I. Mangoni, D. Pinelli, R. Montalti, M. Gelli, L. Caccamo, G. Vennarecci, D. Nicolini, E. Regalia, U. Baccarani, Q. Lai, T. Manzia, E. Tondolo, M. Rendina, A. Perrella, E. Scuderi, B. Antonelli, C. de Waure, M. Angelico, P. Burra, A. Gasbarrini, U. Cillo, Donor-to-Recipient Italian Liver Transplant (DR2-ILTx) Study Group. Liver Transplant Center, “A.Gemelli”Hospital, Catholic University, Rome, Liver Transplant Center, “S. Giovanni Battista” Hospital, University of Turin, Turin, Liver Transplant Center, “S. Orsola” Hospital, University of Bologna, Bologna, Liver Transplant Center, IsMeTT-UPMC, Palermo, Liver TransplantCenter, “Niguarda” Hospital, Milan, Liver Transplant Center, “Ospedali Riuniti”, Bergamo, Liver Transplant Center, University of Modena and Reggio Emilia, Modena, Liver Transplant Center, “S. Martino” Hospital, University of Genoa, Genoa, Liver Transpantation Center, IRCCS Foundation, “Maggiore” Hospital, Milan, Liver Transplant Center, “San Camillo-Forlanini” Hospital, Rome, Liver Transplant Center, “Umberto I” Hospital, Polytechnic University of Marche, Ancona, Liver Transplant Center, National Cancer Institute, IRCCS Foundation, Milan, Liver Transplant Center, University of Udine, Udine, Liver Transplant Center, “Umberto I” Hospital, “La Sapienza” University, Liver Transplant Center, “Tor Vergata” University Hospital, Rome, Liver Transplant Center, “G. Brotzu” University Hospital, Cagliari, Liver Transplant Center, Department of Emergency and Organ Transplant, University of Bari, Bari, Liver Transplant Center, Laparoscopic Hepatobiliary Surgical Unit, “A. Cardarelli” University Hospital, Liver Transplant Center, Hepatobiliary Surgical Unit, “A. Cardarelli” University Hospital, Naples, Liver Transplant Center, Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Epidemiology and Biostatistics Unit, Institute of Hygiene, Catholic University, Rome, Italy E-mail: alfonso.avolio@tin.it

Background Dysregulation of long noncoding RNA (lncRNA) expression contributes to the pathogenesis of many human diseases, including liver diseases. Several lncRNAs have been reported to play a role in the development of hepatocellular carcinoma (HCC). However, most studies have analyzed lncRNAs only in hepatitis B virus (HBV)-related HCC or in a single group of HCC patients regardless of the viral etiology. Methods To investigate whether lncRNAs are differentially expressed in HCC of different viral etiology, we profiled 101 disease-related lncRNAs, including 25 lncRNAs previously associated with HCC, in liver specimens obtained from well-characterized patients with HBV-, hepatitis C virus (HCV)-, or hepatitis D virus (HDV)-associated HCC. Results We identified eight novel HCC-related lncRNAs that were significantly dysregulated in HCC tissues compared to their surrounding non-tumorous tissues. Some of these lncRNAs were significantly dysregulated predominantly in one specific hepatitis virus-related HCC, including PCAT-29 in HBV-related HCC, aHIF and PAR5 in HCV-related HCC, and Y3 in HDV-related HCC. Among the lncRNAs previously reported in HCC, we found that DBH-AS1, hDREH and hPVT1 were differentially expressed in HCC of different viral etiology. Conclusions Our study suggests that HCC of different viral etiology is regulated by different lncRNAs. The identification of lncRNAs unique to specific hepatitis virus-related HCC may provide new tools for improving the diagnosis of HCC and open new avenues for disease-specific therapeutic interventions. Electronic supplementary material The online version of this article (doi:10.1186/s12967-016-1085-4) contains supplementary material, which is available to authorized users.