Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats.

BACKGROUND AND AIMS: Portal hypertension is the main consequence of cirrhosis, responsible for the complications defining clinical decompensation. The only cure for decompensated cirrhosis is liver transplantation, but it is a limited resource and opens the possibility of regenerative therapy. We investigated the potential of primary human amniotic membrane-derived mesenchymal stromal (hAMSCs) and epithelial (hAECs) stem cells for the treatment of portal hypertension and decompensated cirrhosis. METHODS: In vitro: Primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) from cirrhotic rats (chronic CCl4 inhalation) were co-cultured with hAMSCs, hAECs or vehicle for 24 hours, and their RNA profile was analysed. In vivo: CCl4-cirrhotic rats received 4x106 hAMSCs, 4x106 hAECs, or vehicle (NaCl 0.9%) (intraperitoneal). At 2-weeks we analysed: a) portal pressure (PP) and hepatic microvascular function; b) LSECs and HSCs phenotype; c) hepatic fibrosis and inflammation. RESULTS: In vitro experiments revealed sinusoidal cell phenotype amelioration when co-cultured with stem cells. Cirrhotic rats receiving stem cells, particularly hAMSCs, had significantly lower PP than vehicle-treated animals, together with improved liver microcirculatory function. This hemodynamic amelioration was associated with improvement in LSECs capillarization and HSCs de-activation, though hepatic collagen was not reduced. Rats that received amnion derived stem cells had markedly reduced hepatic inflammation and oxidative stress. Finally, liver function tests significantly improved in rats receiving hAMSCs. CONCLUSIONS: This preclinical study shows that infusion of human amniotic stem cells effectively decreases PP by ameliorating liver microcirculation, suggesting that it may represent a new treatment option for advanced cirrhosis with portal hypertension.

Direct-acting antivirals ability to clear intestinal HCV-RNA in liver transplant patients.

The hepatitis C virus mainly infects the liver but is also able to infect and replicate in other body compartments by creating an extra-hepatic reservoir that may influence the persistence of the infection after transplantation. It is unknown whether antiviral drugs affect the viral extra-hepatic sites. We evaluated the ability of pegylated/interferon + ribavirin and sofosbuvir + ribavirin to clear the virus from the gastrointestinal mucosa of liver-transplanted patients with HCV recurrence after transplantation. A total of 51 liver-transplanted patients, 30 treated with pegylated/interferon + ribavirin (ERA1) and 21 treated with sofosbuvir + ribavirin (ERA2), were enrolled, and blood serum and gastrointestinal tissues analyzed for the presence of HCV-RNA. In the ERA1 group, the 46.6% of patients had a sustained viral response to antiviral treatment, and gastrointestinal biopsies were positive for HCV in 73.3% of cases, 54.5% of responders, and 45.5% of non-responders. In the ERA2 group, the 66.6% had a sustained viral response, and gastrointestinal HCV-RNA was present in the 14.3% of patients, all relapsers. Sofosbuvir + ribavirin cleared the intestinal HCV in 85.7% of patients with recurrent HCV infection, while pegylated/interferon + ribavirin cleared it in 26.6% of treated patients, demonstrating the better effectiveness of new direct antiviral agents in clearing HCV intestinal reservoir.

Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997-2010.

This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post-transplant cancers were diagnosed-including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10-year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios - SIR=4.7, 95% CI: 3.2-6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1-17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high-risk recipients like those with ALD.

IL28B polymorphisms of both recipient and donor cooperate to influence IFN treatment response in HCV recurrence after liver transplantation, but IL28B SNPs of the recipient play a major role in IFN-induced blocking of HCV replication.

Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment of HCV-infected patients. This study evaluated the association between SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent infection in HCV-positive patients who underwent liver transplant. We aimed to assess to what extent recipient and/or graft donor IL28B polymorphisms contribute to HCV clearance after transplantation influencing the response to the antiviral treatment. We found that the allele frequencies in donors were in agreement with the pattern expected in the European population. The frequency of favourable genotypes was significantly lower in recipients than in donors, reasonably because the recipients represented a group of patients affected by chronic Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN-alpha/RBV treatment of HCV recurrence is associated with the co-presence of favourable genotypes of both donors and recipients. However, IL28B SNPs of the recipient seem to play a major role in this clinical setting. In particular, homozygosis of rs12979860 favourable genotype in recipients was associated with sustained virological response independently from the donor's genotype. Thus, identification of these SNPs may be useful to predict the response to IFN-based therapy of HCV recurrent infection in liver-transplanted patients.

Liver Transplantation for Hemoperitoneum Secondary to Huge Multiple Hemangiomatosis: A Case Report of a Tele-intensive Care Unit in Deceased-Donor Management.

BACKGROUND: Patients with growing and nonresectable liver hemangiomas should be followed up by a transplant center with extensive experience in complex liver disease. They could be treated on an emergency basis with orthotopic liver transplantation, with an expectation of good long-term results. MATERIALS AND METHODS: We describe the case of a 37-year-old woman with liver hemangiomatosis followed up for 8 years, who presented with bleeding requiring transfusions and developed hemodynamic instability. We listed her for emergency transplant before her sister's living donor work-up could be completed. A liver from a cadaveric donor became available at a small local hospital with no experience in organ donation. Tele-intensive care unit (tele-ICU) technology was used for providing clinical data electronically to physicians, nurses, and other critical care specialists, creating medication orders, and communicating with on-site caregivers to implement changes in donor care. RESULTS: The recipient was transplanted on an emergency basis with a specific customization and application of the telemedicine system in the management of the organ procurement by the recipient team. Tele-ICU technology was used for providing an effective intensive care unit service, managing and stabilizing the deceased donor and allowing the procurement to be carried out uneventfully. CONCLUSIONS: Tele-ICU technology could be a promising resource for emergency transplantation, reducing the urgent need for a living donation and allowing prompt recipient team management of the deceased donor. Our first tele-ICU case offers early confirmation of the feasibility of the telemedicine system in deceased-donor management.

Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients.

BACKGROUND: Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection. AIM: The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness ≥ 9.5 kPa and FIB-4 values ≥ 3.25. The optimal stiffness cut-off according to FIB-4 ≥ 3.25 was evaluated by ROC analysis. RESULTS: No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness ≥ 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79-0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03). CONCLUSION: Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.

Natural course of extrahepatic nonmalignant partial portal vein thrombosis in patients with cirrhosis.

PURPOSE: To define the natural course of extrahepatic nonmalignant partial portal vein thrombosis (PVT), including the progression from partial to complete PVT, in patients with cirrhosis who had undergone multidetector computed tomography (CT). MATERIALS AND METHODS: This study was institutional review board and ethics committee approved. Written informed consent was obtained for each procedure. Forty-two consecutive patients with cirrhosis and untreated extrahepatic, nonmalignant partial PVT were followed up until the final clinical evaluation, liver transplantation, or death. Multidetector CT was used to evaluate the thrombus lumen occlusion, patent lumen area, thrombus area, total lumen area, and diameter of main portal vein, superior mesenteric vein, and splenic vein. Statistical analysis was performed with the Wilcoxon Mann-Whitney U test, χ2 test, Wilcoxon matched-pairs signed-rank test, life-table analysis, Kaplan-Meier method, and log-rank test, as appropriate. RESULTS: After a mean follow-up period of 27 months, partial PVT worsened in 20 (48%) patients, improved in 19 (45%), and was stable in three (7%). The Kaplan-Meier probability of episodes of hepatic decompensation at 1 and 2 years was 41% and 57%; probability of hospital admission for hepatic decompensation, 37% and 54%; and survival rates, 77% and 57%, respectively. There was no clear association between progression or regression of partial PVT and clinical outcome. Multivariate analysis showed that the Child-Pugh score at diagnosis was the only independent predictor of survival (hazard ratio, 1.97; 95% confidence interval: 1.19, 3.23; P=.007) and hepatic decompensation (hazard ratio, 1.51; 95% confidence interval: 1.18, 1.19; P=.001). CONCLUSION: Extrahepatic nonmalignant partial PVT improved spontaneously in 45% of patients with cirrhosis, and the progression of partial PVT was not associated with clinical outcome, which appeared to be dependent on the severity of cirrhosis.

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation.

Although hepatic cell transplantation (CT) holds the promise of bridging patients with end-stage chronic liver failure to whole liver transplantation, suitable cell populations are under debate. In addition to hepatic cells, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being considered as alternative cell sources for initial clinical cell work. Fetal liver (FL) tissue contains potential progenitors for all these cell lineages. Based on the collagenase incubation of tissue fragments, traditional isolation techniques yield only a fraction of the number of available cells. We report a 5-step method in which a portal vein in situ perfusion technique is used for tissue from the late second trimester. This method results in the high viabilities known for adult liver vascular perfusion, addresses the low cell yields of conventional digestion methods, and reduces the exposure of the tissue to collagenase 4-fold. We used donated tissue from gestational weeks 18 to 22, which yielded 1.8 ± 0.7 × 10(9) cells with an average viability of 78%. Because HSC transplantation and MSC transplantation are of interest for the treatment of hepatic failure, we phenotypically confirmed that in addition to hepatic progenitors, the resulting cell preparation contained cells expressing typical MSC and HSC markers. The percentage of FL cells expressing proliferation markers was 45 times greater than the percentage of adult hepatocytes expressing these markers and was comparable to the percentage of immortalized HepG2 liver hepatocellular carcinoma cells; this indicated the strong proliferative capacity of fetal cells. We report a case of human FL CT with the described liver cell population for clinical end-stage chronic liver failure. The patient's Model for End-Stage Liver Disease (MELD) score improved from 15 to 10 within the first 18 months of observation. In conclusion, this human FL cell isolation protocol may be of interest for further clinical translation work on the development of liver cell-based therapies.

Short- and long-term effects of the transjugular intrahepatic portosystemic shunt on portal vein thrombosis in patients with cirrhosis.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) negatively impacts the prognosis in patients with cirrhosis. The aim of our study was to evaluate the effects of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis complicated by PVT. METHODS: Seventy consecutive cirrhotic patients with non-tumoural PVT treated with TIPS for portal hypertension complications from January 2003 to February 2010 in a tertiary-care centre were followed until last clinical evaluation, liver transplantation, or death. RESULTS: TIPS was successfully placed without major procedure-related complications. After TIPS, the portal venous system was completely recanalised in 57% of patients, a marked decrease in thrombosis was observed in 30%, and no improvement was seen in 13%. 95% of patients with complete recanalisation after TIPS maintained a patent portal vein. Predictors of complete recanalisation were a less severe and extensive PVT, de novo diagnosis of PVT, and absence of gastro-oesophageal varices. At follow-up, 1 patient had recurrence of bleeding, and 2 had spontaneous bacterial peritonitis. The rate of TIPS dysfunction at 12 and 24 months was 38% and 85% for bare stent and 21% and 29% for covered stent (p = 0.001), respectively. Occurrence of encephalopathy at 12 and 24 months was 27% and 32%, respectively. Fifteen patients underwent liver transplantation. Survival at 1, 12 and 24 months was 99%, 89% and 81%, respectively. CONCLUSION: Long-term outcome of non-tumoural PVT in patients with cirrhosis treated with TIPS placement is excellent. Prospective randomised studies should investigate whether TIPS placement is the best therapeutic option in patients with cirrhosis who develops non-tumoural PVT.

How to Improve Patients' Perceived Quality of Sleep During Hospitalization Through a Multicomponent "Good Sleep Bundle": A Prospective Before and After Controlled Study.

Introduction: Despite sound evidence on the importance of sleep for human beings and its role in healing, hospitalized patients still experience sleep disruption with deleterious effects. Many factors affecting patients' sleep can be removed or minimized. We evaluated the efficacy of a multicomponent Good Sleep Bundle (GSB) developed to improve patients' perceived quality of sleep, through which we modified environmental factors, timing of nighttime clinical interventions, and actively involved patients in order to positively influence their experience during hospitalization. Methods: In a prospective, before and after controlled study, two different groups of 65 patients each were admitted to a cardiothoracic unit in two different periods, receiving the usual care (control group) and the GSB (GSB group), respectively. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) at the admission, discharge, and 30 days after discharge in all patients enrolled. Comparisons between the two groups evaluated changes in PSQI score from admission to discharge (primary endpoint), and from admission to 30 days after discharge (secondary endpoint). Results: The mean PSQI score difference between admission and discharge was 4.54 (SD 4.11) in the control group, and 2.05 (SD 4.25) in the GSB group. The mean difference in PSQI score change between the two groups, which was the primary endpoint, was 2.49 (SD 4.19). This difference was highly significant (p = 0.0009). Conclusion: The GSB was associated with a highly significant reduction of the negative effects that hospitalization produces on patients' perceived quality of sleep compared with the usual care group.

Changing picture of central nervous system complications in liver transplant recipients.

Central nervous system (CNS) complications are common after liver transplantation (LT). According to the literature, the most common causes are infections and the neurotoxicity of immunosuppressive drugs (cyclosporine and tacrolimus). The aim of this study was to evaluate the incidence, clinical presentations, etiologies, and outcomes of CNS complications in a series of 395 consecutive LT recipients whose immunosuppression regimen was designed for low tacrolimus blood levels. An analysis of the 12-hour trough concentrations of tacrolimus in the study population showed that the target drug levels, which were designed to maintain minimal immunosuppression, were usually achieved. In all, 64 patients (16.2%) developed major neurological symptoms (37 within 30 days of LT). None of the observed CNS complications were caused by infections (viral, bacterial, or fungal), and only 3 of the 395 patients (0.8%) received a diagnosis of tacrolimus-related leukoencephalopathy. Cerebrovascular disease was identified in 15 patients (3.8%; 8 had cerebral hemorrhages, 5 had ischemic strokes, and 2 had subdural hemorrhages). Pontine myelinolysis was found in 2 patients (0.5%). Notably, no clear cause was identified for the remaining 44 cases (11.1%): brain imaging was negative for 22 cases, and diffuse hypoxic changes were present for the other 22. CNS complications were significantly associated with a reduction in 3-month patient survival (88.8% versus 95.4%) and 5-year patient survival (57.3% versus 84.1%). Among the pretransplant variables that were analyzed, the incidence of portosystemic encephalopathy, the peak serum bilirubin levels, and the lowest serum total cholesterol levels were significantly different between the 64-patient group with CNS complications and the asymptomatic group of 331 patients.

Complications in immunosuppressive therapy of liver transplant recipients.

BACKGROUND: In liver transplantation (LT), modern immunosuppressive protocol is focused on early corticosteroid (CS) weaning. The aim of the study was to investigate all early transplant-related complications using Clavien grading system, in order to identify a significant relation in two homogenous groups of consecutive liver transplanted patients, only different for steroid avoidance in immunosuppressive regimen. MATERIALS AND METHODS: One group was treated with a tacrolimus-based CS-free immunosuppressive protocol, the other one underwent tacrolimus plus low dose CS therapy. The preoperative continuous variables analyzed were age, gender, model for end-stage liver disease (MELD) score, and the pre-allocation score for predicting survival following liver transplantation (P-SOFT). RESULTS: There were 39 patients in Group A (CS free) (37.9%), and 64 patients in Group B (CS on board) (62.1%). No statistically significant differences between the two groups were detected regarding the incidence and Clavien grade of complications (P = 0.116). No significant relation was revealed between Clavien rate of complications and tacrolimus-based CS-free immunosuppressive protocol, comparing the two subgroup of patient with P-SOFT score < 6 and ≥ 6 (P = 0.193). This association was noted comparing the two subgroups on tacrolimus plus low dose CS regimen (P = 0.013). CONCLUSION: In this series, the use of CS in sick patient is associated with higher morbidity identified by the Clavien classification.

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.

Impact of blood transfusion on early outcome of liver resection for colorectal hepatic metastases.

BACKGROUND: The use of intra-operative blood transfusion has been associated with worse surgical outcome in patients undergoing liver resection for malignancy. METHODS: In a series of 127 consecutive patients who underwent partial liver resection for colorectal metastases, between July 1999 and March 2010, we studied, post-operative 90 days surgical outcome using Clavien multi-tier grading system, and the effect of a variety of related factors, including type of resection, surgical technique used, concomitant colo-rectal resection, non-tumoral hepatic histological findings, site of primary tumor, and comorbidities, on the incidence of intra-operative blood transfusion. RESULTS: Patients who received blood transfusions during their liver resection were more likely to have a longer post-operative length of stay, to experience Clavien Grade IIIa or worse complication. Undergoing a major resection and the presence of portal fibrosis in the non-tumoral liver tissue were both correlated with an increase in intra-operative blood transfusions. CONCLUSION: These clinical findings suggest that although several significant factors do not seem to influence the short-term outcome of surgery, it is important to be aware of the deleterious effects of the type of resection performed and the presence of portal fibrosis on blood loss during partial liver resection.

Multidetector-row computed tomography (MDCT) for the diagnosis of hepatocellular carcinoma in cirrhotic candidates for liver transplantation: prevalence of radiological vascular patterns and histological correlation with liver explants.

AIM: To define the prevalence of different multidetector-row computed tomography (MDCT) vascular patterns and their histopathological correlation with liver explants, and to evaluate the accuracy of MDCT for the diagnosis of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 125 cirrhotic patients imaged by MDCT before liver transplantation. Three main vascular patterns were identified: hypervascular lesion with washout (Hyper-L-Wo), hypervascular lesion without washout (Hyper-L) and non-hypervascular lesion (Hypo-L). Radiological findings were matched with histopathology of explants. RESULTS: Positive predictive value (PPV) and likelihood ratio (LR) were 95% and 18.66, respectively, for Hyper-L-Wo; 45% and 0.82 for Hyper-L; and 75% and 3 for Hypo-L of 20 mm or larger. Overall accuracy of MDCT for detection and characterisation of HCC was 89% and 43%, respectively. Sensitivity of MDCT for detection and characterisation was related to the lesion size, ranging from 78% (lesion smaller than 10 mm) to 98% (larger than 20 mm) and from 9% to 64%, respectively. MDCT established the accurate stage of disease in 46% of the patients, underestimated in 52% and overestimated in 2%. CONCLUSION: In cirrhotic patients, any Hyper-L-Wo detected by MDCT can be confidently considered to be HCC. Hyper-L larger than 10 mm and Hypo-L of 20 mm or larger are at high risk of HCC. However, even using MDCT and the newest imaging protocols, imaging underestimated the diagnosis of small HCC.

Design, development and validation of a system for automatic help to medical text understanding.

OBJECTIVE: The paper presents a web-based application, SIMPLE, that facilitates medical text comprehension by identifying the health-related terms of a medical text and providing the corresponding consumer terms and explanations. BACKGROUND: The comprehension of a medical text is often a difficult task for laypeople because it requires semantic abilities that can differ from a person to another, depending on his/her health-literacy level. Some systems have been developed for facilitating the comprehension of medical texts through text simplification, either syntactical or lexical. The ones dealing with lexical simplification usually replace the original text and do not provide additional information. We have developed a system that provides the consumer terms alongside the original medical terms and also adds consumer explanations. Moreover, differently from other solutions, our system works with multiple languages. METHODS: We have developed the SIMPLE application that is able to automatically: 1) identify medical terms in a medical text by using medical vocabularies; 2) translate the medical terms into consumer terms through medical-consumer thesauri; 3) provide term explanations by using health-consumer dictionaries. SIMPLE can be used as a standalone web application or can it be embedded into common health platforms for real time identification and explanation of medical terms. At present, it works with English and Italian texts but it can be easily extended to other languages. We have run subjective tests with both medical experts and non-experts as well as objective tests to verify the effectiveness of SIMPLE and its simplicity of use. RESULTS: Non-experts found SIMPLE easy to use and responsive. The big majority of respondents confirmed they were helped by SIMPLE in understanding medical texts and declared their willingness to continue using SIMPLE and to recommend it to other people. The subjective tests, conducted with medical experts on a set of Italian radiology reports, showed an agreement between SIMPLE and the experts, on the highlighted medical terms, that ranges between 74.05 % and 81.16 % as well as an agreement of around 60 % on the consumer term translation. The objective tests showed that the consumer terms, provided by SIMPLE, are, on average, eighteen times more familiar than the relative medical terms so proving, once more, the effectiveness of SIMPLE in simplifying the medical terms. CONCLUSIONS: The performed tests demonstrate the effectiveness of SIMPLE, its simplicity of use and the willingness of people in continuing with its use. SIMPLE provides, with a good agreement level, the same information that medical experts would provide. Finally, the consumer terms are 'objectively' more familiar than the related technical terms and as a consequence, much easier to understand.

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.

TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124 patients.

BACKGROUND & AIMS: Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder secondary to hepatic venous outflow obstruction. Small series of BCS patients indicate that transjugular intrahepatic portosystemic shunt (TIPS) may be useful. However, the influence of TIPS on patient survival and factors that predict the outcome of TIPS in BCS patients remain unknown. METHODS: One hundred twenty-four consecutive BCS patients treated with TIPS in 6 European centers between July 1993 and March 2006 were followed until death, orthotopic liver transplantation (OLT), or last clinical evaluation. RESULTS: Prior to treatment with TIPS, BCS patients had a high Model of End Stage Liver Disease and high Rotterdam BCS prognostic index (98% of patients at intermediate or high risk) indicating severity of liver dysfunction. However, 1- and 5-year OLT-free survival were 88% and 78%, respectively. In the high-risk patients, 5-year OLT-free survival was much better than that estimated by the Rotterdam BCS index (71% vs 42%, respectively). In the whole population, bilirubin, age, and international normalized ratio for prothrombin time independently predicted 1-year OLT-free survival. A prognostic score with a good discriminative capacity (area under the curve, 0.86) was developed from these variables. Seven out of 8 patients with a score >7 died or underwent transplantation vs 5 out of 114 patients with a score <7. CONCLUSIONS: Long-term outcome for patients with severe BCS treated with TIPS is excellent even in high-risk patients, suggesting that TIPS may improve survival. Furthermore, we identified a small subgroup of BCS patients with poor prognosis despite TIPS who might benefit from early OLT.

Arterial chemoembolization/embolization and early complications after hepatocellular carcinoma treatment: a safe standardized protocol in selected patients with Child class A and B cirrhosis.

PURPOSE: To assess the safety of transarterial treatments of hepatocellular carcinoma (HCC), and the statistical correlation of various patient factors with the frequency of complications, in selected patients with cirrhosis when adhering to well-standardized protocols. MATERIALS AND METHODS: Three hundred twenty consecutive patients with unresectable HCC were treated with transarterial chemoembolization, oil chemoembolization, and embolization. A total of 712 treatments were performed, with an average of 2.3 treatments for each patient. The epirubicin dose was adjusted according to defined laboratory criteria. An early complication was defined as one that occurred within 4 weeks of treatment. Complications were classified as minor and major and assessed by using clinical and laboratory data. RESULTS: Of the 712 procedures, 21 complications (2.9%) occurred in 17 of the 320 patients (5.3%). Major complications included acute liver failure (n = 1, 0.1%), variceal bleeding (n = 2, 0.3%), moderate-to-severe ascites (n = 4, 0.6%), sepsis (n = 3, 0.4%), cholecystitis (n = 1, 0.1%), and diverticulitis (n = 1, 0.1%). Minor complications were hepatic artery damage, including spontaneously resolved dissection (n = 3, 0.4%), mild encephalopathy (n = 1, 0.1%), and aspartate aminotransferase/alanine aminotransferase levels greater than 500 U/L (n = 5, 0.7%). The 30-day mortality rate was 0.003% (n = 1). Constitutional syndrome (P = .0001), Child-Pugh score (P = .0001), ascites (P = .037), and the Model for End-Stage Liver Disease score (P = .02) were found to have a statistically significant correlation with complications after univariate analysis. Child-Pugh score (P = .012) and constitutional syndrome (P = .003) were found to have a statistically significant correlation with complications after logistic regression analysis. CONCLUSIONS: Transarterial treatments can be considered safe in patients with Child class A and B cirrhosis when an adjusted dose of epirubicin is used according to body surface, severity of liver disease, and white blood cell count. Accurate patient selection and procedure-related factors may reduce the frequency of complications and help preserve liver function.

The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients.

BACKGROUND: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCB1. We have investigated the effects of possible relevant CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. MATERIAL/METHODS: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C(0)) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T] and 26 [3435C>T]. RESULTS: 87.5% of the population showed a CYP3A5*3/*3 genotype. For the ABCB1 SNPs, in the case of 3435C>T the total frequency observed for the allelic variant was 50%. For the 2677G>T, the total frequency of the allelic variant was 12.5%, lower than in other Caucasian populations and without any significant linkage with 3435C>T. At 3 and 6 months after transplantation, tacrolimus dose requirements were significantly higher in patients receiving a liver with one copy of the *1 allele compared to those homozygous for the *3 allele (0.111+/-0.057 vs. 0.057+/-0.030 [P<0.05] at 3 month and 0.086+/-0.051 vs. 0.044+/-0.025 [P<0.05] at 6 month). For the recipients' genotypes, the presence of at least one *1 copy tended, though not statistically significantly, to increase tacrolimus doses. With regard to the ABCB1 SNPs, they did not show any influence on tacrolimus dosing requirements. CONCLUSIONS: Pharmacogenetic analysis of CYP3A5 in the donor could contribute to determine the appropriate initial dosage of tacrolimus in liver transplant patients.