Search

Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.

Ultrasound (US) is frequently the first line imaging technique used in patients with abdominal pain and clinical suspicion of chronic pancreatitis (CP), but its role in the diagnosis and follow-up of CP is still controversial.We aimed to develop a dedicated score for the US staging of CP and to evaluate the agreement of this score with standard imaging techniques.Ninety consecutive patients with a diagnosis of CP referred to the pancreatic outpatient clinic of A. Gemelli Hospital between June and September 2018 were recruited in the study. Patients underwent pancreatic US to evaluate different morphological parameters to develop an US based score system, called the Gemelli UltraSound Chronic Pancreatitis (USCP) score.The Gemelli USCP score significantly increased according to the Cambridge score for both mean value (p0.0001) and each parameter evaluated (p0.0001). Moreover, we found a significant correlation between the score and laboratory parameters related to pancreatic exocrine insufficiency such as vitamin D, B9, and B12 deficiency and fecal elastase values (p0.0001).The development of a dedicated US score could be useful in the follow up of patients with CP as alternative non-invasive technique to standard radiological imaging.

ObjectiveClinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis.DesignThis multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14+CD16−monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis.ResultsThe algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively.The area under the receiver operating characteristic (AUROC) for NAS level prediction ranged from 83.7% (CI 75.6% to 91.8%) in the discovery cohort to 97.8% (CI 95.8% to 99.8%) in the validation cohort.The algorithm including RAB14 MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% (CI 87.9% to 100%) in the discovery cohort and 99.3% (CI 98.1% to 100%) in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100% and specificity 95.8% in the discovery cohort and 97.6%, 99% and 89.6% in the validation cohort. This novel biomarker was superior to currently used FIB4, non-alcoholic fatty liver disease fibrosis score and aspartate aminotransferase (AST)-to-platelet ratio and was comparable to ultrasound two-dimensional shear wave elastography.ConclusionsThe proposed novel liquid biopsy is accurate, sensitive and specific in diagnosing the presence and severity of NASH or liver fibrosis and is more reliable than currently used biomarkers.Clinical trialsDiscovery multicentre cohort: Bariatric Surgery versus Non-Alcoholic Steatohepatitis, BRAVES, ClinicalTrials.gov identifier:NCT03524365.Validation multicentre cohort: Liquid Biopsy for NASH and Fibrosis, LIBRA, ClinicalTrials.gov identifier:NCT04677101.

Background: Contrast-enhanced ultrasound (CEUS) with second-generation contrast agents performed 1 month after hepatocellular carcinoma (HCC) treatment is almost as sensitive as contrast-enhanced computed tomography (CECT) in depicting the residual tumor. However, the efficacy of CEUS performed early after the procedure is still debated. Aim: We evaluated the diagnostic accuracy (DA) of CEUS for the assessment of tumor response shortly after locoregional therapy in patients with unresectable HCC. Methods: Ninety-four patients with 104 HCC lesions who were scheduled to receive percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization, or combined treatment were enrolled in this study. With CECT at 1-month as the reference standard, the DA of CEUS performed 48-h after the procedure was evaluated. Patients were followed-up to look for tumor or disease progression. Results: Based on CECT findings, 43/104 lesions were diagnosed as having residual viability after 1 month. CEUS performed 48 h after treatment detected residual tumor in 34/43 nodules with treatment failure at CECT with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 79.1, 96.7, 94.4, 86.8, and 89%, respectively. There was a high degree of concordance between CEUS and CECT (kappa coefficient = 0.78). A hyperemic halo was detectable in 35 lesions without a statistically significant difference between concordant and discordant cases. In patients with uninodular disease responders according to 48 h CEUS had a significantly longer mean overall survival and time to progression compared to nonresponders. Conclusion: CEUS performed 48 h after treatment can be considered a reliable modality for the evaluation of the real extent of necrosis and has prognostic value in the assessment of HCC.

Portal vein thrombosis (PVT) represents a well-known complication during the natural course of liver cirrhosis (LC), ranging from asymptomatic cases to life-threating conditions related to portal hypertension and hepatic decompensation. Portal flow stasis, complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development. However, PVT occurrence remains unpredictable and many issues regarding its natural history, prognostic significance and treatment are still elusive. In particular although spontaneous resolution or disease stability occur in most cases of PVT, factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet. Moreover, PVT impact on LC outcome is still debated, as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression. Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases, even if the safer therapeutic option and the optimal therapy duration are still unknown. Nevertheless, their impact on mortality rates should be addressed more extensively. In this review we present the most debated questions regarding PVT, whose answers should come from prospective cohort studies and large sample-size randomized trials.

Aim To evaluate whether changes in bowel perfusion parameters measured by dynamic-CEUS (D-CEUS) can be used for monitoring response to therapy in active Crohn disease (CD). Methods Fifty-four CD patients were evaluated with d -CEUS before (T0) and after 2 (T1), 6 (T2) and 12 weeks (T3) of anti-TNFα therapy. Variations from baseline were calculated for: peak intensity, PI; area under the curve, AUC; slope of wash in, Pw; time to peak, TP; mean transit time, MTT (median percentage values) and were correlated with combined endoscopic/clinical response after 12 weeks and clinical relapse within 6 months. Results 70% of patients achieved combined endoscopic/clinical response (responders). The reduction in PI, AUC, Pw and MTT between T1 and T0 was higher in responders. Relapsers (21%) showed significantly lower reduction in delta PI and Pw at T1 and T2. At T3 they showed a new increase in PI and lower reduction in delta Pw. In relapsers, AUC showed a significantly lower decrease at T2 and T3, TP showed a significant reduction at T3 and MTT showed a progressive increase at the different time-points, reaching the statistical significance at T3. Conclusions d -CEUS might become a reliable predictor of combined endoscopic/clinical response and clinical relapse in CD.

Intestinal ultrasonography has emerged as a cheap, non-invasive and readily accessible modality for the assessment of a number of gastroenterological diseases. Over the last decade, particularly due to the widespread use of biological agents in Inflammatory Bowel Disease (IBD), guidelines regarding management and follow-up advise more regular disease assessment and surveillance in order to guide treatment adjustments, and provide more personalised care. Given the young age of the majority of patients with IBD the availability of an alternative modality to harmful radiation or the risks of endoscopy for this indication offers an appealing advantage. Intestinal ultrasonography has been shown to be as sensitive and specific for detecting IBD as both computed tomography and magnetic resonance enterography, and endoscopic evaluation. More recent developments in the technology of ultrasonography equipment and the use of intravenous contrast agents (contrast enhanced ultrasonography, known as CEUS), have significantly increased the ability to both detect disease location, determine the disease activity and also potentially the difference between fibrotic and inflammatory segments. This review focusses specifically on the value of CEUS for the diagnosis of both Crohn's disease and Ulcerative Colitis, in determining disease activity, extraintestinal complications, determination of fibrosis as well as its more recent use in assessing and predicting response to biological and immunosuppressive therapies.

We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis.We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis.501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67).Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode.

Treatment of Helicobacter pylori infection is becoming a very relevant problem especially in industrialized Countries. Although different therapeutic regimens are currently available, treatment failure remains a growing problem in daily medical practice. Several factors could play a role in the eradication failure, but the most relevant are antibiotic resistance and patient's compliance. While Helicobacter pylori resistance to amoxicillin is rare, clarithromycin and metronidazole resistance varies significantly from close to zero up to 25%. However, metronidazole in vitro resistance exhibits a lower impact on eradication success because resistance in vitro does not reflect that in vivo. Specific guidelines have then been published, mostly based on antibiotic resistance among different geographic areas. Basically, first-line and second-line regimens have been well defined; concerning third-line treatment Maastricht III guidelines suggest to adopt a culture-based approach. Culture is, however, expensive, invasive and available only in few specialized centres. An alternative approach may be to use an empirical strategy, based on the avoidance of repeating similar eradicating schemes in the same patients during the course of different eradicating regimens. For this approach we propose the acronym DANCE (Different Antibiotic No Culture Eradicating) strategy. When correctly applied, this approach showed to reach successful eradication in up to 99.5% of Helicobacter pylori-positive patients.

Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients.

Examinations with a visualisation of the anatomy and pathology of the gastrointestinal (GI) tract are often necessary for the diagnosis of GI diseases. Traditional radiology played a crucial role for many years. Endoscopy, despite some limitations, remains the main technique in the differential diagnosis and treatment of GI diseases. In the last decades, the introduction of, and advances in, non-invasive cross-sectional imaging modalities, including ultrasound (US), computed tomography (CT), positron-emission tomography (PET), and magnetic resonance imaging, as well as improvements in the resolution of imaging data, the acquisition of 3D images, and the introduction of contrast-enhancement, have modified the approach to the examination of the GI tract. Moreover, additional co-registration techniques, such as PET-CT and PET-MRI, allow multimodal data acquisition with better sensitivity and specificity in the study of tissue pathology. US has had a growing role in the development and application of the techniques for diagnosis and management of GI diseases because it is inexpensive, non-invasive, and more comfortable for the patient, and it has sufficient diagnostic accuracy to provide the clinician with image data of high temporal and spatial resolution. Moreover, Doppler and contrast-enhanced ultrasound (CEUS) add important information about blood flow. This article provides a general review of the current literature regarding imaging modalities used for the evaluation of bowel diseases, highlighting the role of US and recent developments in CEUS.

To the Editor: We read with great interest the article by Pozzoni et al. (1) about the effectiveness of Saccharomyces boulardii (S. boulardii) in the prevention of antibiotic-associated diarrhea (AAD) in adults. This is a carefully designed clinical trial, which was conducted with good methodology and low risk of bias. We agree with the authors that AAD prevention is an important topic, especially in hospitalized patients, since it increases costs and hospital length of stay. However, the results of the trial should be interpreted within the context of some limitations.

Background & Aims: Neo-adjuvant transarterial therapies are commonlyused for patients with HCC in the waiting list for liver transplantation (LT)to delay tumour progression, however, their effectiveness is not well-estab-lished. We studied the effect of pre-LT transarterial therapies on post-LTHCC recurrence, using the explanted liver histology to assess therapeutic effi-cacy and the predictors of response to these therapies. Methods: Weincluded 150 consecutive patients from our prospectively compiled database,listed for liver transplantation using the Milan criteria. Transarterial emboli-zation without chemotherapeutic agents was the transarterial therapyused as standard of care. PVA particles were the embolizing agent of choi-ce. Results: Sixty-seven (45%) patients had TAE as bridging therapy to livertransplantation, of which 60 were transplanted after 2001. The majority ofpatients (36, 54%) had partial tumour necrosis after transarterial therapy,whereas 22 (33%) had complete tumour necrosis and 9 (13%) had no necro-sis. HCC post-transplant recurrence was independently associated with noneo-adjuvant transarterial therapy (OR 5.395, 95% CI 1.289–22.577;P = 0.021) and the total radiological size of HCC nodules (OR 1.037, 95%CI 1.006–1.069; P = 0.020). Conclusions: Pre-transplant TAE with the morepermanently occluding PVA particles significantly reduces post-transplantHCC recurrence in patients within the Milan criteria.Hepatocellular carcinoma (HCC) is a major indicationfor liver transplantation (LT) in Europe, representing14% of transplants(1). The selection criteria currentlyused in most centres for listing patients with HCC arethe Milan criteria, i.e. a single lesion up to 5 cm diame-ter or up to three lesions all 3 cm (2). As livertransplantation has become an effective treatment forend-stage liver disease, there is increased organ demandwhich results in prolonged waiting list times (3). Longwaiting list times may result in tumour progression andthus high dropout rates as patients become ineligible,because of increasing tumour size, such that 6- and 12-month dropout rate because of tumour progression are11 and 57% respectively (4).Therefore, neo-adjuvant treatments while the patientis on the waiting list are used in many centres to delaytumour progression and decrease waiting list dropouts.Transarterial therapies [chemo-embolization (TACE) orbland embolization (TAE)], are probably the mostwidely used neo-adjuvant modalities (5). TACE is nor-mally considered as a palliative procedure in patientswho do not have surgical or transplant options andincreases survival in this setting as shown in randomizedcontrolled trials and meta-analyses (6, 7). However, arecent Cochrane meta-analysis has not shown benefit(8), but this evaluation has been disputed (9). In theneo-adjuvant setting, there is no robust evidence of effi-cacy, but there is some evidence of benefit from cohortstudies (10–13). It should be noted that TACE is not astandardized procedure, as reports document differentuse of embolic and chemotherapeutic agents, differentarterial selectivity before embolization, variable emboli-zation particle sizes and different schedules and indica-tions for repeat sessions (14). On the other hand, thetransplant population offers a unique opportunity tostudy objective responses to transarterial therapies basedon explant histology.In this study, we used a cohort of consecutivepatients transplanted for HCC to evaluate (a) the effectsof a uniform protocol of pre-LT transarterial therapies

Collagen proportionate area (CPA) has a better correlation with hepatic venous pressure gradient (HVPG) than with Ishak stage. Liver stiffness measurement (LSM) is proposed as non invasive marker of portal hypertension/disease progression. Our aim was to compare LSM and CPA with Ishak staging in chronic viral hepatitis, and HVPG in HCV hepatitis after transplantation. One hundred and sixty-nine consecutive patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections pre/post liver transplantation (LT), had a liver biopsy combined with LSM (transient elastography), CPA (biopsies stained with Sirius Red and evaluated by digital image analysis and expressed as CPA) and HVPG (measured contemporaneously with transjugular biopsies in LT HCV patients). LSM was dependent on CPA in HBV (r 2 = 0.61, p

Sex and gender differences regarding the epidemiology, clinical features, natural history, and response to therapies in hepatology and gastroenterology may be of major relevance for clinical medicine but have not yet been studied in detail so far. The mechanisms of sex or gender differences in these fields and their clinical implications are still unclear.

Relative adrenal insufficiency (AI) occurs in patients with cirrhosis with sepsis, but not with variceal bleeding. We evaluated adrenal function in cirrhotic patients with and without bleeding.Twenty cirrhotic patients with variceal bleeding were evaluated using the short synacthen test (SST) and 10 using the low-dose synacthen test (LDSST) followed by SST. The control group included 60 stable cirrhotic patients, assessed by LDSST (n = 50) or SST (n = 10), and 14 healthy volunteers. AI was diagnosed using SST, based on peak cortisol levels ≤ 18 μg/dL in nonstressed patients or Δmax9 μg/dL or a total cortisol level10 μg/dL in stressed patients with variceal bleeding-the current criteria for critical illness-related corticosteroid insufficiency. Using LDSST, diagnosis was based on peak concentrations of cortisol ≤ 18 μg/dL in nonstressed patients and25 μg/dL (or Δmax9 μg/dL) in patients with variceal bleeding. We evaluated patients with levels of serum albumin2.5 g/dL, to indirectly assess cortisol binding.All healthy volunteers had normal results from LDSSTs and SSTs. Patients with variceal bleeding had higher median baseline concentrations of cortisol (15.4 μg/dL) than stable cirrhotic patients (8.7 μg/dL, P = .001) or healthy volunteers (10.1 μg/dL, P = .01). Patients with variceal bleeding had higher median peak concentrations of cortisol than stable cirrhotic patients (SST results of 32.7 vs 21 μg/dL, P = .001; LDSST results of 9.3 vs 8.1 μg/dL; nonsignificant), with no differences in Δmax in either test. These differences were greater with variceal bleeding than in stable cirrhotic patients with AI. Subanalysis of patients with albumin levels2.5 g/dL did not change these differences.Cirrhotic patients with variceal bleeding have AI. Despite higher baseline concentrations of serum cortisol and subnormal Δmax values, they did not have adequate responses to stress, and therefore had critical illness-related corticosteroid insufficiency.

Adrenal insufficiency (AI) is reported in critically ill patients with cirrhosis and is associated with increased mortality. It is unclear if AI is an underlying condition or triggered by critical events (e.g. sepsis). We investigated AI in cirrhosis without infection or hemodynamic instability.A total of 101 consecutive patients with cirrhosis were studied. AI was defined by a total serum cortisol (TC)18 μg/dl at 20 or 30 min after injection of 1 μg of tetracosactrin. Transcortin, calculated free cortisol (cFC), and free cortisol index (FCI) were assessed in a subgroup of 41 patients, with FCI12 representing normal adrenal function.AI was present in 38 patients (38%). Child score (median, 10 vs 7, p0.0001), MELD score (median, 17 vs 12, p0.0001), ascites (68% vs 37%, p0.01), basal TC (median,7.6 vs 14.9 μg/dl, p0.001), albumin (28 ± 0.8 vs 33 ± 0.7 g/L, p0.0001), INR (median, 1.6 vs 1.2, p0.0001), total bilirubin (median, 51 vs 31 μmol/L, p0.05), total cholesterol (median, 120 vs 142, p0.05), and LDL (median, 76 vs 81, p0.05) were significantly different between those with and without AI. ROC curves showed a basal TC ≤ 12.8 μg/dl to be a cut-off value closely associated with AI. The cFC was significantly related to TC for baseline values (R=0.94, p0.0001), peak values (R=0.90, p0.0001), and delta values (R=0.95, p0.0001), in patients with and without AI. However, no patient had a FCI12.AI defined by an abnormal response to 1 μg tetracosactrin is frequent in stable patients with cirrhosis, in the absence of infections or hemodynamic instability and is related to the severity of liver disease. However, evaluation of the true incidence of AI should comprise direct assays of free cortisol. Clinical consequences of AI need to be explored.

Received February 14, 2011; accepted May 9, 2011.Liver transplantation for hepatocellular carcinoma(HCC) and cirrhosis is complicated by the prognosis ofboth diseases. Although there is reasonable prognos-tic evidence for the likelihood of surviving cirrhosiswith and without liver transplantation, the issue withHCC is the likelihood of its recurrence as well as itsconsequences. For patients with HCC, there iscurrently only 1 drug (sorafenib) that has been shownto increase survival (in the pretransplant setting), andthe median increase is only 3 months.

Variceal hemorrhage is one of the leading causes of death in patients with cirrhosis, with the 6-week mortality after each episode ranging from 15% to 20%. The two main strategies for primary prevention of variceal bleeding in patients with cirrhosis and varices are the administration of nonselective β-blockers or the obliteration of varices with use of endoscopic band ligation. In this review, we present and critically review the latest data on primary prevention of variceal hemorrhage. We advocate that nonselective β-blockers should be the first line therapy, and band ligation should be offered only in cases of intolerance or side effects. We also explore potential future therapies based on preliminary experimental and clinical data.

Background: Recent publications have shown that performing fibroscan of the spleen (fibrospleen) can predict the development of esophageal varices in patients with cirrhosis of the liver. The aim of the present study was to evaluate the fibrospleen as a diagnostic tool in a broader cohort of patients with liver diseases with and without cirrhosis. Methods: 182 consecutive patients [80 female and 102 male, median age 51.8 years] who underwent a fibroscan test at the University Hospital of Essen, Germany, from September 1st to October 10th received a fibroscan of the spleen after obtaining informed consent. The test was performed using Fibroscan touch™ (Echosens™, France). 46 patients were liver transplant recipients, 57 had a viral hepatitis, 28 an autoimmune and 26 a fatty liver disease, further 19 patients suffered from vascular or genetic liver diseases. The patients were further divided in 3 groups regarding their fibroscan of the liver ( 14 kPa n=63). The fibrospleen was correlated to the flow velocity of the portal vein and spleen size. Statistical analyses were performed using GraphPad Prism v 6.0. Results: In a total of 108 patients a valid fibrospleen was possible. The fibrospleen resulted in generally higher values than the fibroscan of the liver. Between the three groups the mean value increased from 28.8 to 33.4 to 52.2 kPa, respectively. The ratio between fibroscan of the liver and fibrospleen increased from 0.33 to 0.44 to 1.15 between the three groups. These differences were statistically significant. The fibrospleen correlated significantly with fibroscan of the liver (pearson coefficient 0.49; p=0.0001) and the size of the spleen (pearson coefficient 0.57; p

s A.I.S.F. Annual Meeting (Rome, February 25th−26th, 2010) / Digestive and Liver Disease 42 Suppl. 1 (2010) S1–S51 S19 with normal spleen diameter (p 20 ppm or a rise by 12 ppm above baseline following glucose administration was considered as positive. IP was evaluated by the (51)Cr-EDTA permeability test. SIBO prevalence in LC was compared with healthy controls and correlated with LC severity and IP. Results: Twenty-nine out of 56 LC patients had SIBO vs 2 of the 48 healthy controls (51.8% vs 4%, p< 0.0001). SIBO prevalence correlated with the severity of LC (68.2% of Child C pts vs. 56.2% of Child B and 31.2% of Child A pts), with the presence of ascites (66% in ascitic pts vs. 27% in non-ascitic pts), and with a history of SBP (92% of patients with SBP vs. 48% of those without SBP). A significant correlation was found between presence of SIBO and altered IP: it was weak for Child A but significant for Child B and C pts (R = 0.07, NS; R = 0.35, p = 0.005; R = 0.29, p = 0.03, respectively). Conclusions: SIBO seems to have a higher prevalence in LC, correlates with LC severity and altered IP. This association suggests that SIBO may affect intestinal permeability of splancnic vessels and/or peritoneal membranes leading to SBP outbreak in LC. Future interventional studies are needed to confirm these preliminary data. T.N.13 PREDICTORS OF OUTCOME IN CIRRHOTICS ADMITTED TO INTENSIVE CARE UNIT (ICU); SURVIVORS EXHIBITED SIGNIFICANT RISE OF SERUM SODIUM LEVELS AND A FALL IN LACTATE LEVELS AT 48 HOURS M. Garcovich1,2, V. Vemala1, A. Davenport1, E. Dionigi1, S. Shaw1, B. Agarwal1, A.K. Burroughs1. Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK; Dipartimento di Medicina Interna, Universita Cattolica del Sacro Cuor, Rome, Italy Background: Critically ill cirrhotics admitted to ICU have poor prognosis. Factors known to portend worse outcome include mechanical ventilation, development of shock, renal failure and increasing number of organ failure. While a negative impact on mortality of low serum sodium level is observed in stable cirrhotics active on the waiting list for liver transplant, the impact of admission serum sodium and its changes during the course of an acute illness in these patients is not well known. Methods: We retrospective studied a cohort of cirrhotics admitted to ICU between 2005−08 at the Royal Free Hospital. Data were collected on demographic variables, aetiology of liver disease, liver-specific prognostic scores; Child–Turcotte–Pugh (CTP), Model for end-stage liver disease (MELD), United Kingdom model for end-stage liver disease (UKELD), acute physiological score and chronic health points (APACHE II) and sequential organ failure assessment score (SOFA). In addition, data were also collected for serum Na+ and Lactate levels at 0 (on admission) and at 48 hrs. Results: Currently 67 of 125 patients have been enrolled. 51/67 (76.1%) survived ICU. The non-survivors (16/67) had similar demographics as the survivors, had significantly higher mean MELD, UKELD, SOFA and APACHE II scores, and higher admission lactate. Total CTP score was not different between the groups but serum bilirubin level and prothrombin time were significantly higher in the non-survivors. Although the admission Na+ levels in survivors and non survivors were similar, a significant elevation was observed at 48 hrs in the survivors. The trend for serum lactate levels showed a similar pattern i.e., the survivors showed significant reductions at 48 hrs. Conclusions: The reasons for this observed rise in serum Na+ at 48 hrs in the survivors are not obvious. It may signify a better preserved water balance in patients with less severe underlying liver disease. T.N.14 COLLAGEN PROPORTIONATE AREA IN ASSESSING THE AMOUNT OF FIBROSIS IN CHRONIC LIVER DISEASE: DOES HIGH RESOLUTION COMPARED TO CONVENTIONAL IMAGE CAPTURING AND ANALYSIS ALTERS ITS RESULTS? L. Andreana1, G. Isgro1, M. Garcovich1, A. Hall2, F. Grillo2, A.P. Dhillon2, A.K. Burroughs1, T.V. Luong2. The Sheila Sherlock Liver Centre and University Dept. of Surgery, Royal Free Hospital, London, UK; Dept. of Histopathology, Royal Free Hospital

Background/Aims: Hepatolithiasis is a well known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. Methods: Among a total of 257 patients who received treatment for hepatolithiasis from 2002 to 2011 at Korea University Anam and Guro Hospital, 236 patients were eligible for analysis; 92 patients underwent liver resection (resection group) and 144 patients did not (non-resection group). The data were retrospectively collected and analyzed. Results: The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41±41 months). The median tumor occurrence time was 28 (13-111) months. Cholangiocarcinoma occurred 6.5% (6/92) and 6.9% (10/144) in resection and non-resection group respectively (P=0.425). In resection group, cholangiocarcinoma occurred in 3.6% (2/56) of patients with complete stone removal, and in 13.3% (4/ 30) of patients with incomplete stone removal (p=0.591). In non-resection group, cholangiocarcinoma occurred in 5.7% (3/53) of patients with complete stone removal, and in 8.9% (7/79) of patient with incomplete stone removal (p=0.738). When analyzed according to completeness of stone removal regardless of treatment modality, cholangiocarcinoma occurred in 4.6% (5/109) of patients with complete stone removal, and in 10.1% (11/109) of patients with incomplete stone removal (p=0.429). Although the site of stone and tumor occurrence concurred in 10/16 patients (3/6 patients in the resection group, 7/10 patient in the non-resection group), it did not match in 6 patients. On univariate analysis, none of the factors (age, gender, abdominal pain, bile duct stenosis, bile duct dilatation, liver atrophy, residual stone, stone recurrence and liver resection) showed relationship with the incidence of cholangiocarcinoma. Conclusion: There was no difference in the incidence of cholangiocarcinoma according to the treatment modality or completeness of stone removal. Therefore, patients with hepatolithiasis should carefully be followed-up to detect cholangiocarcinoma even after treatment.

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.

Portal vein thrombosis (PVT) is one of the most common complications occurring during the natural course of liver cirrhosis. Even though PVT is often asymptomatic, the worsening of liver function, an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT development. Beyond these clinical manifestations, it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its consequences. Probably PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation tendency. On one hand, PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic livers. On the other hand, vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction, with loss of hepatic tissue (parenchymal extinction) which is replaced by fibrotic tissue. Therefore, PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver disease. At present, a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been demonstrated. Nevertheless, it is not clear if PVT development may worsen cirrhotic patients' outcome by itself. Some authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are contrasting. In this review, we will try to answer these questions, providing a critical analysis of data reported in literature.

Introduction Histological scoring systems diagnose cirrhosis, but not severity of cirrhosis. Computer assisted digital image analysis (DIA) of Sirius red stained sections measures fibrosis morphologically, using segmentation of digital images to measure the relative areas of collagen and of tissue, producing a fibrosis ratio or collagen proportionate area (CPA).1 CPA could have staging and prognostic value for histological cirrhosis. The aim of this study is to evaluate CPA in cirrhosis of mixed aetiology and its relationship with liver decompensation. Methods We evaluated 118 consecutive patients with histological cirrhosis retrospectively: 76 males, mean age 53(±12.31), follow-up mean of 41.6 (±22.03) months after biopsy. At biopsy 63 were compensated (no ascites, bleeding episodes, encephalopaty). Results The mean CPA value in compensated patients was 17.2 (±8.3), in decompensated patients 27.9 (±10.7) (p Cox regression for time to decompensation was evaluated using INR, bilirubin, albumin, sodium, creatinine, Child score and CPA. Indipendently associated variables were CPA (OR 1.13, 95% CI 1.06 to 1.22, p=0.001) and albumin (OR 0.13, 95% CI 0.03 to 0.54, p=0.005). Conclusion CPA increases with worsening cirrhosis and is able to predict decompensation in compensated cirrhosis of mixed aetiologies. This suggests that severity of cirrhosis can be assessed histologically and that it correlates with clinical outcome.

Introduction Liver stiffness (LS) measured by transient elastography (TE) is related to liver fibrosis, which histologically is categorised into stages which do not have quantitatively relationships. Collagen proportionate area (CPA) measured by computer-assisted digital image analysis (DIA) on biopsies stained with Sirius red is an histological method for quantifying collagen in liver biopsies. The aim of this study is to correlate LS to Ishak score and CPA in patients with chronic viral hepatitis. Methods LS was measured by TE in 100 patients with chronic viral hepatitis (HCV, HBV). Results We evaluated 100 patients: 58 male, mean age 46.4 (±11.5). HCV (n=51), mean age 48.8, 28 males, mean CPA (6.4±6.6), mean LS 12.6 (±15.1). Univariately CPA (r 2 0.57 p 2 0.37 p 2 0.37 p 2 0.59, p 2 0.49, p 2 0.55, p 2 0.69, p 2 0.70, p 4 the AUROC for CPA was 0.96 (95% CI 0.90 to 1.03) and the best cut off was 11.7 (90%sensitivity, 100%specificity). For METAVIR F4 AUROC was 0.98 (95% CI 0.96 to 1.01) and the best cut off for CPA was 12.4 (87%sensitivity, 99%specificity). In HBV patients, the AUROC for CPA was absolute (ie, 1, 95% CI 1.00 to 1.00) in both patients with Ishak >4 and patients with METAVIR F4. In the first case the best cut off was 8.9 (100%sensitivity, 100%specificity), in the latter the best cut off for CPA was 10.3 (100%sensitivity, 100%specificity). Conclusion In chronic viral hepatitis, the measurement of CPA which is a continuous quantitative measurement of liver collagen was correlated well with current stage systems. CPA had a much better correlation with TE than METAVIR or Ishak stages. CPA should replace traditional histological staging systems for quantifying fibrosis in comparison with TE.

Introduction Transient elastography is a non-invasive method developed as an alternative to liver biopsy to assess fibrosis severity. In this meta-analysis, we assessed the performance of elastography in diagnosing fibrosis using liver biopsy as the reference standard. Methods Electronic search of MEDLINE, EMBASE, Science citation index and Cochrane Library; and hand-search of major conference abstracts and article references were performed by two authors independently. Included studies used biopsy as reference standard, reported on data necessary to calculate the true-positive, false-positive, true-negative, and false-negative diagnostic results of elastography for a fibrosis stage and had a 3-month maximum interval between tests. METAVIR F2 and cirrhosis were analysed. Study quality was assessed using the QUADAS tool. Data were combined using the hierarchical summary receiver operator characteristics, and bivariate normal random-effects analysis of sensitivity and specificity methods, using the METANDI module. Results We identified 40 eligible studies (32 full papers). No article was assessed as adequate for all the questions in QUADAS. Only nine studies had both an acceptable reference and index test quality. Overall, the summary sensitivity and specificity was 0.79 (95% CI 0.74 to 0.82) and 0.78 (95% CI 0.72 to 0.83) for F2 and 0.83 (95% CI 0.79 to 0.86) and 0.89 (95% CI 0.87 to 0.91) for cirrhosis. With an elastography result at or over the threshold value as determined in each study, for F2 or cirrhosis (“positive” result), the corresponding post-test probability for presence of these stages (if pre-test probability was 50%) was 78%, and 88%, respectively, while values falling below those thresholds (“negative” result), the post-test probability was 21% and 16%, respectively. No optimal stiffness cut-offs for specific fibrosis stages were validated in independent cohorts. There was a wide range and overlap of cut-offs within and between different fibrosis stages. Conclusion Elastography is a good screening test for cirrhosis, with an 88% disease probability following a “positive” measurement, and a slightly worse tool in F=2. However, a “negative” measurement is less accurate, with disease being present in 15–20% of cases depending on fibrosis stage. Validation of liver stiffness cut-offs is required before elastography can be considered as sufficiently accurate for non-invasive diagnosis of fibrosis stages.

s A.I.S.F. Annual Meeting (Rome, February 25th−26th, 2010) / Digestive and Liver Disease 42 Suppl. 1 (2010) S1–S51 S19 with normal spleen diameter (p 20 ppm or a rise by 12 ppm above baseline following glucose administration was considered as positive. IP was evaluated by the (51)Cr-EDTA permeability test. SIBO prevalence in LC was compared with healthy controls and correlated with LC severity and IP. Results: Twenty-nine out of 56 LC patients had SIBO vs 2 of the 48 healthy controls (51.8% vs 4%, p< 0.0001). SIBO prevalence correlated with the severity of LC (68.2% of Child C pts vs. 56.2% of Child B and 31.2% of Child A pts), with the presence of ascites (66% in ascitic pts vs. 27% in non-ascitic pts), and with a history of SBP (92% of patients with SBP vs. 48% of those without SBP). A significant correlation was found between presence of SIBO and altered IP: it was weak for Child A but significant for Child B and C pts (R = 0.07, NS; R = 0.35, p = 0.005; R = 0.29, p = 0.03, respectively). Conclusions: SIBO seems to have a higher prevalence in LC, correlates with LC severity and altered IP. This association suggests that SIBO may affect intestinal permeability of splancnic vessels and/or peritoneal membranes leading to SBP outbreak in LC. Future interventional studies are needed to confirm these preliminary data. T.N.13 PREDICTORS OF OUTCOME IN CIRRHOTICS ADMITTED TO INTENSIVE CARE UNIT (ICU); SURVIVORS EXHIBITED SIGNIFICANT RISE OF SERUM SODIUM LEVELS AND A FALL IN LACTATE LEVELS AT 48 HOURS M. Garcovich1,2, V. Vemala1, A. Davenport1, E. Dionigi1, S. Shaw1, B. Agarwal1, A.K. Burroughs1. Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK; Dipartimento di Medicina Interna, Universita Cattolica del Sacro Cuor, Rome, Italy Background: Critically ill cirrhotics admitted to ICU have poor prognosis. Factors known to portend worse outcome include mechanical ventilation, development of shock, renal failure and increasing number of organ failure. While a negative impact on mortality of low serum sodium level is observed in stable cirrhotics active on the waiting list for liver transplant, the impact of admission serum sodium and its changes during the course of an acute illness in these patients is not well known. Methods: We retrospective studied a cohort of cirrhotics admitted to ICU between 2005−08 at the Royal Free Hospital. Data were collected on demographic variables, aetiology of liver disease, liver-specific prognostic scores; Child–Turcotte–Pugh (CTP), Model for end-stage liver disease (MELD), United Kingdom model for end-stage liver disease (UKELD), acute physiological score and chronic health points (APACHE II) and sequential organ failure assessment score (SOFA). In addition, data were also collected for serum Na+ and Lactate levels at 0 (on admission) and at 48 hrs. Results: Currently 67 of 125 patients have been enrolled. 51/67 (76.1%) survived ICU. The non-survivors (16/67) had similar demographics as the survivors, had significantly higher mean MELD, UKELD, SOFA and APACHE II scores, and higher admission lactate. Total CTP score was not different between the groups but serum bilirubin level and prothrombin time were significantly higher in the non-survivors. Although the admission Na+ levels in survivors and non survivors were similar, a significant elevation was observed at 48 hrs in the survivors. The trend for serum lactate levels showed a similar pattern i.e., the survivors showed significant reductions at 48 hrs. Conclusions: The reasons for this observed rise in serum Na+ at 48 hrs in the survivors are not obvious. It may signify a better preserved water balance in patients with less severe underlying liver disease. T.N.14 COLLAGEN PROPORTIONATE AREA IN ASSESSING THE AMOUNT OF FIBROSIS IN CHRONIC LIVER DISEASE: DOES HIGH RESOLUTION COMPARED TO CONVENTIONAL IMAGE CAPTURING AND ANALYSIS ALTERS ITS RESULTS? L. Andreana1, G. Isgro1, M. Garcovich1, A. Hall2, F. Grillo2, A.P. Dhillon2, A.K. Burroughs1, T.V. Luong2. The Sheila Sherlock Liver Centre and University Dept. of Surgery, Royal Free Hospital, London, UK; Dept. of Histopathology, Royal Free Hospital