C. Bureau

Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: A prospective study

BACKGROUND & AIMS The prognosis of patients with chronic liver disease is to a great extent determined by the presence and degree of portal hypertension (PHT). Hepatic venous pressure gradient (HVPG) has been shown to be an accurate prognostic index in patients with cirrhosis. Transient elastography is a non-invasive procedure that assesses liver fibrosis through the measurement of liver stiffness (LS). In several reports, LS was found to be correlated with HVPG. LS could therefore be useful to identify patients with significant PHT. The aim of the present study was to prospectively assess and to compare the prognostic performances of LS and HVPG in patients with chronic liver disease. METHODS One hundred patients with chronic liver disease underwent LS and HVPG measurements on the same day. Patients were thereafter followed-up for 2 years or until they experienced a complication related to their liver disease. RESULTS Within the two-year follow-up, 41 patients developed, at least, one liver disease related complication. The performances of HVPG and LS for predicting the occurrence of these complications were not significantly different: AUROC 0.815 [0.727-0.903] and 0.837 [0.754-0.920], respectively. When considering only complications related to PHT, both methods were found to be similarly accurate: AUROC 0.830 [0.751-0.910] and 0.845 [0.767-0.823], for HVPG and LS, respectively. When patients were divided in two groups according to a LS value below or above 21.1kPa, actuarial rates of remaining free of any complication at 2 years were 85.4% vs. 29.5%, respectively. When only PHT related complications were considered, these rates were 100% vs. 47.5%, respectively. The performances of LS and HVPG were also similar in the subgroup of 65 patients with cirrhosis. CONCLUSIONS LS proved as effective as HVPG in predicting clinical decompensation and PHT related complications in patients with chronic liver disease. Therefore, LS could be a valuable clinical tool to avoid invasive procedures.

Serum bilirubin and platelet count: a simple predictive model for survival in patients with refractory ascites treated by TIPS.

BACKGROUND & AIMS Refractory ascites in patients with cirrhosis is associated with poor survival. TIPS is more effective than paracentesis for the prevention of recurrence of ascites but increases the risk of encephalopathy while survival remains unchanged. A more accurate selection of the patients might improve these results. The aim of the present study was to identify parameters of prognostic value for survival in patients with refractory ascites treated with TIPS. METHODS One hundred and five consecutive French patients with cirrhosis and refractory ascites treated with TIPS were used to assess parameters associated with 1-year survival. The model was then tested in two different cohorts: a local and prospective one including 40 patients from Toulouse, France, and an external one including 48 patients from Barcelona, Spain. RESULTS The actuarial rate of survival in the first 105 patients was 60% at 1 year. Using multivariate analysis, only lower bilirubin levels and higher platelet counts were independently associated with survival. The actuarial 1-year survival rate in patients with both a platelet count above 75×10(9)/L and a bilirubin level lower than 50 μmol/L [3mg/dl] was 73.1% as compared to 31.2%, in patients with a platelet count below 75×10(9)/L or a bilirubin level higher than 50 μmol/L. These results were confirmed in the two different validation cohorts. CONCLUSIONS The combination of a bilirubin level below 50 μmol/L and a platelet count above 75×10(9)/L is predictive of survival in patients with refractory ascites treated with TIPS. This simple score could be used at bedside to help choose the best therapeutic options.

The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and displays anti-proliferative and pro-apoptotic functions

BACKGROUND & AIMS KLF6 protein is a transcription factor that plays important functions in hepatocellular carcinoma (HCC), which is one of the leading causes of death by cancer worldwide. Previous studies showed the existence of three splice variants of KLF6, termed SV1, SV2, and SV3. An increased SV1/KLF6 mRNA ratio in HCC was already described. In this study, we aimed to investigate the expression of the SV2 variant in HCC samples and its role in hepatic cells. METHODS We measured the expression of the SV2 variant in HCC and adjacent tissue samples by q-RT-PCR. We established IHH and HepG2 stable cell lines over-expressing the SV2 variant and measured cell growth and apoptotic rate. RESULTS We observed a reduced expression of the SV2 variant in HCC samples versus surrounding tissues and normal liver. Interestingly, our findings demonstrate that the over-expression of the SV2 variant in IHH and HepG2 cells leads to a significant reduction of proliferation associated with cell death by apoptosis. We further demonstrate that the SV2 expression leads to an induction of the cell-cycle-controlling p21(CIP/WAF1) and the pro-apoptotic Bax genes, mediated by the p53 protein. We show further that the SV2 expression in IHH and HepG2 cells induces their sensitivity to the anti-cancer drug, gemcitabine. CONCLUSION We reveal a reduced expression of the SV2 variant of KLF6 in HCC samples and describe anti-proliferative and pro-apoptotic functions for this variant in hepatic cells.

Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension

BACKGROUND The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. AIMS To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. METHODS 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. RESULTS The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness (C-statistics=0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy>80%), but were not statistically superior to liver stiffness alone. CONCLUSIONS Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone.

Hepatitis B screening: who to target? A French sexually transmitted infection clinic experience.

BACKGROUND & AIMS Hepatitis B virus (HBV) infection is a major public health burden in France and worldwide. Routine screening for hepatitis B is not currently recommended in France. Medical experts and public health agencies opinions can differ concerning targeting criteria. Our study aims at developing a risk assessment strategy for identifying possible hepatitis B cases among the patients consulting in a French Sexually Transmitted Infection (STI) clinic. METHODS 6194 asymptomatic patients requesting an STI screening were also screened for hepatitis B infection. The association between hepatitis B surface antigen (HBsAg) positivity and/or total hepatitis B core antibody (anti-HBc) positivity and self-reported risk factors for hepatitis were analysed. RESULTS Only male gender, lack of employment, and birth, in medium or high endemic country, were independently associated with HBsAg positivity in multivariate analysis. Sexual behaviour or self-reported vaccination status is therefore not necessary to target high-risk populations. These three simple criteria could save 25% of unnecessary tests and 6-16% undiagnosed hepatitis B compared to usual targeting criteria. CONCLUSIONS To detect HBsAg carriers, only three simple targeting criteria, without taking into account the self-reported vaccination status or sexual behaviour, could improve screening efficiency and save unnecessary testing.

Letter: sorafenib in portal hypertension

*University of Medicine and Pharmacy ‘Iuliu Hatieganu’, 3rd Medical Clinic, Department of Gastroenterology, Cluj-Napoca, Romania. Regional Institute of Gastroenterology and Hepatology ‘O Fodor’, Department of Gastroenterology, Cluj-Napoca, Romania. Department of Hepato-Gastroenterology, Purpan Hospital, CHU, Toulouse, France. INSERM U858 and University of Toulouse, Toulouse, France. E-mail: bogdanprocopet@gmail.com

Pretransplant urinary proteome analysis does not predict development of chronic kidney disease after liver transplantation

Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre‐, peri‐ and post‐transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post‐transplantation using proteome analysis.

P587 PROGNOSTIC VALUE OF AFP LEVELS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: PROSPECTIVE EVALUATION OF 715 CONSECUTIVE PATIENTS PRESENTED AT OUR MULTIDISCIPLINARY COMMITTEE FROM 2006 TO 2011

P586 APPEARANCE OF COMBINED HEPATOCELLULAR CHOLANGIOCARCINOMA IN CIRRHOSIS AT CONTRAST ENHANCED IMAGING TECHNIQUES E. Sagrini, M. Iavarone, S. Vavassori, F. Stefanini, M. Maggioni, I. Pettinari, A. Pecorelli, M. Colombo, L. Bolondi, F. Piscaglia. Digestive Disease and Internal Medicine, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Unit of Gastroenterology 1, UO Anatomia Patologica, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy E-mail: elisabetta.sagrini@gmail.com

Preemptive‐TIPS improves outcome in high‐risk variceal bleeding: An observational study

Patients admitted with acute variceal bleeding (AVB) and Child‐Pugh C score (CP‐C) or Child‐Pugh B plus active bleeding at endoscopy (CP‐B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p‐TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high‐risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p‐TIPS was based on individual center policy. p‐TIPS in the setting of AVB is associated with a lower mortality in CP‐C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP‐B+AB patients was low, and p‐TIPS did not improve it. In CP‐C and CP‐B+AB patients, p‐TIPS reduced treatment failure and rebleeding (1‐year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p‐TIPS must be the treatment of choice in CP‐C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p‐TIPS could be a good treatment strategy for CP‐B+AB patients.

Invasive and Non-invasive Diagnosis of Portal Hypertension in Cirrhosis

In the natural history of any chronic liver disease the occurrence of liver related complications is related to the portal hypertension development. Therefore, in the diagnosis work up of any liver disease the portal hypertension assessment is an indispensable step. The most accurate method for portal hypertension diagnosis is hepatic venous pressure gradient (HVPG), which implies central venous access and the catheterization of the hepatic vein. HVPG is the strongest prognostic marker in chronic liver diseases. It accurately predicts the risk of esophageal varices development and hemorrhage, the risk of decompensation as well as the mortality. Also HVPG represents a method to tailor portal hypertension treatment. However, due to the invasiveness of the procedure, there is an extensive effort to find non-invasive methods that could replace HVPG measurement. By now, only liver stiffness measuring proves to have good performances even there are issues about cut-offs and feasibility in overweight patients.