TIPS prevents further decompensation and improves survival in patients with cirrhosis and portal hypertension in an individual patient data meta-analysis.

BACKGROUND & AIMS: Further decompensation represents a prognostic stage of cirrhosis associated with higher mortality compared with first decompensation. A transjugular intrahepatic portosystemic shunt (TIPS) is indicated to prevent variceal rebleeding and for refractory ascites, but its overall efficacy to prevent further decompensations is unknown. This study assessed the incidence of further decompensation and mortality after TIPS vs. standard of care (SOC). METHODS: Controlled studies assessing covered TIPS compared with SOC for the indication of refractory ascites and prevention of variceal rebleeding published from 2004 to 2020 were considered. We collected individual patient data (IPD) to perform an IPD meta-analysis and to compare the treatment effect in a propensity score (PS)-matched population. Primary outcome was the incidence of further decompensation and the secondary outcome was overall survival. RESULTS: In total, 3,949 individual patient data sets were extracted from 12 controlled studies and, after PS matching, 2,338 patients with similar characteristics (SOC = 1,749; TIPS = 589) were analysed. The 2-year cumulative incidence function of further decompensation in the PS-matched population was 0.48 (95% CI 0.43-0.52) in the TIPS group vs. 0.63 (95% CI 0.61-0.65) in the SOC group (stratified Gray's test, p <0.0001), considering mortality and liver transplantation as competing events. The lower further decompensation rate with TIPS was confirmed by adjusted IPD meta-analysis (hazard ratio 0.44; 95% CI 0.37-0.54) and was consistent across TIPS indication subgroups. The 2-year cumulative survival probability was higher with TIPS than with SOC (0.71 vs. 0.63; p = 0.0001). CONCLUSIONS: The use of TIPS for refractory ascites and for prevention of variceal rebleeding reduces the incidence of a further decompensation event compared with SOC and increases survival in highly selected patients. IMPACT AND IMPLICATIONS: A further decompensation (new or worsening ascites, variceal bleeding or rebleeding, hepatic encephalopathy, jaundice, hepatorenal syndrome-acute kidney injury and spontaneous bacterial peritonitis) in patients with cirrhosis is associated with a poor prognosis. Besides the known role of TIPS in portal hypertension-related complications, this study shows that TIPS is also able to decrease the overall risk of a further decompensation and increase survival compared with standard of care. These results further support the role of TIPS in the management of patients with cirrhosis and portal hypertension-related complications.

The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.

BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.

A Prospective Study Identifying Predictive Factors of Cardiac Decompensation After Transjugular Intrahepatic Portosystemic Shunt: The Toulouse Algorithm.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is now a standard for the treatment of portal hypertension-related complications. After the TIPS procedure, incidence and risk factors of cardiac decompensation are poorly known. The main objectives were to measure the incidence of the onset of cardiac decompensation after TIPS and identify the predictive factors. APPROACH AND RESULTS: All patients with cirrhosis treated with TIPS between May 2011 and June 2016 were considered for inclusion. They received a cardiac assessment by standard biological parameters, transthoracic echocardiography, and right heart catheterization. Patients were followed for 1 year after TIPS insertion. The main endpoint was the incidence of cardiac decompensation requiring hospitalization. One hundred seventy-four patients were treated by TIPS during the period. One hundred patients who underwent a complete cardiac evaluation were included. A cardiac decompensation occurred in 20% of the patients. The parameters associated with the occurrence of severe cardiac decompensation were a prolonged QT interval corrected (462 vs. 443 ms; P = 0.05), an elevated pre-TIPS brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level, an elevated E/A ratio (1.5 vs. 1.0; P = 0.001) and E/e' ratio (11 vs. 7; P < 0.001), and a left atrial dilatation (40 vs. 29 mL/m2 ; P = 0.011). The presence of aortic stenosis was also associated with cardiac decompensation. A level of BNP <40 pg/mL and NT-proBNP <125 pg/mL allowed identifying patients without risk of cardiac decompensation. Additionally, absence of diastolic dysfunction criteria at echocardiography ruled out the risk of further cardiac decompensation. CONCLUSIONS: Hospitalization for cardiac decompensation is observed in 20% of patients in the year after TIPS insertion. Combining BNP or NT-proBNP levels and echocardiographic parameters should help improve patient selection.

Transjugular Intrahepatic Portosystemic Shunts With Covered Stents Increase Transplant-Free Survival of Patients With Cirrhosis and Recurrent Ascites.

BACKGROUND & AIMS: There is controversy over the ability of transjugular intrahepatic portosystemic shunts (TIPS) to increase survival times of patients with cirrhosis and refractory ascites. The high rate of shunt dysfunction with the use of uncovered stents counteracts the benefits of TIPS. We performed a randomized controlled trial to determine the effects of TIPS with stents covered with polytetrafluoroethylene in these patients. METHODS: We performed a prospective study of 62 patients with cirrhosis and at least 2 large-volume paracenteses within a period of at least 3 weeks; the study was performed at 4 tertiary care centers in France from August 2005 through December 2012. Patients were randomly assigned to groups that received covered TIPS (n = 29) or large-volume paracenteses and albumin as necessary (LVP+A, n = 33). All patients maintained a low-salt diet and were examined at 1 month after the procedure then every 3 months until 1 year. At each visit, liver disease-related complications, treatment modifications, and clinical and biochemical variables needed to calculate Child-Pugh and Model for End-Stage Liver Disease scores were recorded. Doppler ultrasonography was performed at the start of the study and then at 6 and 12 months after the procedure. The primary study end point was survival without a liver transplant for 1 year after the procedure. RESULTS: A higher proportion of patients in the TIPS group (93%) met the primary end point than in the LVP+A group (52%) (P = .003). The total number of paracenteses was 32 in the TIPS group vs 320 in the LVP+A group. Higher proportions of patients in the LVP+A group had portal hypertension-related bleeding (18% vs 0%; P = .01) or hernia-related complications (18% vs 0%; P = .01) than in the TIPS group. Patients in LVP+A group had twice as many days of hospitalization (35 days) as the TIPS group (17 days) (P = .04). The 1-year probability of remaining free of encephalopathy was 65% for each group. CONCLUSIONS: In a randomized trial, we found covered stents for TIPS to increase the proportion of patients with cirrhosis and recurrent ascites who survive transplantation-free for 1 year, compared with patients given repeated LVP+A. These findings support TIPS as the first-line intervention in such patients. ClinicalTrials.gov ID: NCT00222014.

Central obesity is associated with non-cirrhotic portal vein thrombosis.

BACKGROUND & AIMS: 30-40% of portal vein thrombosis (PVT) remains of unknown origin. An association between metabolic syndrome (MetS) and peripheral vein thrombosis has been reported but not with PVT, to date. The aim of this study was to investigate the association between MetS and PVT. METHODS: Between 2003 and 2014, all consecutive patients with non-cirrhotic PVT were prospectively included. Patient's characteristics and risks factors were recorded at the time of inclusion. Controls were selected by random in the general population and were matched 1/1 according to age and sex. RESULTS: Seventy-nine patients with PVT were included: 40 present with at least one risk factor for PVT (SPVT) and 39 were found to be idiopathic (IPVT). The prevalence of MetS was 25.6% in SPVT group vs. 47.4% in IPVT group and 17.9% in controls from the general population (C-IPVT: p=0.01). The waist circumference and body mass index were higher in the IPVT group than in the SPVT group (105 vs. 93cm, p=0.004 and 29.4 vs. 25.0kg/m(2), p=0.004) and in the C-IPVT group (105 vs. 92cm, p=0.001 and 29.4 vs. 25.8kg/m(2), p=0.003). Overweight was observed in 82.0% of patients in the IPVT group vs. 44% in the SPVT group (p=0.002) and 51% in the C-IPVT group (p=0.01). The mean visceral fat area was higher in IPVT than in SPVT (18,223mm(2)vs. 12,690mm(2), p=0.02). In multivariate analyses, an increase in waist circumference was the strongest parameter associated with idiopathic PVT. CONCLUSION: Central obesity is associated with PVT and could become one of the main risk factors for digestive thromboses.

Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study.

BACKGROUND & AIMS: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy. METHODS: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA. RESULTS: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed. CONCLUSIONS: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication.

Pre-transjugular intrahepatic portosystemic shunts (TIPS) prediction of post-TIPS overt hepatic encephalopathy: the critical flicker frequency is more accurate than psychometric tests.

UNLABELLED: Transjugular intrahepatic portosystemic shunts (TIPS) is a second-line treatment because of an increased incidence of overt hepatic encephalopathy (OHE). A better selection of patients to decrease this risk is needed and one promising approach could be the detection of minimal hepatic encephalopathy (MHE). The aim of the present prospective study was to determine whether pre-TIPS minimal hepatic encephalopathy was predictive of post-TIPS OHE and to compare Psychometric Hepatic Encephalopathy Sum Score(PHES) and the Critical Flicker Frequency (CFF) in this setting. From May 2008 to January 2011, 54 consecutive patients treated with TIPS were included. PHES and CFF were performed 1 to 7 days before and after TIPS at months 1, 3, 6, 9, and 12 or until liver transplantation or death. Before TIPS, MHE was detected by PHES and CFF in 33% and 39% of patients, respectively. After the TIPS procedure, 19 patients (35%) experienced a total of 64 episodes of OHE. OHE developed significantly more often inpatients for whom an indication for TIPS had been refractory ascites, with a history of OHE or of renal failure, lower hemoglobin level, or MHE as diagnosed by CFF. Post-TIPS OHE was more accurately predicted by CFF than by PHES. Absence of MHE at CFF had a good negative predictive value (91%) for the risk of post-TIPS recurrent OHE, defined as the occurrence of three or more episodes of OHE or of one episode which lasted more than 15 days. The absence of pre-TIPS history of OHE and a CFF value equal to or greater than 39 Hz had a 100% negative predictive value for post-TIPS recurrent OHE. CONCLUSION: Aiming to decrease the rate of post-TIPS HE, the use of CFF could help selecting patients for TIPS.

Screening of esophageal varices by esophageal capsule endoscopy: results of a French multicenter prospective study.

BACKGROUND AND STUDY AIM: Esophageal video capsule endoscopy (ECE) is a new technique that allows examination of the esophagus using a noninvasive approach. The aim of this study was to compare ECE with esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal varices in patients with cirrhosis. PATIENTS AND METHODS: A total of 330 patients with cirrhosis and with no known esophageal varices were prospectively enrolled. Patients underwent ECE first, followed by EGD (gold standard). The endoscopists who performed EGD were blind to the ECE result. Patient satisfaction was assessed using a visual analog scale (maximum score 100). RESULTS: A total of 30 patients were excluded from the analysis because they did not undergo any endoscopic examinations. Patients (mean age 56 years; 216 male) had mainly alcoholic (45 %) or viral (27 %) cirrhosis. The diagnostic indices of ECE to diagnose and correctly stage esophageal varices were: sensitivity 76 % and 64 %, specificity 91 % and 93 %, positive predictive value 88 % and 88 %, and negative predictive value 81 % and 78 %, respectively. ECE patient satisfaction scored significantly higher than EGD (87 ±â€Š22 vs. 58 ±â€Š35; P < 0.0001). CONCLUSIONS: ECE was well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension. The sensitivity of ECE is not currently sufficient to replace EGD as a first exploration in these patients. However, due to its excellent specificity and positive predictive value, ECE may have a role in cases of refusal or contraindication to EGD. ECE might also improve compliance to endoscopic follow-up and aid important therapeutic decision making in the prophylaxis of bleeding. TRIAL REGISTRATION: EudraCT (ID RCB 2009-A00532-55) and ClinicalTrials.gov (NCT00941421).

Use of early-TIPS for high-risk variceal bleeding: results of a post-RCT surveillance study.

BACKGROUND & AIMS: In a recent randomized international clinical trial (RCT) in high-risk cirrhotic patients with acute variceal bleeding, the early use of transjugular intrahepatic portosystemic shunt (TIPS) was associated with marked and significant reductions in both treatment failure and mortality. The aim of this study was to confirm these results in clinical practice in the same centers of the RCT study. METHODS: We retrospectively reviewed patients admitted for acute variceal bleeding and high risk of treatment failure (Child C <14 or Child B plus active bleeding), treated with early-TIPS (n=45) or drugs+endoscopic therapy (ET) (n=30). RESULTS: Patients treated with early-TIPS had a much lower incidence of failure to control bleeding or rebleeding than patients receiving drug+ET (3 vs. 15; p <0.001). The 1-year actuarial probability of remaining free of this composite end point was 93% vs. 53% (p <0.001). The same was observed in mortality (1-year actuarial survival was 86% vs. 70% respectively; p=0.056). Actuarial curves of failure to control bleeding+rebleeding and of survival were well within the confidence intervals of those observed in the RCT. CONCLUSIONS: This study supports the early use of TIPS in patients with cirrhosis and a high-risk variceal bleeding.

Early use of TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients). RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events. CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)

Transient receptor potential vanilloid 4 activated inflammatory signals by intestinal epithelial cells and colitis in mice.

BACKGROUND & AIMS: Ligand-gated calcium channels have been reported to be involved in the pathogenesis of inflammatory bowel disease. One family member, transient receptor potential vanilloid 4 (TRPV4), is activated by arachidonic acid derivatives that might be released on inflammation, yet its role in gastrointestinal inflammation has not been characterized. We investigated whether TRPV4 activation participates in intestinal inflammation and its expression and functions in the gastrointestinal tract. METHODS: TRPV4 expression was studied in human colon samples, human intestinal epithelial cell lines (Caco-2 and T84), and inflamed colons of mice. Calcium mobilization and cytokine release were analyzed in intestinal epithelial cells exposed to the selective TRPV4 agonist 4α-phorbol-12,13-didecanoate (4αPDD). Mice were killed 3, 6, or 24 hours after intracolonic administration of 4αPDD; inflammatory parameters were measured in their colon tissues, and paracellular colonic permeability was measured by the passage of (51)Cr-EDTA from the colon lumen to the blood. RESULTS: High levels of TRPV4 were detected in Caco-2 cells and in epithelial cells of human colon tissue samples; its expression was up-regulated in colons from inflamed mice compared with noninflamed control mice. Administration of 4αPDD to Caco-2 and T84 cells caused a dose-dependent increase in intracellular calcium concentration and chemokine release. In mice, intracolonic administration of 4αPDD caused colitis to develop 3 to 6 hours later; inflammation resolved by 24 hours. Increased colonic permeability was observed in vivo 3 hours after intracolonic administration of 4αPDD. CONCLUSIONS: TRPV4 is expressed and functional in intestinal epithelial cells; its activation in the gastrointestinal tract causes increases in intracellular calcium concentrations, chemokine release, and colitis.

Modifying the protease, antiprotease pattern by elafin overexpression protects mice from colitis.

BACKGROUND & AIMS: Colonic tissues of patients with inflammatory bowel disease have been reported to have increased proteolytic activity, but no studies have clearly addressed the role of the balance between proteases and antiproteases in the pathogenesis of colitis. We investigated the role of Elafin, a serine protease inhibitor expressed by skin and mucosal surfaces in human inflammatory conditions, and the proteases neutrophil elastase (NE) and proteinase-3 (PR-3) in mice with colitis. METHODS: We studied mice with heterozygous disruptions in NE and PR-3, mice that express human elafin (an inhibitor of NE and PR-3), and naïve mice that received intracolonic adenoviral vectors that express elafin. Trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulphate (DSS) was used to induce colitis. Protease, cytokine levels, and NF-κB activity were measured in colons of mice. Caco-2 and HT29 cells were studied in assays for cytokine expression, permeability, and NF-κB activity. RESULTS: Elafin expression or delivery re-equilibrated the proteolytic balance in inflamed colons of mice. In mice given TNBS or DSS, transgenic expression of elafin or disruption of NE and PR-3 protected against the development of colitis. Similarly, adenoviral delivery of Elafin significantly inhibited inflammatory parameters. Elafin modulated a variety of inflammatory mediators in vitro and in vivo and strengthened intestinal epithelial barrier functions. CONCLUSIONS: The protease inhibitor Elafin prevents intestinal inflammation in mouse models of colitis and might be developed as a therapeutic agent for inflammatory bowel disease.

Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities.

UNLABELLED: Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC ≤30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n = 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, ≤30 mm in diameter 74%). Focal-lesion incidence was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus 13.2%, P = 0.067) but incidence of lesions ≤10 mm was increased (41% in Gr3M versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence (P = 0.13) or in prevalence of tumors ≤30 mm in diameter (79% versus 70%, P = 0.30) was observed between the randomized groups. CONCLUSION: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures.

Acute kidney injury in patients with cirrhosis: Prospective longitudinal study in 405 patients.

BACKGROUND: Acute kidney injury (AKI) is common in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed new definitions of AKI in order to improve the prediction of outcomes. Our aim was to assess the prevalence and prognostic value of ICA 2015 - AKI criteria in hospitalised patients with cirrhosis. METHODS: We prospectively collected data from 405 consecutive cirrhotic patients admitted to the hospital between November 2016 and November 2017. AKI was diagnosed at inclusion according to ICA 2015 criteria, and was assessed to predict 30-day and 90-day in-hospital mortality. RESULTS: AKI was diagnosed in 78 (19.3%) patients. AKI was independently associated with 90-day death (HR 7.61; 95% CI 4.75-12.19; p < 0.001). In hospital, 30-day and 90-day survival was lower in the group of patients with AKI compared to the group with no AKI (72% vs. 98%, p < 0.001; 64% vs. 96%, p < 0.001; and 49% vs. 81%, p < 0.001, respectively). Patients with stage 1a AKI had a lower 30-day and 90-day survival compared to the group of patients who did not develop AKI (71% vs. 96%, p < 0.001, and 71% vs. 91%, p < 0.01, respectively) and better survival than patients with more severe AKI (71% vs. 40%, p < 0.01). CONCLUSIONS: AKI was independently associated with mortality in patients with cirrhosis, even at the very early 1a stage. Response to treatment improved survival, and was inversely proportional to the stage of AKI, which suggests that treatment should be started at the earliest stage of AKI.

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.

Hepatitis E virus and chronic hepatitis in organ-transplant recipients.

Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.