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Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct-Acting Antiviral Treatment Failure in Patients With Hepatitis C?

ABSTRACT: Direct-acting antiviral (DAA) therapies have revolutionized the treatment of chronic hepatitis C virus infection, achieving sustained virological response (SVR) rates of >90% even in patients with advanced liver cirrhosis. Having observed an unusual case of repeated DAA therapy failures in a patient with a transjugular intrahepatic portosystemic shunt (TIPS), we assessed a possible association between prior TIPS placement and DAA failure. A structured search of our clinical database revealed 10 patients who had received DAA therapy after TIPS placement. At the time of therapy, most patients (8; 80%) presented with a Child-Pugh score B, and the following DAA regimens were used: sofosbuvir/ledipasvir ± ribavirin (5 patients), sofosbuvir/daclatasvir ± ribavirin (3), sofosbuvir/velpatasvir (2), and sofosbuvir/velpatasvir/voxilaprevir (1). In total, 5 patients (50%) achieved an SVR, whereas a virological relapse occurred in the other half of the cases, including 2 patients with multiple relapses. In this patient cohort, SVR rates were unusually low for all regimens: sofosbuvir/ledipasvir ± ribavirin, 3/5 (60%); sofosbuvir/daclatasvir ± ribavirin, 2/3 (66%); sofosbuvir/velpatasvir, 0/2 (0%); and sofosbuvir/velpatasvir/voxilaprevir, 0/1 (0%), and patients with a TIPS made up a relevant proportion of DAA failures in patients with cirrhosis at our center: sofosbuvir/ledipasvir, 2/18 (11%); sofosbuvir/daclatasvir, 1/4 (25%); sofosbuvir/velpatasvir, 2/3 (66%); and sofosbuvir/velpatasvir/voxilaprevir, 1/1 (100%). Conclusion: We observed a high rate of virological relapse in patients with a TIPS who received DAA treatment and therefore postulate that TIPS placement may be a possible risk factor for DAA failure due to the profound hemodynamic changes evoked by the intervention. Longer treatment duration or addition of ribavirin might be warranted in these patients.

SUBMITTER: Piecha F

PROVIDER: S-EPMC6492468 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct-Acting Antiviral Treatment Failure in Patients With Hepatitis C?

Piecha Felix F Gänßler Jan-Michael JM Jordan Sabine S Ergen Can C Ittrich Harald H Kluwe Johannes J Pischke Sven S Lohse Ansgar W AW Schulze Zur Wiesch Julian J

Hepatology communications 20190318 5

Direct-acting antiviral (DAA) therapies have revolutionized the treatment of chronic hepatitis C virus infection, achieving sustained virological response (SVR) rates of >90% even in patients with advanced liver cirrhosis. Having observed an unusual case of repeated DAA therapy failures in a patient with a transjugular intrahepatic portosystemic shunt (TIPS), we assessed a possible association between prior TIPS placement and DAA failure. A structured search of our clinical database revealed 10 ...[more]

PMID: 31061950

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Project description:Background and aimsTransjugular intrahepatic portosystemic shunt (TIPS) is used for decompressing clinically significant portal hypertension. The aims of this study were to evaluate clinical outcomes and adverse events associated with this procedure.MethodsRetrospective single-center study including 78 patients submitted to TIPS placement between January 2015 and November 2018. Follow-up data were missing in 27 patients, and finally 51 patients were included in the study sample. Data collected from individual registries included demographics, comorbidities, laboratory results, complications, and clinical results according to the indication.ResultsAverage pre-TIPS portosystemic pressure gradient decreased from 18.1 ± 5 to 6 ± 3 mm Hg after TIPS placement. Indications for TIPS were refractory ascites (63%, n = 49), recurrent or uncontrolled variceal bleeding (36%, n = 28), and Budd-Chiari syndrome (1.3%, n = 1). TIPS-related adverse events occurred in 29/51 (56.8%) patients, with hepatic encephalopathy (HE) in 21 (41%) patients, sepsis in 3, liver failure in 2, hemolytic anemia in 1, acute pulmonary edema in 1, and capsular perforation in 1 patient. Mean follow-up was 15.7 ± 15 months. First-month mortality was 11.7% (n = 6) (sepsis, n = 3; acute liver failure, n = 2; and recurrence of variceal bleeding, n = 1) and was significantly higher for patients with Child-Pugh >9 points (p = 0.01), model of end-stage liver disease (MELD) scores >19 (p = 0.02), and for patients with a history of HE before the procedure (p = 0.001). Older age (p = 0.006) and higher levels of creatinine (p = 0.008) were significantly higher in patients developing HE after TIPS. Ascites persisted in 21.2% (7/33 patients) and was more frequent in patients with lower baseline albumin levels (p = 0.003). Recurrent variceal bleeding occurred in 22% (n = 4/18 patients) and was more frequent in patients with lower baseline hemoglobin levels (p = 0.03).ConclusionTIPS is effective in up to 80% of patients presenting with variceal bleeding or refractory ascites. Careful patient selection based on age and HE history may reduce adverse events after TIPS.

Project description:Acute deterioration of liver cirrhosis (e.g., infections, acute-on-chronic liver failure [ACLF]) requires an increase in cardiac contractility. The insufficiency to respond to these situations could be deleterious. Left ventricular global longitudinal strain (LV-GLS) has been shown to reflect left cardiac contractility in cirrhosis better than other parameters and might bear prognostic value. Therefore, this retrospective study investigated the role of LV-GLS in the outcome after transjugular intrahepatic portosystemic shunt (TIPS) and the development of ACLF. We included 114 patients (48 female patients) from the Noninvasive Evaluation Program for TIPS and Their Follow-Up Network (NEPTUN) cohort. This number provided sufficient quality and structured follow-up with the possibility of calculating major scores (Child, Model for End-Stage Liver Disease [MELD], Chronic Liver Failure Consortium acute decompensation [CLIF-C AD] scores) and recording of the events (development of decompensation episode and ACLF). We analyzed the association of LV-GLS with overall mortality and development of ACLF in patients with TIPS. LV-GLS was independently associated with overall mortality (hazard ratio [HR], 1.123; 95% confidence interval [CI],1.010-1.250) together with aspartate aminotransferase (HR, 1.009; 95% CI, 1.004-1.014) and CLIF-C AD score (HR, 1.080; 95% CI, 1.018-1.137). Area under the receiver operating characteristic curve (AUROC) analysis for LV-GLS for overall survival showed higher area under the curve (AUC) than MELD and CLIF-C AD scores (AUC, 0.688 versus 0.646 and 0.573, respectively). The best AUROC-determined LV-GLS cutoff was -16.6% to identify patients with a significantly worse outcome after TIPS at 3 months, 6 months, and overall. LV-GLS was independently associated with development of ACLF (HR, 1.613; 95% CI, 1.025-2.540) together with a MELD score above 15 (HR, 2.222; 95% CI, 1.400-3.528). Conclusion: LV-GLS is useful for identifying patients at risk of developing ACLF and a worse outcome after TIPS. Although validation is required, this tool might help to stratify risk in patients receiving TIPS.

Dataset Information

Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct-Acting Antiviral Treatment Failure in Patients With Hepatitis C?

Publications

Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct-Acting Antiviral Treatment Failure in Patients With Hepatitis C?

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