Management of splanchnic vein thrombosisKey points

Summary: The expression splanchnic vein thrombosis encompasses Budd-Chiari syndrome and portal vein thrombosis. These disorders have common characteristics: they are both rare diseases which can cause portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, among which myeloproliferative neoplasms represent the most common; a rapid comprehensive work-up for risk factors of thrombosis is needed in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis and in those with porto-sinusoidal vascular liver disease. The presence and nature of underlying liver disease impacts the management of portal vein thrombosis. Indications for anticoagulation in patients with cirrhosis are growing, while transjugular intrahepatic portosystemic shunt is now a second-line option. Due to the rarity of these diseases, studies yielding high-grade evidence are scarce. However, collaborative studies have provided new insight into the management of these patients. This article focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, portal vein thrombosis without underlying liver disease, or cirrhosis with non-malignant portal vein thrombosis

Continuum of hepatitis C care in France: A 20-year cohort study.

Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study.We established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment.In total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4-2.9), age > 45 years (HR 1.5, 95%CI 1.02-2.3), patient acceptance of care (HR 9.3, 95%CI 5.4-16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4-16.0), and absence of cancer (HR 6.7, 95%CI 1.6-27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC.Our 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection

Evolution and phenotypic characterization of HBV quasispecies in compliant patients experiencing unexplained entecavir treatment failure Running title: Entecavir, viral resistance & whole genome

International audienceEntecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present before treatment in patient #1. HBs Ag immune escape mutations were present before treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). These results provided a unique insight into the evolution of HBV quasispecies during entecavir treatment, addressing the whole HBV genome and not only the Pol/RT domain. Our results suggest that mutations selected outside of the Pol/RT domain could contribute to entecavir treatment failure, not by an increased level of resistance, but by an immune escape mechanism, in synergy with immunosuppressive drugs

Revisiting HBV resistance to entecavir with a phenotypic approach

International audienceTreatment adaptation after hepatitis B virus (HBV) treatment failure relies on genotypic resistance testing. However, the results of such tests are not always consistent with treatment response. These discrepancies may be due to differences in resistance levels between isolates with the same genotypic resistance testing profiles. We explored this hypothesis by investigating six cases of entecavir treatment failure with an integrative strategy combining genotypic and phenotypic resistance testing, medical record review and therapeutic drug monitoring. Among isolates with genotypic reduced susceptibility to entecavir, one displayed a higher level of resistance to entecavir (mean fold change in entecavir IC50 of 1 508 ± 531 vs. 318 ± 53, p=0.008). This isolate harbored a substitution (rt250L) at a position reported to be associated with resistance (rt250V). Reversion to wild-type amino acid at this position partially restored susceptibility to entecavir, confirming that the rt250L mutation was responsible for the high level of resistance to entecavir. This is the first description of entecavir treatment failure associated with selection of the rt250L mutation without other entecavir resistance mutations. One isolate with genotypic resistance to entecavir, harboring the rt173L mutation, displayed a lower level of resistance than the other, harboring the rt202G mutation (mean fold change of 323 ± 124 vs. 6 036 ± 2 100, p=0.20). These results suggest that isolates harboring the rt250L mutations should be considered resistant to entecavir, whereas isolates harboring the rt173L mutations should be considered to display reduced susceptibility to entecavir. An integrative approach to antiviral drug resistance in HBV would provide a more accurate assessment of entecavir treatment failures and help to improve the accuracy of genotypic testing algorithms

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

International audienceBACKGROUND: 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

Occurrence of a specialist consultation within one year after the first positive test for HCV, assessed by logistic regression (N = 205).

<p>Occurrence of a specialist consultation within one year after the first positive test for HCV, assessed by logistic regression (N = 205).</p

Selection of the study population for assessment of the HCV infection CoC.

<p>HCV: Hepatitis C Virus; CoC: continuum of care; Ab: antibody.</p

Kaplan-Meier curves for CoC up to step 4 (antiviral treatment), by sex, period, and age: 1993–2013.

<p>HCV: Hepatitis C Virus;CoC: continuum of care of HCV-infected patients between HCV testing and antiviral treatment; M: male; F: female P1: screening period 1993–1997; P2: screening period 1998–2013.</p