We evaluated the safety and efficacy of Biotest-HCIG, a human hepatitis C immune globulin to prevent HCV recurrence by neutralizing remaining HCV reservoirs in patients on pre-LT HCV AVT at the time of LT. Methods: In this phase 3, open-label randomized study, wait-listed patients with chronic HCV infection (all genotypes) treated with any AVT and who achieved HCV RNA <100 IU/ml prior to LT were eligible. In total, 84 patients will be randomized 1:1:1 to Biotest-HCIG (200 mg/kg or 300 mg/kg given on the day

of LT and for 10 weeks post-LT) or observation. The primary endpoint is post-LT sustained Tyrosine Kinase Inhibitor Library virologic response (pTVR), defined as HCV RNA <43 IU/ml at 12 wks

post-LT treatment. Post-transplant immunosuppression is site-specific. Results: To date, AZD4547 mouse 17 subjects (all male, median age 59 yrs, 100% genotype 1, 94% with hepatocellular carcinoma, 12% with living donors) have undergone LT. Pre-LT AVT was telaprevir/peginterferon/ribavirin (RBV) (12%), sofosbuvir/RBV (76%) or sofosbuvir/simeprevir (12%) given for a median of 51 days (range 14-164 days) pre-LT with all patients achieving HCV RNA <43 IU/mL pre-LT (71% also undetectable). With median post-LT follow-up of 8 wks, post-LT HCV recurrence has been documented in 2 patients - at wk 2 (control) and wk 3 (200 mg Biotest-HCIG) post-LT. Overall, 11/12 (92%) of Biotest-HCIG-treated patients have maintained undetectable HCV RNA compared to 4/5 (80%) of controls (Table). Among 4 patients who were medchemexpress viremic at the time of LT and randomized to Biotest-HCIG, all have undetectable HCV RNA at median 9 wks follow-up. Biotest-HCIG-related side effects were infrequent and there were no discontinuations

due to adverse events. Conclusion: Biotest-HCIG is safe and well-tolerated. To date, HCV recurrence rates in patients on pre-LT AVT are lower in Biotest-HCIG-treated patients compared with controls (8% vs 20%) and all patients viremic at LT who received Biotest-HCIG have undetectable HCV RNA. These preliminary results suggest Biotest-HCIG may be beneficial as an adjuvant therapy for HCV patients on AVT undergoing LT. Disclosures: Norah Terrault – Advisory Committees or Review Panels: Eisai, Biotest; Consulting: BMS, Merck; Grant/Research Support: Eisai, Biotest, Vertex, Gilead, AbbVie, Novartis, Merck Sanjaya K. Satapathy – Advisory Committees or Review Panels: Gilead Elizabeth C. Verna – Advisory Committees or Review Panels: Gilead; Grant/ Research Support: Salix, Merck Thomas D. Schiano – Advisory Committees or Review Panels: vertex, salix, merck, gilead, pfizer; Grant/Research Support: massbiologics, itherx Sher Linda – Grant/Research Support: Biotest John M.

[12, 13] In this review, we describe NGS systems and discuss the application of these advanced technologies in hepatology. THE NGS IS now generally defined as the sequencing technology that employs parallel sequencing processes producing thousands or millions of sequence reads simultaneously. Rothberg and colleagues first succeeded in sequencing the Mycoplasma genitalium genome with 96% coverage and 99.96% accuracy in a single GS20 run.[13] The GS20 was the first NGS sequencer put on the market by 454 Life Sciences. In the following years, Roche

(Basel, Switzerland) absorbed 454 Life Sciences and extended GS20 to a new version learn more of the GS FLX titanium series. The GS FLX titanium series used a parallel pyrosequencing system capable of data output from 100 Mb to 500 Mb per run with a 400–500 bp read length. The pyrosequencing of this sequencer is based on measuring the pyrophosphate generated by the DNA polymerization reaction.[14, 15] DNA is fractionated into the fragments of 300–800 bp and these DNA fragments are ligated with short adapters that contain the binding of one fragment to a signaling pathway streptavidin-coated bead.

Emulsion polymerase chain reaction (PCR) is carried out for fragment amplification, with water droplets containing one bead and PCR reagents immersed in oil. When the PCR amplification cycles are completed, denaturation beads carrying single-stranded DNA clones are placed into the wells of a fiber-optic slide. On the slide, amplified DNA bound to each of the beads containing sulfurylase and luciferase are sequenced. When one nucleotide is added to the complementary template by the polymerase reaction, a charge-coupled device (CCD) sensor can record the light signal from luciferin. Of note, the signal strength is proportional to the number of nucleotides.[13] This technology is defined as “sequencing-by-synthesis” and is called pyrosequencing in this system. GENERALLY, THE ROCHE/GS FLX titanium series, the Solexa Genome Analyzer (Illumina, San Diego, CA, USA) and the ABI

SOLiD system are now classified as second-generation 上海皓元 NGS systems. However, the GS FLX series could obtain smaller amounts of data per run than the Illumina or SOLiD systems. Therefore, some technologists believe that Illumina and SOLiD sequencers are second-generation NGS systems. The Solexa sequencing system, acquired by Illumina, was commercialized in early 2007. The Illumina Genome Analyzer is also based on the “sequencing-by-synthesis” to produce short sequence reads of millions of surface amplified DNA fragments simultaneously. Starting with fragmentation of the genome DNA, adaptor-ligated DNA fragments are attached to the surface of a glass flow cell. The flow cell is separated into eight channels and the surfaces of the channels have covalently attached oligos complementary to the adaptors and ligated to the library DNA fragments.

5B). These findings support the possibility that PBGs and the epithelial network may serve as a reservoir of epithelial cells either to differentiate into or repopulate the mucosa during the regenerative response of the bile duct unit after an injury. To directly examine the proliferative

potential of PBGs, we quantified cellular proliferation by BrdU uptake in two models of cholestasis. First, we counted the number of BrdU+/CK19+ cells after IP administration of RRV into newborn mice. Infection of RRV soon after birth is a well-established injury model of the biliary epithelium and shares phenotypic features of human biliary atresia, the most common cause of chronic cholestatic liver disease in children.[19] Selleckchem Proteasome inhibitor We found an unexpectedly high baseline number of BrdU+ cells in age-matched controls (receiving

saline rather than RRV), both in CK-19+ cells of PBGs and the peribiliary epithelium and in CK-negative cells in the submucosal compartment of the duct along the entire length of EHBDs (Fig. 7). After RRV, the percentage of BrdU+/CK19+ epithelial cells did not change from controls (12% ± 3% versus 12% ± 2%; P = 0.8), neither did PBG cells (7% ± 3% versus 10% ± 5%; P = 0.25) at day 3, but increased in both the epithelium (18% ± 6% versus 8% ± 3%; P = 0.009) and PBGs (20% ± 8% versus 7% ± 6%; P = 0.01) http://www.selleckchem.com/products/PD-0325901.html at day 4. These findings are also reproduced when the results of BrdU+ cells are expressed for all epithelial cells together (mucosa plus PBGs; Fig. 7). We were unable to quantify BrdU+/CK19+ cells reproducibly beyond day 4 because of the widespread epithelial loss that typically begins on day 5 after RRV (data not shown). To investigate whether the high baseline BrdU uptake in control newborn

mice was the result of a normal growth phase of postnatal development, we compared the BrdU uptake by CK19+ cells in ducts of unchallenged neonatal and adult mice. We found that baseline BrdU uptake decreased in adult 上海皓元医药股份有限公司 mice in both epithelial cells (10% ± 3% neonate versus 1% ± 1% adult; P < 0.0001) and PBG cells (9% ± 6% neonate versus 1% ± 1% adult; P = 0.0004; Supporting Fig. 3). To assess cellular proliferation in adult mice, we quantified BrdU+/CK19+ cells after surgical ligation of the CBD. Though the percentage of BrdU+/CK19+ cells remained low at baseline levels at 6 and 12 hours after BDL, BrdU+/CK19+ cells of PBGs and the epithelium underwent a dramatic surge to 39% in PBGs and 33% in the epithelium at 24 hours (P = 0.002 and P < 0.001, respectively, when compared to sham operation) or 39% for ligation and 1% for sham when analyzing all cell types collectively for the entire duct (P < 0.001; Fig 8).

57 Studies from East London reported a low incidence of IBD in Bangladeshi migrants in the 1980s.37,38 A more recent study has shown an increase in CD incidence in Bangladeshi migrants from 2.3 (1981–1989) to 7.3 (1997–2001), and an increase in UC incidence from 2.4 (1981–1989) to 8.2 (1997–2001).39 In this study, most UC patients (13 of 16) were born in Bangladesh as compared to 8/19 CD cases.

These increases in IBD coincided with a decrease in the incidence of abdominal tuberculosis.39 In the Northwest of England a recent report described a higher prevalence and lower mean age at diagnosis of UC in the adult South Asian population than the Caucasian population.58 In Canada, there have been a number of recent studies from British Columbia.42,59,60 A pediatric study from Vancouver showed a higher prevalence of both UC and CD in the pediatric South Asian (Indian) population compared with other ethnic groups, including Ensartinib solubility dmso Caucasian children. The majority (84%) of the South Asian patients were the children of immigrants.42

These South Asian patients had a male predominance and more extensive colonic disease than the non-South Asian patient population.42 A single center study from check details Vancouver reported rates of hospitalization in CD patients of Caucasian, South Asian (East India, Pakistan, Sri Lanka) and Pacific Asian (Chinese, Japanese, Korean) ethnicity at 7.8, 7.7 and 2.1 per hundred thousand pro rata for each ethnicity of the total Vancouver population, respectively. Rates of hospitalization in UC patients were higher in

South Asians (6.8) than Caucasians (5.1) and Pacific Asians (0.8).59 An earlier study from Vancouver reported the mean duration of residence in Canada for South Asian (mostly Indian) migrants before developing IBD was 8.9 years for CD and 13.5 years for UC.60 There was also an older mean age of patients born overseas (mostly India) than those born in Canada.60 In a study from Quebec, a lower proportion of people reporting to be immigrants was an independent predictor of lower CD incidence rates.61 In the United States, studies on different ethnicities in IBD have mainly reported on the African American medchemexpress and Hispanic populations;62–65 however, some studies have included Asian data.66 In southern California, prevalence rates for Asians (5.6) and Hispanics (4.1) were much lower than those for Caucasians (43.6) and Afro-Caribbeans (29.8).41 A recent study from Sweden found a decreased incidence of IBD in immigrants (including Asia) compared to native-born Swedes. This decreased incidence did not persist for the local-born children of Asian immigrants.43 A recent study of national hospital discharge data from 500 hospitals in North America calculated separately for different race groups the change in the proportion of hospitalizations for IBD between 1994 and 2006.

2 and 9 x 109 viable hepatocytes. Serum bilirubin levels increased initially in both patients after the first procedure up to 530 μmol per liter. Thereafter serum bilirubin decreased continuously to 50% of pre-transplant levels for more than 6 months. The boy experienced a sudden increase of serum bilirubin to pre-transplant levels 6 months after the first infusion associated with a scabies infection. Despite intensified

phototherapy serum bilirubin did not improve. Due to the risk of encephalopathy we decided together with the family to list him for orthotopic liver transplantation. The girl still remains on significantly decreased serum bilirubin levels and is on the waiting list for further hepatocyte infusions. This case report confirms that hepatocyte transplantation can be a useful treatment for patients with Crigler-Najjar find more Selumetinib in vivo syndrome type I. Pre-conditioning patients with partial hepatectomy prior to cell transplantation is safe. Additional patients will need to be evaluated before conclusions can be drawn on the efficacy of this procedure as compared to traditional hepatocyte transplantation. Disclosures: Stephen Strom

– Stock Shareholder: Stemnion, Yecuris The following people have nothing to disclose: Carl Jorns, Antal Nemeth, Greg Nowak, Helen Zemack, Lisa-Mari Mörk, Helen Johansson, Roberto Gramignoli, Björn Fischler, Ewa C S. Ellis, Bo-Göran Ericzon Background and Aim: Silibinin (Sil) has been proven to have anti-viral activity in humans and it has been successfully used in our center in a randomized, double-blind, placebo-controlled study for HCV recurrence treatment in liver transplant patients. Sil has also immune-modulating properties by modulating dendritic cells (DC) function. DC are antigen-presentig cells playing, along with regulatory T cells (Treg), a pivotal role in controlling allo-immune response, as well as HCV infection. Immune regulatory molecules expressed by DCs, including PDL1(B7 homologue-1=programmed death ligand-1), ICOS-L, CD39 and the non-classical HLA class I molecule HLA-G and the immunoglobulin-like transcript(ILT)4, have been shown to regulate

T cell responses, including the induction of Treg. The PD-1/PD-L1 pathway on medchemexpress Treg is described as one of the mechanisms responsible for balancing HCV T cell responses. So far, the enumeration of DCs and Tregs and the expression of immune regulatory molecules on DC and PD-1 on Treg have not been examined in HCV recurrence and Sil treatment after liver transplant. Aim of the study is to analyze circulating DC subsets and Treg and the expression of costimulatory/coregulatory molecules in liver transplant patients receiving Sil. Material and methods: 15 liver transplant patients with HCV recurrence received iv infusion of Sil (20 mg/kg/day) for 14 consecutive days. We examined by flow cytometry, before and at the end of treatment, the expression of CD86, PD-L1, ICOSL, CD39, HLA-DR, HLA-G, IL-T4 in circulating monocytoid(m) and plasmacytoid(p) DC and of PD-1 on Treg.

A promising option for cancer treatment is the use of epigenetic drugs which inhibit tumor growth by several mechanisms including restoring the expression of epigenetically silenced tumor suppressor genes and miRNA.[84] We recently found that a HDAC inhibitor, suberoylanilide hydroxamic acid, suppressed hepatitis C virus RNA replication via the epigenetic mechanism in a replicon cells[85] in addition to induction of apoptosis in liver cancer cells through enhanced expression of several specific miRNA (paper in preparation). These findings suggested that an epigenetic approach Selleck Ibrutinib could potentially play not

only anticancer but also antiviral roles in HCC treatment. Moreover, inhibitors of DNA methylation and histone deacetylation can work

synergistically to suppress growth of cancer cell lines both in vitro and in vivo. Many epigenetic drugs have shown promising results in clinical trials and recent advances in research suggest a new anticancer effect of this class of drugs. However, these drugs have some problems to be resolved such as specificity of DNA methylation inhibition. Current drugs for inhibitors of DNA methylation and HDAC cannot target specific genes and miRNA and may activate some oncogenes and oncogenic miRNA. Further studies are necessary FK506 to develop promising drugs which can target specific genes and miRNA with minimal side-effects. By inducing expression of tumor suppressor genes and

miRNA, epigenetic treatment not only inhibits the growth of HCC, but may also inhibit the invasiveness and metastatic potential of HCC. THIS WORK WAS supported by a Grant-in-Aid for Young Scientists A (23680090 to Y. S.) and a Grant-in-Aid for Scientific Research C (24590993 to H. S.) from the Japan Society for the Promotion of Science (JSPS), Takeda Science Foundation (to Y. S.) and Inaida Foundation (to H. S.). “
“Chronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, MCE公司 demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management. In this cross-sectional observational study, treatment-naïve Han ethnic adults with recently confirmed chronic HCV infection were enrolled at 28 hospitals across China. HCV genotype and host interleukin 28B (IL28B) genotypes were determined and compared with patient demographic parameters and medical status. Among the 997 HCV-positive patients analyzed, 56.8% were infected with HCV genotype 1b, followed in prevalence by genotypes 2, 3, and 6, with substantial regional variation. Overall, 84.1% of patients were IL28B genotype CC (rs12979860), with little regional variation. Cirrhosis was reported in 10.

In summary, the proposed staging system provides transparent information about the anatomical location of the tumor along the bile duct (which is labeled “B”), the involvement of the portal vein (“PV”), the involvement of the hepatic artery (“HA”), the volume of the future

remnant liver (“V”), the lymph node (“N”), and metastases status (“M”). Additionally, the tumor size (“T”), the tumor form (“F”), and the underlying disease (“D”) are important pieces of information that are now included and may http://www.selleckchem.com/products/PLX-4032.html help us to better stage PHC. The staging should ideally be performed before surgery (e.g., after portal vein embolization) and after surgery, and it should include all intraoperative information and results from macroscopic and microscopic examinations. With the publication of this new classification system, we will implement a new registry that will be available at www.cholangioca.org. The authors thank Carol De X-396 Simio (University Hospital Zurich) for her wonderful work in preparing

the drawings for the new classification system. “
“Cholangiocarcinoma arising in the large bile ducts undergoes a multistep carcinogenesis process in chronic biliary diseases, and biliary intraepithelial neoplasia is known as a precursor lesion. This study examined the expression of S100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance. Immunohistochemical analysis was performed for

the expression of S100A2, S100A4, S100A6, and S100P. Bile concentrations of S100P were measured using enzyme-linked immunosorbent medchemexpress assay. The immunohistochemical expression of the S100 proteins was increased in biliary intraepithelial neoplasia as well as invasive adenocarcinoma of perihilar cholangiocarcinoma. Among the proteins, S100P expression was most drastically increased during the multistep carcinogenesis process. In cases with perihilar and extrahepatic cholangiocarcinoma, the immunohistochemical expression of S100A2 in cholangiocarcinoma cells significantly correlated with the histological grade, lymph node metastasis, clinical stage, and a poor survival rate of the patients. The bile levels of S100P were increased significantly in patients with cholangiocarcinoma compared with those in patients with lithiasis. Receiver operating characteristic curve analysis showed that S100P bile concentration was an indicator of cholangiocarcinoma with a sensitivity of 93% and a specificity of 70%. These results suggest that S100P may be useful for the detection of cholangiocarcinoma as tissue and bile biomarkers, and the immunohistochemical expression of S100A2 is a potential prognostic marker in cholangiocarcinoma patients. “
“Autoimmune hepatitis (AIH) is a chronic, progressive necroinflammatory disease putatively caused by loss of tolerance to hepatic autoantigens.

30 The data reported here support a different ICG-001 supplier model in which the CD8+ T cells respond to an AAV2 vector-encoded transgene expressed in hepatocytes and are primed without CD4+ T cell help by direct presentation of antigen. The absence of cross-priming is consistent with several other features of the AAV vectors. First, cell death and the subsequent phagocytosis of apoptotic bodies is a route by which cellular antigen enters the cross-presentation

pathway,34 but these vectors are noncytopathic so this pathway of antigen presentation would not be favored. Second, whereas transduction of liver cells with adenovirus resulted in robust synthesis of type 1 IFN, this type of response was not elicited by AAV vectors.35 The type 1 IFNs play diverse roles in induction of specific immunity, and one of these roles is the promotion of cross-presentation.36 The evidence in favor of a direct-primed response raises the question of how the T cells could actually be engaged. Although hepatocytes are separated from circulating T cells by an endothelial barrier, this endothelium is fenestrated and direct contact between T cells and underlying hepatocytes can occur.12 In our model, the hepatocytes

are the only cells transduced with the AAV vector. Thus, both the ultrastructural evidence and the expression pattern of AAV favor the model that hepatocytes are directly priming the CD8+ T cells. Our Alpelisib in vivo data also support the interpretation that AAV2-ova did not induce a CD4+ T cell response, and that, furthermore, the CD8+ T cell MCE response was not modified by the absence of CD4+ T cell help. In similar studies using D0.11.10

T cells, the lack of a readily detectable immune response was attributed either to the induction of T cell anergy16 or to the differentiation of the T cells into classic Tr3 cells expressing CD25 and the transcription factor forkhead box P3 (FoxP3).37 However, even if such cells were generated, a local immune response occurred in their presence. The CD8+ T cell response to AAV was associated with elevated expression of the coinhibitory molecule PD-1. The PD-1 molecule is associated with a senescent phenotype, characteristic of inactive T cells found in the liver during chronic infections, such as with lymphocytic choriomeningitis virus and HCV.38, 39 The regulation of PD-1 expression on CD8+ T cells is not fully understood, but our data contribute to this question by showing that the antigen-specific induction of PD-1 on CD8+ T cells in the liver was not different in mice lacking MHC class II; therefore, we do not see an essential role either for CD4+ T helper cells, or for CD4+ T regulatory cells, in the induction of PD-1.

The authors declare no conflict of interest. “
“Background and Aims:  To assess the validity of biopsy-based tests (histology, culture, and urease test) and serology in detecting current H. pylori infection for the peptic ulcer patients who had gastric bleeding. Methods:  A total of 398 peptic ulcer patients were enrolled and divided into two groups, according to the presence or absence of bleeding. The diagnosis for

current H. pylori infection was verified using the gold standard combining individual H. pylori tests. Sensitivity, specificity, and positive and negative predictive values of the culture, Campylobacter-like organism (CLO) test (urease test), histology, and serology were compared. Results:  Of the total study population (N = 398), 157 (39.4%) patients were categorized into the bleeding group. The sensitivities of the culture (40.0%) and CLO (85.0%) in the bleeding group were significantly lower

Selleck Deforolimus than culture (58.1%) and CLO (96.4%) in the nonbleeding group (p = .012 and p < .001, respectively). In the bleeding group, the sensitivity of CLO (85.0%) was significantly lower than histology (92.5%) and serology (97.4%) (p = .013 and p = .002, respectively), which was not found in the nonbleeding group. The specificity of serology in the bleeding group (56.3%) was significantly lower than that of nonbleeding group (74.2%) (p = .038). Similarly, the specificity of serology was significantly check details lower than the other H. pylori tests in the bleeders. Conclusions:  Bleeding decreased the sensitivity of H. pylori

tests in patients with peptic ulcer, especially in urease test or culture. In contrast, histology was found to be a quite reliable test, regardless of the presence of bleeding. “
“Background:  Mongolian gerbils that are experimentally infected with Helicobacter pylori develop a chronic inflammation that is similar to natural infections in humans. The aim of this study was to compare the antigens 上海皓元医药股份有限公司 of H. pylori cagPAI+ and cagPAI− strains that are expressed during Meriones unguiculatus colonization. Materials and Methods:  We identified H. pylori cagPAI+ and cagPAI− strain antigens via Western blotting of samples from Mongolian gerbils that were subjected to unique, mixed, and sequential bacterial infections. Results:  The antigens from the J99/CG3 (cagPAI+) strain had a lower molecular weight than the antigens from the 251F/CG3 (cagPAI−) strain. There were fewer identified antigens in the single unique infections compared with the mixed and sequential infections. The number of recognized antigens that had a frequency of recognition >60% was higher for the simultaneous and sequential infection groups compared with the single infection group. A 57-kDa antigen was present in >60% of the samples and four of the five experimental groups.

Because subgenotype 1b is common in our population, in the absence of quasispecies analysis, it is difficult to ascertain that the subgenotype

1b cases are recurrences versus de novo reinfection. Whatever the underlying mechanism, for the treatment of chronic HCV in patients coinfected with HBV, prolonged follow-up after the end of treatment would be needed to confirm the sustained seroclearance of HCV RNA. In patients with HCV monoinfection, successful anti-HCV therapy has markedly decreased the incidence of HCC and liver-cause mortality.16 In addition to the cure of HCV infection in the short term, determining whether anti-HCV therapy with peginterferon plus ribavirin could decrease Kinase Inhibitor Library the

incidence of HCC and improve overall survival in HCV/HBV-coinfected patients will require further long-term follow-up studies. During the treatment of HCV/HBV coinfection, virologic response of HBV to peginterferon Everolimus manufacturer and the possible reappearance of HBV after the control of HCV are two major clinical issues that need to be addressed. We found that HBV virologic response was obtained in 53% of coinfected patients with pretreatment hepatitis B viremia after LTFU. Intriguingly, posttreatment HBsAg clearance was noted in

5% medchemexpress of coinfected patients annually, a finding that is consistent with the results of our previous pilot study.17 This figure is far beyond the previously reported spontaneous or treatment-induced HBsAg clearance of 0% to 3% annually.18-22 On the other hand, as much as 62% of the 76 coinfected patients whose pretreatment serum HBV DNA was undetectable had a reappearance of HBV. Nevertheless, the reappearance of HBV did not result in clinically evident hepatitis, and none of the patients received another course of antiviral therapy due to HBV reactivation. The significance of HBV reappearance after effective treatment of HCV in patients with chronic HCV/HBV coinfection requires further study.23 In conclusion, combination therapy of peginterferon alfa-2a and ribavirin appears to be just as effective and durable for the treatment of HBsAg-positive patients chronically infected with active chronic HCV as it is in patients with HCV monoinfection. Annually, ∼5% of coinfected patients developed HBsAg seroclearance posttreatment. Notably, this group of patients may still develop HCC even after achieving HBsAg seroclearance, thus they should be kept under regular surveillance even after SVR.