“
“People with haemophilia face many treatment decisions, which are largely informed by evidence from observational studies. Without evidence-based ‘best’ treatment options, patient preferences play a large role in decisions regarding therapy. The shared decision-making (SDM) process allows patients and health care providers to make decisions selleck products collaboratively based on available evidence, and patient preferences. Decision tools can help the SDM process. The objective of this project was to develop two-sided decision tools, decision boxes for physicians and patient decision aids for patients, to facilitate SDM for treatment decisions in

haemophilia. Methods. Development of the decision tools comprised three phases: topic selection, prototype development and usability testing with targeted end-users. Topics were selected using a Delphi survey. Tool prototypes were based on a previously validated framework and were Selleck CDK inhibitor informed by systematic literature reviews. Patients, through focus groups, and physicians,

through interviews, reviewed the prototypes iteratively for comprehensibility and usability. Results. The chosen topics were: (i) prophylactic treatment: when to start and dosing, (ii) choosing factor source and (iii) immunotolerance induction: when to start and dosing. Intended end users (both health care providers and haemophilia patients and caregivers) were engaged in the development process. Overall perception of the decision tools was positive, and the purpose of using the tools was well received. Conclusions. This study demonstrates the feasibility of developing decision tools for haemophilia treatment decisions. It also provides anecdotal evidence of positive perceptions of such tools. Future directions include assessment of the tools’ practical value and impact on selleck chemical clinical

practice. “
“We recently showed in a single centre trial that low-dose secondary prophylaxis in severe/moderate haemophilia patients with arthropathy is feasible and beneficial. However, this regimen has not been validated in a multicentre setting and what obstacles are there to prophylaxis remain unclear. (i) Benefit study: to confirm the benefits of similar prophylaxis protocol in severe/moderate haemophilia A (HA) in a multicentre setting in China. (ii) Follow-up obstacle study: to investigate obstacles in compliance to prophylaxis treatment. (i) Benefit study: severe/moderate HA children with arthropathy from 15 centres were enrolled to undergo an 8-week on-demand treatment, followed by 6 to 12-week low-dose secondary prophylaxis. Outcomes compared in the two periods include joint and severe bleeding, daily activities and factor consumption.

“
“People with haemophilia face many treatment decisions, which are largely informed by evidence from observational studies. Without evidence-based ‘best’ treatment options, patient preferences play a large role in decisions regarding therapy. The shared decision-making (SDM) process allows patients and health care providers to make decisions PF-02341066 order collaboratively based on available evidence, and patient preferences. Decision tools can help the SDM process. The objective of this project was to develop two-sided decision tools, decision boxes for physicians and patient decision aids for patients, to facilitate SDM for treatment decisions in

haemophilia. Methods. Development of the decision tools comprised three phases: topic selection, prototype development and usability testing with targeted end-users. Topics were selected using a Delphi survey. Tool prototypes were based on a previously validated framework and were Opaganib solubility dmso informed by systematic literature reviews. Patients, through focus groups, and physicians,

through interviews, reviewed the prototypes iteratively for comprehensibility and usability. Results. The chosen topics were: (i) prophylactic treatment: when to start and dosing, (ii) choosing factor source and (iii) immunotolerance induction: when to start and dosing. Intended end users (both health care providers and haemophilia patients and caregivers) were engaged in the development process. Overall perception of the decision tools was positive, and the purpose of using the tools was well received. Conclusions. This study demonstrates the feasibility of developing decision tools for haemophilia treatment decisions. It also provides anecdotal evidence of positive perceptions of such tools. Future directions include assessment of the tools’ practical value and impact on click here clinical

practice. “
“We recently showed in a single centre trial that low-dose secondary prophylaxis in severe/moderate haemophilia patients with arthropathy is feasible and beneficial. However, this regimen has not been validated in a multicentre setting and what obstacles are there to prophylaxis remain unclear. (i) Benefit study: to confirm the benefits of similar prophylaxis protocol in severe/moderate haemophilia A (HA) in a multicentre setting in China. (ii) Follow-up obstacle study: to investigate obstacles in compliance to prophylaxis treatment. (i) Benefit study: severe/moderate HA children with arthropathy from 15 centres were enrolled to undergo an 8-week on-demand treatment, followed by 6 to 12-week low-dose secondary prophylaxis. Outcomes compared in the two periods include joint and severe bleeding, daily activities and factor consumption.

2). Importantly, in agreement with our data, substituting “A” with “C” at position 1 of the

SMARCB1 promoter had been associated with decreased PARP1-dependent transcriptional activity.41 Within the PARP1 binding site of the HTLV Tax RE, mutating nucleotides 5 and 6 from “CA” to “AC” abolished PARP1 binding, whereas substitutions at positions 2 and 3 were less important for the functional specificity of the motif.34 Furthermore, in line with the deleterious effects of nucleotide substitution, changing position 5 from “C” to “T” at the Bcl-6 PARP1 binding site resulted in abrogation of PARP1-dependent transcription.42 These data are selleckchem congruent with our findings that nucleotide positions 5 and 6 are critical for PARP1-dependent transcriptional activation, whereas nucleotide positions 2 and 3 of the octamer are less so. Thus, the “RNNWCAAA” octamer may be used to describe the PARP1 motif that also reflects the relative contribution of each nucleotide position to bind PARP1 required for transcription. PARP1 hyperactivity has been associated with various disease states, such

as cancer.43, 44 A survey of 37 HCC patient tumor samples with its matched nontumor tissue showed that PARP1 mRNA is, on average, 21.11-fold (range, 20.98 to 21.21) above the mean of nontumor tissues (Supporting Table 3) and, therefore, Olaparib cost indicates that the PARP1 levels in the HepG2 liver cell line is moderately elevated from physiological levels. Suppression of PARP1 enzymatic activity by general PARP inhibitors is thought to have therapeutic potential, as they have been shown to enhance the cytotoxic potential of DNA-damaging agents in clinical trials.43, 44 In contrast to binding DNA strand breaks for DNA repair, the capacity for PARP1 to ADP-ribosylate histone H1 surprisingly decreased when bound by the PARP1 motif (Fig. 4). Similar to how HBV DNA impairs cellular PARP1 functions, we propose that exogenous DNA bearing the PARP1 binding motif can function as a cognate ligand for PARP1 that interferes with its ability to carry out DNA repair, enhancing synthetic lethality of chemotherapeutic

this website agents. Indeed, transfection of a synthetic construct bearing tandem repeats of the HBVCP PARP1 binding motif was able to increase cytotoxicity of HepG2 HCC cells induced by etoposide and bleomycin (Fig. 5). Because affinity pull-down with the PARP1 binding motif produced PARP1 as the only interacting (Fig. 1), this specificity of the PARP1 binding motif for PARP1 would be advantageous over current PARP inhibitors, potentially reducing adverse effects associated with inhibition of other PARP family members targeted by general PARP inhibitors.28, 45 Understanding how PARP1 inhibition is achieved by engaging a specific DNA binding motif would also shed light on how the enzyme is allosterically regulated.

2). Importantly, in agreement with our data, substituting “A” with “C” at position 1 of the

SMARCB1 promoter had been associated with decreased PARP1-dependent transcriptional activity.41 Within the PARP1 binding site of the HTLV Tax RE, mutating nucleotides 5 and 6 from “CA” to “AC” abolished PARP1 binding, whereas substitutions at positions 2 and 3 were less important for the functional specificity of the motif.34 Furthermore, in line with the deleterious effects of nucleotide substitution, changing position 5 from “C” to “T” at the Bcl-6 PARP1 binding site resulted in abrogation of PARP1-dependent transcription.42 These data are Torin 1 congruent with our findings that nucleotide positions 5 and 6 are critical for PARP1-dependent transcriptional activation, whereas nucleotide positions 2 and 3 of the octamer are less so. Thus, the “RNNWCAAA” octamer may be used to describe the PARP1 motif that also reflects the relative contribution of each nucleotide position to bind PARP1 required for transcription. PARP1 hyperactivity has been associated with various disease states, such

as cancer.43, 44 A survey of 37 HCC patient tumor samples with its matched nontumor tissue showed that PARP1 mRNA is, on average, 21.11-fold (range, 20.98 to 21.21) above the mean of nontumor tissues (Supporting Table 3) and, therefore, learn more indicates that the PARP1 levels in the HepG2 liver cell line is moderately elevated from physiological levels. Suppression of PARP1 enzymatic activity by general PARP inhibitors is thought to have therapeutic potential, as they have been shown to enhance the cytotoxic potential of DNA-damaging agents in clinical trials.43, 44 In contrast to binding DNA strand breaks for DNA repair, the capacity for PARP1 to ADP-ribosylate histone H1 surprisingly decreased when bound by the PARP1 motif (Fig. 4). Similar to how HBV DNA impairs cellular PARP1 functions, we propose that exogenous DNA bearing the PARP1 binding motif can function as a cognate ligand for PARP1 that interferes with its ability to carry out DNA repair, enhancing synthetic lethality of chemotherapeutic

this website agents. Indeed, transfection of a synthetic construct bearing tandem repeats of the HBVCP PARP1 binding motif was able to increase cytotoxicity of HepG2 HCC cells induced by etoposide and bleomycin (Fig. 5). Because affinity pull-down with the PARP1 binding motif produced PARP1 as the only interacting (Fig. 1), this specificity of the PARP1 binding motif for PARP1 would be advantageous over current PARP inhibitors, potentially reducing adverse effects associated with inhibition of other PARP family members targeted by general PARP inhibitors.28, 45 Understanding how PARP1 inhibition is achieved by engaging a specific DNA binding motif would also shed light on how the enzyme is allosterically regulated.

2). Importantly, in agreement with our data, substituting “A” with “C” at position 1 of the

SMARCB1 promoter had been associated with decreased PARP1-dependent transcriptional activity.41 Within the PARP1 binding site of the HTLV Tax RE, mutating nucleotides 5 and 6 from “CA” to “AC” abolished PARP1 binding, whereas substitutions at positions 2 and 3 were less important for the functional specificity of the motif.34 Furthermore, in line with the deleterious effects of nucleotide substitution, changing position 5 from “C” to “T” at the Bcl-6 PARP1 binding site resulted in abrogation of PARP1-dependent transcription.42 These data are INCB024360 molecular weight congruent with our findings that nucleotide positions 5 and 6 are critical for PARP1-dependent transcriptional activation, whereas nucleotide positions 2 and 3 of the octamer are less so. Thus, the “RNNWCAAA” octamer may be used to describe the PARP1 motif that also reflects the relative contribution of each nucleotide position to bind PARP1 required for transcription. PARP1 hyperactivity has been associated with various disease states, such

as cancer.43, 44 A survey of 37 HCC patient tumor samples with its matched nontumor tissue showed that PARP1 mRNA is, on average, 21.11-fold (range, 20.98 to 21.21) above the mean of nontumor tissues (Supporting Table 3) and, therefore, Selleck ABT-199 indicates that the PARP1 levels in the HepG2 liver cell line is moderately elevated from physiological levels. Suppression of PARP1 enzymatic activity by general PARP inhibitors is thought to have therapeutic potential, as they have been shown to enhance the cytotoxic potential of DNA-damaging agents in clinical trials.43, 44 In contrast to binding DNA strand breaks for DNA repair, the capacity for PARP1 to ADP-ribosylate histone H1 surprisingly decreased when bound by the PARP1 motif (Fig. 4). Similar to how HBV DNA impairs cellular PARP1 functions, we propose that exogenous DNA bearing the PARP1 binding motif can function as a cognate ligand for PARP1 that interferes with its ability to carry out DNA repair, enhancing synthetic lethality of chemotherapeutic

this website agents. Indeed, transfection of a synthetic construct bearing tandem repeats of the HBVCP PARP1 binding motif was able to increase cytotoxicity of HepG2 HCC cells induced by etoposide and bleomycin (Fig. 5). Because affinity pull-down with the PARP1 binding motif produced PARP1 as the only interacting (Fig. 1), this specificity of the PARP1 binding motif for PARP1 would be advantageous over current PARP inhibitors, potentially reducing adverse effects associated with inhibition of other PARP family members targeted by general PARP inhibitors.28, 45 Understanding how PARP1 inhibition is achieved by engaging a specific DNA binding motif would also shed light on how the enzyme is allosterically regulated.

05). Conclusion: NSAID associated ulcer bleeding mainly occurred in stomach with more multiple ulcers, while patients seldom complained of epigastric pains. These ulcers were more common in 60-year-old selleck chemicals llc or above patients, who suffered from more severe anemia. Key Word(s): 1. NSAID; 2. peptic ulcer; 3. bleeding; Presenting Author: DIANCHUN FANG Additional Authors: YU FANG, DONGFENG CHEN, WANGYING REN Corresponding Author: DIANCHUN FANG Affiliations:

A member of standing committee, Association of Chinese Digestive Disease; The First Affiliated Hospital, Chongqing Medical University; Daping Hospital; The Affiliated Hospital of The Armed Police Medical College Objective: Cervical heterotopic gastric mucosa is an area of heterotopic columnar mucosal islands resided in upper esophagus, and leads to a series of esophageal and extraesophageal symptoms and complications. In this study, we aimed to determine the prevalence of heterotopic gastric mucosa patch in Chinese population, evaluate the association of heterotopic patch with demographic and clinical characteristics and identify the endoscopic and histological features. Methods: A total of 101395 patients referred to three endoscopy units Epacadostat in vivo for elective endoscopy were enrolled between February 2008 and June 2010. Heterotopic

gastric mucosal patch was examined during the withdrawal of the endoscope, and the macroscopic characteristics of the patch were documented. learn more Biopsies were obtained from the

patch and detected by the staining with hematoxylin and eosin. Helicobacter pylori were evaluated by the staining with Wartin-Starry. Results: The prevalence of heterotopic gastric mucosa in Chinese population was 0.4%. The gender and age between patients with and without heterotopic patch were equally distributed. A majority of patients had single-patch (71.4%), and the remaining had double- (20%) and multiple-patch (8.6%) within the upper esophagus. The size of patch and the distance to the frontal incisor teeth from patch varied dramatically. Most of the heterotopic patches were characterized by flat surface (93.6%), and the remaining by slightly elevated surface. The mucosal gland with fundic-type (51.4%) was primary histological characteristics within heterotopic mucosa, and the glands with antral-type (10.2%) and transitional-type (15.5%) were also observed. A 3.1% prevalence of intestinal metaplasia and a 1.4% prevalence of dysplasia were identified in the heterotopic patch, suggesting the necessity of endoscopic follow-up. The patients with a prevalence of 10% suffered helicobacter pylori colonization, while 8.3% of the patients presented mucosal atrophy within heterotopic patch. The esophageal and extraesophageal complains were remarkable in patients with heterotopic patch. We found dysphagia (OR = 6.836) and epigastric discomfort (OR = 115.

05). Conclusion: NSAID associated ulcer bleeding mainly occurred in stomach with more multiple ulcers, while patients seldom complained of epigastric pains. These ulcers were more common in 60-year-old PI3K Inhibitor Library clinical trial or above patients, who suffered from more severe anemia. Key Word(s): 1. NSAID; 2. peptic ulcer; 3. bleeding; Presenting Author: DIANCHUN FANG Additional Authors: YU FANG, DONGFENG CHEN, WANGYING REN Corresponding Author: DIANCHUN FANG Affiliations:

A member of standing committee, Association of Chinese Digestive Disease; The First Affiliated Hospital, Chongqing Medical University; Daping Hospital; The Affiliated Hospital of The Armed Police Medical College Objective: Cervical heterotopic gastric mucosa is an area of heterotopic columnar mucosal islands resided in upper esophagus, and leads to a series of esophageal and extraesophageal symptoms and complications. In this study, we aimed to determine the prevalence of heterotopic gastric mucosa patch in Chinese population, evaluate the association of heterotopic patch with demographic and clinical characteristics and identify the endoscopic and histological features. Methods: A total of 101395 patients referred to three endoscopy units EX 527 concentration for elective endoscopy were enrolled between February 2008 and June 2010. Heterotopic

gastric mucosal patch was examined during the withdrawal of the endoscope, and the macroscopic characteristics of the patch were documented. learn more Biopsies were obtained from the

patch and detected by the staining with hematoxylin and eosin. Helicobacter pylori were evaluated by the staining with Wartin-Starry. Results: The prevalence of heterotopic gastric mucosa in Chinese population was 0.4%. The gender and age between patients with and without heterotopic patch were equally distributed. A majority of patients had single-patch (71.4%), and the remaining had double- (20%) and multiple-patch (8.6%) within the upper esophagus. The size of patch and the distance to the frontal incisor teeth from patch varied dramatically. Most of the heterotopic patches were characterized by flat surface (93.6%), and the remaining by slightly elevated surface. The mucosal gland with fundic-type (51.4%) was primary histological characteristics within heterotopic mucosa, and the glands with antral-type (10.2%) and transitional-type (15.5%) were also observed. A 3.1% prevalence of intestinal metaplasia and a 1.4% prevalence of dysplasia were identified in the heterotopic patch, suggesting the necessity of endoscopic follow-up. The patients with a prevalence of 10% suffered helicobacter pylori colonization, while 8.3% of the patients presented mucosal atrophy within heterotopic patch. The esophageal and extraesophageal complains were remarkable in patients with heterotopic patch. We found dysphagia (OR = 6.836) and epigastric discomfort (OR = 115.

Receiver operating characteristic (ROC) analysis was performed to determine the sensitivity and specificity with 95% confidence intervals (CIs) for the following variables at different previously proposed cutoff values: ceruloplasmin (cutoffs of 20, 14, and 10 mg/dL were considered),18 basal 24-hour urinary copper [cutoffs of 100 (1.6 μmol/24 hours) and 40 μg/24 hours (0.6 μmol/24 click here hours) were considered],2 and 24-hour urinary copper after PCT [cutoffs of 1575 (25 μmol/24 hours), 500 (8 μmol/24 hours), and 200 μg/24 hours (3.2 μmol/24 hours) were considered].9, 11 Linear regression analysis was applied to assess the dependence of urinary copper excretion and

liver copper contents on age, and the Pearson correlation coefficient (r) was defined. All P values were based on two-tailed comparisons, and those less than 0.05 were considered to indicate statistical significance. All statistical analysis was performed with GraphPad Prism 5.00 for Mac (GraphPad Software, San Diego, CA). In Figure 1, WD patients and control subjects are plot-scattered with respect to the

results for each diagnostic test for WD. In Fig. 2, ROC curves for ceruloplasmin, basal 24-hour urinary copper, and 24-hour urinary copper after PCT are shown. The serum ceruloplasmin concentration was significantly lower in children with WD (9.6 ± 1.3 mg/dL) versus controls (27.45 ± 0.9 mg/dL, P < 0.0001). Notably, only 2 of 40 WD patients (5%) had serum ceruloplasmin levels > 20 mg/dL, selleck screening library whereas 13 (32.5%) had values between 10 and 20 mg/dL. Among control http://www.selleckchem.com/products/azd9291.html subjects, 10 of 58 (17.24%) had ceruloplasmin levels ≤ 20 mg/dL: 4 had CDG, 3 had NAFLD, 2 were picked up by familial screening and did not carry any mutation, and 1 had congenital hepatic fibrosis. It is remarkable that all children with CDG had hypoceruloplasminemia. We performed an ROC analysis of ceruloplasmin for 40 WD patients and all 58 control subjects. The analysis suggested that the most useful cutoff value was 20 mg/dL, which had a sensitivity of 95% (95% CI = 83%-99.4%) and a specificity of

84.5% (95% CI = 72.6%-92.6%). Basal 24-hour urinary copper excretion was significantly higher in patients with WD (138.9 ± 15.1 μg/24 hours) versus controls (20.9 ± 2.9 μg/24 hours, P < 0.0001). Among WD patients, 12 of 38 (31.5%) and 7 of 38 (18.4%) had basal urinary copper levels < 100 μg/24 hours and < 40 μg/24 hours, respectively. Among seven children with urinary copper levels < 40 μg/24 hours (four males and three females, median age = 3 years, range = 1.3-8), five were picked up with familial screening. In the control group, 4 of 58 patients (6.8%) had urinary copper levels ≥ 40 μg/24 hours: 2 had NAFLD, 1 had NRH, 1 had AIH type 2, and all had urinary copper levels < 100 μg/24 hours. An ROC analysis of 38 WD patients and 58 controls confirmed that a threshold of 40 μg/24 hours (sensitivity = 78.9%, 95% CI = 62.7%-90.

, the

results of which only hint at the potential for pharmacological misadventure. The first important limitation of the study is that the studies were conducted in healthy volunteers, not liver transplant recipients with recurrence of HCV. Both telaprevir and boceprevir are primarily cleared through hepatic metabolism, Histone Methyltransferase inhibitor with only small amounts appearing in urine. As HCV infection has biologically meaningful effects on hepatic function, including inhibition of mitochondrial cytochromes,14 the effects of standard doses of telaprevir and boceprevir on CNI clearance are likely to be magnified in liver transplant recipients with HCV infection through reduced clearance and greater exposure to telaprevir and boceprevir. The effect of HCV on posttransplant cytochrome function is apparent clinically in the metabolism of tacrolimus and cyclosporine, which increases by approximately 30% following clearance this website of HCV in liver transplant recipients.15, 16 The effect of telaprevir/boceprevir administration on tacrolimus and cyclosporine levels and exposure is thus likely to be highly variable during the course of antiviral therapy. In addition, the effects of multiple co-administered doses of telaprevir (or boceprevir) cannot be accurately predicted from the study by Garg et al., as drug dosing only minimally overlapped in this study, probably before the maximal effect on tacrolimus

and cyclosporine pharmacokinetics was achieved. The reported magnitude of the effects of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus are greater than those reported for ritonavir and lopinavir, highly potent cytochrome P450 inhibitors.17 This has important implications. A tacrolimus dose of less than 1 mg/wk can be sufficient to maintain adequate blood tacrolimus concentrations in patients on ritonavir/lopinavir, with further dosing not required

for 3 to 5 weeks, depending on liver check details function.18 It should also be noted that cyclosporine and tacrolimus are only two of the many agents that transplant recipients receive that are metabolized by cytochrome P450. Others include sirolimus, mycophenolate, macrolides, HIV antivirals, Ca2+ channel blockers, statins, analgesics and many more. The potential for medically significant drug interactions in liver transplant recipients who might receive telaprevir/boceprevir is almost limitless. Should any liver transplant recipients receive these HCV protease inhibitors? I would counsel that three criteria should be met by any recipient who for whom telaprevir or boceprevir is prescribed:  1. There should be evidence of aggressive histological recurrence of HCV (e.g. ≤ stage 3 fibrosis) in the absence of hepatic decompensation;  2. The patient should be treated by physicians experienced in managing complex drug-drug interactions; and  3.

, the

results of which only hint at the potential for pharmacological misadventure. The first important limitation of the study is that the studies were conducted in healthy volunteers, not liver transplant recipients with recurrence of HCV. Both telaprevir and boceprevir are primarily cleared through hepatic metabolism, JNK pathway inhibitors with only small amounts appearing in urine. As HCV infection has biologically meaningful effects on hepatic function, including inhibition of mitochondrial cytochromes,14 the effects of standard doses of telaprevir and boceprevir on CNI clearance are likely to be magnified in liver transplant recipients with HCV infection through reduced clearance and greater exposure to telaprevir and boceprevir. The effect of HCV on posttransplant cytochrome function is apparent clinically in the metabolism of tacrolimus and cyclosporine, which increases by approximately 30% following clearance http://www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html of HCV in liver transplant recipients.15, 16 The effect of telaprevir/boceprevir administration on tacrolimus and cyclosporine levels and exposure is thus likely to be highly variable during the course of antiviral therapy. In addition, the effects of multiple co-administered doses of telaprevir (or boceprevir) cannot be accurately predicted from the study by Garg et al., as drug dosing only minimally overlapped in this study, probably before the maximal effect on tacrolimus

and cyclosporine pharmacokinetics was achieved. The reported magnitude of the effects of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus are greater than those reported for ritonavir and lopinavir, highly potent cytochrome P450 inhibitors.17 This has important implications. A tacrolimus dose of less than 1 mg/wk can be sufficient to maintain adequate blood tacrolimus concentrations in patients on ritonavir/lopinavir, with further dosing not required

for 3 to 5 weeks, depending on liver selleck function.18 It should also be noted that cyclosporine and tacrolimus are only two of the many agents that transplant recipients receive that are metabolized by cytochrome P450. Others include sirolimus, mycophenolate, macrolides, HIV antivirals, Ca2+ channel blockers, statins, analgesics and many more. The potential for medically significant drug interactions in liver transplant recipients who might receive telaprevir/boceprevir is almost limitless. Should any liver transplant recipients receive these HCV protease inhibitors? I would counsel that three criteria should be met by any recipient who for whom telaprevir or boceprevir is prescribed:  1. There should be evidence of aggressive histological recurrence of HCV (e.g. ≤ stage 3 fibrosis) in the absence of hepatic decompensation;  2. The patient should be treated by physicians experienced in managing complex drug-drug interactions; and  3.