Showing posts with label Starting HCV Treatment. Show all posts
Showing posts with label Starting HCV Treatment. Show all posts

Saturday, March 10, 2018

Patient To Patient Video - Treating HCV according to genotype with a focus on HCV genotype 3

Patient To Patient Video 
Happy Saturday folks, here is a new patient friendly video launched by Hepatitis C activist Greg Jefferys, with a look at current therapies used to treat the hepatitis C virus across all HCV genotypes.

Website
Generic Hepatitis C Drugs
Greg is the founder of Hepatitis C Buyers Club, formed to help people buy generic Harvoni or Epclusa. Visit his website and watch treatment videos, learn about symptoms or possible treatment side effect. Finally, make sure to read Greg's latest articles over at HepMag.

On This Blog
2018 HCV Genotypes and Treatment
Offered on this page is research updates with a focus on treating HCV according to genotype using FDA approved and investigational medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities.

Drugs Used To Treat Hep C
The following HCV Guidelines offer treatment recommendations using current HCV medications based on HCV Genotype and history of treatment. Which include treatment-naive patients (patients who have never used HCV medications to treat the virus) and treatment-experienced patients (patients who have previously taken HCV medications).

The following pages include guidance for management of treatment-naive patients.
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5 or 6

The following pages include guidance for management of treatment-experienced patients.
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5 or 6

Stay current with all guideline updates, "click here."

Enjoy your weekend, thank you Mr. Jefferys!
Tina

Wednesday, January 17, 2018

Treating Chronic Hepatitis C Infection: A Call to Action for Primary Care Providers

Experts And Viewpoints, January 2018
Treating Chronic Hepatitis C Infection in Primary Care
New treatment guidelines aim to support primary care clinicians in the treatment of hepatitis C infection. 

COMMENTARY
Treating Chronic Hepatitis C Infection: A Call to Action for Primary Care Providers

Christine A. Kerr, MD; Josh S. Aron, MD
January 17, 2018

Despite a revolutionary opportunity to end the global HCV epidemic, there clearly is a need for a concerted effort to help many more people benefit from curative therapy. It is evident that we, as healthcare providers, must step up our efforts to reach and treat patients who can benefit from DAA therapy. Only 9% of the 4 million Americans living with HCV have been successfully treated.


Friday, July 21, 2017

Medscape TV - Episode 2: Considerations Before HCV Therapy

Medscape TV - Hepatitis C Virus: Containing the Threat

July 17, 2017

June 21, 2017
EPISODE 1 - Strides and Obstacles

Six Episode Series
In the past few years, a new class of direct-acting antiviral agents has made the treatment of HCV easier and more effective than ever before, with cure rates nearing 100%, even among HIV-positive patients. But not all patients with HCV who are eligible for antiviral treatment are identified, and even fewer are being referred for care. Thus, HCV infection remains a significant risk for progression to cirrhosis, liver failure, and hepatocellular carcinoma. Liver specialists at two prestigious Chicago medical centers confront the key issues in the management of patients with chronic HCV infection.

Coming Soon
Episode 3 - Hope and Uncertainty
Episode 4 - New Regimens
Episode 5 - Dealing With Chronic Disease
Episode 6 - Strategies for Prevention
Free registration may be required

Wednesday, June 21, 2017

Medscape New HCV Video Series - Hepatitis C Virus: Containing the Threat

Medscape - New Video Series
Hepatitis C Perspective

Hepatitis C Virus: Containing the Threat
About this Series
In the past few years, a new class of direct-acting antiviral agents has made the treatment of HCV easier and more effective than ever before, with cure rates nearing 100%, even among HIV-positive patients. But not all patients with HCV who are eligible for antiviral treatment are identified, and even fewer are being referred for care. Thus, HCV infection remains a significant risk for progression to cirrhosis, liver failure, and hepatocellular carcinoma. Liver specialists at two prestigious Chicago medical centers confront the key issues in the management of patients with chronic HCV infection.

View: Episode 1/ Strides and Obstacles

Coming Soon


Begin here
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Tuesday, April 18, 2017

Listen - Hepatitis C: What If You Do Not Treat?

Hepatitis C: What If You Do Not Treat?
April 17, 2017Special Report, Hepatitis C, Infection

Tuesday, November 29, 2016

What’s Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment

ORIGINAL RESEARCH ARTICLE

First Online: 23 November 2016
DOI: 10.1007/s40271-016-0207-7

What’s Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment

Donna M. Evon1 • Carol E. Golin2 • Teodora Stoica1 • Rachel E. Jones1 • Sarah J. Willis3 • Joseph Galanko1 • Michael W. Fried1

Full Text

Abstract
Background and Objectives

Multiple treatment options with direct-acting antivirals are now available for hepatitis C virus (HCV). Study aims were to understand (1) the informational topics patients want to have to make informed treatment decisions; (2) the importance patients place on each topic; and (3) the topics patients prioritize as most important.

Methods

We used a mixed-methods study of two samples recruited from an academic liver center. Participants were not currently on treatment. Sample I (n = 45) free listed all informational topics deemed important to decision making. Raw responses were coded into several broad and subcategories. Sample II (n = 38) rated the importance of the subcategories from Sample I and ranked their highest priorities on two surveys, one containing topics for which sufficient research existed to inform patients (‘static’), and the other containing topics that would require additional research.

Results

The topics listed by Sample I fell into six broad categories with 17 total subcategories. The most oft-cited informational topics were harms of treatment (100%), treatment benefits (62%), and treatment regimen details (84%). Sample II rated 16 of 17 subcategories as “pretty important’ or “extremely important”. Sample II prioritized (1) viral cure, (2) long-term survival, and (3) side effects on the survey of topics requiring additional research, and (1) liver disease, (2) lifestyle changes, and (3) medication details on the second survey of the most important static topics patients needed.

Conclusions

Patients weighed several informational topics to make an informed decision about HCV treatment. These findings lay the groundwork for future patient-centered outcomes research in HCV and patient-provider communication to enhance patients’ informed decision making regarding direct-acting antiviral treatment options.

Key Points for Decision Makers
Patients contemplating hepatitis C virus treatment want a great deal of information to make informed treatment decisions.

The most commonly cited informational topics included treatment harms such as side effects, treatment benefits such as viral cure, details of the treatment regimen, details about the virus, liver disease, and the risks of not receiving treatment.

The most important topics that require additional investigation were information about viral cure, long-term survival, and treatment side effects. The most important topics for which we have sufficient information that can be shared with patients include liver disease, lifestyle changes needed for treatment, and details about the medications and treatment protocol.

Continue To Full Text Article - Download PDF

Full Text Articles @ Henry E. Chang
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

Thursday, November 6, 2014

Identifying Patients With Chronic Hepatitis C in Need of Early Treatment and Intensive Monitoring

Alimentary Pharmacology & Therapeutics
Systematic Review

Identifying Patients With Chronic Hepatitis C in Need of Early Treatment and Intensive
Monitoring Predictors and Predictive Models of Disease Progression

M. A. Konerman, S. Yapali, A. S. Lok

Aliment Pharmacol Ther. 2014;40(8):863-879.

Abstract
Background Advances in hepatitis C therapies have led to increasing numbers of patients seeking treatment. As a result, logistical and financial concerns regarding how treatment can be provided to all patients with chronic hepatitis C (CHC) have emerged.
Aim To evaluate predictors and predictive models of histological progression and clinical outcomes for patients with CHC.
Methods MEDLINE via PubMed, EMBASE, Web of Science and Scopus were searched for studies published between January 2003 and June 2014. Two authors independently reviewed articles to select eligible studies and performed data abstraction.
Results Twenty-nine studies representing 5817 patients from 20 unique cohorts were included. The outcome incidence rates were widely variable: 16–61% during median follow-up of 2.5–10 years for fibrosis progression; 13–40% over 2.3–14.4 years for hepatic decompensation and 8–47% over 3.9–14.4 years for overall mortality. Multivariate analyses showed that baseline steatosis and baseline fibrosis score were the most consistent predictors of fibrosis progression (significant in 6/21 and 5/21, studies, respectively) while baseline platelet count (significant in 6/13 studies), aspartate and alanine aminotransferase (AST/ALT) ratio, albumin, bilirubin and age (each significant in 4/13 studies) were the most consistent predictors of clinical outcomes. Five studies developed predictive models but none were externally validated.
Conclusions Our review identified the variables that most consistently predict outcomes of patients with chronic hepatitis C allowing the application of risk based approaches to identify patients in need of early treatment and intensive monitoring. This approach maximises effective use of resources and costly new direct-acting anti-viral agents.

Introduction

With the introduction of more efficacious and less toxic drugs, treatment of chronic hepatitis C (CHC) is evolving at a rapid pace. The two new direct-acting anti-viral agents (DAA), simeprevir and sofosbuvir, increase rates of sustained virological response (SVR) with shorter treatment durations compared to prior therapies.[1,2] Along with advances in therapy, there has been a focus on the public health impact of CHC. The Centers for Disease Control and Prevention, the Institute of Medicine, and the United States Preventive Services Task Force, have prioritised hepatitis C awareness, screening and diagnosis.[3–5] Treatment is also being advocated as a means to prevent hepatitis C virus (HCV) infection. As a result of these processes, the pool of potential treatment candidates is expected to balloon. This has caused the conundrum in HCV treatment to shift from 'Can we improve the efficacy and tolerability of HCV treatment?' to 'Can we afford to treat all patients with CHC?'

At the core of the dilemma is the high cost of these new drugs. The estimated wholesale price of a 12-week course of sofosbuvir in the United States (US) is $84 000 and of simeprevir $66 000.[6,7] These staggering costs exclude retail markup, and associated cost of pegylated interferon (IFN), ribavirin, physician visits and laboratory tests. While these new treatment regimens have SVR rates of 80–90%, and SVR has been shown to decrease cirrhosis complications, hepatocellular carcinoma (HCC) and liver-related mortality, even resource-replete countries like the US cannot afford to treat all those who are infected.[1,2,8] The logistical and financial barriers are much higher in resource-limited countries, many of which have higher prevalence of HCV infection than western countries. Clinicians and health policy makers will need to determine an optimal yet practical approach to provide these highly efficacious, but extremely costly therapies to this burgeoning patient population.

One solution is to adopt a risk-stratified approach that targets therapy to those at the greatest risk of disease progression. There have been many studies investigating risk factors for disease progression in patients with CHC but few have employed a longitudinal study design in generalisable patient populations using data that are routinely available in clinical practice. Results of the existing studies have also not been systematically summarised in a single document. Therefore, we performed a systematic review of the literature to (i) identify factors predictive of disease progression (fibrosis progression and clinical outcomes) in patients with CHC and (ii) assess existing predictive models.

Methods
Data Sources and Search Strategy
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations in conducting this systematic review.[9] With the assistance of a medical research librarian, we performed serial literature searches for English and non-English articles. MEDLINE (via PubMed), EMBASE, Web of Science and Scopus were searched using the following keywords: 'cirrhosis' or 'liver cirrhosis' or 'fibrosis', 'hepatitis C' or 'hepatitis C, chronic' or 'chronic hepatitis C', 'disease progression' or 'progression' or 'decompensation'. Boolean operators and medical subject heading terms as well as other controlled vocabulary were used to enhance electronic searches. An example of specific search strategy details is shown in Table S1 http://onlinelibrary.wiley.com/store/10.1111/apt.12921/asset/supinfo/apt12921-sup-0001-TableS1-S6.docx?v=1&s=130e5a4e31352228b5691bb0dcf446af48e7576f.

All human subject studies published in full-text or abstract were eligible for inclusion. The search was limited to publications from 2003 to 2014 as this 10-year period contained the most contemporary and relevant data with respect to treatment and current practice. Additional studies of interest were identified by hand searches of bibliographies and cited reference tracking and consultation with clinical experts on the topic. The initial search was performed in October 2013 and the search was last updated on 2 June 2014.

Study Eligibility and Selection Criteria
Two authors (M.A.K. and A.S.L.) sequentially determined study eligibility. Studies were initially screened by the first author; decisions about study inclusion were made independently by both authors (M.A.K and A.S.L). Differences in opinion regarding study inclusion were resolved through consensus. Studies were included if they: (i) included human studies with participants 18 years of age or older; (ii) systematically evaluated predictors of fibrosis progression and/or clinical outcomes for patients with CHC; and (iii) used a longitudinal cohort study design. We focused on studies of untreated patients but also included studies with a mix of treated and untreated patients provided that <20% of the study population achieved SVR and results were stratified by treatment outcomes. For studies evaluating predictors of fibrosis progression, we selected studies only when paired biopsy was used to assess progression.

We excluded studies that enrolled (i) patients co-infected with hepatitis B (HBV) or human immunodeficiency virus (HIV); (ii) patients with additional causes of chronic liver disease; (iii) patients with prior liver transplantation and (iv) specific groups of patients (e.g. thalassaemia patients) only. These patient populations were excluded because they likely have different rates and risk factors for disease progression compared to the general population of patients with CHC. In addition, studies that evaluated HCC as the only outcome of interest were excluded as we were interested in broad clinical outcomes for patients with CHC, and predictors of HCC development alone may not be the same as predictors of disease progression in CHC in general. Lastly, studies that focused on predictors that are not readily available clinically (e.g. genetic or other serum markers for which commercial assays are not available, and experimental imaging techniques) were excluded given that they would not be relevant to current clinical practice.

Definition of Variables and Outcomes
Patients with CHC were defined as those with detectable HCV ribonucleic acid (RNA). We were interested in two outcomes: histological progression and clinical progression. The definition of histological progression was an increase of ≥1 METAVIR (range 0–4) or Ishak (range 0–6) fibrosis stage on follow-up liver biopsy. The definition of clinical progression encompassed the progression from compensated to decompensated cirrhosis, and liver-related or overall mortality. The definition of compensated cirrhosis was based on histology when available (Ishak fibrosis score ≥5 or METAVIR 4) or on the combined results of other noninvasive testing including laboratory tests and imaging. Decompensated cirrhosis was defined by the presence of any of the following: ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding or hepatic encephalopathy (HE). The presence of HCC as defined by histology or American Association for Study of Liver Diseases radiological criteria was variably included as a clinical outcome.[10]

Data Abstraction and Validity Assessment

Data from eligible studies were abstracted by two authors (M.A.K. and S.Y.) using a standardised template adapted from the Cochrane Collaboration.[11] For all studies, we recorded: study design, sample size, patient population characteristics, duration of follow-up, predictor variables studied, outcomes measured, criteria used to define these outcomes and measures of association/predictiveness of risk for these outcomes. We accepted the outcome definitions as stated by each study without independently validating or reviewing their data. Study authors were directly contacted for additional, unpublished data.

Assessment of Risk of Bias and Study Quality
Two authors (M.A.K and S.Y.) independently assessed the risk of study bias and study quality. Since all the included studies were nonrandomised cohort studies, the Newcastle-Ottawa scale was used to judge study quality as recommended by the Cochrane Collaboration.[12] This scale uses a star system to assess the quality of a study based on three domains: selection of the study population, comparability of the study groups and method of outcomes assessment. For our review, given that no study had a comparison group, we excluded comparability components of the scale across all studies. Studies which received stars in every domain were assessed as being of high quality.

Data Synthesis and Analysis
Given the substantial variation in the design, methods and inclusion/exclusion criteria within our included studies, meta-analysis was not performed. Two authors (M.A.K. and S.Y.) qualitatively synthesised the results of the included studies, focusing on the risk factors evaluated and their independent predictiveness in terms of the outcomes measured and patient populations studied. Studies were categorised according to the outcome of interest: predictors of histological progression, predictors of clinical outcomes or studies investigating both clinical and histological outcomes. All authors had access to the study data and had reviewed and approved the final manuscript.

Results
Studies Included in the Systematic Review
After removal of duplicate entries, 2257 unique articles were identified by our systematic literature search (Figure 1). On the basis of abstract review, 69 were selected for full-text review. Two study authors classified 29 articles as meeting the predefined criteria for analysis. In total, these 29 studies included 5817 unique patients from 20 separate patient cohorts. Sixteen of these studies investigated predictors of histological progression, eight studies evaluated predictors of clinical outcomes, and the remaining five studies investigated both histological and clinical outcomes.[13–41] Fourteen studies included treatment-naïve patients only, five included both treatment-naïve and treatment-experienced patients, eight included treatment-experienced patients only, and two studies did not describe the treatment status of the patients. We contacted four authors to obtain additional unpublished data.

Click on image to enlarge


Flow diagram of studies included in the systematic review. aMany studies met multiple exclusion criteria. Each study was coded under a single criterion only. bIncludes animal models, paediatric populations, patients who had previously undergone liver transplant, patients with chronic liver disease other than HCV monoinfection, evaluation of only specific subsets of populations with CHC. cIncludes studies that were descriptive papers only, studies that did not specifically evaluate for predictors of histological or clinical progression, and studies that evaluated predictors that are not readily clinically available. dIncludes studies that focused on risk factors for the development of HCC only, and studies where some patients achieved SVR and the results were not stratified based on response to treatment.

Characteristics of Studies on Histological Progression
A total of 21 studies evaluated predictors of histological progression. The studies included populations from Europe (n = 10), Asia (n = 2), and North (n = 8) and South America (n = 1). Only one study was prospective with the remaining 20 being retrospective analyses of previously collected data. The sample size for included studies varied (range 36–622 patients) with the majority having <200 patients (n = 14). A number of studies had overlapping cohorts. Four studies were derived from the Hepatitis C Anti-viral Long-term Treatment Against Cirrhosis (HALT-C) cohort, a US multi-centre randomised controlled trial to evaluate the safety and efficacy of low dose pegylated IFN in CHC patients with advanced fibrosis who failed to respond to prior IFN therapy. Four other pairs of studies drew from the same cohort of patients.[17,21,25,29,33,35,38,41] These studies were included in the review despite overlapping cohorts given differences in predictors examined, outcomes evaluated and criteria for selection of subsets of patients analysed within the overall larger cohort. The average duration of follow-up ranged from a median of 2.5–10 years.

The studies had varied inclusion and exclusion criteria as detailed in Table 1. Among the non-HALT-C studies, 11 studies had explicit requirements for baseline Ishak/METAVIR fibrosis stage. Five studies required minimal or no fibrosis at baseline and the remaining six studies required lack of cirrhosis on initial biopsy. Only 14 studies described criteria used to determine adequacy of biopsy specimens. The majority of the studies had a single pathologist blinded to clinical data score the biopsies while the HALT-C study had a panel of pathologists review the biopsies and consensus staging was recorded. Exclusionary alcohol intake was described in nine studies though the cut-off amounts and methods for ascertaining alcohol intake varied across the studies. The studies were predominately comprised of male patients in their late 30s to early 50s.

Characteristics of Studies of Clinical Outcomes
A total of 13 studies evaluated predictors of clinical outcomes. Six studies were conducted in the US (including 5 HALT-C studies), five in Europe and two in Asia. Only two studies were prospective with the remaining 11 being retrospective analyses. Sample size in each study varied from 52 to 1457 patients. Apart from the HALT-C studies, there was only one additional overlapping cohort.[36,37] The average duration of follow-up ranged from a median of 2.3 to a maximum of 14.4 years. Compared to studies on histological progression, the studies on clinical outcomes consisted of patients who were older, had more advanced fibrosis at baseline, and were more likely to be treatment experienced.

Incidence of Histological Progression
A summary of the specific outcomes evaluated and incidence of these outcomes in each study is displayed in Table 2, Table 3 and Table 4. For studies where the outcome was defined as ≥1 fibrosis stage increase on follow-up biopsy (n = 13), the incidence of that outcome ranged from 21–61% over a range of follow-up of 2.5–10 years.[14,16,18,21,25,28–33,35,41] Studies applying a stricter definition of fibrosis progression (≥2 stage increase on follow-up biopsy, n = 3) had less variability in range of incidence of outcome, reporting 22–34% over a range of follow-up of 3.5–5.8 years.[13,23,26] Studies with higher rates of fibrosis progression tended to have longer follow-up durations (>6 years), though there were several studies with follow-up of ≥6 years that had low rates of fibrosis progression. No identifiable differences in patient characteristics between studies with high vs. low incidence of fibrosis progression were noted.

Incidence of Clinical Progression
Studies assessing risk factors for clinical progression (n = 13) included several distinct outcomes. Four studies evaluating progression from compensated to decompensated cirrhosis reported an incidence between 13% and 40% over a range of follow-up of 2.3–14.4 years.[15,24,31,34] No clear pattern was identified between length of follow-up or patient characteristics and rate of outcomes. Notably, the definition of decompensation varied across studies. Four studies evaluating the incidence of overall mortality reported incidences between 8% and 47%. The range of follow-up for these studies was 3.9–14.4 years, with a higher rate of outcomes reported in studies with longer duration of follow-up.[15,27,39,40] The remaining studies used an aggregate outcome encompassing a broad range of clinical end points including decompensation, increase in Child–Turcotte–Pugh score, development of HCC, liver transplant and liver related as well as overall mortality. The reported incidence of this aggregate outcome was 13–31% over a range of follow-up of 3.5–6.3 years.[19,20,23,26,36,37]

Predictors of Histological Progression
A detailed list of the predictors evaluated and the results of univariate analysis is provided in Tables S3–S5 http://onlinelibrary.wiley.com/store/10.1111/apt.12921/asset/supinfo/apt12921-sup-0001-TableS1-S6.docx?v=1&s=130e5a4e31352228b5691bb0dcf446af48e7576f. For each study, the predictor variables were categorised as follows: (i) baseline clinical characteristics including demographics and relevant co-morbidities; (ii) baseline laboratory results; (iii) baseline histological features or (iv) longitudinal laboratory and histology results.
All studies investigating predictors of histological progression evaluated baseline clinical characteristics, baseline laboratory results and baseline histology results except for Tamaki et al. who did not evaluate baseline histological features.[38] Only half of the studies evaluated longitudinal variables which were predominantly serial aminotransferase levels. Longitudinal biopsy results such as changes in steatosis score or histological activity index (HAI) were assessed in only five studies.[16,22,28–30] The predictors that were most consistently evaluated are listed in Figure 2a. The most common clinical characteristics assessed were age, gender, HCV genotype, alcohol intake, body mass index (BMI) and biopsy interval, and the most common laboratory values evaluated were platelet count and ALT levels. Baseline histological features were also frequently investigated predictors and were included in >70% of studies.

Click on image to enlarge


Figure 2.
List of variables identified to have significant predictive value for (a) histological and (b) clinical progression.

Multivariable analysis was performed in all but two studies.[19,31] Variables found to be independently predictive of histological progression are listed in Table 2 and Table 4. Among all the variables assessed, baseline steatosis was most consistently reported as independently predictive of subsequent fibrosis progression (significant on multivariate analysis in 6 of 21 studies) with an odds ratio (OR) [(95% confidence interval (CI)] of 4.8 (1.3–18.3) to 14.3 (2.1–111.1).[12,16,18,20,24,27] Notably, one study found that effect of baseline steatosis on fibrosis progression was dependent on baseline fibrosis stage.[20] Baseline Ishak/METAVIR fibrosis stage was the next most consistently identified independent predictor of histological progression (significant on multivariable analyses in five of 21 studies).[20,25,30,33,35] Only one of these studies reported the effect size, with adjusted relative risk of 1.93 (95% CI 1.3–9.0).[35] Figure 2a depicts the number of studies in which individual variables were significantly or not significantly predictive of histological progression on multivariate analyses.

Predictors of Clinical Outcomes
All 13 studies examining predictors of clinical outcomes included baseline clinical characteristics and laboratory results (Tables S4 and S5 http://onlinelibrary.wiley.com/store/10.1111/apt.12921/asset/supinfo/apt12921-sup-0001-TableS1-S6.docx?v=1&s=130e5a4e31352228b5691bb0dcf446af48e7576f). Baseline histology was assessed in only eight studies though biopsies were performed in every study. Only three studies incorporated longitudinal data which consisted of serial laboratory values only.[23,24,36] The predictors that were most consistently evaluated are listed in Figure 2B. The most common clinical characteristics assessed were age, gender and BMI; the most common laboratory values evaluated were platelet count and ALT level.

Multivariable analysis was performed in all but two studies.[19,31] The variables found to be independently predictive of clinical progression are listed in Table 3 and Table 4. Among the variables assessed, baseline platelet count was the most consistent independent predictor of clinical outcomes (significant on multivariate analysis in six of 13 studies) followed by age, baseline AST/ALT ratio, albumin and bilirubin (each significant in four studies).[15,24,26,36,37,39] Figure 2B depicts the number of studies in which individual variables were significantly or not significantly predictive of clinical outcomes in multivariate analyses.

Mathematical Prediction Models

Five studies provided prediction models, three for fibrosis progression and four for clinical outcomes (Table S6 http://onlinelibrary.wiley.com/store/10.1111/apt.12921/asset/supinfo/apt12921-sup-0001-TableS1-S6.docx?v=1&s=130e5a4e31352228b5691bb0dcf446af48e7576f).[23,26,32,39,40] Four of the models were derived from the HALT-C study. All the prediction models are primarily comprised of baseline laboratory results. Only one of the models incorporated longitudinal data. None of the models had been validated in external CHC cohorts and only two models reported the associated area under the receiver operating characteristic curve.[23,40]

Quality Assessment and Risk of Bias
Studies evaluating predictors of histological progression were of varying quality, whereas studies investigating predictors of clinical outcomes or studies investigating combined outcomes were all of high quality except for one study.[31] Six studies on histological progression included a small number of patients with advanced fibrosis or cirrhosis on initial biopsy who were not able to progress according to the author's definition.[17][18, 25, 28, 33, 38] Two studies evaluated select cohorts (Levine et al. evaluated untreated Irish women who acquired HCV infection during pregnancy only, and Livingston et al. evaluated only treatment naïve Alaska Native and American Indian persons) and were scored as having limited representativeness.[30,31] The remaining studies were scored as being at least somewhat representative of the average patient with CHC in the community (Table S2 http://onlinelibrary.wiley.com/store/10.1111/apt.12921/asset/supinfo/apt12921-sup-0001-TableS1-S6.docx?v=1&s=130e5a4e31352228b5691bb0dcf446af48e7576f).

Discussion
Although there is abundant literature on the topic of predictors of histological and clinical outcomes for patients with CHC, only 29 studies met our inclusion criteria which captured studies with a longitudinal study design in broad patient populations. Within the 29 studies included, the incidence of outcomes varied widely: 16–61% during a median follow-up of 2.5–10 years for fibrosis progression; 13–40% over 2.3–14.4 years for hepatic decompensation; and 8–47% over 3.9–14.4 years follow-up for overall mortality. The wide range in incidence of outcomes highlights the heterogeneity in patient population evaluated, stage of liver disease at enrollment, duration of follow-up, and definition of outcomes. Interestingly, higher rates of outcomes did not clearly correlate with longer durations of follow-up or more advanced disease at baseline across studies, pointing to more complex underlying interactions driving outcomes. Although the incidence data were not conducive to providing consensus outcome rates, we were able to identify risk factors that have most consistently been associated with outcomes of interest. Baseline steatosis and fibrosis score were the most consistent predictors of fibrosis progression and baseline platelet count, AST/ALT ratio, albumin, bilirubin and patient age were the most consistent predictors of clinical outcomes.
The variables identified as being most predictive of outcomes were not unexpectedly markers of more advanced liver disease. Though the overall finding that patients with more advanced disease are at higher risk for adverse outcomes is not novel, our study is the first to systematically identify the specific risk factors from among the many markers of advanced liver disease that portends worse prognosis. For example, among the laboratory markers of more advanced liver disease, platelet count, bilirubin, albumin and AST/ALT ratio conveyed meaningful risk information whereas INR, AST, ALT and MELD score did not. Differences in study design made it difficult to identify clear cut-off values for each predictor apart from platelet count with values ≤150 000/uL consistently associated with worse prognosis. Furthermore, individual laboratory markers may be less reliable in predicting outcomes than panels of markers such as aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Fibrotest and/or measurements of liver stiffness. The finding that patients with more advanced disease have greater risk of disease progression suggests there may be subsets of patients who are rapid progressors. Understanding whether some patients are destined to be rapid progressors and being able to identify these patients at an early stage will help target limited resources to treat those patients who will derive the most benefit. Though none of the existing predictive models have been externally validated, the model developed by Ghany and colleagues is most readily applicable in clinical practice as it is based on routinely available data and evaluates important liver-related clinical outcomes.[26]

Examining the results in more detail yielded several useful insights. First, the finding of steatosis as a predictor of outcomes highlights a potential modifiable risk factor associated with disease progression. This is particularly relevant given the evolving obesity epidemic. Our data suggest that patients may benefit from aggressive lifestyle interventions in addition to other standard of care treatment for patients with CHC. The prognostic information gained from baseline liver biopsy results suggests that liver biopsies not only provide information regarding current staging of liver disease but also useful prognostic information. As performance of liver biopsies continue to decline, evaluating whether noninvasive assessment of fibrosis and steatosis will provide the same prognostic information would be important. Though only one study included in our review used an additional modality to assess liver fibrosis in conjunction with biopsy, this study showed that liver stiffness measurements were associated with overall mortality.[40]

Our review also highlights several areas for improvement for future studies on predictors of disease progression in CHC. Analysis of the individual predictive value of each risk factor found that there was a notable lack of incorporation of longitudinal variables. In the few studies that did assess longitudinal data, these variables were usually restricted to laboratory values, predominantly AST and ALT levels. These models do not mirror clinical practice where assessments of risk of disease progression are based on the pattern of a patient's test results over time. Models restricted to only baseline data also cannot distinguish between patients with similar initial data but who go on to have distinct disease courses and outcomes. Future studies can also benefit from implementing standardised definitions and criteria for outcomes and employing a panel of investigators to adjudicate outcomes as the variability in definition of predictor and outcome variables was one of the biggest challenges.


There are other limitations to our review such as sample selection bias, sampling error and misclassification bias in studies requiring paired biopsies. In the majority of studies, biopsies were assessed by a single pathologist and criteria for adequacy of biopsies was described in only 14 of 21 studies. Finally, the variability in duration of follow-up impacts not only incidence rates of outcomes but also predictiveness of variables examined.

In summary, this systematic review demonstrated that while there is an abundance of literature on factors associated with histological and/or clinical progression in CHC, there is a lack of longitudinal studies of representative, untreated, well characterised patients followed for a sufficiently long duration to allow the development of simple prediction models. Despite the limitations inherent to the existing literature, we were able to identify specific risk factors that have been consistently identified as being independently predictive of disease progression. By selecting studies consisting of broad patient populations and those that evaluated routinely obtained clinical data, our findings can be generalised to and applied in many clinical settings. From a policy standpoint, we have highlighted that it is possible to identify patients at higher risk for adverse outcomes. Policies that target costly new HCV therapies to these patients who would derive the most benefit will maximise their cost effectiveness. The availability of risk prediction tools that can be applied in the clinic will help both physicians and patients decide whether to embark on HCV treatment now or to wait for more affordable treatment. These types of tools will be particularly important in resource-limited countries and must therefore be validated in broad patient populations.

References

1.Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368: 1878–87.
2.Janssen Therapeutics. Olysio (simeprevir): Full prescribing information, 2013.
3.Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C; 2010 January 11, 2010.
4.Moyer VA. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2013; 159: 349–57.
5.Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep 2012; 4: 1–32.
6.Gilead. U.S. Food and Drug Administration Approves Gildead's Sovaldi (Sofosbuvir) for the Treatment of Chronic Hepatitis C, 2013.
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8.Murphy EL. The increasing burden of mortality from viral hepatitis in the United States. Ann Intern Med 2012; 157: 149–50; author reply 150.
9.Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8: 336–41.
10.Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020–2.
11.Higgins J, Green R. Cochrane handbook for systematic reviews of interventions version 5.0.2, 2009.
12.Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses, 2009.
13.Baran B, Gulluoglu M, Soyer OM, et al. Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C. J Viral Hepatitis 2014; 21: 111–20.
14.Boccato S, Pistis R, Noventa F, Guido M, Benvegnu L, Alberti A. Fibrosis progression in initially mild chronic hepatitis C. J Viral Hepatitis 2006; 13: 297–302.
15.Bruno S, Zuin M, Crosignani A, et al. Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol 2009; 104: 1147–58.
16.Castera L, Hezode C, Roudot-Thoraval F, et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut 2003; 52: 288–92.
17.Colletta C, Smirne C, Fabris C, et al. Value of two noninvasive methods to detect progression of fibrosis among HCV carriers with normal aminotransferases. Hepatology 2005; 42: 838–45.
18.Cross TJ, Quaglia A, Hughes S, Joshi D, Harrison PM. The impact of hepatic steatosis on the natural history of chronic hepatitis C infection. J Viral Hepatitis 2009; 16: 492–9.
19.Dienstag JL, Ghany MG, Morgan TR, et al. A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology 2011; 54: 396–405.
20.Everhart JE, Lok AS, Kim HY, et al. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology 2009; 137: 549–57.
21.Fabris C, Falleti E, Cussigh A, et al. The interleukin 28B rs12979860 C/T polymorphism and serum cholesterol as predictors of fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases. J Med Virol 2012; 84: 747–55.
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32.Mummadi RR, Petersen JR, Xiao SY, Snyder N. Role of simple biomarkers in predicting fibrosis progression in HCV infection. World J Gastroenterol 2010; 16: 5710–5.
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Friday, October 11, 2013

Ensuring Treatment Success in HCV: 10 Ways Providers Can Improve Patient Outcomes

 
Greetings,
Here we are with Friday upon us, and another work week about to end.

My weekend plans include purchasing a dozen Halloween cookies to be placed strategically on a cookie sheet for my grandchildren to enjoy.

In protest I have stopped baking until the government shutdown is over, which has allowed nanna some extra time to play with her new smartphone.

How about you? Do you have any weekend plans? Maybe take a long lovely drive or catch up on some reading? Or better yet visit Clinical Care Options (CCO) and check out their new HCV learning activity.

CCO just launched a Video Module offering ten recommendations for improving treatment outcomes in patients receiving HCV therapy. HoChong Gilles RN, MS, FNP, and April G. Long RN, MS, FNP both experienced healthcare professionals present us with information on managing side effects, adherence to therapy, complex treatment regimens and stopping rules.

*Free registration is required

Tips for navigating the CME
Once you launch the program "click next under the video" to view the next segment. If prompted to answer questions during the CME "click next at the bottom of the activity." I have provided a highlight of each discussion below.



Ensuring Treatment Success in HCV: 10 Ways Frontline Providers Can Improve Patient Outcomes

Faculty: HoChong Gilles RN, MS, FNP, April G. Long RN, MS, FNP
Released: 10/4/2013

Introduction  At this time the presenters prompt us to answer the questions provided under the video, simply click next to skip the questions and proceed.

Meet Early and Often to Address Anemia - Medication dose reduction

Adherence Strategies - Tips for taking medications                

Use Care Contracts or “Statements of Understanding” - Consent for care, patient awareness of lab appointments and side effects.                

 Check HbA1c in Every Patient: Diabetic or Otherwise - Keeping diabetes under control

Give Patients the Gift of (Your) Time - Giving patients the time needed to validate side effect and other concerns

Making Educated Partners Out of Friends and Family - Addressing social history - home support.

Use HCV’s Natural History Against It and Build Hope - Providing education about the disease and counseling regarding likelihood of achieving SVR.

Managing the Therapeutic “Betrayal” of Stopping Rules - Addressing a high baseline viral load and just missing the cut off for stopping rules.               

Recommend or Provide Treatments for Common Adverse Events Before They Are Needed - Preventative strategies such as being well hydrated, staying out of direct sunlight, and anal discomfort advice for patients using Telaprevir - Oh boy..........               

Find and Stick With 1 Specialty Pharmacy - The importance of using a pharmacy with a HCV team.

End Matter - Information on taking the CME test, we skip this part folks.

Need to run now friends, time to pick up those cookies I plan on baking this weekend. Stay safe and enjoy your weekend. See you soon... 
 
 

Wednesday, August 21, 2013

Hepatitis C Virus (HCV) Infection: Looking Beyond the Interferon Alfa Era

Hepatitis C Virus (HCV) Infection: Looking Beyond the Interferon Alfa Era

New York, NY - June 25, 2013

Sorry folks, I am a bit late bringing this to you.

In June over at the IAS–USA website an interactive and highly enjoyable question and answer course was launched. The easy to follow activity is offered in both an audio and webcast format.

Hepatitis C patients taking part in the CME are given an opportunity to learn more about the virus, disease progression, treatment regimens and side effects - to name a few. For instance in this presentation by Kenneth E. Sherman, MD, PhD: HCV is a LIVER Disease, the in-depth "question and answer" lecture discusses non-invasive methods for the assessment of liver fibrosis, biopsy,  liver fibrosis, and cirrhosis with an emphasis on HCV as a liver disease.

Listen to the audio below, and Watch the Webcast here. After clicking on the webcast, scroll to the bottom of the page, click on “I have read these instructions and understand them,” to begin activity. All course topics are provided below, view all webcasts at the IAS–USA website.

The good news - no registration required!



Overview of the Basics of HCV Infection Management: Optional Precourse Workshop for Practitioners Who are New to HCV Care
Robert T. Schooley, MD

Welcome to the Annual IAS-USA New York HCV Course
Robert T. Schooley, MD; David L. Thomas, MD, MPH

HCV Treatment Now? When and How to Manage HCV in Treatment-Naive and Treatment-Experienced Patients
Mark Sulkowski, MD

HCV is a LIVER Disease
Kenneth E. Sherman, MD, PhD

Practical Management of Adverse Effects in Patients with Chronic HCV Infection
Jennifer J. Kiser, PharmD

Strategies for Treating HCV in HIV/HCV Coinfected Patients: A Case-Based Panel Discussion
Arthur Y. Kim, MD

The "Grab Bag": Selected Hot Topics in Viral Hepatitis Management
Kenneth E. Sherman, MD, PhD

Cure Without Interferon Alfa: Scientific Basis and Clinical Evidence
David L. Thomas, MD, MPH

The Fragile Relationship Between HCV and Its Human Host
Robert T. Schooley, MD
 
View all webcasts available online at the IAS–USA website.

Of Interest
Hepatitis C Online Course
Don't miss this recent "Hepatitis C Online Course" funded by the CDC and brought to you by a collaboration between the University of Washington and the International Antiviral Society-USA (IAS-USA)

Tuesday, August 20, 2013

Treatment approaches- Treat HCV now or wait and management of adverse events

Hi Folks,
When a new HCV learning activity is released online this blog provides background information, and links to the new video, article or CME.

In July and August two learning activities were published over at Medscape, both presented in an interview format.

*Like any site offering continuing medical education (CME), it requires a free quick registration to participate.

In the most recent CME, Paul Y. Kwo, MD, professor of medicine at Indiana University School of Medicine describes a case scenario of a 59-year-old man with hepatitis C who has cirrhosis thus motivated to begin treatment now instead of waiting for future therapies.

As noted by Dr. Kwo in the CME;

With new agents on the horizon, it is important to identify those patients who cannot afford to wait for new treatments. There are also patients whose clinical characteristics allow for treatment delay but who are highly motivated and wish to initiate treatment right away.

In regard to side effects Dr. Kwo remarked:

There are some other issues to be aware of with both of these HCV protease inhibitors.[7,13] Gastrointestinal side effects occur with both telaprevir and boceprevir. Boceprevir causes dysgeusia, which usually does not lead to treatment discontinuation. Clinicians should also know that boceprevir is associated with slightly higher levels of neutropenia as well as anemia. There are some perianal symptoms with telaprevir that sometimes require management.[7,13] We use topical hydrocortisone cream. Mesalamine suppositories and topical lidocaine can also be used to address this issue during the 12 weeks of telaprevir therapy. To address the gastrointestinal issues associated with the protease inhibitors as well as with PEG-IFN and RBV, we may use loperamide or fiber supplements.

Click here to begin.

In the second CME Andrew J Muir, MD., Director of GI/Hepatology Research at Duke Clinical Research Institute discusses eligibility and adherence in standard therapy for genotype 1 patients comprising of HCV protease inhibitor-based triple therapy -Telaprevir or Boceprevir.

Dr. Muir discusses the standard of care for HCV genotype 1 patients

The current standard of care for treatment of chronic HCV genotype 1 infection in the United States is the combination of PEG-IFN-alfa, RBV, and one of the HCV NS3/4A protease inhibitors boceprevir or telaprevir.[1] In clinical studies, the addition of boceprevir or telaprevir to the previous standard of care for these patients (ie, PEG-IFN plus RBV) was associated with a significantly increased rate of sustained virologic response (SVR) in both treatment-naïve and previously treated patients

Dr. Muir comments on the promise of new agents to treat hepatitis C;

The guidelines recommend that treatment should be considered in all patients who qualify; we take that approach on a case-by-case basis to determine whether treatment is appropriate for an individual patient at this time. A number of the new HCV agents are expected to become available in the next few years, and we expect that there will be an IFN-free regimen available for HCV genotype 2 and 3 by late 2013, and hopefully for genotype 1 by 2015 or so. The question, then, is this: Should you treat the patient now, or wait until these new therapies are available?

Click here to begin.
                         
Medscape Education Gastroenterology

CME Released: 08/14/2013
Timely and Appropriate Care for Chronic HCV Infection: Therapy Selection and Adverse Event Management
On June 17, 2013, Medscape spoke to Paul Y. Kwo, MD, professor of medicine at Indiana University School of Medicine and medical director of liver transplantation at Indiana University Health, Indianapolis, to discuss the current HCV treatment approaches and provide a case-based illustration of the decision of whether a patient is a candidate for treatment with the current standard of care, and to detail management of adverse events associated with HCV therapy.

CME Released: 07/31/2013
Providing Timely and Appropriate Care for Chronic HCV Infection: Patient Readiness and Likelihood of Response
This represented a new paradigm in the management of HCV. On May 29, 2013, Medscape spoke to Andrew J Muir, MD, Associate Professor of Medicine and Director of GI/Hepatology Research at Duke Clinical Research Institute in Durham, North Carolina, to discuss the current HCV treatment approaches and provide a case-based illustration of the decision whether a patient is a candidate for treatment with the current standard of care.

Saturday, August 17, 2013

Documentary - Breaking the Silence: Voices of Chronic Hepatitis C

Hi Folks,
As once a hepatitis C patient myself, I was deeply touched while viewing this awe inspiring documentary from Janssen Therapeutics.  For 17 minutes the viewer with hepatitis C is not alone, for 17 minutes normal people just like you and me share their story, diagnosis and family struggles. Support of family and friends is critical, but no matter how much our loved ones may empathize with us - connecting with other people living with the virus is invaluable.

 

**View the video or read the transcript here.

Next in Breaking the Silence: Voices of Chronic Hepatitis C

Published on Aug 16, 2013
As part of our commitment to hepatitis C, Janssen Therapeutics has created Breaking the Silence: Voices of Chronic Hepatitis C, which focuses on the experiences that patients, caregivers, and providers face during their journey with hepatitis C. We hope you enjoy this special documentary.
 

Monday, June 3, 2013

Drugs Go From Hit to Dud in $15 Billion Hepatitis Race: Health

Drugs Go From Hit to Dud in $15 Billion Hepatitis Race: Health

Simeon BennettJun 03, 2013 3:38 am ET

June 3 (Bloomberg) -- Jean-Michel Pawlotsky has déjà vu.

The doctor in the town of Creteil, just outside Paris, is telling hepatitis C patients to delay treatment until later this year, when two new drugs that may boost their chances of defeating the lethal liver infection hit the market.

It’s the same advice he offered two years ago, when earlier medicines developed by Vertex Pharmaceuticals Inc. and Merck & Co. were poised for approval. Now he says those drugs, hailed as breakthroughs in 2011, will soon be superseded by products from Gilead Sciences Inc. and Johnson & Johnson.

The pace of innovation, spurred by drugmakers jostling for a slice of a market that may reach $15 billion by 2018, has turned hepatitis C research into one of the fastest-developing areas of medicine. That boosted Gilead’s shares to a record last month, and left others like Vertex facing dwindling sales as their products quickly go from revolutionary to outdated.

“Things are moving very fast,” Pawlotsky, who teaches medicine at the University of Paris-Est, said by phone. “People are frustrated, they want more, better.”

Hepatitis C, an infectious disease that can scar the liver and afflicts about 170 million people worldwide, is still treated largely with injections that can take six months to clear the virus, sometimes don’t work, and cause side effects ranging from flu-like symptoms to depression. If untreated for longer periods, hepatitis C can cause cancer.

Gilead, a newcomer to the field, in April applied for regulatory clearance of a drug known as sofosbuvir. The pill may become the Foster City, California-based company’s top-selling product by 2015, and reach sales of $6.3 billion by 2016, according to the average of nine analyst estimates compiled by Bloomberg. The stock has more than doubled in the past year on optimism about the pill.

Drug Deluge

Until 2011, there was only one standard treatment: the generic antiviral ribavirin, together with a weekly injection called pegylated interferon, sold by Roche Holding AG and Merck.

Two years ago, doctors and patients embraced the new drugs from Vertex and Merck because they boosted cure rates to about 80 percent from 50 percent. But they came with more side effects, including skin rashes and the risk of birth defects.

In clinical studies, newer formulations from Gilead and J&J show similar or better results in ridding patients of the disease, and fewer risks. Both may win regulatory approval this year. Johnson & Johnson’s Janssen unit applied in March for clearance of its product, simeprevir, which was developed by Medivir AB. Other drugs from AbbVie Inc. and Bristol-Myers Squibb Co. are in late-stage trials.

Much Promise

“It’s not often you’re in a field that moves so fast and offers so much promise,” said Graham Cooke, a clinician at Imperial College London. “We’ve had very difficult treatments for so long, and we’re now in this era of incredible throughput from the pipeline.”

Vertex, of Cambridge, Massachusetts, gets 76 percent of its revenue from Incivek, the hepatitis drug it developed with Janssen, which markets the treatment as Incivo in Europe. The drug won U.S. regulatory approval in May 2011 and prescriptions and sales reached a peak in the fourth quarter of that year, but have declined since. The drug may only garner sales of $669 million this year, the average of 12 analyst estimates compiled by Bloomberg.

“We recognize that fewer patients are starting treatment for hepatitis C, however there are still patients who want or need to be treated now,” Erin Emlock, a spokeswoman for Vertex, said by e-mail. “Three of four people who start treatment today get Incivek, a number that’s unchanged since launch.”

‘Almost Unethical’

To stoke demand, Incivo’s booth at a meeting of the European Association For the Study of the Liver in Amsterdam in April featured a video with the message, “Treat now to take your patient’s life off hold.”

Some doctors agree. The practice of delaying treatment to wait for better drugs, known as warehousing, is “irrational, and almost unethical,” said Mitchell Shiffman, a clinician who sees about 1,000 new hepatitis C patients a year at the Liver Institute of Virginia. “If a patient can be cured now, why do you want to tell them to wait?”

French doctor Pawlotsky says people with mild disease aren’t harmed by a short delay. Most of his patients want to try the new drugs by participating in clinical trials, he says.

“Obviously if we thought that the new treatments would come in something like five or six years, we would not warehouse,” he said. “But it’s a matter of months.”

Mark Thursz, the secretary-general of the European Association for the Study of the Liver, says many people he has put on experimental drugs are faring better than those using treatments now on the market.

$100,000 Treatment

“Our patients are struggling with the current regimes,” Thursz said. “The sooner we can get the new drugs licensed and in the clinic for our patients, the better.”

Gilead may charge up to $100,000 per patient for a course of sofosbuvir, according to ISI Group in New York. The drugmaker says it doesn’t comment on drug prices before they’re approved, but says the medicine can shorten treatment times to as little as 12 weeks, from as long as a year now.

Even as doctors disagree on whether to delay treatment, they’ve got one eye on the next wave of drugs. At least three are in the final stage of clinical trials and may become available within two years.

‘Therapeutic Jacuzzi’

Gilead is testing a combination of sofosbuvir with an experimental drug called ledipasvir in a cocktail that cured 100 percent of patients in a mid-stage trial presented in Amsterdam in April. AbbVie’s three-in-one combo won designation as a “breakthrough therapy” from the U.S. Food and Drug Administration on May 6, meaning it may be reviewed more quickly, after a study showed it cured 96 percent of patients after 24 weeks. Bristol-Myers Squibb’s three-in-one experimental combo won the same accelerated status just weeks earlier.

That means yet more difficult decisions about whether to treat or wait, said Dominique Larrey, a doctor at Saint-Eloi Hospital in Montpellier, France.

“I tell my students it’s like we’re in a therapeutic jacuzzi,” he said. “Each bubble is a new drug.”

--Editors: Marthe Fourcade, David Rocks.

http://washpost.bloomberg.com/Story?docId=1376-MMXTHO6VDKHT01-0A2DL7VBGE8BHO2UFP2HR2HLVT