Listen: LA County treating few people for hepatitis C

  • Wednesday, August 24, 2016
  • Posted by HCV New Drugs
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LA County treating few people for hepatitis C
Rebecca Plevin
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Health Services, which provides health care for about half a million low-income people, started dispensing these drugs a little over a year ago. As of the beginning of this month, the department had approved hepatitis C treatment for a total of 160 people; 81 have completed or begun treatment.

Compare that with the San Francisco Health Network, which serves about 65,000 people overall. It began treating patients for hepatitis C a little less than two years ago. As of late June, it had treated 631 people for hepatitis C.

Read the article or listen to the program..

The Complex Math Behind Spiraling Prescription Drug Prices

The Complex Math Behind Spiraling Prescription Drug Prices
By KATIE THOMASAUG. 24, 2016

This is an update of an article that was published earlier this year.

The soaring cost of prescription drugs has generated outrage among politicians and patients. Some cancer drugs carry price tags of more than $100,000 a year, and health plans are increasingly asking people to shoulder a greater share of the cost.

What is the controversy over drug pricing all about?
Much of the attention has focused on a handful of pharmaceutical companies that have snapped up old drugs and then aggressively raised prices, sometimes by more than 1,000 percent.

Read the article, here...



August - Recruiting and upcoming hepatitis C clinical trials

August - Recruiting and upcoming hepatitis C clinical trials 

This is not a complete list of HCV clinical trials, to find out if a study is enrolling patients in your area please click here, or here for hepatitis trials listed by state.

Learn more about drugs used to treat hepatitis C by viewing the following links;

I highly suggest you begin with this incredible new blog recently launched by HCV Advocate; HCV Medications Blog. The blog is easy to navigate with treatment information listed clearly by HCV genotype. ​In addition each month HCV Advocate puts out a newsletter with helpful articles about living with or treating the virus. An overview of approved drugs or agents still under investigation is offered as well.

Hepatitis C Cures: New Drugs and Treatment Discussed
Hepatitis C can now be cured. There are new FDA approved medicines to treat hepatitis C with over a 95% cure rate. Dr. Joseph Galati with Liver Specialists of Texas discusses the new drugs including Epclusa, Zepatier, Harvoni, Sovaldi, Viekira Pak, and Olysio.

News Updates - Epclusa
Gilead's Epclusa®  FDA approved June 28,2016 is a once-daily, fixed-dose combination of Sovaldi with velpatasvir (GS-5816) a pangenotypic NS5A inhibitor, for the treatment of genotype 1-6 chronic hepatitis C virus (HCV) infection.

Category: Epclusa

Approved Treatments for Hepatitis C

Treating HCV According To Genotype

August - Recruiting and upcoming hepatitis C clinical trials

Spain
This study is currently recruiting participants
Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination (FDC) and Sofosbuvir/Velpatasvir FDC and Ribavirin in Participants With Chronic Genotype 3 HCV Infection and Cirrhosis
Please refer to this study by its ClinicalTrials.gov identifier: NCT02781558
Contacts - Locations
Contact: Gilead Study Team 342-2097alerts@gilead.com
Condition: Hepatitis C Virus Infection
Interventions: Drug: SOF/VEL; Drug: RBV

Find Out More

Maryland
This study is currently recruiting participants
Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Subjects With Previous DAA Experience
Please refer to this study by its ClinicalTrials.gov identifier: NCT02745535
Condition: Chronic Hepatitis C
Intervention: Drug: Sofosbuvir/Velpatasvir/GS-9857
Contacts
Contact: Eleanor Wilson, MD 410-706-1710 ewilson@ihv.umaryland.edu
Contact: Jennifer Hoffmann, MSN/MPH 410-706-0294 jhoffmann@som.umaryland.edu 
Locations
United States, Maryland
Institute of Human Virology Recruiting
Baltimore, Maryland, United States, 21201

This study is not yet open for participant recruitment
Please refer to this study by its ClinicalTrials.gov identifier: NCT02783976
Contacts - Locations
Contact: 334-1685 Gilead Study Team GS-US-334-1685@gilead.com
Condition: HCV Infection Intervention: Drug: SOF Sponsor: Gilead Sciences
verified May 2016 (Source: ClinicalTrials.gov)
May 24, 2016

This study is currently recruiting participants
Sofosbuvir/Velpatasvir Fixed Dose Combination in Participants With Chronic Hepatitis C Virus Infection Who Have Received a Liver Transplant
Please refer to this study by its ClinicalTrials.gov identifier: NCT02781571
Contacts - Locations
Contact: Gilead Study Team 342-2104alerts@gilead.com
Condition: Hepatitis C Virus Infection Intervention: Drug: SOF/VEL Sponsor: Gilead Sciences

Some locations are open for participant recruitment
Please refer to this study by its ClinicalTrials.gov identifier: NCT02786537
Contacts
Contact: Gilead Study Team 342-2104alerts@gilead.com  
Condition: Chronic Hepatitis C Interventions
Drug: sofosbuvir/ledipasvir; Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: elbasvir/grazoprevir
Sponsors: University of North Carolina, Chapel Hill; Patient-Centered Outcomes Research Institute; Merck Sharp & Dohme Corp.; AbbVie - verified May 2016 (Source: ClinicalTrials.gov)

Locations
United States, Arkansas
Liver Wellness Center
Not yet recruiting
Little Rock, Arkansas, United States, 72205
Contact: Lynn Frazier, ARNP    501-687-9300    LFRAZIER@ADCLR.COM   
Principal Investigator: Alonzo Williams, MD         
United States, California
UCSD Medical Center
Not yet recruiting
San Diego, California, United States, 92103
Contact: Sharon Quigley    858-657-5147    sjquigley@ucsd.edu   
Principal Investigator: Alexander Kuo, MD         
UCSF/San Fran General Hospital
Not yet recruiting
San Francisco, California, United States, 94110
Contact: Yu-Chi Lapid       Yu-Chi.Lapid@ucsf.edu   
Principal Investigator: Mandana Khalili, MD         
Univ of California, San Francisco
Recruiting
San Francisco, California, United States, 94143
Contact: Daisy Rios    415-476-8063    daisy.rios@ucsf.edu   
Principal Investigator: Nora Terrault, MD         
United States, Connecticut
Yale University Digestive Diseases
Recruiting
New Haven, Connecticut, United States, 06520
Contact: Claudia Bertuccio    203-785-2204      
Principal Investigator: Joseph Lim, MD         
United States, District of Columbia
Georgetown University
Recruiting
Washington, District of Columbia, United States, 20007
Contact: Erica Christian       erica.christian@gunet.georgetown.edu   
Principal Investigator: Coleman Smith, MD         
United States, Florida
University of Florida
Recruiting
Gainesville, Florida, United States, 32610-0272
Contact: Patrick Horne, ARNP    352-273-9500    PATRICK.HORNE@MEDICINE.UFL.EDU   
Contact: Briana Foerman, BS    352-294-5152    briana.foerman@medicine.ufl.edu   
Principal Investigator: Giuseppe Morelli, M.D.         
University of Florida, Jacksonville
Recruiting
Jacksonville, Florida, United States, 32209
Contact: Kelly Jackman, PHD    904-633-0070    kelly.jackman@jax.ufl.edu   
Principal Investigator: Miguel Malespin, MD         
University of Miami/Schiff Center for Liver Diseases
Recruiting
Miami, Florida, United States, 33136
Contact: Eva Pavicic       epavicic@med.miami.edu   
Contact: Maria Onate-Silva       mlourdeso@med.miami.edu   
Principal Investigator: Eugene Schiff         
Orlando Immunology Center
Recruiting
Orlando, Florida, United States, 32803
Contact: Jeff Dinsmore    407-409-7125    jdinsmore@oicorlando.com   
Principal Investigator: Federico Hinestrosa, MD         
United States, Georgia
Internal Medicine Associates of Wellstar Atlanta Medical Center
Recruiting
Atlanta, Georgia, United States, 30312
Contact: Howard Brown    404-265-4194    dyardmon3@gmail.com   
Principal Investigator: Brian Pearlman, MD         
United States, Illinois
Northwestern University
Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Sara Lescano    312-694-0243    sara.lake@northwestern.edu   
Principal Investigator: Josh Levitsky, MD         
United States, Indiana
Indiana University Medical Center
Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Martha Mendez, RN    317-278-4633    mwmendez@iupui.edu   
Principal Investigator: Paul Kwo, MD         
United States, Maryland
John Hopkins University
Recruiting
Lutherville, Maryland, United States, 21093
Contact: Stephanie Katz, MSN,RN    443-287-9605    SSNEDDO2@JHMI.EDU   
Contact: Stacey Reese    410-955-9944    SREESE2@JHMI.EDU   
Sub-Investigator: Mark Sulkowski, MD         
Principal Investigator: Juhi Moon, MD         
United States, Michigan
University of Michigan
Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Diane White, CCRP    734-763-6647    dfwhite@umich.edu   
Principal Investigator: Anna SF Lok, MD         
United States, Minnesota
University of Minnesota
Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Stacy Valenzuela    612-624-9926      
Principal Investigator: Mohamed Hassan, MD         
United States, Missouri
Saint Louis University
Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Kristina L Wriston, RN    314-977-9400    KWRISTON@SLU.EDU   
Contact: Caroline Vemulapalli-Forrest       cvemulap@slu.edu   
Principal Investigator: Adrian DiBisceglie, MD         
United States, Nebraska
University of Nebraska Medical Ctr
Recruiting
Omaha, Nebraska, United States, 68198
Contact: Beth Kos, BSN    402-559-3652    MEKOS@UNMC.EDU   
Principal Investigator: Mark Mailliard, MD         
United States, New Mexico
Southwest CARE Center
Recruiting
Santa Fe, New Mexico, United States, 87505
Contact: Joanna Pierce       jpierce@southwestcare.org   
Contact: Christopher Gallegos       cgallegos@southwestcare.org   
Principal Investigator: Joel N Gallant, MD         
United States, New York
Weill Cornell Medical College
Recruiting
New York, New York, United States, 10021
Contact: Marlene Feron-Rigodon, RN    646-962-2085    maf2062@med.cornell.edu   
Principal Investigator: Robert Brown, MD         
Columbia University Medical Center
Recruiting
New York, New York, United States, 10032
Contact: Jennie Chavis    212-305-3839    jc4380@cumc.columbia.edu   
Principal Investigator: Elizabeth Verna, MD         
Mountain View Medical Center
Recruiting
Valatie, New York, United States, 12184
Contact: Ananth Ramani    518-943-1943    ramani489@yahoo.com   
Principal Investigator: Anathakrishnan Ramani, MD         
United States, North Carolina
University of North Carolina at Chapel Hill
Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Tiffany Pritchett, B.A.       tpritch@med.unc.edu   
Contact: Renee Blanchard    919-843-5936    renee_blanchard@med.unc.edu   
Principal Investigator: Michael W. Fried, M.D         
Duke University Medical Center
Recruiting
Durham, North Carolina, United States, 27710
Contact: Loranda Ross    919-681-2941    loranda.ross@duke.edu   
Principal Investigator: Andrew Muir, MD         
United States, Ohio
University of Cincinnati
Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Liz Stambrook, BSN    513-584-2363    LIZ.STAMBROOK@UCHEALTH.COM   
Contact: Diane Daria       dariade@ucmail.uc.edu   
Principal Investigator: Kenneth Sherman, MD         
United States, Pennsylvania
University of Pennsylvania
Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kelly Borges    215-615-3755    kelly.borges@uphs.upenn.edu   
Principal Investigator: Rajender Reddy, MD         
United States, Texas
Research Specialist of Texas
Recruiting
Houston, Texas, United States, 77030
Contact: Christina McNeil    713-634-5110    cmcneil@texasliver.com   
Contact: Wilma Regalado       wregalado@texasliver.com   
Principal Investigator: Joseph Galati, MD         
United States, Virginia
Bon Secours St. Mary 's Hospital of Richmond (Liver Institute of Virginia)
Recruiting
Richmond, Virginia, United States, 23226
Contact: Susan Vollum, RN, CRC    804-977-8921    susan_vollum@bshsi.org   
Principal Investigator: Mitchell L. Shiffman, MD         

Please refer to this study by its ClinicalTrials.gov identifier: NCT02581189
Contacts
Contact: Nabil Ackad, MD 514-832-7439 nabil.ackad@abbvie.com
Contact: Catherine Pinsonnault, BS 514-832-7015 catherine.pinsonnault@abbvie.com
Locations
Canada

Condition: Chronic Hepatitis C
Intervention:

Japan
This study is currently recruiting participants
Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Participants With Chronic HCV
Please refer to this study by its ClinicalTrials.gov identifier: NCT02671500
Condition: Hepatitis C Virus Infection
Intervention: Drug: SOF/VEL
Locations
Malaysia

University of Malaya Recruiting
Kuala Lumpur, Malaysia, 59100
Hospital Tengku Ampuan Afzan Recruiting
Pahang, Malaysia, 25100
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119074
Singapore General Hospital Recruiting
Singapore, Singapore, 169608

This study is currently recruiting participants
Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Participants With Chronic Genotype 2 HCV Infection
Please refer to this study by its ClinicalTrials.gov identifier: NCT02738333
Locations -  Japan
Contacts
Contact: Gilead Study Team GS-US-337-1903@gilead.com
Condition: Hepatitis C Virus Infection
Interventions: Drug: LDV/SOF; Drug: SOF; Drug: RBV  

This study is currently recruiting participants
Please refer to this study by its ClinicalTrials.gov identifier: NCT02615145
Locations
Germany
Condition: Chronic Hepatitis C

This study is currently recruiting participants
Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Hungary - VERITAS
Please refer to this study by its ClinicalTrials.gov identifier: NCT02636608
Locations
Hungary
Condition: Chronic Hepatitis C

This study is currently recruiting participants
Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study
Please refer to this study by its ClinicalTrials.gov identifier: NCT02798315
Locations
Kuwait
Condition: Chronic Hepatitis C

This study is currently recruiting participants
The Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in France
Please refer to this study by its ClinicalTrials.gov identifier: NCT02618928
Locations
France
Condition: Chronic Hepatitis C

Elderly patients with chronic hepatitis C: Efficacy and safety of direct acting antiviral treatment and clinical significance of drug–drug interactions

The efficacy and safety of direct acting antiviral treatment and clinical significance of drug–drug interactions in elderly patients with chronic hepatitis C virus infection


Vermehren, K.-H. Peiffer, C. Welsch, G. Grammatikos, M.-W. Welker, N. Weiler, S. Zeuzem, T. M. Welzel, C. Sarrazin
First published: 23 August 2016
Full publication history DOI: 10.1111/apt.13769

Summary
Background
Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy.

AimTo investigate the efficacy, tolerability and potential for drug–drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort.

MethodsA total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged ≥65 years (n = 137) of whom 41 patients were ≥75 years.

ResultsSustained virological response rates were 98% and 91% in patients aged ≥65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients ≥65 years with cirrhosis (median, three per patient; range, 0–10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.).

ConclusionsElderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.

Introduction
Chronic infection with the hepatitis C virus (HCV) is a major health burden worldwide and approximately 500 000 people die each year from HCV related liver diseases.[1]
According to estimates by the Centers for Disease Control (CDC), elderly persons are disproportionally affected by HCV and despite the recent approval of highly efficient direct antiviral agents (DAAs) the rates of cirrhosis and hepatocellular carcinoma are predicted to rise in the near future.[2]

Age has been a major limitation of interferon-based treatment, mainly due to increasing prevalence of comorbidity, poor tolerability and overall reduced efficacy in this population.[3] Patients aged 65 years and older were mostly excluded from clinical trials while large-scale real-world database studies showed lower sustained virological response rates and higher withdrawal rates due to side effects in this patient population.[4]

With the recent approval of all-oral DAAs, treatment access has expanded to interferon ineligible/intolerant patient populations, including persons of older age. However, despite the overall excellent tolerability of interferon-free DAA combination therapies, elderly patients, especially those aged 75 years and older were again excluded from most clinical trials.[5-8] In a recent retrospective analysis of four phase 3 trials of the HCV NS5A inhibitor ledipasvir plus the HCV polymerase inhibitor sofosbuvir in patients with HCV genotype 1 infection, only 24/2293 (1%) of the study population were aged 75 or older.[9]

Given the fact that current HCV treatment regimens are both more efficient and better tolerated than interferon-based therapies, the number of elderly patients who will receive anti-HCV treatments is likely to increase. Whether the increased prevalence of comorbidity and concurrent medications in elderly patients is associated with higher rates of adverse events and/or treatment failure is not known. Moreover, the use of ribavirin in these patients may pose a greater risk for associated side effects such as cough, rash and haemolytic anaemia.[10]

In this study, we aimed to assess the efficacy and safety of DAA regimens as well as the clinical significance of potential drug–drug interactions with concomitant medications in patients aged ≥65 years (including subgroup analysis of patients ≥75 years) in a large real-world cohort.

Methods
Study cohortConsecutive patients who presented to our outpatient clinic for treatment of chronic HCV infection after the approval of sofosbuvir (January 2014) until September 2015 were included in the analysis. Patients with HIV and/or HBV co-infection and patients with previous solid organ transplantation (kidney, liver, pancreas) were excluded. Patients who received pegylated interferon as part of their treatment regimen and those who received DAA combinations that are currently no longer recommended (e.g. sofosbuvir and ribavirin in HCV genotype 1) were also excluded.

Thus, all patients received one of the following five regimens: (i) sofosbuvir (SOF; nucleoside NS5B polymerase inhibitor) and ledipasvir (LDV; NS5A inhibitor) ± ribavirin (RBV) in genotypes 1, and 4–6, (ii) SOF and daclatasvir (DCV; NS5A inhibitor) ± RBV in genotypes 1 and 3, (iii) paritaprevir/ritonavir (PTV; ritonavir boosted protease inhibitor), ombitasvir (OBV; NS5A inhibitor) and dasabuvir (DSV; non-nucleoside NS5B polymerase inhibitor) ± RBV in genotype 1 (3D regimen), (iv) SOF and simeprevir (SMV; NS3 protease inhibitor) ± RBV in genotype 1 and (v) SOF + RBV in genotypes 2 and 3. RBV was administered based on current guideline recommendations.[11, 12] RBV dose adjustments were done according to the label recommendations.

Assessment of baseline and treatment-related patient parametersDemographic baseline parameters, concomitant medications, laboratory tests as well as safety and efficacy data were retrospectively and anonymously analysed from electronic hospital charts. Efficacy was assessed at 12 weeks after the end of treatment. A sustained virologic response (SVR) was defined as negative HCV RNA at this time point.

Definition of old age Patients of old age were defined as being 65 years and older. This population can be divided into the young-old (ages 65–74), the old-old (ages 75–84), and the oldest-old (85 years and older) as previously described.[13]

Baseline and efficacy data as well as safety and clinical significance of drug–drug interactions were assessed in patients aged 65 years and older. Comparisons were made between groups of patients aged ≥65 years and <65 years. Subgroup analyses were performed for patients aged 75 years and older (old-old and oldest-old combined). No subgroup analysis was performed for the only patient aged 86 years.

Assessment of drug–drug interactions (DDIs) and treatment modificationsA web-based tool developed by the University of Liverpool (available at www.hep-druginteractions.org) was used for risk assessment of potential drug–drug interactions (DDIs) based on patients concomitant medications and the respective antiviral regimen. The DDI database is free for use. Interactions can be assessed by first choosing one or more DAAs from a context menu followed by choosing one or more combination drugs or drug classes. A summary of results and detailed descriptions are displayed hereafter. In addition, the respective prescribing information was also used (as of January 2016).

Potential DDIs were assigned to distinct risk categories according to the predicted level of significance (based on hep-druginteractions.org nomenclature); that is, 0 = interaction has not been assessed; 1 = no clinically significant interaction expected; 2 = potential interaction that may require close monitoring, alteration of drug dosage or timing of administration; 3 = co-administration either not recommended or contraindicated. Thus, category 2 and 3 DDIs were considered clinically significant. Outpatient medications with category 3 DDIs were either stopped prior to antiviral therapy or a different DAA regimen was chosen.

In patients taking medications with category 2 DDIs, the respective drugs were either stopped, dose-modified or closely monitored, as previously recommended.[14]

Calculation of glomerular filtration rateThe Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used for estimating the glomerular filtration rate (GFR) in this study. The CKD-EPI equation uses a 2-slope ‘spline’ to model the relationship between GFR and serum creatinine, age, sex and race.[15]

Assessment of ribavirin-induced haemolytic anaemiaThe occurrence of RBV induced haemolytic anaemia was assessed at treatment weeks 2, 4, 8 and 12 relative to the baseline haemoglobin level.
Significant anaemia was defined as an absolute decline in haemoglobin levels <10 g/dL and/or a decline of greater than 3 g/dL. Ribavirin dose reductions were made according to the manufacturer's recommendations and no erythropoetin was used in this study.

Statistics
All statistical analyses were performed using GraphPad Prism version 5 for Mac (La Jolla, CA, USA). Descriptive statistics are shown as mean ± s.d. or median and range. Comparisons between groups were made using parametric t-tests or nonparametric Mann–Whitney U-tests, where appropriate. P < 0.05 were considered statistically significant.

Ethics
The study was conducted according to the declaration of Helsinki. The ethics committee of the University Hospital Frankfurt approved the retrospective analysis of anonymous patient data.

Results
Baseline characteristics
A total of 541 patients treated with all-oral DAA combination regimens were included in this study. One hundred and thirty-seven subjects were aged 65 years and older. Of these, 96 were aged 65–74 years, 40 were aged 75–84 years and one patient was 86 years old at the start of antiviral therapy.

Among patients aged ≥65 years, the mean age was 71 years (range, 65–86 years), 47% were men (n = 66/137), genotype 1b was the predominant HCV subtype (n = 84/137; 61%) and 47% (n = 64/137) had cirrhosis. The majority (n = 76/137; 56%) of patients aged ≥65 years had failed a prior course of interferon-based therapy. Baseline characteristics of the total study population according to age groups are shown in Table 1.

Table 1. Demographic and clinical characteristics of the study cohort (n = 541)

<65 years n = 404≥65 years n = 13765–74 years n = 96≥75 years n = 41
  1. eGFR, estimated glomerular filtration rate; SD, standard deviation.
  2. a Treatment experienced = nonresponse or relapse to prior peg-Interferon/ribavirin therapy.
Mean age (range)51 (18–64)72 (65–86)69 (65–74)78 (75–86)
Male gender, n (%)252 (62)64 (47)46 (48)18 (44)
HCV Genotypea, n (%)
1a124 (31)36 (26)26 (27)10 (24)
1b171 (42)84 (61)58 (61)26 (64)
2/383 (21)15 (11)10 (10)5 (12)
Other26 (6)2 (2)2 (2)
Cirrhosis, n (%)157 (39)64 (47)40 (42)24 (59)
Treatment experienced, n (%)a229 (57)76 (55)55 (57)21 (51)
Mean HCV RNA [log10] (SD)6.0 (0.8)6.1 (0.6)6.1 (0.7)6.1 (0.5)
Mean eGFR [mL/min] (SD)97.5 (16.7)76.5 (17.4)78.9 (17.3)70.3 (16.5)
Mean haemoglobin [g/dL] female/male (SD)14.8 (1.8)/13.7 (1.3)13.4 (1.6)/14 (1.9)13.9 (1.9)/13.5 (1.4)13.1 (1.8)/14.2 (2.0)

Treatment regimens and efficacy
The distribution of treatment regimens across the different age groups is shown in Table 2.
Table 2. Treatment regimens according to age groups (patients aged 65 years and older are subdivided into patients aged 65–74 years and patients aged 75 years and older)

Treatment regimen, n (%)<65 years (n = 404)≥65 years (n = 137)65–74 years (n = 96)≥75 years (n = 41)
  1. SOF, sofosbuvir; LDV, ledipasvir; RBV, ribavirin; DCV, daclatasvir; PTV, paritraprevir; OBV, ombitasvir; DSV, dasabuvir; SMV, simeprevir.
SOF/LDV ±RBV185 (46)68 (50)48 (50)20 (48)
SOF +DCV ±RBV75 (19)21 (15)12 (13)9 (22)
PTV/OBV ±DSV ±RBV57 (14)22 (15)18 (19)4 (10)
SOF +SMV ±RBV46 (11)13 (10)9 (9)4 (10)
SOF +RBV40 (10)13 (10)9 (9)4 (10)

Overall, SVR was achieved by 98% (n = 134/137) of patients aged 65 years and older. There was no virological treatment failure in patients who received at least 80% of the intended treatment duration and the SVR rate in these patients was 100% (n = 134/134).

Two patients stopped treatment prematurely and one patient died during treatment and the cause of death was considered unrelated to the antiviral treatment (see below). Two patients aged ≥65 years discontinued treatment prematurely: One GT1b patient treated with LDV/SOF discontinued all medications after 2 weeks due to acute kidney injury, and one GT1b patient treated with PTV/OBV +DSV +RBV discontinued all medications after 1 week due to grade 3 hyperbilirubinaemia. This patient was later diagnosed with gilbert's syndrome, which most likely explains the unusually high PTV-associated hyperbilirubinaemia. Both patients had positive HCV RNA during follow-up. One patient died during the treatment period. The cause of death (multi-organ failure following haemorrhagic shock after femoral arterial catheterisation) was considered unrelated to the DAA therapy.

SVR was observed in 91% (n = 369/404) of patients <65 years. A total of 21 patients experienced virological relapse or nonresponse. Two patients stopped treatment prematurely: One patient discontinued treatment because of worsening of pre-existing depression after 6 weeks and one patient discontinued treatment after 4 weeks because of debilitating fatigue. Eleven patients were lost to follow-up during or after antiviral therapy. One patient died during the treatment period. The cause of death (multi-organ failure following haemorrhagic shock after variceal bleeding) was considered unrelated to the DAA therapy.

If only patients <65 years of age with known virological outcome and who received at least 80% of the intended treatment duration were considered, the SVR rate was 95% (n = 369/390; see Figures 1 and 2 for an overview of SVR rates according to genotypes, age and treatment regimen).


Figure 1. SVR rates in patients with HCV genotype 1/4 infection (n = 430) according to treatment regimen and age groups. Only patients who completed ≥80% of the intended treatment duration and who had a known virological outcome are included. Treatment regimens included the following: ledipasvir/sofosbuvir ±ribavirin (LDV/SOF±RBV), daclatasvir +sofosbuvir ±ribavirin (DCV+SOF±RBV), paritaprevir/r/ombitasvir±dasabuvir ±ribavirin (PTV/OBV±DSV±RBV) and simeprevir +sofosbuvir ±ribavirin (SMV+SOF±RBV). SVR data are shown for patients <65 years vs. patients ≥65 years of age. In addition, a subgroup analysis is shown for patients ≥75 years of age.



Figure 2.
SVR rates in patients with HCV genotype 3 infection (n = 57) according to treatment regimen and age groups. Only patients who completed ≥80% of the intended treatment duration and who had a known virological outcome are included. Treatment regimens included the following: daclatasvir +sofosbuvir ±ribavirin (DCV+SOF±RBV), ledipasvir/sofosbuvir ±ribavirin (LDV/SOF ±RBV), and sofosbuvir +ribavirin (SOF+RBV). SVR data are shown for patients <65 years vs. patients ≥65 years of age. In addition, a subgroup analysis is shown for patients ≥75 years of age. **no patients aged 65 years and older were treated with LDV/SOF or SOF+RBV.

All genotypes and treatment regimens were affected by virological failure: LDV/SOF ± RBV (n = 4), SOF and DCV ± RBV (n = 6), PTV/OBV + DSV (n = 2), SOF and SMV ± RBV (n = 6) and SOF + RBV (n = 3).

Frequencies of concomitant medications

A total of 152 different concomitant medications were taken by the patients in our study cohort (n = 81 in patients ≥65 years). The most common drug classes that were taken by >5% of the study cohort included proton pump inhibitors (10%), nonselective beta-blocking agents (9%), thyroid hormones (8%), loop diuretics (8%), angiotensin-converting enzyme inhibitors (8%), vitamin D supplements (7%), selective beta-blocking agents (6%) and insulin preparations (5%).

Overall, the number of patients who took concomitant medications was significantly higher in patients aged ≥65 years compared to <65 years (79% vs. 51%; P < 0.0001). Furthermore, the number of patients who took 4 or more regular concomitant medications was significantly higher in patients ≥65 years compared to <65 years (34% vs. 17%; P < 0.0001).

In patients <65 years, the median number of drugs per patient was 1 (range, 0–12). In patients ≥65 years, the median number of drugs per patient was 2 (range, 0–10). In patients ≥75 years vs. 65–74 years, the number of drugs per patients was not different.

The median number of drugs per patient was increased in patients ≥65 years who also had cirrhosis (3; range, 0–10). In cirrhotic patients ≥75 years, the median number of drugs was higher compared to patients without cirrhosis (median no. of drugs, 3 vs. 2).
Potential for drug–drug interactions between DAAs and concomitant medications

Based on DDI risk classification from the hep-druginteractions.org database, category 2/3 DDIs were predicted for 35% (n = 189/541) of the total study population (60% of patients with concomitant medications).

The proportion of predicted category 2/3 DDIs was significantly higher in patients ≥65 years compared to patients <65 years (54% vs. 28%; P < 0.0001). There was no difference in category 2/3 DDIs between patients aged 65–74 years vs. ≥75 years (55% vs. 51%; P = N.S.). The frequencies of potentially clinically significant DDIs (category 2/3) according to age and DAA regimen are shown in Figure 3.


Figure 3.
Frequencies of predicted clinically significant drug–drug interactions (defined as category 2/3 interactions according to the hep-druginteractions.org database) between concomitant medications and antiviral therapy according to treatment regimen and age groups (n = 541). All listed patients had ≥1 drug of concomitant medications predicted to cause DDIs.

For patients treated with LDV/SOF±RBV, the most common concomitant drug classes involved in potentially significant DDIs (DDI category 2/3) were beta-blocking agents in 16% (n = 30/185) and 34% (n = 23/68) and proton pump inhibitors in 11% (n = 21/185) and 25% (n = 16/68) of patients <65 and ≥65 years of age respectively. For patients treated with DCV+SOF±RBV, the most common concomitant medications at risk for significant interactions were beta-blocking agents in 19% (n = 14/75) and 29% (n = 6/21) and thyroid hormones in 11% (n = 8/75) and 24% (n = 5/21) of patients <65 and ≥65 years of age respectively. For patients treated with PTV/OBV±DSV±RBV, significant interactions were primarily expected for thyroid hormones in 12% (n = 7/57) and 45% (n = 10/21) and alfa- and beta-blocking agents in 14% (n = 8/57) and 23% (n = 5/22) of patients <65 and ≥65 years of age respectively. Finally, for SMV-containing regimens, the most common drug classes at risk for clinically significant interactions were beta-blocking agents in 13% (n = 6/46) of patients <65 years and statins that were co-administered in 15% (n = 2/13) of patients ≥65 years of age.

The most common concomitant medications with potential category 2/3 DDIs and respective action taken before and during antiviral therapy to avoid such DDIs are shown in Table 3.
Table 3. Description of potential drug–drug interactions (DDIs) with commonly used co-medications in patients with chronic HCV infection. The colour scheme represents a traffic light labelling system to highlight the signficance level of expected DDIs according to the hep-druginteractions.org website: green = no DDI expected; amber = potential DDI expected; red = co-administration not recommended/contraindicated. Suggested actions that should be taken to avoid DDI-related adverse events are also given



Safety and adverse events
The occurrence of adverse events was documented in 77% (n = 417/541) of patients. A total of 63% (n = 264/417) patients experienced at least one adverse event during the treatment period. Adverse events were generally mild and the number of adverse events was not significantly different between patients <65 years and patients ≥65 years respectively (63% vs. 65%; P = N.S.). We observed no significant increase in adverse events potentially related to DDIs (e.g. dizziness, bradycardia or GI disturbances in patients with concomitant carvedilol treatment; TSH changes in patients treated with levothyroxine).

The most common adverse events were fatigue (35% and 37%), dyspnoea (11% and 15%; only patients on RBV treatment affected), headache (22% and 11%), pruritus (7% and 10%), rash (7% and 2%) and insomnia (6% and 7%) in patients <65 and ≥65 years of age respectively.
Estimated glomerular filtration rate (eGFR)

At baseline, the eGFR (CKD-EPI) was 97.5 mL/min for patients <65 and 76.5 mL/min for ≥65 years of age (P < 0.0001). The eGFR in patients between 65 and 74 years was 78.9 mL/min and 70.3 mL/min in patients ≥75 years of age (P = 0.0038). For all age groups and treatment regimens with and without SOF, eGFR values showed no significant changes over the course of antiviral treatment (P = N.S.).

Ribavirin-induced anaemia
RBV was co-administered in 42% (n = 168/404), 43% (n = 59/137) and 49% (n = 20/41) of patients <65 years, ≥65 years and ≥75 years of age respectively. Significant anaemia occurred in 34% (n = 20/59) and 35% (n = 7/20) of ≥65 years and ≥75 years of age respectively.

The rates of patients aged ≥65 years who experienced at least one adverse event (any event) were 68% (n = 40/59) and 32% (n = 25/78) with and without RBV respectively. In patients aged ≥75 years, these rates were 70% (n = 14/20) and 38% (n = 8/21) with and without RBV respectively. Side effects typically associated with RBV use, including haemolytic anaemia, skin rash and cough were observed in 42% (n = 25/59) and 55% (n = 11/21) of patients ≥65 years and ≥75 years of age respectively.

Discussion
Until recently, treatment options in elderly patients with chronic HCV infection were limited, mainly due to contraindications and side effects associated with IFN-based therapies.[3] Moreover, lower SVR rates and higher rates of treatment discontinuation were reported.[4, 16-18] The recent approval of highly effective IFN-free regimens has led to a paradigm change with improved options for difficult-to-cure patients, including those of older age.[19] Interestingly, despite improved safety profiles of all-oral DAA treatments, elderly patients were once again excluded from most clinical trials. Despite this, a recent retrospective analysis of the LDV/SOF approval trials showed high SVR rates in patients ≥65 years of age.[9] However, older patients represented a mere 12% of the total study population and the proportion of patients aged 75 years and older was only 1% (n = 24).

In our retrospective study, we included a large proportion of elderly patients (25%). The different combinations of all-oral DAA therapies showed comparable efficacy in patients aged ≥65 years and younger patients. Moreover, when specifically looking at genotype 1 patients treated with the currently most widely used regimens (LDV/SOF ±RBV or PTV/OBV +DSV ±RBV), SVR rates exceeded 95% in both age cohorts, and this was also true in the subgroup of patients ≥75 years of age. While DAA treatment seems to be feasible in virtually all patients regardless of age and comorbidities, the question arises whether old patients should always be considered for antiviral therapy. On the one hand, progression to cirrhosis has been shown to be an age-dependent process.[20] However, given the high costs of current DAA regimens, treatment priority should clearly be given to patients with advanced liver disease whereas treatment is not recommended in patients with limited life expectancy.[12] Obviously, the decision to treat elderly patients or not is greatly influenced by local guidelines and/or reimbursement policies as well as societal considerations. On the other hand, if cirrhosis is not present in elderly patients despite a long history of HCV infection, progression to cirrhosis may never occur. In our study, 41% of patients aged 75 and older had no cirrhosis at the time of DAA treatment. Thus, prevention of fibrosis progression was not the main driver for treatment initiation in these patients. Indeed, only a mild disease progression has been observed in several studies, particularly in women, despite a long history of HCV infection.[21, 22] However, despite this favourable course of disease, high levels of psychological distress and impaired quality of life due to debilitating fatigue may still be present in many of these patients.[21] Presence of such factors and other extrahepatic manifestations which have been shown to increase with age[23] may justify the decision to treat older patients, even in case advanced liver disease is not present. This is supported by recent data that suggest that DAA therapies are associated with significantly improved patient-reported outcomes and even favourable short-term health economic outcomes.[24, 25]

While more and more patients are being treated for HCV infection outside of clinical trials, the risk for potentially serious DDIs is increasing.[14] In our study, older patients took significantly more concomitant medications, which reflects the increasing morbidity in the ageing HCV population.[26] Moreover, our study showed that the number of drugs taken by an individual patient was highest in patients aged 65 and older who also had cirrhosis. This may be attributable to the particularly high number of cardiovascular drugs and diuretics in this population.

Management of potential DDIs had become particularly important after the approval of the first-generation protease inhibitors telaprevir and boceprevir which are strong inhibitors and substrates of the P-glycoprotein (P-gp) and cytochrome P450 3A4.[27, 28] This led to a greater awareness of potential DDIs in patients treated for HCV infection. Consequently, a DDI website was launched by the University of Liverpool in 2010 that provides a comprehensive DDI database (www.hep-druginteractions.org) that is free for use.

Currently recommended DAAs still show some interactions with P-gp and cytochrome P450 enzymes, albeit only to a much lesser extent than telaprevir and boceprevir.[27]

Our study had a high proportion of patients taking concomitant medications that could potentially lead to significant DDIs during antiviral therapy. The predicted proportion of potentially significant DDIs was particularly high in elderly patients. More than half of elderly patients were predicted to have significant DDIs. Interestingly, all DAA regimens were affected by potentially significant DDIs. In elderly patients, the risk was highest in patients treated with DCV and SOF whereas similar frequencies of potential DDIs were predicted for patients treated with LDV/SOF and the OBV/PTV+DSV regimen.

Proton pump inhibitors (PPIs) have recently been associated with a higher risk of virological failure in patients treated with LDV/SOF.[29] The negative impact of PPIs, however, does not seem to derive from true DDIs but changes in drug absorption.[30] Simultaneous administration of PPIs resulted in only slightly decreased LDV AUC and Cmax that were not judged to be clinically relevant. In contrast, co-administration of PPIs and PTV/ritonavir significantly decreased omeprazole AUC and Cmax due to induction of CYP2C19 by ritonavir which may lead to decreased PPI efficacy.[31]

In our study, actions were taken to reduce the impact of potentially significant DDIs as previously proposed.[14] However, for many concomitant medications, no reliable prediction for potential DDIs is available because of the lack of clinical data. Here, potential DDIs are predicted based upon metabolic pathway interactions. This emphasises the need for comprehensive pharmacovigilance networks to meet the challenges of treating elderly and/or multimorbid patients.

In our study, no significant adverse events attributable to DDIs were noted. Indeed, despite the higher number of drugs taken and the higher frequency of predicted DDIs in elderly patients, the number of adverse events was not different between the two age groups. This may again be attributable to the meticulous DDI assessment before treatment initiation and careful monitoring thereafter. In addition, although the use of RBV increased the number of adverse events particularly in elderly patients, significant anaemia was not higher than in younger patients.

Our study has several limitations, including the retrospective design and the heterogeneous number of treatment regimens. However, this is currently the largest real-world DAA experience among elderly patients that also assesses the potential clinical impact of DDIs.

In conclusion, our study shows that all approved IFN-free DAA regimens are highly effective in elderly patients, especially those aged 75 years and older, while concomitant drugs pose a risk for potentially serious DDIs. Use of a free accessible Internet-database and careful management during therapy can effectively prevent DDI-associated adverse events and treatment failure.

Authorship
Guarantor of the article: JV.
Author contributions: JV, CW and CS contributed to the study design and concept. All authors contributed to the acquisition of data and reviewed versions of the manuscript and provided critical comments. JV interpreted the data and drafted the manuscript.

All authors approved the final version of the manuscript.
Acknowledgements

Declaration of personal interests: JV served as a speaker and/or consultant for Abbott, AbbVie, Bristol-Myers Squibb, Medtronic and Gilead. MWW served as a speaker and/or consultant for Amgen, Bayer, Bristol-Myers Squibb, Gilead, Novartis and Roche. SZ served as a speaker and/or consultant for AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck. TMW served as a speaker and/or consultant for AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim and Janssen. CS served as a speaker and/or consultant for Abbott, AbbVie, Achillion, Bristol-Myers Squibb, Gilead, Janssen, Merck, Qiagen, Roche and Siemens. He also received research grants from Abbott, Gilead, Janssen, Qiagen, Roche and Siemens. All other authors declare that they have no competing interests.

Declaration of funding interests: None.

Exercise Could Save Your Liver

Exercise Could Save Your Liver

Posted on August 23, 2016 by Ruth Kava

It’s pretty widely known that chronic over-indulgence in alcoholic beverages can play havoc with one’s liver — in extreme cases ending up with cirrhosis and a non-functioning organ. But non-drinkers can also have liver problems. In particular, there is one called non-alcoholic fatty liver disease, or NAFLD, which is a risk factor for chronic liver disease and cardiovascular disease, according to the authors of a recent report  in JAMA Internal Medicine. NAFLD is a condition in which triglycerides (fats) accumulate within liver cells. If the accumulation is extensive enough it can trigger inflammation and a condition known as steatosis, which can then progress to irreversible cirrhosis.

The authors of the report conducted a randomized clinical trial to investigate the effects of different levels of exercise on NAFLD in obese Chinese adults. Led by Dr. Hui-Jie Zhang from the First Affiliated Hospital of Xiamen University, Xiamen, China, they randomly assigned 220 adults (40-65 years of age) with  abdominal obesity and NAFLD – documented by MRI – to one of three exercise conditions. They were particularly interested in ascertaining whether vigorous versus moderate exercise differently affect NAFLD. The three groups were:

  • VM: vigorous exercise for 6 months followed by moderate exercise for 6 months.
  • M: moderate exercise for 12 months
  • C: control — no exercise program.
Participants in the VM group jogged on a treadmill for 30 minutes, 5 days per week, at an intensity equal to 65-80 percent of maximum predicted heart rate. After 6 months, they switched to a moderate level of activity. At this level they walked briskly (about 120 steps per minute) for 30 minutes, 5 days per week. This was about 45-55 percent of maximum heart rate. The M group did the moderate level of activity for the entire 12 months of the study. The C group was asked not to change their activity level. And all three groups were instructed not to change their customary dietary intake.
The primary outcome of the trial was the change in intra-hepatic triglyceride content, or IHTG between the start of the study and at 6 and 12 months. The investigators found that at 6 months, both the VM and M groups IHTG contents were significantly lower than those of the C group. By 12 months, although the differences were smaller, they were still significantly less than the C group. The two exercise groups’ IHTG were not significantly different.

The body weight, waist circumference and blood pressure were significantly lower in the VM group than the M and C groups at 6 months; at 12 months they both differed from the C group but not from each other.  However, when the researchers controlled for weight loss, the differences in IHTG were no longer significant between the exercise and control groups. Thus, the authors concluded “Vigorous and moderate exercise were equally effective in reducing intra-hepatic triglyceride content; the effect appeared to be largely mediated by weight loss.”

One must note that the extent to which these results can be generalized to non-Asian populations isn’t known — there are different cut points for obesity in Asian populations which don’t apply, for example, to Western populations. Thus the effects of exercise on the liver might well be different. However, considering the benefits of exercise for a number of health-related endpoints, there hardly seems to be anything to lose in trying to replicate these levels of exercise.

About Ruth Kava
Dr. Ruth Kava is Senior Nutrition Fellow at the American Council on Science and Health. -
View all posts by Ruth Kava

This entry was posted in Disease, Medicine and Pharmaceuticals, News and Views and tagged exercise, NAFLD, non-alcoholic fatty liver disease, obesity.

http://acsh.org/news/2016/08/23/exercise-could-save-your-liver/


Link To: The Current treatment recommendations in HCV liver transplant recipients

Current treatment recommendations in HCV liver transplant recipients

Hello everyone, today I hope to offer a bit of information to all those brave people waiting for a liver transplant. You may wish to either file the information away for future reference or pass it along.  

The Good News

Interferon-free treatments are showing promise for treatment of hepatitis C after liver transplantation, with high SVR rates and few drug related adverse effects, it is nothing short of a miracle. 

We start with an article about treating recurrent HCV, or treating HCV after liver transplantation.

The Research

In the May issue of Current Opinion in Gastroenterology, Paul Y Kwo, M.D., reported on five effective all oral  therapies for patients who develop recurrent HCV after liver transplantation; Sovaldi, Harvoni, Daklinza, Olysio, and Viekira Pak    

The article is available online for free over at Medscape, here is a summary:
Historically, postliver transplant patients with chronic hepatitis C have had worse outcomes than nonhepatitis C-related causes because of accelerated fibrosis posttransplantation and the lack of effective well tolerated therapies for hepatitis C, and posttransplant hepatitis C patients have been considered a special population. Since 2013, we have entered the era of all oral direct acting antiviral agents for hepatitis C with sustained response rates that are consistently above 90% in nontransplant patients.

Recent findings: The introduction of direct acting antiviral agents to posttransplant patients has demonstrated that sustained virologic response rates that are comparable with nontransplant patients can be achieved with excellent tolerability. The combinations of (Sovaldi) sofosbuvir/ribavirin, (Harvoni) ledipasvir/sofosbuvir/ribavirin, (Daklinza) daclatasvir/sofosbuvir/ribavirin, sofosbuvir/ (Olysio) simeprevir /- ribavirin, and (Viekira Pak) paritaprevir/ombitasvir/dasabuvir/ribavirin have all achieved high sustained response rates posttransplants. The previously dreaded complication of fibrosing cholestatic hepatitis C can now be effectively treated.

Summary:
Author Paul Y Kwo, M.D., professor of medicine at the Indiana University School of Medicine, summed it up nicely, the good doctor wrote; In the era of all oral therapies, no patient who undergoes transplant for hepatitis C-related cirrhosis should have their graft fail because of recurrent hepatitis C. It is expected that long-term survival of those who undergo orthotopic liver transplant for HCV-related cirrhosis will be comparable to those without hepatitis C.

Read the full article; Direct Acting Antiviral Therapy After Liver Transplantation

Guidelines

Next a summary for the treatment of Patients who Develop Recurrent HCV Infection Post-Liver Transplantation, updated July 6, 2016 by the AASLD/IDSA.

Last month the American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America and International Antiviral Society-USA updated their hepatitis C guidelines to reflect several important developments, including the treatment of Patients who Develop Recurrent HCV Infection Post-Liver Transplantation. This ever changing document is updated when new HCV drugs are approved, and new real world data is established.

Current treatment recommendations in liver transplant recipients 

All of the AASLD/IDSA recommended regimens for post-transplant treatment of HCV are interferon-free regimens. For a summary of the recommendations see the summary boxes, or read the recommendations here.

Summary Box

Genotype 1 or 4
Recommended Regimens for Treatment-naïve and -Experienced Patients with HCV Genotype 1 or 4 Infection in the Allograft, Including Those with Compensated Cirrhosis
Recommended regimens are listed in groups by level of evidence, then alphabetically.
  • Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with weight-based ribavirin for 12 weeks is a Recommended regimen for patients with HCV genotype 1 or 4 infection in the allograft, including those with compensated cirrhosis.
    Rating: Class I, Level A

     
  • Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for patients with HCV genotype 1 or 4 infection in the allograft, including those with compensated cirrhosis.
    Rating: Class I, Level B
Recommended Regimens for Treatment-naïve Patients with HCV Genotype 1 or 4 Infection in the Allograft and with Compensated Liver Disease, Who Are Ribavirin Ineligible
Recommended regimens are listed in groups by level of evidence, then alphabetically.
  • Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for treatment-naïve patients with HCV genotype 1 or 4 infection in the allograft and with compensated liver disease, who are ribavirin ineligible.
    Rating: Class I, Level B

     
  • Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for patients with HCV genotype 1 or 4 infection in the allograft and with compensated liver disease, who are ribavirin ineligible.
    Rating: Class II, Level C
Recommended Regimen for Treatment-naïve and -Experienced Liver Transplant Recipients with Decompensated Cirrhosis (Child Turcotte Pugh [CTP] Class B or C) Who Have HCV Genotype 1 or 4 Infection in the Allograft
  • Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for liver-transplant recipients with decompensated cirrhosis (CTP class B or C) who have HCV genotype 1 or 4 infection in the allograft.
    Rating: Class I, Level B
Alternative Regimens for Patients with HCV Genotype 1 Infection in the Allograft, Including Those with Compensated Cirrhosis
  • Daily simeprevir (150 mg) plus sofosbuvir (400 mg) with or without weight-based ribavirin for 12 weeks is an Alternative regimen for patients with HCV genotype 1 infection in the allograft, including those with compensated cirrhosis.
    Rating: Class I, Level B

     
Alternative Regimens for Patients with HCV Genotype 1 Infection in the Allograft, Including Those with Early-stage Fibrosis (Metavir Stage F0-F2)
  • Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) with weight-based ribavirin for 24 weeks is an Alternative regimen for patients with HCV genotype 1 infection in the allograft, who have early-stage fibrosis (Metavir stage F0-F2).
    Rating: Class I, Level B
Genotype 2
Recommended Regimens for Treatment-naïve and -Experienced Patients with HCV Genotype 2 Infection in the Allograft, Including Those with Compensated Cirrhosis
Recommended regimens are listed in groups by level of evidence, then alphabetically.
  • Daily daclatasvir (60 mg) plus sofosbuvir (400 mg), with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for patients with HCV genotype 2 infection in the allograft, including those with compensated cirrhosis.
    Rating: Class II, Level A

     
  • Daily sofosbuvir (400 mg) and weight-based ribavirin for 24 weeks is a Recommended regimen for patients with HCV genotype 2 infection in the allograft, including those with compensated cirrhosis.
    Rating: Class II, Level C
Recommended Regimen for Treatment-naïve and -Experienced Patients with HCV Genotype 2 Infection in the Allograft, Including Those with Compensated Cirrhosis, Who Are Ribavirin Ineligible
  • Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for patients with HCV genotype 2 infection in the allograft, including those with with compensated cirrhosis, who are ribavirin ineligible.
    Rating: Class II, Level C
Recommended Regimen for Treatment-naïve and -Experienced Liver-Transplant Recipients with Decompensated Cirrhosis (Child Turcotte Pugh [CTP] Class B or C) Who Have HCV Genotype 2 Infection in the Allograft
  • Daily sofosbuvir (400 mg) and ribavirin (initial dose 600 mg/day, increased monthly by 200 mg/day as tolerated to weight-based dose) for 24 weeks is a Recommended regimen for liver-transplant recipients with decompensated cirrhosis (CTP class B or C) who have HCV genotype 2 infection in the allograft.
    Rating: Class II, Level C
Genotype 3
Recommended Regimen for Treatment-naïve and -Experienced Patients with HCV Genotype 3 Infection in the Allograft, Including Those with Compensated Cirrhosis
  • Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks is a Recommended regimen for patients with HCV genotype 3 infection in the allograft, including those with compensated cirrhosis.
    Rating: Class II, Level A
Recommended Regimen for Treatment-naïve and -Experienced Patients with HCV Genotype 3 Infection in the Allograft, Including Those with Compensated Cirrhosis, Who Are Ribavirin Ineligible
  • Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks is a Recommended regimen for patients with HCV genotype 3 infection in the allograft, including those with compensated cirrhosis, who are ribavirin ineligible.
    Rating: Class II, Level C

Last but not least patient friendly articles written by and for transplant recipients.

Website




By Karen Hoyt

Recent Posts
The Performance Trap
Turning Down Sweets: Rude or Smart
World Hepatitis C Day
Cirrhosis is a Pain in the Neck
Finding Liver Cancer

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Established in 1999, the TransplantBuddies site provides information about the transplant process, resources covering drugs and side effects, and daily discussions about living life as a transplant patient. The site also includes members' photos and life stories covering experiences of both transplant recipients and donors.

Of Interest
Aug 18
DAA therapy may reduce number of LT candidates
“We suggest designing long-term multinational observational studies on patients who have been listed for decompensated [HCV] cirrhosis and subsequently delisted because of clinical improvement,” Belli and researchers wrote. – by Janel Miller

Aug 16, 2016
The patient perspective: Waiting for the liver

May 23, 2016
Treatment of Chronic Hepatitis C in Patients With Cirrhosis
What is the safest and most effective way to treat patients with chronic hepatitis C with cirrhosis?

May your journey be safe and successful.

Tina