Sofosbuvir Interferon-free therapy alters lipid metabolism, glucose homeostasis in chronic HCV patients

Interferon-free therapy alters lipid metabolism, glucose homeostasis in chronic HCV patients

SAN FRANCISCO – Patients with chronic hepatitis C treated with an interferon-free regimen consisting of sofosbuvir and ribavirin experienced changes in LDL, triglycerides, hemoglobin A1C and metabolic and hepatic lipid gene expression in a study presented at ID Week 2013.

Eric Meissner, MD, PhD, and colleagues administered sofosbuvir with low- or full-dose ribavirin to 60 treatment-naive patients with chronic hepatitis C genotype 1 for 24 weeks, and periodically measured hemoglobin A1C (HbA1c) and serum lipid levels. Paired liver biopsy specimens also were collected from seven patients before and at end of treatment (EOT), and targeted quantitative RT-PCR was performed for genes related to the metabolism of glucose and lipids.

Fifty-five patients completed the study, and 38 maintained a sustained virologic response 24 weeks after EOT (SVR24), with the remainder relapsing after EOT. Investigators observed increases in LDL (91 ± 4 mg/dL to 104 ± 5 mg/dL; P=.0027) and decreases in triglycerides (137 ± 10 mg/dL to 98 ± 8 mg/dL; P<.0001) 4 weeks after treatment initiation, changes that were sustained through EOT.

Patients who relapsed had lower LDL levels than patients who achieved SVR24 at baseline (78 ± 7 mg/dL vs. 97 ± 5 mg/dL; P=.031) and at 48 weeks (82 ± 7 mg/dL vs. 109 ± 6 mg/dL; P=.005), but no difference was observed during treatment or at EOT. Regardless of outcome, glycosylated hemoglobin (HbA1c) was lower 24 weeks after EOT compared with baseline among 39 evaluable patients (P=.0033).

All seven patients who provided biopsy specimens achieved SVR24. Among them, lipid transport genes APOB, APOC3 and APOL3 had significantly up-regulated intrahepatic expression at EOT, while lipid assembly and signaling genes LEPR and MTTP were down-regulated.

“Our data demonstrate changes in lipid metabolism pathways and glucose homeostasis in CHC genotype-1 infection following interferon-free antiviral therapy,” the researchers concluded. “The early changes in LDL and triglycerides associated with treatment implicate a direct effect of viral clearance on lipid homeostasis.”

Disclosure: Susanna Naggie, MD, reports serving as a grant investigator and scientific advisor, as well as receiving consulting fees and grants, from Gilead Sciences. Keyur Patel, MD, reports serving as a consultant and scientific advisor and receiving a consulting fee from Gilead. John McHutchison, MD, is an employee and shareholder at Gilead.

For more information:

Meissner EG. #1830. Presented at: ID Week 2013; Oct. 2-6, San Francisco

http://www.healio.com/infectious-disease/hepatitis-resource-center-2013/interferon-free-therapy-alters-lipid-metabolism-glucose-homeostasis-in-chronic-hcv-patients

Addition of daclatasvir to interferon-based HCV therapy improved treatment response, shortened duration

ID Week, October 2-6, 2013, San Francisco

Addition of daclatasvir to interferon-based HCV therapy improved treatment response, shortened duration
October 9, 2013
SAN FRANCISCO – Patients with hepatitis C treated with daclatasvir in addition to pegylated interferon and ribavirin had better response rates within shorter treatment duration than those who received peginterferon and ribavirin alone in a study presented at ID Week 2013.

Interferon-free regimen safe,effective for patients with HCV genotype 1
October 8, 2013
SAN FRANCISCO – A regimen of daclatasvir, asunaprevir, and a non-nucleoside NS5B inhibitor yielded high sustained virologic response rates among patients with hepatitis C genotype 1 in a study presented at ID Week 2013.

As many as 80,000 people with hepatitis C virus (HCV) infection could die yearly in the United States

CDC Figures Annual US Mortality in People With HCV Could Top 80,000: HCV Mortality Under-reported, Mortality Rate 12 Times Higher than General Population, HCV+ Die 15 Years Younger than General Population

ID Week, October 2-6, 2013, San Francisco

The annual ID Week meeting featured the latest research and approaches to prevention, diagnosis, treatment, and epidemiology of infectious diseases.

Jules Levin the founder and executive director of NATAP continues to report on the conference providing commentary, abstracts, slides and reports, available here.

This study with an article written Mark Mascolini examined liver-related mortality in people infected with HCV living in the U.S. The investigators calculated death rates based on US census data from 2006-2010 and 12 million death certificates for residents during the same time period. The researchers concluded that 80% of death certificates did not list HCV as cause of death. Only 15,000 deaths were listed on the death certificate as having HCV infection, Mark Mascolini explains.....

Excerpt:

By Mark Mascolini 

As many as 80,000 people with hepatitis C virus (HCV) infection could die yearly in the United States, according to results of a multicohort analysis from 2006 through 2010 [1]. People with HCV died at an average age 15 years younger than people in the general population. 

From 2.7 to 3.9 million people in the United States have chronic HCV infection. To estimate all-cause and liver-related mortality among HCV-positive US residents, the Centers for Disease Control and Prevention (CDC) examined electronic medical records of adults who had at least one health system encounter from January 2006 through December 2010 in four integrated healthcare systems. In the resulting Chronic Hepatitis Cohort Study (CHeCS), the investigators identified those who died from 2006 through 2010. They compared CHeCS mortality findings with data from the national Multiple Cause of Death (MCOD) study in the same period.

From 2006 through 2010, the CDC team considered 11,703 people with chronic HCV representing 0.5% of patients in the 2.1-million person CHeCS cohort. Among people with HCV, 1590 (14%) died during the study period. Most people who died were 45 to 59 years old (60%), followed by the group 60 and older (34%). Men accounted for two thirds of the deaths (68%), whites for 50%, and blacks for 35%. Almost three quarters of those who died (72%) had a median household income between $15,000 and $50,000, while 25% had a higher income.

Compared with MCOD data, mortality was 12 times higher in CHeCS. Age-adjusted mortality in CHeCS compared with MCOD was 61 times higher for HCV infection (relative risk [RR] 61.4), 29 times higher for liver cancer (RR 28.8), 24 times higher for nonalcohol-related liver disease (RR 24.4), 10 times higher for HIV infection (RR 9.8), 6 times higher for alcohol-related liver disease (RR 6.2), and 86 times higher for unspecified hepatitis-related disease (RR 86.1) (P < 0.0001 for all).

Age averaged 59 years in CHeCS members who died, 15 years younger than the all-cause death age in US national data.

Among the 1590 CHeCS members who died, only 306 (19%) had HCV infection listed as an underlying cause on their death certificate. Among people who died of liver cancer, only 32% had HCV listed as an underlying cause. Death certificates did not list HCV for most deaths regardless of whether the deaths were liver-related or not. Among CHeCS members who died, medical records (ICD-9 codes) noted liver disease in 63%, and FIB-4 scores indicated liver disease in 76%.

"Even in these well-characterized HCV patients," the CDC team concluded, "HCV was noted in only 19% of death certificates." Based on this finding, the researchers estimated that more than 80,000 US residents with HCV died in 2010. They noted that chronic liver disease recorded in two thirds of CHeCS members who died "suggests that 53,000 patients are dying not only with, but possibly from HCV."

Continue Reading - View Abstract and Slides here

Conference Coverage At Healio

Healio reports on the increase of  all-cause mortality in persons living with HCV. The video provided below describes the risk for extrahepatic manifestations and other medical problems in HCV rather the disease is mild or advanced such as heart disease, diabetes, cancers but not just liver cancer - lung and endocrine malignancies.

Identification of hepatitis C crucial in addressing disease
SAN FRANCISCO — Eliot Godofsky, MD, director of the University Hepatitis Center in Sarasota, Fla., discusses strategies to improve the identification of hepatitis C patients. Up to 70% of people with hepatitis C are unaware of their infection status, many of whom were born between 1945 and 1965.

Complete Conference Coverage At NATAP

ID Week, October 2-6, 2013, San Francisco

 

• Lack of HCV Genetic Diversity Tied to Higher Liver Disease Risk in Women With HIV - (10/07/13)
   
• High Referral of HCV Patients to Specialists But Low Treatment Initiation Rate - Barriers to Care & Treatment - (10/07/13)
   
• CDC Figures Annual US Mortality in People With HCV Could Top 80,000: HCV Mortality Under-reported, Mortality Rate 12 Times Higher than General Population, HCV+ Die 15 Years Younger than General Population - (10/07/13)
   
• Cumulative Viral Load Predicts Morbidity/Mortality in Perinatally Infected Children - written by Mark Mascolini - (10/07/13)
   
• Rash in 10% of Taiwanese Starting Once-Daily Darunavir--and 7% Dropout Rate - written by Mark Mascolini - (10/07/13)
   
• 15% of HIV+ Adults in NY Clinics Still Seronegative for Measles, Mumps, Rubella - written by Mark Mascolini - (10/07/13)
   
• Six-Month HIV Suppression Better With Single-Tablet Regimens Than Multitablet Combos - written by Mark Mascolini - (10/07/13)
   
• Low Risk but Twice Higher Risk of Suicidal Thoughts or Acts on First-Line Efavirenz - written by Mark Mascolini - (10/07/13)
   
• Lack of ART Tied to Tripled Mortality in Veterans With Community-Acquired Pneumonia - written by Mark Mascolini - (10/07/13)
   
• Sofosbuvir and Peginterferon Alfa-2a/Ribavirin for Treatment-Naïve Genotype 1-4 HCV-Infected Patients Who Are Coinfected With HIV - (10/07/13)
   
• Optimization of an Interferon-free Hepatitis C Virus Therapy Regimen Containing the HCV NS3/4A Protease Inhibitor Faldaprevir, the Non-nucleoside NS5B Inhibitor Deleobuvir, and Ribavirin for Genotype-1b-infected Patients - (10/07/13)
   
• Barriers to Hepatitis C Treatment in an HIV-HCV Co- Infected Cohort - (10/07/13)
   
• Telaprevir-based triple therapy for elderly patients with genotype 1 chronic hepatitis C - (10/07/13)
   
• Does Knowledge Influence Reporting Practices when Screening for Hepatitis C in Pregnant Women? - (10/07/13)
   
• Cumulative Viremia-Copy Years Predicts Morbidity and Mortality in Perinatally HIV-Infected Children - (10/07/13)
   
• Assessing Vitamin D Testing and Supplementation Patterns in a Large Inner City Clinic - (10/07/13)
   
• Current Alcohol and Substance Use in HIV-infected and HIV/HCV-co-infected Patients in Routine Clinical Care across the U.S. - (10/07/13)
   
• Single tablet regimens do not necessarily translate into more durable HIV treatments: "initial use of RAL-based regimens was associated with a better outcome........patients starting HAART with RAL were less likely to change regimen...... the main reason for 1st line discontinuation/switch remain the adverse effects, very few virological failure were observed" - (10/07/13)
   
• Pilot Study to Evaluate Intramyocardial Lipid Accumulation in HIV+ Patients Receiving Highly Active Antiretroviral Therapy (HAART) - (10/07/13)
   
• Long-Term Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Compared to Efavirenz/Emtricitabine/Tenofovir DF in HIV-1-Infected, Treatment-Naïve, Black Versus Non-Black Subjects - (10/07/13)
   
• STaR Study: Association of Efficacy Outcomes with Baseline HIV-1 RNA and CD4 Count and Adherence Rate for the Single-Tablet Regimens Rilpivirine/Emtricitabine/Tenofovir DF and Efavirenz/Emtricitabine/Tenofovir DF in ART-Naïve Adults - (10/07/13)
   
• HIV+ Individuals on ART Are At Risk of Polypharmacy: More Medication Increases Mortality - (10/04/13)
   
• Comorbidity prevalence and its influence on non-ARV comedication burden among HIV positive patients - (10/04/13)
   
• Safety and Efficacy of Dolutegravir (DTG; GSK1349572) in Treatment-Experienced HIV-1 Infected Adolescents: 24-week Results from IMPAACT P1093 - (10/04/13)
   
• Outcomes Differ for HIV-Infected Patients Receiving Care at Hospital vs. Community-Based Clinics - (10/04/13)
   
• "The Clinical Role and Cost-effectiveness of Long-acting Antiretroviral Formulations" - Long-Acting ARV Formulations Could Improve Survival in People With Poor Adherence - written by Mark Mascolini - (10/04/13)
   
• Comorbidity Rate, Non-ARV Prescriptions Higher in HIV-Positives Than Matched Controls - written by Mark Mascolini - (10/04/13)
   
• Non-AIDS Death Rate Jumps From Early to Recent ART Era in Large Single-Site Study - written by Mark Mascolini - (10/04/13)
   
• Higher Intramyocardial Lipids in Antiretroviral-Treated Men Than in HIV-Negatives - written by Mark Mascolini - (10/04/13)
   
• Dolutegravir Effective at 24 Weeks in Adolescents Replacing Failing Regimen - written by Mark Mascolini - (10/04/13)
   
• Once-Daily Etravirine Effective Through 24 Weeks in Three-Center Study - written by Mark Mascolini - (10/04/13)
   
• Community or Hospital HIV Clinic? Patient Profiles, Outcomes Differ in 4-Year Study - written by Mark Mascolini - (10/04/13)