This blog is all about current FDA approved drugs to treat the hepatitis C virus (HCV) with a focus on treating HCV according to genotype, using information extracted from peer-reviewed journals, liver meetings/conferences, and interactive learning activities.
Risk Of Developing Liver Cancer After HCV Treatment
(HealthDay News) — Interferon-free direct-acting antiviral (DAA) therapy is beneficial for hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis, according to a study published online Aug. 2 in Hepatology.
Laura Gragnani, Ph.D., from the University of Florence in Italy, and colleagues conducted a prospective evaluation of the efficacy and safety of sofosbuvir-based DAA therapy, individually tailored according to the latest guidelines. The evaluation was conducted in a cohort of 44 patients with HCV-associated MC.
The researchers found that MC had evolved into an indolent lymphoma with monoclonal B cell lymphocytosis in two patients. All patients had negative HCV viremia at weeks 12 and 24 post-treatment; all had clinical response of vasculitis at this point. There were significant decreases in the mean Birmingham Vasculitis Activity Score from baseline through 24 weeks; significant decreases were also seen in the mean cryocrit value. Partial clinical response of vasculitis and about a 50 percent decrease of cryocrit were seen in the two patients with MC and lymphoma, although none experienced a significant decrease in monoclonal B cell lymphocytosis. Fifty-nine percent of patients had adverse events, although they were generally mild.
"Interferon-free, guideline-tailored therapy with DAA is highly effective and safe for HCV-associated MC patients," the authors write. "The overall 100 percent rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients."
The age that hepatitis C was acquired may have an impact on prognosis. A number of studies have reported that individuals who are infected with hep C at older ages tend to have a worse prognosis than those who acquire hep C while young. People over age 40 more likely to develop HCV-related liver cancer. Age can also have a negative impact on liver transplantation survival; older liver transplant recipients have a significantly lower survival rate than younger patients...
Related:
July 27 Battling hepatitis C in the elderly
Plenty of studies have been done globally for younger adults, but seniors have different risk factors and comorbidities, notes an article in Clinical Gastroenterology and Hepatology journal. “Although the safety and efficacy of hepatitis C therapies have been extensively studied in patients between ages of 18 and 65, patients who are over 65 still remain an understudied and difficult to treat population,” the authors write...
July 17 Treatment of Chronic Hepatitis C in the Aged – Does It Impact Life Expectancy? A Decision Analysis
Since currently complications of HCV mostly affect members of the elderly population, they are in urgent need of effective HCV treatment. The approach we suggest for the treatment of patients over 70 with chronic HCV is illustrated in Fig 3. For those patients who have no major co-morbidities, more than moderate fibrosis, and a life expectancy greater than one year, there is a possibility of offering treatment. This needs to be presented to the patient and discussed before a final decision...
Aug 12
CNN
Marijuana will remain a Schedule l controlled substance, which declares it has "no currently accepted medical use and a high potential for abuse," the Drug Enforcement Administration said Thursday. This keeps the drug in the same category as heroin, LSD and Ecstasy...
Policy change could accelerate development of treatments derived from the drug.
Study finds clues to fibrosis progression in chronic HCV infection
Aug 11
Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with alanine aminotransferase–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study...
A annual festival to raise money , promote awareness of natural healing plants and support legalization of them. This event is held @ Sycamore campground .
As a terminator of hepatitis C virus (HCV) infection, sofosbuvir-based direct-acting antiviral agent (DAA) regimens have achieved great success in the eradication of HCV in patients with hepatitis C and related end stage liver diseases[[1], [2]]. Recently, we read with interest the studies by Reig et al.[3 and Kozbial et al.[4 on the surprisingly high incidence of hepatocellular carcinoma (HCC) recurrence and occurrence in patients with advanced liver diseases during interferon-free therapy and after sustained virologic response (SVR), respectively. Notably, the time interval between the initiation of DAAs (or SVR) and tumour occurrence is very short. These studies promote the current awareness and understanding of the risk for hepatocarcinogenesis in the era of DAAs. However, similar episodes have not frequently been observed in Chinese patients until now...
Related Alcohol Intake Increases Risk for HCC in Patients With HCV-Related Cirrhosis
July
Alcohol consumption — including light-to-moderate — was associated with an increased risk for hepatocellular carcinoma among patients with hepatitis C virus infection-related cirrhosis, according to published findings.
Liver Transplant
National proposal aims for fairer liver transplant distribution
August 11, 2016 by Sean D. Hamill, Pittsburgh Post-Gazette
The organization that oversees the nation's transplant system said Wednesday that it believes a new proposal would greatly reduce geographic disparities that make getting a liver transplant harder in some areas of the country and easier in others...
Hospitals across the United States are throwing away less-than-perfect organs and denying the sickest people lifesaving transplants out of fear that poor surgical outcomes will result in a federal crackdown..
One of the biggest health threats to people living with chronic hepatitis B is a toxic, nearly invisible mold called aflatoxin found in corn, peanuts, peanut butter, almonds, Brazil nuts, walnuts and pistachios. People with hepatitis B who eat food with high levels of aflatoxins face a liver cancer risk that is 60-times above average. In addition to nuts and grains like quinoa, aflatoxin can be found in figs, milk and cheese, soybeans, dried spices and cottonseed. It is less common in rice, as long as rice is hulled, which removes aflatoxin mold.....
Summertime Foods to Help Hepatitis C
July 28
By Karen Hoyt
When it’s summertime and the weather is high, you need to eat good food to stay strong with hepatitis C. Since the garden goods are easy to find, use this time to...
Many patients with liver disease use complementary and alternative medicines (CAMs) despite some being potentially hepatotoxic, often don’t tell their healthcare providers.
These were the findings of researchers at Duke University School of Medicine who analysed data from the 2012 [US] National Health Interview Survey. Of 647 adults with liver disease, 41% reported using CAMs in the prior year, compared with 33% of adults without liver disease. The most common modality was herbs and supplements (23%), and 3% of respondents reported consumption of a potentially hepatotoxic substance in the previous 30 days. Only a small proportion of CAM therapies were used specifically for liver disease, with milk thistle being the most common. Among respondents with liver disease, CAMs were used more commonly for anxiety or depression, fatigue, and substance use. The majority believed that these therapies improved health. Nearly one-third of therapies were not reported to healthcare providers, mostly because they don’t ask...
Reference - Complementary and alternative medicine use in United States adults with liver disease. Henson JB, Brown CL, Chow SC et al. J Clin Gastroenterol. 2016 Jul 29. [Epub ahead of print]
FDA Updates Draft Guidance for Dangerous Dietary Supplements
Aug 12
The U.S. Food and Drug Administration issued a revised draft guidance to improve dietary supplement companies’ new dietary ingredient premarket safety notifications to the agency. These notifications help the agency identify safety concerns before products reach consumers...
Related 15 Supplement Ingredients to Always Avoid
July
With the help of an expert panel of independent doctors and dietary-supplement researchers, Consumer Reports identified 15 supplement ingredients that are potentially harmful. The risks include organ damage, cancer, and cardiac arrest. The severity of these threats often depends on such factors as pre-existing medical conditions as well as the quantity of the ingredient taken and the length of time a person has been exposed to the substance....
First Published: 27 April 2016 Vol: 7, Pages: 80–83 DOI: 10.1002/cld.541
Often, it is difficult to identify the culprit ingredient that is responsible for liver damage among a multitude of different components within a particular supplement. However, some ingredients have been associated with hepatotoxicity. We aim to review those ingredients that have been implicated in liver injury and, in doing so, give the practitioner a rationale to implicate a supplement containing them as a cause for injury...
New, highly curative hepatitis C therapy is both safe and effective as a treatment option for people who inject drugs receiving opioid substitution therapy according to the results of a world-first clinical trial led by professor Gregory Dore at the Kirby Institute at UNSW Australia and published today in the Annals of Internal Medicine...
A Regimen for HCV-Infected Patients Who Fail Direct-Acting Antiviral Therapy
Atif Zaman, MD, MPH reviewing Lawitz E et al. Gastroenterology 2016 Jul 30. Gane E et al. Gastroenterology 2016 Jul 30.
Combination fixed-dose sofosbuvir-velpatasvir plus GS-9857 was highly effective in phase II studies.
Although infrequently, direct-acting antiviral agents (DAAs) fail in treating chronic hepatitis C virus (HCV) infection and treatment-induced resistance can develop. Treatment options are limited for this population.
In companion phase II, industry-funded studies, researchers evaluated the safety and efficacy of daily triple therapy with sofosbuvir (an NS5B inhibitor; 400 mg), velpatasvir (a second-generation NS5A inhibitor with a high barrier to resistance; 100 mg), and GS-9857 (an investigational, next-generation NS3/4A protease inhibitor; 100 mg) in treatment-naive and treatment-experienced (i.e., previously failed DAAs) patients with HCV genotypes 1–6 infections.
In one open-label trial involving 197 HCV genotype 1 patients, all treatment-naive patients without cirrhosis who received 8 weeks of triple therapy achieved sustained virologic response at 12 weeks posttreatment (SVR12). Among treatment-naive patients with cirrhosis, treated for 8 weeks, SVR12 rates were 81% with added weight-based ribavirin and 94% without ribavirin. A small cohort without cirrhosis receiving 6 weeks of therapy achieved an SVR12 of 71%. Treatment-experienced patients with or without cirrhosis received 12 weeks of triple therapy, and all achieved SVR12.
Another open-label trial involved 128 patients with different HCV genotypes (58% genotype 3, 26% genotype 2). Among treatment-naive patients without cirrhosis, who received 6 weeks of triple therapy, SVR12 was 88%; among those with cirrhosis, treated for 8 weeks, SVR12 was 93%. Among treatment-experienced patients with or without cirrhosis, who received therapy for 12 weeks, SVR12 was 100% with cirrhosis and 97% without.
In both studies, the most common adverse effects were headache, fatigue, nausea, and diarrhea. Discontinuation rates due to adverse events were ≤2%.
Comment
This triple-DAA regimen was highly effective across HCV genotypes when given for 8 weeks in treatment-naive patients and 12 weeks in treatment-experienced patients with and without cirrhosis. A 6-week regimen was less effective, and adding ribavirin added no benefit. If subsequent phase III trials produce similar results, we might soon have a simple and effective 8–12-week regimen that is pangenotypic and ribavirin-free.
Note to readers: At the time NEJM Journal Watch reviewed these papers, their publisher noted that they were not in final form and that subsequent changes might be made.
Editor Disclosures at Time of Publication
Disclosures for Atif Zaman, MD, MPH at time of publication Nothing to disclose
Citation(s):
Lawitz E et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with genotype 1 hepatitis C virus infection in an open-label, phase 2 trial. Gastroenterology 2016 Jul 30; [e-pub]. (http://dx.doi.org/10.1053/j.gastro.2016.07.039)
Gane E et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with HCV genotype 2, 3, 4, or 6 infections in an open-label, phase 2 trial. Gastroenterology 2016 Jul 30; [e-pub]. (http://dx.doi.org/10.1053/j.gastro.2016.07.038)
GS-9857 in Patients With Chronic Hepatitis C Virus Genotype 1–4 Infection
A Randomized, Double-blind, Dose-ranging Phase 1 Study
In summary, administration of multiple doses of GS-9857 was well tolerated and resulted in a robust decline of HCV RNA levels in patients with genotype 1–4 HCV infection. Notably, the potent antiviral activity of GS-9857 was preserved in the presence of commonly observed NS3 mutations associated with resistance to protease inhibitors. GS-9857 demonstrated linear PK when administered at doses ranging from 50 to 300 mg under fasting conditions. The median half-life of GS-9857 ranged from 29 to 42 h, conducive to once-daily dosing. Lastly, GS-9857 has demonstrated additive antiviral activity when evaluated in vitro in combination with sofosbuvir or velpatasvir.[5] Together, these data support the further development of once-daily GS-9857 in combination with other DAAs for the treatment of patients with chronic HCV infection....
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
In Case You Missed It
HCV Therapy of Genotype 3: Is It Still a Challenge?
Published on 07/22/2016
By Ramakrishna Behara and Nancy Reau
Hepatitis C genotype 3 accounts for 30 percent of all infections secondary to hepatitis C and is the second most common genotype worldwide, behind genotype 1. Estimates report that in the U.S., it accounts for 8 to 13 percent of infections. Historically, genotype 3 has been uniquely challenging to manage in large part due to lower response to therapy combined with high rates of steatosis, fibrosis progression and a disproportionately high rate of hepatocellular carcinoma. With the launch of the first wave of interferon-free treatment, many of the direct-acting antivirals (DAA) had higher overall sustained virologic response (SVR) to genotype 3 but did not compare to the SVR rate for treatments approved for genotype 1. Thus, recent drug development has focused on pan-genotypic agents to equalize efficacy across all genotypes...
Weekend Video
A cure at what cost? More states easing restrictions on Hepatitis C treatments
Published on Aug 12, 2016
The new Hepatitis C drugs have come with a big catch: the price tag. It's difficult to know the exact cost — public and private payers negotiate private agreements with drug companies — but one of the main drugs, Sofosbuvir (the brand name is Sovaldi), has been listed at $1,000 a pill before discounts. It's taken once a day for up to three months, often in combination with other drugs, making the cost of a cure upwards of $100,000.
Increased risk suicide death associated with hospitalization for infection
Being hospitalized with infection was associated with an increased risk of suicide death and the highest risk of suicide was among those individuals with hepatitis and HIV or AIDS, according to a study published online by JAMA Psychiatry.
While psychological predictors of suicide have been studied extensively, less attention has been paid to the effect of biological factors, such as infection.
Helene Lund-Sørensen, B.M., of Copenhagen University Hospital, Denmark, and coauthors used Danish nationwide registers to investigate associations between infectious diseases and the risk of death by suicide.
All individuals 15 or older living in Denmark from 1980 through 2011 were included, resulting in study population of more than 7.2 million individuals. A history of infection was defined as one or more infection diagnoses since 1977. Infections were grouped into categories, including pathogen (i.e. bacterial, viral, others) and infection type (i.e. sepsis, hepatitis, genital, central nervous system, HIV or AIDS, etc.).
Among the more than 7.2 million individuals, there were 809,384 (11.2 percent) hospitalized with infection during follow-up. There were 32,683 suicides during follow-up and of those 7,892 (24.1 percent) individuals had been previously diagnosed with infection during hospitalization.
Study results suggest hospitalization with infection was linked to a 42 percent higher risk of suicide death compared to those individuals without infection. Also, the more infections and the longer the treatment, the higher the apparent risk for death by suicide, according to the results.
While there may be several potential causal links between infection and suicide, this study cannot conclusively show causality. The authors suggest their findings support literature linking infections, proinflammatory cytokines and inflammatory metabolites to increased risk of suicidal behavior. They also note that an association between infection and suicide could also be an epiphenomenon or be impacted by other factors. The psychological effect of being hospitalized with a severe infection might affect the risk of suicide.
The authors note several study limitations, including the inability to determine whether the hospital treatment itself or disability due to severe infection might explain some of the risks for suicide and whether other risk factors for suicide, such as depression, may be associated with self-care issues and therefore linked to the incidence and severity of infections.
"Our findings indicate that infections may have a relevant role in the pathophysiological mechanisms of suicidal behavior. Provided that the association between infection and the risk of death by suicide was causal, identification and early treatment of infections could be explored as a public health measure for prevention of suicide. Still, further efforts are needed to clarify the exact mechanisms by which infection influences human behavior and risk of suicide," the study concludes.
(JAMA Psychiatry. Published online August 10, 2016. doi:10.1001/jamapsychiatry.2016.1594. Available pre-embargo to the media at http://media.jamanetwork.com.)
Editor's Note: The article contains funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Ascertaining Whether Suicides Are Caused by Infections "Strengthening the case for a possible causal role of infections in the pathogenic process that leads to suicide, these researchers show that an increased risk of suicide was associated with the length of treatment and with an increasing number of hospitalizations with infections. Individuals with seven or more infections had an increased risk of suicide of almost 300 percent," write Lena C. Brundin, M.D., Ph.D., and Jamie Grit, B.Sc., of the Van Andel Research Institute, Grand Rapids, Mich., in a related editorial.
(JAMA Psychiatry. Published online August 10, 2016. doi:10.1001/jamapsychiatry.2016.1470. Available pre-embargo to the media at http://media.jamanetwork.com.)
Editor's Note: The article contains conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Probably the most common question I am asked, is regarding a special diet to follow if you have liver problems. Here is an updated answer to these questions. Continue reading...
Study finds clues to fibrosis progression in chronic HCV infection
By: WHITNEY MCKNIGHT, Hospitalist News Digital Network August 10, 2016
FROM THE JOURNAL OF INFECTIOUS DISEASES
Vitals
Key clinical point: Fibrosis progression is not linear in chronic HCV infection.
Major finding: Between the first and follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Data source: A review of 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013.
Disclosures: Dr. Talal and Dr. Jacobson disclosed numerous industry relationships, including with Abbott, AbbVie, and Gilead. The study was supported by the Troup Fund of the Kaleida Health Foundation and the Greenberg Foundation for Medical Research.
Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with alanine aminotransferase–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.
Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.
To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected.
In a study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).
Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).
Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.
Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.
The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.
Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years).
Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.
Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.
The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.
Part of the answer comes down to the type of health care many Hepatitis C sufferers receive. Of the 3 million Americans affected by this disease, a full third of them are Medicaid eligible. Medicaid recipients frequently face major difficulties in accessing primary care and health care screenings, which are essential to detecting Hepatitis C (it can often be asymptomatic) and treating the patient before major liver damage has been done.
The other key obstacle facing Medicaid recipients currently struggling with Hepatitis C is access to effective treatment once a diagnosis has been received. Recently, the National Association of Medicaid Directors (NAMD), an association which represents state directors of Medicaid programs across the country, called on Congress to address the strain that the cost of Hepatitis C treatment is placing on the nation’s largest health insurer.
Aided by new funds from Congress, the Department of Veterans Affairs (VA) is extending new antiviral treatments to all veterans with hepatitis C treated within its sprawling health care system—regardless of the stage of their illness and whether they contracted these infections during military service.
The government agency is now beginning hepatitis C antiviral therapy for 1100 patients a week—double the figure from a year ago—and hopes to increase that number to 2000 patients a week by the end of this year, said David Ross, MD, director of the VA’s HIV, hepatitis, and public health pathogens programs. At the same time, the VA is trying to screen all veterans born between 1945 and 1965, who account for more than 75% of hepatitis C infections.
This “enormous effort” has required a redesign of care within the VA, Ross noted. Five medical centers in San Francisco; Ann Arbor, Michigan; Richmond, Virginia; Portland, Oregon; and West Haven, Connecticut, are leading that initiative, disseminating training and expert advice on hepatitis C throughout the VA, the nation’s largest integrated health care system.
Hepatitis C – What Is Veterans Affairs Hiding For Profiteer Of Hep C Cure? Benjamin Krause
After CBS reported that Ray Schinazi made $400 million profit on a Hepatitis C cure, as a VA employee, the agency started playing a game of hide-the-pea.
The short version of Schinazi’s research were his discoveries of an HIV therapeutic and Hepatitis C cure. He developed those drugs while a full-time VA employee under his company named Pharmasset. Schinazi then sold Pharmasset to Gilead for $11 billion
