Tag Archives: hepatitis C

Coffee and Caffeine Associated With Less Fibrosis Among Patients with Hepatitis C

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Perhaps I need to start drinking coffee.  In the absence of smoking or alcohol, it is reported to have a number of benefits. A recent study (N Khalaf et al. Clin Gastroenterol Hepatol 2015; 13: 1521-31) found that a “modest daily caffeine intake (as little as 100 mg) may protect against advanced hepatic fibrosis in men with chronic HCV infection.” This cross-sectional study of veterans with chronic HCV looked at 910 patients.  Patients were divided into controls with mild fibrosis (F0-F3) based on FibroSURE compared with those with F3/F4-F4 advanced fibrosis.  FibroSURE estimates are based on an algorithm which incorporates α2-macroglobulin, apolipoprotein A1, haptoglobin, total bilirubin, γ-glutamyl -transpeptidase, and alanine amiontransferase. Key findings:

  • Caffeinated coffee was higher among controls than those with advanced fibrosis (1.37 vs 1.05 cups/d, P=.038)
  • Overall caffeine ingestion was also higher in the controls; 66% of controls consumed >100 mg/day compared with 58% of those with advanced fibrosis.

Limitation: observaitonal, retrospective study with self-reported coffee/caffeine consumption. Related blog posts:

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Hepatitis C : New and Newer Treatments

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A recent study (KR Reddy et al. Hepatology 2015; 62: 79-86) shows that the combination of ledipasvir/sofosbuvir is a safe, effective therapy for patients with genotype 1 Hepatitis C (HCV) and compensated cirrhosis.

The authors performed a post-hoc analysis of seven clinical trials in 513 treatment-naive and previously treated patients; 69% were previously treated. Key findings:

  • Overall, 493 (96%) achieved an SVR12; 98% of treatment-naive patients achieved an SVR12.
  • However, many patients in this analysis had received ribavirin.  In those treated without ribavirin (ledipasvir/sofosbuvir alone), the SVR12 was 90%.
  • Most common adverse effects included headache (23%), fatigue (16-19%), and asthenia (14-16%).

Bottomline: While ledipasvir/sofosbuvir was effective in this population, the 90% SVR12 is not as good as 96%.  This leads to the question of whether ribavirin is needed as well.

Related & briefly noted: SA Alqahtani et al. Hepatology 2015; 62: 25-30.  Ledipasvir/sofosbuvir treatment (8-24 weeks) resulted in SVR of 97% (with or without ribavirin) among the 1952 patients treated in the ION-1, ION-2, and ION-3 studies.

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From FDA (July 24th): FDA approves new treatment for chronic hepatitis C genotype 3 infections

“The U.S. Food and Drug Administration today approved Daklinza (daclatasvir) for use with sofosbuvir to treat hepatitis C virus (HCV) genotype 3 infections. Daklinza is the first drug that has demonstrated safety and efficacy to treat genotype 3 HCV infections without the need for co-administration of interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection….

The safety and efficacy of Daklinza in combination with sofosbuvir were evaluated in a clinical trial of 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection. Participants received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks and were monitored for 24 weeks post treatment. The studies were designed to measure whether a participant’s hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured.

Results showed that 98 percent of the treatment-naive participants with no cirrhosis of the liver and 58 percent of the treatment-naive participants with cirrhosis achieved sustained virologic response. Of the participants who were treatment-experienced, 92 percent with no cirrhosis of the liver and 69 percent with cirrhosis achieved sustained virologic response. Daklinza labeling carries a Limitations of Use statement to inform prescribers that sustained virologic response rates are reduced in HCV genotype 3 infected patients with cirrhosis.”

From FDA (July 24th): FDA approves Technivie for treatment of chronic hepatitis C genotype 4

“The U.S. Food and Drug Administration today approved Technivie (ombitasvir, paritaprevir and ritonavir) for use in combination with ribavirin for the treatment of hepatitis C virus (HCV) genotype 4 infections in patients without scarring and poor liver function (cirrhosis).

Technivie in combination with ribavirin is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for co-administration of interferon, an FDA-approved drug also used to treat HCV infection…

The safety and efficacy of Technivie with ribavirin were evaluated in a clinical trial of 135 participants with chronic HCV genotype 4 infections without cirrhosis. Ninety-one participants received Technivie with ribavirin once daily for 12 weeks. Forty-four participants received Technivie once daily without ribavirin for 12 weeks. The studies were designed to measure whether a participant’s hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured.

Results showed that 100 percent of the participants who received Technivie with ribavirin achieved a sustained virologic response. Of those who received Technivie without ribavirin, 91 percent achieved sustained virologic response.”

Garden of the Gods, Colorado Springs

Garden of the Gods, Colorado Springs

Updated HCV Guidelines Published

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The American Association for the Study of Liver Diseases (AASLD) has published updated Hepatitis C guidelines. The complete guidance is available online at www.hcvguidelines.org.

An updated edition of Recommendations for Testing, Managing, and Treating Hepatitis C is now published in HEPATOLOGY. This condensed version of the Guidance includes a summary of recommendations regarding treatment with direct-acting antiviral drugs. Download the PDF now.

Authors are now able to cite the guidelines in their publications as an Accepted Article, doi: 10.1002/hep.27950.

“Mutant Ninja Viruses”

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Yesterday’s post “Understanding HCV Treatment Failures with Sofusbuvir” provided a summary of why patients with hepatitis C virus (HCV) genotype 3 may not respond to therapy. Now a terrific article (Hepatology 2015; 61: 471-80, editorial, titled “Mutant Ninja Viruses” 421-23) looks at why some patients with the favorable HCV genotype 2 may fail to respond.

By using extensive genotyping data and sequencing, the authors were able to determine why some patients with genotype 2 did not respond to combination therapy with ribavirin/sofusbuvir.  These patients were characterized by as genotype 2 based on Siemens VERSANT HCV Genotype INNO-LiPA 2.0 Assay.  This assay “looks at conserved sequences in the 5′ region of the virus.” However, these patients were genotyped as well using a technique to examine the 3′ region of the virus.  From among more than 2000 samples, the two assays gave divergent results in 0.5% of the cases with the 5′ end indicating genotype 2 and the 3′ end indicating genotype 1.

What is happening?

  • Detailed analyses of these discordant viruses showed that they were hybrid viruses with a crossover point located in the NS2/NS3 region.
  • In patients with these hybrid viruses, only 3 of 11 responded to therapy, indicating that they behave like genotype 1 patients.

Bottomline: “These novel viruses are true viral Ninjas hiding a challenging array of ‘difficult-to-cure’ genotype 1 enzymes under an ‘easy-to-cure’ genotype 2 coat.

Understanding HCV Treatment Failures with Sofusbuvir

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While the new treatments for hepatitis C have improved dramatically in terms of cure rates and side effects (and pharmaceutical companies bottom-line), there are still patients who do not respond, especially those with genotype 3.  A recent study (Hepatology 2015; 61: 56-65) has provided some information into why this is happening.

A division of the FDA looked into five sofosbuvir (SOF) trials and performed sequencing to characterize potential resistance-associated substitutions.

Key findings:

  • Nonstructural protein 5B (NS5B) substitutions, L159F and V321A, emerged in 2.2%-4.4% of subjects who failed SOF treatment.
  • Baseline substitutions in 316 were associated with a reduced response in HCV genotype 1b subjects.
  • This study identified only 11 patients with genotype 3 with potentially relevant substitutions.

Bottomline: In the vast majority of patients, no resistance-associated substitution could be identified, indicating that we have a lot to learn why some patients are not responding.

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Theses Eggs Contain Eggs!

Theses Eggs Contain Eggs!  Is the “allergen information” really necessary in this case?

Good News for Starbucks & Coffee Vendors

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This blog has posted a number of favorable reports on coffee, even though I’m not a coffee enthusiast.  In general, coffee has favorable health effects when it is not paired with alcohol or tobacco.

A recent coffee study (Gastroenterol 2015; 148: 118-25) shows an association between coffee intake and reduced incidence of liver cancer and death from chronic liver disease in the U.S.

Here’s a link to a summary of the article: GastroHepNews Coffee and Liver Disease

  • During an 18-year follow-up period, there were 451 incident cases of hepatocellular carcinoma and 654 deaths from chronic liver disease.
  • Compared with non-coffee drinkers, the researchers noted that those who drank 2–3 cups per day had a 38% reduction in risk for hepatocellular carcinoma.
  • Those who drank ≥4 cups per day had a 41% reduction in hepatocellular carcinoma risk.
  • Compared with non-coffee drinkers, participants who consumed 2–3 cups coffee per day had a 46% reduction in risk of death from chronic liver disease, and those who drank ≥4 cups per day had a 71% reduction.
  • The inverse associations were similar regardless of the participants’ ethnicity, sex, body mass index, smoking status, alcohol intake, or diabetes status.

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More liver-related news: Man with infected hepatitis C sentenced to 3 years for spitting in officer’s face (from The Republic/AP News)

Does Anyone Know Why This Toilet is in our Parking Garage?

Does Anyone Know Why This Toilet is in our Office Parking Garage?

HCV: When to Spike the Ball

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When a team scores a touchdown in football, often one sees a player spike the ball in celebration.  The equivalent of spiking a ball rarely happens in medicine.  That being said, a recent study (Hepatology 2015; 61: 41-45) indicates that after treatment sofosbuvir regimens, you can celebrate if you have a sustained virological response (SVR) at 12 weeks (SVR12).

The authors conducted a retrospective review of five trials with 863 patients with HCV genotypes 1-6.  “Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24.” Of the patients who relapsed, most (77.6%) did so within 4 weeks of completing therapy.

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Diabetes and Hepatitis C –A Bad Combination

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Until recently (see next post tomorrow), it has been well-recognized that there is a connection between chronic hepatitis C infection and diabetes mellitus (DM) (related previous post: Treating HCV Helps Diabetics | gutsandgrowth).  More data confirms that the development of diabetes is associated with increased risk of poor outcomes in HCV-infected patients.

  • Hepatology 2014; 60: 807-14
  • Hepatology 2014; 60: 823-31

In the first study, the authors used a nation-wide cohort comprising >99% of the Taiwanese population.  Among a random sample of 1 million enrollees, 6,251 adult chronic HCV patients were identified from 1997-2009.  Among those who developed DM during the study period (not before), after adjustment for confounding variables, diabetes was an independent predictor for cirrhosis (hazard ratio (HR) =2.5, P<0.001) and hepatic decompensation (HR=3.56, P+0.003).

In the second study, the authors identified consecutive chronic HCV-infected patients with cirrhosis who were hospitalized between 2006-2008 (n=348).  At baseline, 40% had DM.  DM was independently associated with development of ascites (P=0.057), renal dysfunction (P=0.004), bacterial infections (P=0.007), and hepatocellular carcinoma (P=0.016).  The authors suggest that improving diabetes control may improve the outcome of cirrhosis.

Take-home message: New-onset diabetes is a marker for progressive liver disease in patients with chronic HCV infection.  Whether diabetes has a causal role in HCV patient deterioration remains unclear.

Also noted, from Healio Gastroenterology, a recent study suggests that sofusbuvir/ledipasvir reduces HCV-related complications, here’s link: Sofusbuvir/ledipasvir Abstract

Understanding the Costs and Benefits of HCV Treatment

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A useful editorial in JAMA (available free online –) provides a useful overview of HCV treatments in terms of costs and strategies for using new therapies.

A couple of useful points

  • Given the cost of medications, many are using the newer therapies in those who absolutely need treatment now and waiting for costs to improve in others
  • “The ultimate approach to cost will be lower prices, which will occur as more products create competition.”
  • “This fall, an oral combination of sofosbuvir and ledipasvir will be introduced that inhibits both the NS5B polymerase and NS5A polymerase and has been shown to reduce treatment to an 8-week course with cure rates of more than 95%.2 Now, a chronic disease that affects millions of Americans can be cured by well-tolerated oral medications.”
  • Because of the large number of potential patients, “the simple math is that treatment of patients with HCV could add $200 to $300 per year to every insured American’s health insurance premium for each of the next 5 years.”

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HCV Guidelines Updated

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For those trying to stay up-to-date, a headline from The Onion: “Nation’s Third-Graders Now Eating At A Ninth-Grade Level”   .

And, from American Association for the Study of Liver Diseases (AASLD):

AASLD and the Infectious Diseases Society of America (IDSA), in collaboration with the International Antiviral Society-USA (IAS-USA), released the latest section of www.hcvguidelines.org.

The new section, “When and in Whom to Initiate HCV Therapy,” offers clinicians information on:

  • How to prioritize patients who will derive the most benefit, or will have the greatest impact on limiting further HCV transmission.
  • When to treat patients with complications such as advanced fibrosis, compensated cirrhosis, liver transplant, or severe extra-hepatic complications.
  • Additional conditions that warrant prioritization of treatment.

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