Friday, February 8, 2013

HCV News Rewind-Case report: telaprevir patient w-skin rash and eosinophilia switches to boceprevir

Hello folks,
Having survived yet another week of cold weather its time to roll out Friday's edition of HCV rewind.

We begin with a case report; of a patient with a telaprevir rash and eosinophilia, who had resolution of dermatologic side effects after switching to boceprevir and achieved SVR with only 15 weeks, published online @ Clinical Infectious Diseases - provided by Jules Levin @ NATAP.

Telaprevir and Boceprevir 

Case report highlights successful management of telaprevir skin rash and anal discomfort by switching to boceprevir

Telaprevir to Boceprevir Switch Highlights Lack of Cross-Reactivity
Clin Infect Dis (15 February) 2013
Provided by  NATAP

Hepatitis C viral protease inhibitors increase sustained virologic response rates compared to interferon and ribavirin but also add side effects. Telaprevir and boceprevir are structurally similar, and share cross-resistant mutations. This case report highlights successful management of telaprevir skin rash and anal discomfort by switching to boceprevir.

Hepatitis C virus (HCV) genotype 1 has historically been difficult to treat, with clinical trial success rates of pegylated interferon (peginterferon), and ribavirin much lower than for genotypes 2 or 3 (SVR in 46% vs 76%, respectively) [1]. Fortunately, new protease inhibitors are increasing efficacy, but side effects can result in treatment interruptions and failures. In treatment-naive noncirrhotic patients, sustained virologic response (SVR) rates of 75% and 66% have been shown for telaprevir-based and boceprevir-based regimens, respectively [2]. However, in one study, 56% of patients receiving telaprevir experienced a rash, 29% experienced anal discomfort (hemorrhoids, pain, or pruritus), and 17% discontinued therapy prematurely due to side effects, compared to only 4% in the placebo arm [3].

While minor side effects associated with telaprevir do not require telaprevir discontinuation, 5% of patients develop a severe rash that necessitates stopping telaprevir immediately. Drug-related eosinophilia and severe systemic illness (DRESS) and Stevens-Johnson syndrome (SJS) are life-threatening reactions that occur rarely with telaprevir [4]. The transition point from tolerable to life-threatening reactions is indistinct. Telaprevir and boceprevir are both linear α-ketoamides with striking molecular similarities. Cross-reaction is possible, especially when substituting one structurally similar drug for another, as in the case of protease inhibitors. Various ß-lactams can exhibit cross-reactivity or molecular mimicry [5], but data for HCV protease inhibitors are unavailable.

The side-effect profile of protease inhibitors can cause alterations in the treatment plan. If telaprevir is discontinued before week 8, the effect on SVR and optimal treatment duration becomes unclear. While response-guided therapy can lead to SVR in 6 months, even 6 months may be unattainable for patients experiencing side effects. However, viral kinetic modeling suggests that only 12 weeks of telaprevir/peginterferon/ribavirin (T/P/R) therapy may be sufficient in compliant patients if the viral decline is rapid [6]. Challenging this modeling data is the result from the 12-week arm of the Protease Inhibition for Viral Evaluation (PROVE) 1 study of telaprevir, suggesting that <24 weeks of therapy is not optimal for all patients [7].

Presented here is a patient with a telaprevir rash and eosinophilia, who had resolution of dermatologic side effects after switching to boceprevir and achieved SVR with only 15 weeks of report to follow.....
View Case Report and Full text @ NATAP

Research Article Eligibility and Safety of Triple Therapy for Hepatitis C: Lessons Learned from the First Experience in a Real World Setting

The aim of our study was to analyze the eligibility and safety of new triple therapy concepts for the treatment of chronic HCV genotype 1 infection in a real world setting of a German tertiary referral center.
Full text available here

Incivek - Telaprevir

IL28B genotype had limited effect on telaprevir response in HCV patients
Patients with interleukin 28B CC genotype had a slightly better response to hepatitis C treatment with pegylated interferon, ribavirin and telaprevir than those with the CT or TT genotypes in a recent study, read more here.

Interferon-based treatment

Frequency of Thyroid Dysfunctions during Interferon Alpha Treatment of Single and Combination Therapy in Hepatitis C Virus-Infected Patients: A Systematic Review Based Analysis

Thyroid dysfunction is the commonest endocrinopathy associated with HCV infection due to interferon-based treatment. This comprehensive and systematic review presents the available evidence for newly developed thyroid antibodies and dysfunctions during interferon treatment (both single and combination) in HCV patients.
Continue to full text

Gilead Sciences - Sofosbuvir, formally GS-7977

Monday Gilead Sciences announced results from two Phase III studies, one called FISSION and the other called NEUTRINO.

In both studies treatment-naïve patients underwent a 12-week course of the once-daily nucleotide sofosbuvir. In FISSION the two drug combo of sofosbuvir and ribavirin was tested, and in NEUTRINO, sofosbuvir in combination with ribavirin and pegylated interferon was used.

Published yesterday over at Seeking Alpha is an article for investors breaking down both Phase III studies written by Amit Cohen, he writes;

The FISSION study enrolled approximately 500 treatment-naïve patients with HCV genotype 2 or 3 (at a 1:3 ratio) and evaluated the safety and efficacy of 12 weeks of GS-7977 + RBV vs. 24 weeks of PEG-IFN and RBV. The primary endpoint of the trial is SVR12 (sustained viral response at week 12 after treatment is completed). FISSION was a non-inferiority trial in which the bottom end of the 95% confidence interval of sofosbuvir's SVR rate had to be within 15% of the SVR rate of PEG-IFN. With the weakest part of sofosbuvir's profile being its activity in GT 3 patients, and a 3:1 ratio of GT 3 vs GT 2 in the study, there was some chance that the noninferiority margin could have been missed. In fact, the expectations for FISSION had come down significantly after the release of POSITRON data during Q4:12. In POSITRON sofosbuvir + RBV produced SVR rates of 93% in genotype 2 patients and 61% in genotype 3 patients.

While the FISSION data were perhaps a bit below this bar, they were overall consistent. Overall 20% of patients in the study had compensated cirrhosis, and 72% had GT 3 infection. FISSION met its primary endpoint with 67% (170/253) of sofosbuvir + RBV patients achieving SVR, versus 67% in the PEG-IFN + RBV group. The 95% confidence interval for the comparison ranged from -7.5 to +8.0 percent, meeting the predefined criteria for non-inferiority. Sofosbuvir produced a 97% SVR rate in GT 2 patients, and a 56% in GT 3 patients, compared to 78% and 63% for PEG-IFN in those respective populations.

Little new information is given about sofosbuvir's side effect profile, although the press release does note that "The most common adverse events in the sofosbuvir plus RBV arm occurring in >10% of the patients were fatigue, headache, nausea, insomnia, and dizziness." 3 patients (1%) on sofosbuvir discontinued treatment due to adverse events, compared to 26 (11%) on PEG-IFN/RBV.

Conclusion: These results are highly encouraging considering sofosbuvir plus ribavirin is an all‐oral regimen that is taken for 12 weeks versus the current standard‐of‐care (24 weeks). While SVR rates were lower in this trial relative to the Phase II, there were different baseline characteristics (greater proportion of genotype 3 patients) and therefore the FISSION study should support regulatory approval. With the success of FISSION removing the biggest near-term risk to sofosbuvir's development, the results are an incremental positive for GILD.

The second study, NEUTRINO, was an open-label, multicenter study in treatment-naïve patients. The trial recruited 327 GT 1,4,5, and 6 patients, and all were dosed with 400mg sofosbuvir QD plus PEG/RBV for 12 weeks. 17% of patients had compensated cirrhosis, while 89% had GT 1 HCV. The primary endpoint of the trial is SVR. The NEUTRINO study closely reflects the design of the ATOMIC trial in which 12 weeks of sofosbuvir, pegylated interferon and ribavirin were also given. Data from ATOMIC released at the EASL meeting in April 2012 showed that 90% (47/52) of patients in the arm that received 12 weeks of sofosbuvir+PEG/RBV achieved SVR12. The NEUTRINO results were very consistent with those of ATOMIC. In NEUTRINO 90% of sofosbuvir/PEG/RBV achieved SVR, well above the historical control SVR rate of 60%. Importantly, sofosbuvir/PEG/RBV was able to achieve such a high SVR rate in GT 1 patients with only 12 weeks of dosing. Most of the side effects seem attributable to PEG-IFN/RBV and include fatigue, headache, nausea, insomnia, and anemia.

Conclusion: After 327 patients were treated for 12 weeks, the study met its primary efficacy endpoint of superiority compared with a predefined historical control SVR rate of 60% in the same patient population. Overall, this data is encouraging, especially when one considers the typical results seen with the current standard‐of‐care.

Going forward, data from one more ongoing Phase III study ((FUSION)) evaluating 12 or 16 weeks of sofosbuvir plus ribavirin in 200 treatment‐experienced patients with genotype 2/3 HCV is fully enrolled and SVR12 results are expected in the first quarter of 2013. Collectively, results from the FISSION, FUSION, NEUTRINO, and POSITRON will form the basis of Gilead's initial regulatory filing for sofosbuvir, which is expect by the middle of 2013.
Read more @ Seeking Alpha

 Mericitabine pegylated interferon and ribavirin regimen

Mericitabine improved outcomes from peginterferon/ribavirin therapy for chronic HCV

Pockros PJ. Hepatology. 2013;doi:10.1002/hep.26275.
February 8, 2013

The addition of mericitabine to a pegylated interferon and ribavirin regimen for patients with chronic HCV safely improved treatment efficacy in a recent study.

In a phase 2b, multicenter, double blind trial, researchers randomly assigned treatment-naive patients with chronic HCV genotype 1 or 4 to receive either 1,000 mg mericitabine (Genentech) (n=81) or placebo (n=85) twice daily for 24 weeks, in addition to a 48-week regimen of pegylated interferon alfa-2a and ribavirin. Treated patients who achieved extended rapid virologic response (eRVR, defined as HCV RNA levels below 15 IU/mL between weeks 4 and 22) discontinued therapy after 24 weeks, while remaining patients completed the peginterferon/ribavirin regimen.

“Most believe that nucleoside polymerase inhibitors [NPI] will be the backbone of antiviral therapies for HCV,” researcher Paul J. Pockros, MD, director of the Liver Disease Center and the SC Liver Research Consortium at Scripps Clinic in La Jolla, Calif., told “The first NPI was R1626 (balapiravir), [which] proved to be potent, but toxic. Therefore, the critical need was to develop a safe NPI.”

Throughout treatment and follow-up, treated patients had higher rates of virologic response than placebo recipients. eRVR occurred in 60.5% of mericitabine recipients and 12.9% of placebo patients, while 56.8% of treated patients achieved sustained virologic response (SVR) vs. 36.5% of placebo recipients. Higher SVR rates among mericitabine recipients persisted after subdivision for IL28B genotype (77.8% vs. 56% among CC genotypes; 44.1% vs. 16.2% for non-CC genotypes) and cirrhosis (38.1% vs. 21.7% among cirrhotic patients; 63.3% vs. 41.9% among noncirrhotic patients). Relapse occurred in 27.7% of treated and 32% of placebo patients.

Adverse events, including fatigue, headache and nausea, occurred similarly for treated and placebo patients. Treated patients experienced more serious adverse events (6.2% vs. 3.5%), although fewer were forced to discontinue treatment for safety-related reasons.

“A 24-week response-guided combination regimen of mericitabine 1,000 mg BID plus Peg-IFN-a2a/RBV is well tolerated and more effective than a standard 48-week course of Peg-IFN-a2a/RBV,” Pockros said. “However, it is not as potent as sofosbuvir, the competing NPI currently in phase 3 development.”

Disclosure: See the study for a full list of relevant disclosures.
Source - Healio

Failed - Idenix Pharmaceuticals ending development of IDX184 and IDX19368

CNBC Reported;
The two Idenix drugs, IDX184 and IDX19368, as well as another drug from Bristol-Myers Squibb Co. called BMS-986094, work in similar ways. All three products are nucleotide inhibitors, meaning they are designed to prevent the hepatitis C virus from making copies of itself.

In August Bristol-Myers halted testing of BMS-986094 after one patient in the clinical trial died of heart failure following treatment. The drugmaker eventually abandoned development of the product.
Idenix has said there are important differences between the drugs, but the Food and Drug Administration placed IDX184 on clinical hold Aug. 16. At the time, it was Idenix's most advanced experimental drug. The FDA also had placed a hold on IDX19368, which hadn't begun patient dosing.

The company submitted cardiac safety data on IDX184 to the FDA in December, but said Monday it received word from the FDA this month that the programs for both IDX184 and IDX19368 would remain on hold.

"Although we are choosing not to continue our IDX184 and IDX19368 programs, we intend to maintain our strong presence in developing nucleotide polymerase inhibitors for HCV (hepatitis C virus) based on our broad discovery platform," said Ron Renaud, Idenix's president and chief executive.
Read the press release from Idenix here

Big Pharma

Transgene Won’t Sign TG4040 Partnership Soon, CEO Says
By Albertina Torsoli
Transgene SA is reviewing the strategy for its experimental hepatitis C treatment and is unlikely to find a partner for the therapeutic vaccine soon, Chief Executive Officer Philippe Archinard said.
The French drug researcher, controlled by the Merieux family, is developing the TG4040 compound for use with the injection drug interferon, a standard treatment that will probably soon be replaced by newer medicines taken in the form of pills, Archinard said in a telephone interview....
Read more @ Bloomberg 

How Drug Companies Are Boosting Profits Through Tax Gimmicks, Not New Medicine
By Pat Garofalo
In the last few years, tech companies have gotten very good at using offshore tax havens to drive down their effective tax rates. And they evidently have some company. The Wall Street Journal noted today that drug companies are also increasingly using offshore tax gimmicks to drive down their tax rates, boosting profits without investing in new medicines:
Gilead Sciences Inc. GILD -0.23% said its rate could “decline over time” if a hepatitis C drug it is developing receives approval, because of steps the company has taken to lower taxes on the drug’s sales.....
Continue reading here...

For Your Viewing Pleasure

In the spirit of new HCV drugs, we are presented with a video from the one and only Ira Jacobson, MD. The video highlights the new protease inhibitors-triple therapy and interferon-free combinations currently in clinical trials.
View "Hepatitis C: Present Management and Future Directions" Ira Jacobson, MD and another shorter video, Hepatitis C Management - Professor Ira M Jacobson 


Non-Invasive Tests For Liver Cirrhosis
Listen to Podcast here

Hemorrhagic ascites leads to worse outcomes in cirrhotic patients
The presence of hemorrhagic ascites is predictive of poor outcome in patients with cirrhosis, according to recent results.In a retrospective case-control study, researchers evaluated the records of 1,113 patients with cirrhosis and ascites who received paracentesis at a single hospital between 2003 and 2010. Hemorrhagic ascites (HA) was identified in 214 cases, and outcomes within this group were compared with those of 642 matched controls with cirrhosis and ascites.
Read more here...

Vibriosis, Deadly Disease Associated With Raw Oysters, May Get More Common As Ocean Warms


Vincent Rhodes, 57, is one of the latter. When he visited Florida with his wife in July 2012, he was already suffering from cirrhosis of the liver, but he was relatively asymptomatic. None of his doctors had ever told him to avoid raw oysters because of his condition.

Just hours after Rhodes ate a dozen oysters at a beachside restaurant south of Tampa, Fla., he fell seriously ill. His wife, Diana, insisted he go to the hospital. On the way there, he recalls, Diana told him his skin “looked completely gray.” Rhodes’ health worsened in the hospital, as Dishon’s had. He was in the Intensive Care Unit for three days. He ended up staying in the hospital for about a week before going home to Colorado.
Continue reading @ The Huffington Post


Donor liver quality: an interview with Dr Eric Orman

Please can you give a brief introduction to liver transplantation?
Liver transplantation is a surgical procedure in which a liver (or part of a liver) is removed from a donor and placed into a recipient. Although some transplants use a portion of the liver of living donors, the vast majority of donors are deceased.

Liver transplant is life saving and is the only treatment option for many patients with liver failure, liver cancer, and a variety of other ailments. More than 70% of patients remain alive 5 years after their transplant. In 2012, more than 5,000 liver transplants were performed in the US.

How does organ availability place constraints on the transplant community?
More than 1,000 patients die on the transplant list each year waiting for a liver; the supply of donor livers is the limiting factor in the number of procedures that can be performed. We rely mostly on livers from deceased donors (as opposed to living relatives or friends), so it is essential that we maximize the number of deceased organ donors.

To this end, the transplant community has tried to expand the donor pool by using more “extended criteria donors”. This group includes older donors, donors with fatty livers, and donation after cardiac death (DCD) donors. DCD donors are those who undergo organ procurement shortly after the breathing machine and blood pressure medications are stopped and after the heart stops beating. This is in contrast to standard donation after brain death (DBD), in which the donor is declared brain dead, and the lungs and heart continue to get supported during the organ procurement process.

What features does a high quality donor liver have?
The issue of donor quality is an important one, because we know that donor factors can impact the outcomes for recipients after transplant. Many studies have been performed looking at this question, and there are many factors that can be considered markers of a “high quality” donor. After transplant, patients do better if the liver donor was young and had brain death following trauma. Other issues are important as well.

Fatty liver, which is strongly associated with diabetes, obesity, and metabolic syndrome, is becoming increasingly common, and studies suggest that up to 1/3 of adults in the US have fatty livers. Donor livers with more fat in them tend to do worse after transplant, so these livers are typically judged to be low quality.

Another big issue is that livers from DCD donors also don’t do as well after transplant. This may be because the surgeons have to wait a few minutes after the heart stops beating before procuring organs, so the liver is not receiving blood flow for a period of time prior to procurement. This is not an issue for brain dead donors, because the heart and lungs are supported during the procurement.

What are the main reasons why a donor liver may be unused?
We all want the absolute best outcomes for our patients, so when an organ is judged to be of poor quality, transplant centers can refuse to use the liver to avoid a bad outcome and complications after the transplant. So there are many factors that are weighed in the decision to use or not use a liver, and many have to do with the quality of the donor.

Our study, using US national transplant data, looked at the characteristics of organ donors whose livers were not used, and not surprisingly, increasing donor age, diabetes, obesity, and DCD were all associated with non-use. The data do not reliably record fatty liver, but we surmise that diabetes and obesity were markers of fatty liver. Interestingly, from 2004 to 2010, non-use of DCD donor livers increased four-fold. This probably reflects the accumulating experience that DCD livers are in fact worse than standard DBD livers.

How has the availability of high quality donor livers changed over recent years?
The diabetes and obesity epidemics are impacting the public health in many ways, and organ donation and transplantation is yet another example. Fatty liver is becoming a leading cause of severe liver disease and cirrhosis and is accounting for more and more of the patients who need a transplant.

On the donor side, fatty liver is also becoming more common. We found in our study that the number of organ donors with diabetes and obesity is increasing and that organ donors are, on average, getting older. So more of our donors have “low quality” livers.

We also found that the number of donors who are DCD has increased, while the number of standard DBD donors has actually decreased. How, or even if, these two trends are related is not really known.

How does this compare to the availability of other donor organs?
There is a shortage of all solid organs, and demand is not being met for any group. Kidneys may be the best comparison group. Although the above factors also affect the quality of donor kidneys, the impact of some of these factors may not be as great. For instance, DCD kidneys may not be as good as standard kidneys, but they probably do better than DCD livers, so DCD is not as big of a deal for the kidney transplant community.

What do you think is the reason for the downward trend in the availability of high quality donor livers?
The aging population and the obesity and diabetes epidemics are clearly responsible for much of the trend in quality and liver availability. The other big emerging issue is DCD. We found that between 1995 and 2010, the percentage of donors who were DCD increased from 1% to 11%. When we combined that with the increasing reluctance to use DCD, we found that DCD accounted for more than a quarter of liver non-use in 2010.

If DCD was simply being used to expand the existing donor pool, this wouldn’t matter. The problem is that standard DBD is decreasing. We don’t know why this is happening. Some have suggested that doctors are getting better at neurological management, so we are avoiding brain death in more patients. Others have hinted that donors who are not yet brain dead are being taken off of life support and used as DCD donors before they have had time to progress to brain death. But the truth is that we really don’t know.

What impact has this trend had?
The total number of liver transplants performed in the US has been declining since 2006. Lower donation rates are responsible for some, but not all, of the decline. Increasing non-use of donated livers is contributing to the declining numbers of transplants as well. This may become more problematic as demand for livers continues to increase.

How can the donor pool be increased and are there any plans in place to achieve this?
Many of the strategies to increase the donor pool have focused on increasing extended criteria donation and DCD. These strategies may be helpful for the kidney transplant community, but unfortunately, these are the very livers that are likely to go unused and therefore may not improve our capacity to perform more liver transplants. Currently, work is under way to try to improve outcomes for these lower quality livers, for instance through better organ preservation techniques after liver procurement. Of course the best way to increase the donor pool is simply to get more people to agree to become organ donors.

Are there any dangers of using more inferior organs?
The stakes can be high for liver transplant recipients. Patients who receive low quality donor livers are more likely to develop complications with their bile ducts, which are the tubes that drain bile from the liver into the intestines. Such complications can lead to infections and liver graft damage. Studies have shown that these patients are more likely to develop graft failure. Patients who receive such livers may also incur longer hospital stays and increased costs.

How far do you think we are from being able to transplant bionic organs?
There is a lot of research being conducted looking at xenotransplantation, which is the transplantation of organs from one species to another. For instance, a promising approach would be transplanting a pig liver into a human. Given the ongoing shortage of donor livers, this would be a boon to the liver transplant community. Unfortunately, many barriers to this type of treatment exist and much more research needs to be done before this will become a reality.

Where can readers find more information?
Our recent study and the accompanying editorial can be found here:
More information on organ transplantation and donation can be found here:

Would you like to make any further comments?
The decision about whether or not to use a particular donor liver can be a difficult one, and both donor and recipient factors and individual preferences play important roles. Our work is a simplification of some of these issues, but the overall trends in donor quality are concerning, particularly given the on-going declines in transplant volume.

Liver Cancer

Launch of New Patient-Focused Website at

To provide accurate, easy-to-understand information to people diagnosed with liver cancer, the Hepatitis B Foundation has created the first patient-focused website,

The website aims to help people better understand how liver cancer is diagnosed and how it can be treated or prevented. In addition, includes a Drug Watch of potential new liver cancer therapies, an expanding directory of liver cancer specialists, and a clinical trials listing.
Read More @ Hepatitis B Foundation

Extrahepatic Manifestations - Insulin resistance, type 2 diabetes and hypertension

In this analysis titled "Associations of chronic hepatitis C with metabolic and cardiac outcomes" the association of chronic hepatitis C with risk factors for cardiovascular diseases were examined, view the paper online in the February issue of Alimentary Pharmacology & Therapeutics.

The researchers concluded; Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes and hypertension) and congestive heart more here.

Milk Thistle

Published online this week in the journal Antioxidants, is a look at different brands of commercially sold silymarin, the researchers collected 45 different products from local stores and then analyzed them for their silymarin content, antioxidant activities, and antiviral activity against HCV.
Download the full text here


Vitamins? The Magic Bullet Against Hepatitis C

Hans L Tillmann
Expert Review of Anti-Infective Therapy

Evaluation of: Rocco A, Compare D, Coccoli P et al. Vitamin B12 supplementation improves rates of sustained viral response in patients chronically infected with hepatitis C virus.

Gut doi:10.1136/gutjnl-2012-302344 (Epub ahead of print) (2012).

Vitamin B12 was first mentioned to have a role in HCV treatment approximately a decade ago, but it has not been well translated into clinical medicine. Recently, however, a randomized trial has reported significantly better response at all time-points during therapy with pegylated interferon plus ribavirin, if such therapy was combined with vitamin B12. This correlates with reports on vitamin B12 being able to inhibit HCV in vitro and a report that vitamin B12 levels were related to treatment response. If further validated, vitamin B12 is another vitamin reported to be beneficial for HCV therapy. Vitamin D had repeatedly been reported to be associated with response to HCV therapy. It will be interesting to see whether vitamins such as B12 and D will remain relevant in the light of direct antivirals.
Continue reading at Medscape or here on the blog.


Epidemiology and treatment of hepatitis C genotypes 5 and 6

CANADIAN JOURNAL OF GASTROENTEROLOGYAlthough HCV genotypes 5 and 6 are prevalent in certain geographical areas, they are studied less extensively. HCV genotypes 5 and 6 are uncommon in Canada and account for less than 5% of HCV-infected Canadians. However, immigration and travel can alter the epidemiology of these uncommon genotypes. The present article reviews and summarizes the available data regarding the epidemiology and treatment of HCV genotypes 5 and 6. Genotype 5 is endemic in the northern part of South Africa while genotype 6 is reported primarily in Asia. Available data show that 48 weeks of treatment with a combination of pegylated interferon and ribavirin lead to a higher sustained virological response compared with HCV genotypes 1 and 4. None of the approved direct-acting antiviral agents is currently recommended for the treatment of HCV genotypes 5 or 6.
Download full text here

Hepatitis C Virus Diversity and Hepatic Steatosis

Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects throughout the viral lifecycle, with hepatic steatosis frequently observed in patients with chronic HCV infection.

Hepatic steatosis is most common in patients infected with genotype 3 viruses, possibly due to direct effects of genotype 3 viral proteins. Hepatic steatosis in patients infected with other genotypes is thought to be mostly due to changes in host metabolism, involving insulin resistance in particular.

Specific effects of the HCV genotype 3 core proteins have been observed in cellular models in vitro: mechanisms linked with a decrease in microsomal triglyceride transfer protein activity, decreases in the levels of peroxisome proliferator-activating receptors, increases in the levels of sterol regulatory element-binding proteins, and phosphatase and tensin homologue downregulation. Functional differences between the core proteins of genotype 3 viruses and viruses of other genotypes may reflect differences in amino acid sequences. However, bioclinical studies have failed to identify specific 'steatogenic' sequences in HCV isolates from patients with hepatic steatosis. It is therefore difficult to distinguish between viral and metabolic steatosis unambiguously, and host and viral factors are probably involved in both HCV genotype 3 and nongenotype 3 steatosis.
Full Text Available @ Medscape

Transmission - Clinical Setting

95 patients infected with hepatitis C linked to Chinese clinic

Ninety-five people have been hospitalized after a private clinic gave them injections suspected to be contaminated with hepatitis C, Chinese state media say.
The official Xinhua News Agency says 120 patients who received treatment at the clinic in Liaoning province were traced and screened for the disease and 95 of those are suspected to have been infected with hepatitis C.

It said Tuesday that local authorities were tipped off that patients who had received varicose vein treatment could be infected. It says the case is being investigated.

The hepatitis C virus causes a liver disease which can range from a mild illness lasting a few weeks to a serious, lifelong condition that can lead to cirrhosis of the liver or liver cancer.

Hepatitis C contamination tied to health care facilities has been a recent concern in the United States.

Last year, traveling lab tech David Kwiatkowski was charged with stealing syringes of the powerful painkiller fentanyl from the cardiac catheterization lab at New Hampshire's Exeter Hospital and replacing them with saline-filled syringes tainted with his own blood. Thirty-two people in New Hampshire have been diagnosed with the same strain of hepatitis C that Kwiatkowski carries, along with six in Kansas, five in Maryland and one in Pennsylvania.

In January 2012, two western New York hospitals warned its insulin pens may have been used by multiple patients, potentially risking more than 2,600 patients with bloodborne infections such as hepatitis B and C, and HIV.

More than 150,000 U.S. patients have been impacted by unsafe injection practices since 2001, according to Centers for Disease Control and Prevention, causing serious health damage by exposing patients to bloodborne illnesses, such as hepatitis and HIV, and to life-threatening bacterial infections.
Source - CBS/AP


Risk of hep C transmission via breast milk is “infinitesimally small”
A doctor in Canada says there is virtually no risk of a mother with hepatitis C passing the virus to her child by breastfeeding.
The comment comes after a couple from Edmonton launched a $3.2-million lawsuit, claiming that their baby was given breast milk supplied by another woman who was infected with the disease...
Continue reading @ Hepatitis C News


How men with HIV can safely become dads

SF Chronicle Feb 7 2013

Deon was in jail when he tested positive for HIV.

He knew that his long-term girlfriend was HIV-positive, and they hadn't taken many precautions to keep him safe. So he wasn't surprised by the diagnosis, but the news was still crushing.

"I was devastated," said Deon, 32, a San Francisco resident who asked that his last name not be used. "I didn't know if I was going to live. I didn't know if my social life was basically over. I didn't know how I was ever going to have a family."

Nearly five years later, Deon has a new girlfriend. And this month, she will give birth to their first child - a girl who, like her mother, is not infected with HIV. Deon, whose infection is so well controlled that the virus is undetectable in his blood, will have his family.

"She's due Feb. 20," Deon said. "I can't wait."
Continue reading here...

HIV associated with nonresponse to HBV vaccine

Irungu E. J Infect Dis. 2013;207:402-410.
February 7, 2013

Adults in Kenya had similar responses to hepatitis B virus vaccination as those from high-income countries, recent data indicate.

Although vaccine nonresponse was higher among participants with HIV, revaccination of the nonresponders increased the response to 95%, researchers from University of Washington and the Kenyatta National Hospital in Nairobi, Kenya, reported in the Journal of Infectious Diseases.
The prospective interventional study included 603 participants, of whom 310 had HIV. All of the participants were concurrently enrolled in the Partners PrEP study and were screened for HBV. Those who were susceptible to the disease were given the HBV vaccine regimen.

Six months after vaccination, 111 of the patients (35.8%) with HIV did not have protective HBV surface antibody titers vs. 42 of the 293 patients (14.3%) without HIV. In a multivariate analysis of the participants with HIV, sex and CD4 counts were associated with nonresponse. Men were more likely to be nonresponders as were participants who had CD4 counts of less than 500 cells/mcL.

Among the nonresponders with HIV, 102 completed the revaccination, of whom 72 developed a positive antibody response after the first dose and another 16 developed an antibody response after the third dose. Among those with HIV, the cumulative response was 64.2% after the initial series, 89% after the first revaccination dose and 94.9% after the complete revaccination series. Factors associated with nonresponse after revaccination included low BMI, a HIV-1 RNA of more than 50,000 copies/mL at baseline and a longer time to revaccination.

“Our findings add to the body of research on HBV vaccine immune responses and may help guide policy on the best practices for revaccinating HIV-1 infected persons who do not respond to the standard HBV vaccination schedule,” the researchers wrote.
Source - Healio

Healthy You

Your Fingernails and Your Tongue: What Do They Say About Your Liver?
It’s interesting how our body shows physical signs that tell us of the condition of our internal systems and organs, including our liver. Many of us are not aware of these signs – some may even argue the reliability of these external manifestations. Still, as we keep an open mind for the sake of health and well-being, many health experts invite us to take a closer look at our fingernails and tongue, as they can tell us important things about our liver.
Read more here..


Monitor the state of your liver at least once a year to determine if the disease is progressing and if cirrhosis or liver cancer is developing.

Review all medications with your physician. Some over-the-counter and alternative medicines can harm the liver.

Have periodic ultrasound and alpha-fetoprotein blood tests for liver cancer.

If pregnant, be sure to tell your physician you are a hepatitis B carrier so your baby will receive hepatitis B vaccine and immune globulin at birth.

On routine visits, remind your doctor, dentist, and other healthcare providers that you are a hepatitis carrier.

Stay informed about research developments regarding treatments so you are able to make the best decisions. Research is ongoing to improve the treatment for chronic hepatitis C (HCV) and hepatitis B (HBV) infections and develop a vaccine for HCV.

Happy Valentine’s Day: Dinner, Sex and Hepatitis C

By Nicole Cutler, L.Ac.

Valentine’s Day celebrations often include plans to indulge in an elaborate meal – and aspirations for physical intimacy. Tempted by a desire to make the date special and encouraged by delicious-sounding menus, February 14th may be one of the few times a year couples make reservations to dine out. Despite a growing general awareness of the importance of healthful eating, special restaurant menus for Valentine’s Day are commonly laden with rich, sinful dishes. Besides potentially interfering with sexual libido, those with Hepatitis C risk provoking liver inflammation with this type of fat-filled feast. As an alternative, consider cooking your own Valentine’s Day dinner – relying on dishes that will help you feel in the mood.
Read more @ Hepatitis Central

Shingles immunity from chicken pox vaccine unclear, experts say

I was around eight years old when I got chicken pox, and I remember there was a lot of scratching and calamine lotion involved. These days, you don’t really hear about kids catching chicken pox, thanks to a vaccine approved by the FDA in 1995.

Had a chicken pox vaccine been available to me as a child, would I now be immune to developing shingles, a disease caused by the same virus? An article in today’s San Francisco Chronicle describes how experts, including Ann Arvin, MD, who led research that helped explain immune responses to varicella zoster (the virus that causes chicken pox), are uncertain of the answer. But:

In the meantime, [Arvin] offers advice to adults over 50 who fear shingles’ wrath: Get the shingles vaccine. Zostavax, which is also created from a weakened form of varicella, boosts adults’ ability to fight the existing virus if it reactivates. The FDA approved the vaccine for people 50 and over in 2011, after a study of 22,000 people showed that people who had the vaccine were 70 percent less likely to get shingles within a year than people who received a placebo…
Source - Scope


The Final Steps in My Hepatitis C Treatment Journey

I'm nervous. Or is it anxious? Either way I am out-of-sorts and, quite frankly, I just want the next 10 days to fly by as quickly as possible.

You see, I go for my six month post Hepatitis C treatment blood work this weekend and apparently I am all freaked out about it.
Continue reading @ Oh My Aches And Pains

Hepatitis C: A Scrabbled Brain

by Lucinda Porter, RN

As a person living with hepatitis C, the symptom that is the most difficult for me to handle is neurocognitve dysfunction, commonly referred to as brain fog.
Read more @ Lucinda 

Off The Cuff

If The Drug Is Cheap, It Must Be Good?

By Ed Silverman

Yes, you read that correctly. In an era when more high-priced biologics are being introduced all the time, consumers believe that a truly vital medicine is less expensive. Why? Consumers believe prices are based on need, not profit, and assume the risk of getting a serious illness is higher when the drug is cheaper, according to a new study. As a result, they are also more likely to seek treatment.
Read more @ Pharmalot

I'm So Serious

The armchair as a fitness trainer - Lazy boy workout ??

Researchers are presenting an armchair that brings the gym right into your living room at the push of a button.

An intelligent armchair that we can not only comfortably sink into in front of the television, but one that also motivates us to keep ourselves healthy and fit.

If you dare read more @ Medgadget

Just For Fun

Play The Really Big Hepatitis C Crossword Puzzle - That Will Not Fit Nicely On My Blog

Created by this blogger sitting in a fitness armchair while watching TV.

To restart the puzzle refresh this page

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