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In This Issue:
Top 10 News of 2010
Alan Franciscus, Editor-in-Chief
HealthWise: Vitamin D and the Liver
Lucinda K. Porter, RN
Lucinda K. Porter, RN
AASLD 2010: Part 2
Alan Franciscus, Editor-in-Chief
HCV Advocate Eblast
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Top 10 News of 2010
—Alan Franciscus, Editor-in-Chief
It’s that time of year again when the staff of HCSP and the HCV Advocate compile the top news stories about hepatitis C. It seems like I was just sitting down compiling a list for 2009, but what a year this has been for drug development, diagnostic tools and discoveries–all of which provide insights that expand our knowledge and understanding of the hepatitis C virus.
The top story of the year is shared by telaprevir and boceprevir followed by important news stories that are not necessarily in order of importance.
Top News Story of the Year
HCV Protease Inhibitors—Telaprevir and Boceprevir. Both drugs finished their phase III clinical studies in 2010. When boceprevir and telaprevir were combined with pegylated interferon and ribavirin the studies showed an increase in the number of people who can be cured. In addition some people who achieved a rapid and dramatic decrease in HCV RNA (viral load) early on in treatment were able to shorten the duration of treatment. The higher response rates were seen in people who had never been treated (treatment naïve) and in people who had been treated before but did not achieve an SVR. The added good news is that in the groups that traditionally have had poor treatment response rates—African Americans, Hispanics and people with cirrhosis—the treatment response rates are vastly improved.
Of note: Vertex completed their application to the Food and Drug Administration (FDA) for marketing approval of telaprevir—approval is expected by mid-2011.
- DAA Combinations: Various combinations of Direct Acting Antivirals (DAAs) are being studied with and without pegylated interferon plus ribavirin. There are currently six clinical trials using combinations of polymerase, protease and/or NS5A inhibitors from Pharmasset, Boehringer, BMS, Gilead, Genentech and Vertex. The big question—can treatment with just DAAs (without pegylated interferon and ribavirin) achieve a viral cure? This is the most pressing question that has not been answered; but most experts believe that it’s only a matter of time before the right combination(s) will be developed, tested and found to completely suppress the hepatitis C virus permanently.
- HCV NS5A Inhibitors: Scientists are not really sure of the role of the NS5A protein in the replication process, but various NS5A inhibitors have been studied and found to produce steep declines in HCV RNA and are believed to be pan-genotypic—that is, they work against all HCV genotypes. Various NS5A’s are in phase I studies and a combination of Bristol-Myers Squibb’s NS5A and a protease inhibitor are in combination studies with and without interferon and ribavirin.
- The First Covalent HCV Protease Inhibitor: In November it was announced that Avila Therapeutics developed a covalent HCV protease inhibitor. It is believed that the covalent line will be able to permanently inhibit the hepatitis C virus from replicating. Now we just need to study it in healthy volunteers and people with hepatitis C to make sure it is safe and effective.
- IL28B: People with HCV genotype 1 who have a certain variation called CC genotype are more than twice as likely to respond to treatment. The effect of the variation is less predictive of treatment response in non-genotype 1 patients, but more studies are needed. This will also be a factor in the development of new DAA treatments because interferon will be part of the mix—at least for now. But it is believed that the potency of the DAAs will help to overcome some of the limitations of interferon, including the absence of the variation. The test for finding out the type of variation is now available through Lab Corp and it will be a very effective tool in helping to guide the treatment decision process.
- OraQuick HCV Rapid Antibody Test (whole blood draw): This test was approved by the Food and Drug Administration mid-year and will become an important tool for providing rapid results (after 20 minutes) allowing for pre- and post-testing counseling messages as well as linkage to care. The big advancement in HCV testing, however, will be the approval of the finger prick and oral swab. These approvals are expected in 2011.
- HCV and the Brain: It has been known for some time that the hepatitis C virus passes the blood-brain barrier, but what takes place in the brain has remained a mystery. Now, researchers from the University of Alberta have shown that the hepatitis C virus infects brain tissue causing inflammation, damaging certain neurons and inhibiting the removal of debris from the brain. Hopefully, this research will lead to medications that can help to inhibit the hepatitis C virus from passing the blood brain barrier and possibly reverse some of the damage.
- HCV Treatment Improves Survival: Two reports came out in 2010 that looked at possible improvements in liver health as the result of HCV treatment. The first, out of the Scripps Clinic, retrospectively studied 1571 HCV patients who were treated with interferon or interferon plus ribavirin. The authors found that achieving a cure or becoming HCV RNA (viral load) undetectable during treatment improves liver health and survival. The other study, HALT-C, analyzed patient records and concluded that the progression to liver cancer was less in the group that was treated. In addition, patients who were treated for at least 2 years were found to have a considerably lower incidence of liver cancer compared to the control groups of people who were not treated.
- HCV and Fat: An important study was released which found that the hepatitis C virus uses lipid or fat cells to replicate. Furthermore, a key enzyme—DGAT1—was found to be critical in the production of lipid or fat cells that are required by HCV to replicate. Better yet, DGAT1 inhibitors have been developed and some are in clinical trials for treating other ailments. The next step is to study the DGAT1 inhibitors in people with hepatitis C to find out if DGAT1 inhibitors could prevent replication and lead to permanent eradication of HCV.
- Growing HCV: In what may be the most important scientific development of the year in hepatitis C, scientists from MIT and Rockefeller University have been able to grow a strain of the hepatitis C virus in a liver cell. If this can be replicated in other strains of hepatitis C we might finally be able to find out what kills HCV and identify more medications to treat HCV.
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HEALTHWISE: Vitamin D and the Liver
—Lucinda K. Porter, RN
Vitamin D is frequently in the news, presenting interesting, but conflicting information. At the recent Liver Meeting sponsored by the AASLD, there were at least two posters about vitamin D and chronic hepatitis C virus (HCV) infection. On November 30, 2010, the Institute of Medicine of the National Academies (IOM) released its vitamin D consensus report. This month’s Healthwise discusses vitamin D—what it is, why we need it, how much we need, how to get enough, and what those of us with hepatitis C need to know about this supplement.
The liver is essential for the production of vitamin D. A prohormone (precursor to a hormone), vitamin D is activated first by the liver; then by the kidneys. Vitamin D enters the body two ways—via sunlight or by consuming it. When exposed to sunlight’s ultraviolet B (UVB) rays, the skin manufactures vitamin D and the bloodstream transports D to the liver. If consumed by way of food or dietary supplements, vitamin D is circulated to the liver for activation.
The best-known disease associated with vitamin D deficiency is rickets, a condition that causes softening and deformity of the bones. During the industrial era in northern United States and Europe, children working in factories lacked sunlight, making them susceptible to rickets. Scientist discovered the link between vitamin D and rickets, and beginning in the 1930’s, children were given a daily dose of cod liver oil. Fortifying milk with vitamin D dramatically reduced rickets in the U.S. Children were quite happy to drink milk rather than smelly fish oil.
If you scan the news, it looks like vitamin D is a wonder supplement, suggesting that vitamin D does more than just protect the bones. There are reports linking vitamin D to muscle tissue, inflammation, and the immune system. Lab, animal, and epidemiological data suggest a possible link between low vitamin D levels, cancer, diabetes, high blood pressure, cardiovascular disease, multiple sclerosis, gum disease, rheumatoid arthritis, and osteoarthritis.
Since the vitamin D research is confusing, the governments of the U.S. and Canada asked the IOM to clarify the issue. In its report “Dietary Reference Intakes for Calcium and Vitamin D,” the IOM thoroughly reviewed all available research and made the following conclusions:
- Vitamin D is vital to bone health, but has not been proven to have any other healthy benefits.
- The current recommended daily allowance for vitamin D (RDA) needs to be increased.
- More vitamin D is not better. The total daily vitamin D intake for adults and children over age 9 should not exceed 4000 International Units (IU) per day. The totals for infants and children under age 9 are less and vary according to age.
Although the IOM’s report is exhaustive, it is not necessarily perfect. The IOM based its recommendations on a literature review, rather than the gold-standard randomized, double-blind, placebo study. Other researchers are voicing their objections about the IOM’s report, stating that the report is not conclusive and should not make across the board recommended daily allowances that don’t take geography into consideration.
What we do know is that older adults with insufficient vitamin D are at risk for osteopenia (bone thinning) and osteoporosis (bone loss), which may lead to fractures and other complications. With age, the skin’s ability to utilize sun as a source of vitamin D is compromised. Adequate supplementation is the best insurance policy.
Vitamin D and Liver Disease
People with liver disease are susceptible to vitamin D deficiency according to an article titled “Prevalence of Vitamin D Deficiency in Chronic Liver Disease” (Digestive Diseases and Science, September 2010). In this study, researchers Arteh, Narra, and Nair from the University of Tennessee Health Science Center in Memphis, TN looked at 118 patients: 43 with HCV cirrhosis, 57 non-cirrhotic patients with HCV, and 18 patients who had cirrhosis from a cause other than HCV. Arteh and colleagues found that 92% of patients with chronic liver disease had vitamin D deficiency. One-third of these had severe vitamin D deficiency; African American females had the highest risk.
Looking further at the role of vitamin D and liver disease, a team of researchers presented a poster at the 2010 Liver Meeting. In “Vitamin D Metabolites Inhibit Replication of the Hepatitis C Virus” by Gutierrez et al. presented laboratory data showing vitamin D’s ability to inhibit HCV replication. More research is needed to understand the relationship of vitamin D, liver cells and HCV.
Also at the 2010 Liver Meeting, Mouch and Assy presented a poster titled “Vitamin D Supplementation Improves Viral Response in Chronic Hepatitis C Genotype 2/3 Patients Treated with Peg Interferon Alpha and Ribavirin.” This small study looked at 40 HCV patients with genotypes 2 and 3. Baseline levels of vitamin D were measured, before treating all subjects with standard HCV medications. Half of the subjects were also given 1000 to 4000 IU/day of vitamin D, depending on their baseline vitamin D levels.
Despite the fact that the vitamin D group had higher body mass and viral loads, those who took additional vitamin D had better treatment outcomes. It was also noted that those who had lower vitamin D levels at baseline were more likely not to respond to HCV treatment.
Taking Vitamin D
Your medical provider can order a simple blood test to see if you are getting sufficient vitamin D. The IOM recommends that vitamin D levels should be above 20 nanograms per milliliter of blood.
Although we get most of our vitamins from food, vitamin D is more readily obtained from the sun and supplementation. It is naturally available in a few foods, such as fatty fish (salmon, sardines, and mackerel), fish liver and beef liver. Fortified foods are the highest source of dietary vitamin D for those living in the U.S.
Sun exposure is a good source of vitamin D, but it is a not a perfect source. First, there is not enough UV energy in the winter above 42 degrees north latitude (above Boston or the northern border of California). People living in much of Canada and Alaska have less than 6 months of sufficient UV energy from the sun to produce sufficient vitamin D. Second, UV is a potential carcinogen and most experts suggest avoiding direct sunlight or using sunscreen.
In ideal circumstances, 5 to 30 minutes of sun exposure to the arms, and legs or face three times weekly in sunny weather (between 10 AM and 3 PM) will yield sufficient vitamin D. However, darker skin, older age, obesity and other factors may interfere with obtaining adequate D levels. Sunscreen, a necessary protection from skin cancer, melanoma, and interferon-related photosensitivity reduces vitamin D exposure.
Certain medications may interfere with production of vitamin D. The most common of these are anti-seizure medications such Dilantin, weight loss drugs such as Xenical and Alli, the cholesterol-lowering medication cholestyramine and steroids, such as Prednisone.
The best way to insure sufficient vitamin D intake is with dietary supplements. The IOM recommends 600 IU/day for children and adults ages 1 to 70. The RDA for adults over age 71 is 800 IU/day of vitamin D. Keep in mind that if you get vitamin D from the sun and fortified foods, you may already be getting sufficient vitamin D. Do not take more vitamin D than your medical provider recommends.
Excess Vitamin D
Vitamins are classified as water-soluble (dissolves in water) or fat-soluble (dissolves in fat). Water soluble vitamins B and C are eliminated from the body fairly quickly. Fat-soluble vitamins A, D, E and K are stored in the liver. Therefore, it is possible to have excess fat-soluble vitamins stored in the liver, particularly vitamin A.
Excess vitamin D is rare as the amount that produces toxicity is quite high. Adults taking 50,000 IU/day for several months can reach toxic levels. The symptoms of vitamin D toxicity are nausea, vomiting, loss of appetite, excessive urination, excessive thirst, weakness, nervousness, itching, and eventually kidney failure. The IOM advises no more than 4000 IU/day for adults and children over age 9.
Now that the winter months are shortening the amount of sun we are exposed to, take a moment to assess your vitamin D intake. If you have liver disease, such as hepatitis C, are over age 70, or have any factors that may interfere with your body’s production of vitamin D, talk to your medical provider about a blood test to measure the levels. Getting enough vitamin D is a simple, relatively inexpensive way of protecting your health.
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—Lucinda K. Porter, RN
Article: Pegylated Interferon plus Optimized Weight-Based Ribavirin Dosing Negate the Influence of Weight and Body Mass Index on Early Viral Kinetics and Sustained Virological Response in Chronic Hepatitis C, V. Pattullo, N. C. Ravindran, T. Mazzulli, D. K. H. Wong, E. J. Heathcote.
Source: Journal of Viral Hepatitis Volume 17, Issue 12, pages 834–838, December 2010.
The goal of this retrospective study was to determine whether weight or body mass index (BMI) influenced response to hepatitis C treatment. The study looked at subjects with chronic hepatitis C virus (HCV) who were treated with peginterferon plus weight-based ribavirin. The findings from 134 subjects looked at rapid viral response (RVR) and sustained viral response (SVR). The study group average was genotype 1 (57%), BMI 26.7 ± 4.5 kg/m2, with a ribavirin dose of 13.9 ± 2.6 mg/kg/day.
The Bottom Line: The conclusions showed that neither body weight nor BMI influenced RVR or SVR. When weight-based ribavirin is prescribed, the RVR was a more likely positive predictor of SVR than were genotype, viral load, body weight or BMI.
Editorial Comment: Although this report contradicts previous information about BMI and response to treatment, this study is limited in its power to be compelling. First, this is a small study, so more data are needed. Second, the research is retrospective, rather than prospective. Data collection from randomized, double-blind, placebo controlled studies carry more weight than data collected when researchers look backward at the data. Imagine the difference if you are told that there is a treasure chest in your house versus being told that there is something valuable in your house. If you look for a treasure chest, you might only look in places that are large enough to hide a chest, but you might miss a stock certificate hidden in a smaller place. Scientists try to be objective, but it is harder to do so when looking back at available data.
Article: Predictors of Early Treatment Discontinuation among Patients with Genotype 1 Hepatitis C and Implications for Viral Eradication, Lauren A. Beste, George N. Ioannou, Meaghan S. Larson, Michael Chapko, Jason A. Dominitz.
Source: Clinical Gastroenterology and Hepatology, Volume 8, Issue 11, Pages 972-978, November 2010.
This research looked at risk factors that led to early discontinuation of treatment in chronic hepatitis C virus (HCV) patients with genotype 1 who were prescribed 48 weeks of treatment. This study used retrospectively collected data from all HCV patients with genotype 1 who were treated with standard pegylated interferon and ribavirin from 2002–2007 by Veterans Affairs. There were 11,019 subjects.
More than half of the patients completed 80% of the prescribed 48 weeks. Nearly 17% were non-responders, and were discontinued early; approximately 31% discontinued for other reasons.
Factors most associated with early termination before week 12 were cirrhosis, diabetes, pretreatment substance use disorder, hemoglobin, and lack of hematopoietic growth factor.
Looking at patients who had a confirmed response to treatment, discontinuation between weeks 12–24 was associated with higher baseline levels of creatinine, depression, and lack of growth factor use.
No independent factors correlated among patients who responded to treatment but discontinued sometime between 24–48 weeks.
The Bottom Line: The researchers recommend further evaluation of the use of growth factors in order to help patients avoid early discontinuation of HCV treatment. Further recommendations include looking at other risk factors for early termination of treatment, such as pre-existing substance use, depression, cirrhosis, or diabetes.
Editorial Comment: Although this is a retrospective study, the large study population makes the data more significant. However, growth factors do have potentially risky side effects, and the data on this are somewhat conflicting. The researchers’ advice for further study of growth factor use and other variables that may lead to early discontinuation is good.
Article: Patient-To-Patient Transmission of Hepatitis C Virus (HCV) during Colonoscopy Diagnosis, Fernando Gonzalez-Candelas, Silvia Guiral , Rosa Carbo, Ana Valero, Hermelinda Vanaclocha, Francisco Gonzalez and Maria A Bracho.
Source: Virology Journal, September 8, 2010.
It is estimated that between 10 to 40% of patients infected with hepatitis C virus (HCV) state they do not have a known risk factor. Researchers have been trying to discover possible explanations for these cases. Since a reported case of HCV transmission during a colonoscopy appeared in the New England Journal of Medicine (1997), researchers have been evaluating the possible transmission of HCV through this and other medical procedures.
In this retrospective study, researchers looked at the possible transmission of hepatitis C virus (HCV) in two patients who had undergone colonoscopy at the same endoscopy unit. Both patients were HCV-negative prior to the procedure; three months later, each was diagnosed with HCV found when each attempted to donate blood. Blood samples were analyzed from all other patients who had undergone colonoscopies in the same frame; two more HCV+ case were found out of 36 possible cases. Of these four cases, 3 had genotype 1b; 1 had genotype 2c and was eliminated as unrelated. Extensive genetic testing pointed to the likelihood that two of the patients acquired HCV from the HCV+ patient who had the colonoscopy prior to them.
The Bottom Line: The researchers were able to show transmission of HCV from patient-to-patient. However, the exact mode of transmission was unclear. The three patients had the same medical staff, medications, room, and blood collection. Transmission could have occurred at some point during the colonoscopy, from the tools used during the procedure, the anesthesia procedures, or via other breaks in safety practices.
Editorial Comment: The transmission of HCV from one patient to another during a colonoscopy is known as a nosocomial infection, likely occurring because of hospitalization or medical care. There have been only a few reported cases of HCV transmission during colonoscopy, despite the fact that more than 6 million are performed annually (Philadelphia Business Journal, March 2004). Medical procedures are generally safe as they are heavily safe-guarded against transmission of microorganisms. Unfortunately, mistakes do happen. A person’s chances of dying from undiscovered colon cancer because of refusal of a colonoscopy are greater than dying after acquiring HCV during a colonoscopy. On the other hand, we all want to avoid premature death, so if you have concerns about HCV transmission during colonoscopy, you can request this information from your endoscopy center.
Article: Evaluation of Acute Hepatitis C Infection Surveillance: United States, 2008. Reported by RM Klevens, DDS, Div of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; RA Tohme, MD, EIS Officer, CDC.
Source: Morbidity and Mortality Weekly Report (MMWR) November 5, 2010 / 59(43); 1407-1410.
The Centers for Disease Control and Prevention (CDC) publishes the MMWR every week, occasionally featuring an aspect of viral hepatitis. Responding to predictions that chronic hepatitis C virus (HCV) infection is expected to place a huge burden on our medical system from 2010 to 2019, the Institute of Medicine (IOM) recommended an intensive evaluation of the system that monitors viral hepatitis cases. Using acute hepatitis cases in 2008, the CDC compared two surveillance systems: National Notifiable Diseases Surveillance System (NNDSS) and the Emerging Infections Program (EIP).
Every week, state health departments voluntarily report NNDSS data, including new cases of HCV to the CDC via an electronic system. The data include demographics (name and address are not reported), clinical information (e.g., date of onset, date of diagnosis, jaundice, hospitalization, and death), and risk factor exposures occurring 6 weeks to 6 months before illness onset. No laboratory results are sent to CDC through this system.
In 2008, the CDC launched a program to monitor 28 million people with the EIP system funding it in six states, 34 counties in New York, and New York City. EIP collects more information than the NNDSS, including laboratory reports. Staff members using EIP directly contact healthcare providers to complete the EIP forms, and report acute HCV cases to the CDC on a monthly basis.
The Bottom Line: The NNDSS was flawed, with missing data and delays in reporting. Due to budget constraints, several states were unable to handle the volume of cases, leading to a back load of unrecorded cases. Without complete, accurate, and timely surveillance, public health departments are not capable of identifying and quickly reacting to outbreaks, prevention measures are not put into place and those with acute HCV are not being treated early enough. The EIP appears to be effective at identifying outbreaks of HCV.
The CDC recommends employing a nationwide EIP system in order to improve HCV surveillance, in order to intervene early and reduce the overall morbidity and mortality associated with HCV infection.
Editorial Comment: The treatment for acute HCV is very effective with slightly fewer side effects since it uses interferon without ribavirin. Trying to identify HCV in its acute stages is sensible, compassionate, and a good use of public health funds.
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AASLD 2010: Part 2
—Alan Franciscus, Editor-in-Chief
In the first part of our coverage of the American Association for the Study of Liver Diseases Conference (AASLD) — click here— I focused exclusively on the new Direct-Acting Antivirals (DAAs). In part two of our AASLD coverage I will discuss information released about pegylated interferon, long-term sustainability of a viral cure, and other important and interesting information.
The IDEAL Study
The IDEAL study, which was conducted using PegIntron or Pegasys plus ribavirin to treat HCV genotype 1 treatment-naïve patients, has given us a wealth of information about everything from treatment response to the identification of the variation in the IL28B gene region (cc genotype) that was shown to be present in the majority of people who achieved a sustained virological response (HCV RNA or viral load negative 24 weeks after the last dose of HCV medication). This year there were two retrospective analyses released at AASLD:
- Site Performance in Academic vs. Community-Based Centers: Seventy-six academic centers enrolled 2,799 patients (63%) and 42 community-based centers enrolled 1,165 patients (37%). The authors analyzed the side effects, discontinuation rates, SVR rates, and adherence and compared them to see if there were differences in treatment care and response. It was found that there were no differences in adherence, side effects, rates of treatment discontinuation, on-treatment response or SVR between academic and community centers.
- Fasting Glucose and Lower Rates of SVR: 3,070 patients in the IDEAL study were tested for fasting blood glucose levels prior to treatment and at certain time points during therapy. Patients who had greater than an A1C 8.5% were excluded from the study.
Note: A1C measures the amount of sugar in the blood–a typical non-diabetic patient has a level of A1C of 6.5 or lower.
The authors concluded that patients who had impaired glucose or diabetes were less likely to achieve an SVR and were more likely to relapse after treatment was completed. However, the glucose levels did not correlate with SVR, but it was noted that the patients with A1C > 8.5 were excluded from the study, which could have biased this particular conclusion. The authors noted that a study was needed to assess improvement in glucose levels prior to treatment to find out if improved glucose levels translated to better treatment outcomes.
Two studies reviewed data to find out if treatment improved overall survival. The first study was of 103 patients who were treated by the National Institutes of Health (NIH) beginning in 1984 with interferon or pegylated interferon with or without ribavirin. Only 3 patients (<3%) relapsed after achieving an SVR. The follow-up period was .05 to 22 years. No cases of liver decompensation, cancer or liver-related death were reported.
Comments: It’s important to remember that back when these studies were being conducted viral load tests were not as sensitive, which means that some people who were classified as achieving an SVR may have had a low viral load. This most likely explains the 3% of people who became viral load positive after achieving an SVR. Studies of Pegasys and PegIntron data that goes back at least 5 years show that less than 1% of people relapse after achieving an SVR. The most important take away message is that after this long follow-up period there were improvements in liver health and survival—this is a remarkable finding.
The second study was from the HALT-C study and looked at long-term outcomes of people who had advanced fibrosis and who were treated with a low dose (maintenance) of Pegasys for up to 48 months. The first analyses of the data that included follow-up of up to 4.6 years did not find any improvement in overall survival. BUT now that there has been 6.1 years of follow-up it was found that the incidence of HCC or liver cancer was 8.1% in the HALT-C group compared to 13.8% in the control group. Furthermore, patients who were treated for a minimum of 2 years had considerably lower incidence of liver cancer compared to the untreated control group.
Comments: This is all very good news because even in the absence of achieving an SVR patients were able to improve the health of their livers.
PEG lambda is a different type of pegylated interferon that Bristol-Myers Squibb is developing for the treatment of chronic hepatitis C. PEG lambda or IL-29 (once-a-week or once-every-two-week injection) belongs to a new class of interferons called type 3. Although it is in very early development some small studies have shown that it may be as effective as pegylated interferon (Pegasys and PegIntron) and produce fewer side effects.
Below is a recap of a couple of small studies released at this year’s conference:
- Study 1: HCV Genotypes 1, 2, 3, or 4 were given a single injection of PEG lambda (11-12 patients per dose group—80, 120, 180 or 240 mcg/kg). It was found that the drug uptake following the single dose was similar across all genotypes, patient demographics, and IL28B genotypes. The study was found to support once-a-week dosing.
- Study 2: 57 treatment-naïve HCV genotype 1, 2, 3, and 4 patients were given either the above doses of PEG lambda or Pegasys. Based on early viral decline (first and second phase slopes) PEG lambda was found to be as effective as Pegasys. It was also noted that the effect of IL28B was similar between the different variations of CC, CT/TT genotypes.
- Study 3: 55 HCV genotype 1, 2, 3, or 4 treatment-naïve patients received a single dose of the above PEG lambda or Pegasys followed 2 weeks later by the same weekly doses of PEG lambda/ribavirin, or Pegasys/ribavirin for 24 weeks in patients with genotypes 2 and 3, or for 48 weeks for patients with genotypes 1 and 4. Interim 12-week results found that the viral declines were similar between genotypes. It was noted that there were less blood-related side effects in the PEG lambda containing arms.
Comments: These are important studies for a few reasons:
- Most experts believe that we will be able to eliminate interferon from future HCV treatment with a combination of DAAs, but this hasn’t been conclusively proven. If it turns out that interferon is needed for complete suppression of HCV, PEG lambda will offer another treatment option.
- PEG lambda may be more convenient if it can be dosed every two weeks instead of the current pegylated interferons which are dosed once a week. But the studies to date are concentrating on a once-a-week dose.
- PEG lambda may cause less blood-related side effects, such as neutropenia (low white blood cells) and anemia (low red blood cells).
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