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February 2013 HCV Advocate

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In This Issue:

HCV in Water, Containers and Filters
Alan Franciscus, Editor-in-Chief

HCV Snapshots
Lucinda K. Porter, RN

HealthWise: - The Happy Hepper
Lucinda K. Porter, RN


Liver Cancer in People with Hepatitis C: Part 1—Benefits of Antiviral Therapy
Liz Highleyman


New Phase III Interferon-Free Studies
Alan Franciscus, Editor-in-Chief




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HCV in Water, Containers and Filters
—Alan Franciscus, Editor-in-Chief

The most common transmission route for hepatitis C is from sharing HCV infected needles and drug preparation tools.  Before the discovery of an HCV cell culture system—Japanese fulminant hepatitis (JFH1) HCV isolate—there was basically only one solid science study that told us the length of time that HCV can survive outside the body.  Since the cell culture discovery, however, there have been many important findings for knowledge and prevention of HCV transmission.

This article will summarize the important findings to date and provide information about a new study that concentrated on water, water bottles, and filters. 

The Studies
The first study that looked at the time that HCV could live on surfaces was conducted by the Centers for Disease Control and Prevention (CDC).  At the time a cell culture was not available so a chimpanzee—the only other animal that could be infected with HCV—was inoculated with HCV.  The chimpanzee’s blood was dried (7 days, 4 days and overnight) and reconstituted.  It was found that the hepatitis C virus could survive on surfaces for at least 16 hours but no longer than 4 days.1  

In 2010 a study was released detailing how long the hepatitis C virus lives inside a syringe.  The study found that the hepatitis C virus can live for up to 63 days in a high volume tuberculin syringe with a detachable  needle compared to 7 days in a low volume syringe (insulin syringe with permanent needles).2

 Another important study released in 2011 looked at the effect of commercially available disinfectants and the temperature required to kill the hepatitis C virus.  The published results found that commercially available disinfectants reduced the infectivity of HCV to undetectable levels with 1-propanol as the most effective disinfectant.  The results on the effect of heat on the hepatitis C virus found that when spoons and cookers were heated for 80-95 seconds to a temperature of 67-70oC (152.6 – 1580F) HCV was undetectable.  Injectors use spoons and a cooker to heat heroin, but Holly Hagen, in an accompanying editorial, stated that based on research only about 15% of people who inject drugs (PWID) heat drug solutions for more than 45 seconds, with most injectors heating solutions for less than 15 seconds.3,4

Researchers lead by V. Thibault studied pooled works (50 swabs/cotton pads, 20 cups, 20 vials, 10 filters and 60 syringes) and analyzed them for HCV RNA and found that 43.8% of all pooled materials tested positive for HCV RNA.  Swabs accounted for the highest rate of detectability with 80% testing positive for HCV RNA.  In the second part of the study (to validate the findings in the first part) pooled works were collected (60 swabs, 90 cups, 50 vials of water, and 260 syringes).  HCV RNA was detected in 28% of the pooled works and 83% of the swabs.5

J. Doerrbecker and colleagues conducted the most recent study:  “Sharing drug preparation equipment a potential source of hepatitis C transmission.”6  The authors addressed the length of time that HCV RNA could be detected in water, water containers and filters.

Key findings of the study include:

  • Water:  HCV RNA was detectable in the water for greater than 3 weeks. 

  • Bottles:  HCV RNA was detectable in water bottles even after the bottles were rinsed out.  Water bottles made of aluminum or plastic retained HCV RNA longer than water bottles made of glass.

  • Filters:  about 10% of filters wrapped in foil—a common practice among injectors— remained positive for HCV RNA after 24 and 48 hours. 

This current study and the other studies listed above answer important questions about how HCV is transmitted and more importantly how to prevent transmission of HCV especially among PWID.  While sterile syringes are an important prevention tool and are well recognized  prevention measures that are easily teachable—other transmission routes may be even more important and more difficult to tackle, but with the right education there is a potential to dramatically reduce the transmission of HCV among PWID.  The strategies that advocate that one use only “One Kit for One Hit” and for PWID to ONLY use their own needles and works seem to be the best advice based on the findings of these studies.

Endnotes  

  1. Environmental Stability of Hepatitis C Virus (HCV): Viability of Dried/Stored HCV in Chimpanzee Infectivity Studies. Kris Krawczynski, Miriam J. Alter, Betty H. Robertson, Ling Lu, John E. Spelbring, Karen A. McCaustland, Centers for Disease Control and Prevention, Atlanta, GA.
  2. Paintsil E, He H, Peters C, Lindenbach BD, Heimer R. Survival of hepatitis C virus in syringes: implication for transmission among injection drug users. J Infect Dis 2010; 202:984–90.
  3. Doerrbecker J et al. Inactivation and survival of hepatitis C virus on inanimate surfaces. J Infect Dis, online edition, doi: 101093/infdis/jir535.
  4. Agent, Host, and Environment: Hepatitis C Virus in People Who Inject Drugs,Holly Hagan. J Infect Dis. (2011) doi: 10.1093/infdis/jir654.
  5. Thibault V et al. Hepatitis C transmission in injecting drug users: could swabs be the main culprit? J Infect Dis, online edition, doi: 101093/infdis/jir650.
  6. Transmission of Hepatitis C Virus Among People Who Inject Drugs: Viral Stability and Association With Drug Preparation Equipment.  Juliane Doerrbecker et al. J Infect Dis. (2013) 207 (2): 281-287. doi: 10.1093/infdis/jis677.

For more information, be sure to check out these Fact Sheets from HSCP



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HCV Snapshots:
—Lucinda K. Porter, RN

Article: Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C by Gane E, Stedman C, Hyland R, et al. 
  Source: New England Journal of Medicine, January 3, 2013; 368:34-44

This Phase 2 study used sofosbuvir, an oral direct-acting nucleotide polymerase inhibitor to treat 8 groups of non-cirrhotic patients with chronic hepatitis C virus (HCV) infection.  A total of 95 HCV genotype 1, 2 or 3 patients were assigned to a regimen. All groups received 400 mg sofosbuvir (once daily) plus ribavirin (weight-based twice daily) for 12 weeks. One group of previously untreated genotype 2 or 3 patients (10) received sofosbuvir plus ribavirin for 12 weeks. 100% had a sustained virologic response (SVR) at 24 weeks. This research was conducted in two stages, but all groups are listed along with results.

  • Three groups of previously untreated genotype 2 or 3 patients (10 each) received sofosbuvir, ribavirin, and peginterferon alfa-2a for 4, 8, or 12 weeks; 100% SVR at 24 weeks.

  • Previously untreated genotype 2 or 3 patients (10) received only sofosbuvir for 12 weeks; 60% SVR at 24 weeks.

  • Previously untreated genotype 2 or 3 patients (10) treated for 8 weeks with a triple drug regimen—sofosbuvir, peginterferon and ribavirin; 100% SVR at 24 weeks.

  • Group of previously untreated genotype 1 patients (25) received sofosbuvir, peginterferon and ribavirin for 12 weeks; 84% SVR at 24 weeks.

  • Group of genotype 1 patients (10) with no response to prior treatment received sofosbuvir, peginterferon and ribavirin for 12 weeks; 10% SVR at 24 weeks.

All 95 patients completed treatment. Side effects for those taking only sofosbuvir or sofosbuvir and ribavirin were less severe than those taking peginterferon. There was no neutropenia or thrombocytopenia in groups not taking peginterferon.

The Bottom Line: Sofosbuvir plus ribavirin for 12 weeks may be effective for treatment-naive patients with HCV genotype 1, 2, or 3 infection.

Editorial Comment: Sofosbuvir is a drug to watch. These numbers are small, so we need more data as well as studies that include responder-relapsers to previous treatment.  We also need studies that include cirrhotic, post-transplant and HIV/HCV coinfected patients.

 

Article: Exploratory Study of Oral Combination Antiviral Therapy for Hepatitis C by Poordad F, Lawitz E, Kowdley K, et al.
  Source: New England Journal of Medicine, January 3, 2013; 368:45-53

This 12-week, phase 2 study enrolled 50 non-cirrhotic HCV genotype 1 patients. All patients received ABT-333 (an HCV NS3 protease inhibitor) and ribavirin. Additionally they received one of two daily doses of ABT-450/r, a potent inhibitor of the HCV NS3 protease (ABT-450) combined with ritonavir.

  • Group 1: previously untreated patients (19), received 250 mg of ABT-450 and 100 mg of ritonavir ; SVR was 95%.

  • Group 2: previously untreated patients (14), received 150 mg of ABT-450 and 100 mg ritonavir; SVR was 93%.

  • Group 3: included patients who had had a null or partial response to previous therapy with peginterferon and ribavirin, received 150 mg of ABT-450 and 100 mg of ritonavir; SVR was 47%.

The most common side effects were mild, including abnormal liver-function tests, fatigue, nausea, headache, dizziness, insomnia, itching, rash, and vomiting. Four patients had severe events: fatigue, pain, vomiting, and high bilirubin.

The Bottom Line: Much like combinations using sofosbuvir, ABT-333 and ABT-450/r plus ribavirin for 12 weeks looks promising as an effective treatment for HCV genotype 1 patients who have never been treated before.

Editorial Comment: ABT-333 and ABT-450/r are two drugs to watch. These numbers are small, so we need more data as well as studies that include responder-relapsers to previous treatment.  We also need studies that include cirrhotic, post-transplant and HIV/HCV coinfected patients.

 

Article: Association between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis by van der Meer A, Veldt B, Feld J, et al.

  Source: Journal of the American Medical Association published online, December 26, 2012; 308(24):2584-2593

This multicenter long-term follow-up study conducted in Europe and Canada, enrolled 530 patients with chronic HCV infection. All had proof of advance liver fibrosis or cirrhosis; all started an interferon-based treatment regimen between 1990 and 2003. The purpose of the study was to examine the association between sustained virological response (SVR) and all-causes of mortality in patients with chronic HCV infection and advanced liver disease.

Patients were followed up for an average of 8.4 years. Average age at beginning of assessment period was 48 years; the majority (70%) were men. More than a third (192 pts/36%) achieved SVR; 13 patients with SVR and 100 without SVR died. SVR was associated with reduced risk of all-cause mortality and reduced risk of liver-related mortality or transplantation.  Of those who developed liver cancer, 7 had achieved SVR vs. 76 without SVR. Older age and severe alcohol use (more than 50 g/d) were risk factors for liver failure and liver cancer.

The Bottom Line: SVR is associated with a four times reduced risk of mortality for HCV patients with advanced liver disease.

Editorial Comment: In previous studies we have seen that HCV increases the risk of death from all causes, particularly the most common diseases, such as cardiovascular disease and cancer. This study suggests that an SVR reduces that risk.

 

Article: Hepatitis C Cure After 6 Months of Telaprevir-Based Therapy in an HIV-Infected Man by Edward R. Cachay
  Source: Clinical Infectious Diseases (2013) 56(1): 163-164 first published online September 21, 2012

This case study was published as a journal correspondence. A 28-year-old man infected with HIV and HCV underwent HCV treatment with telaprevir for the first 12 weeks, and pegylated-interferon and ribavirin for a total of 48 weeks of HCV therapy. His HIV antiretroviral therapy included tenofovir/emtricitabine, atazanavir and ritonavir. Two years prior, this patient had been treated with peginterferon and ribavirin, which were stopped due to lack of viral response.

After starting the second round of HCV treatment, this patient’s week 1 HCV viral load was 503,520 IU/mL; week 3 was 7189; week 4 was <43.  He remained undetectable at weeks 12 and 24. The patient did not return to the clinic after completing 24 weeks of HCV therapy and a review of pharmacy records confirmed that the patient failed to refill medications after his week 24 appointment. 

Eventually the patient was reached, admitting to a methamphetamine relapse and stopping HCV treatment after 24 weeks. He returned to the clinic and his HCV viral load was still non-detectable.

The Bottom Line: This HIV/HCV coinfected patient sustained a virologic cure after only 24 weeks of HCV treatment using 12 weeks of telaprevir.

Editorial Comment: There is an urgent need for more studies treating HIV/HCV coinfection. Simultaneously, we need better tools for helping patients with relapse prevention, particularly during and following HCV treatment.  Note: SVR to treatment does not protect patients from contracting HCV again if they are re-exposed.



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HEALTHWISE: The Happy Hepper
—Lucinda K. Porter, RN

If I could skip a month, it probably would be February. When this cold, wet month rolls around, enthusiasm for my New Year’s resolutions has waned. Valentine’s Day makes matters worse. Chocolate sabotages my already failed resolutions and I’d rather receive a gift from a hardware catalog than lacy lingerie.  Besides, who wears skimpy undergarments when the weather is chilly? It is a good thing that February is a short month.

I have just described an attitude problem, and a bad attitude does not help my health or fend off hepatitis C’s relentless assault.  In fact, the opposite is true—happy people tend to live healthier and longer lives.  Exploring the relationship of health and happiness, professors Ed Diener and Micaela Chan measured subjective well-being (SWB). They reviewed more than 160 studies of human and animal subjects, and found a “clear and compelling relation to physical health and longevity.”1 According to Diener and Chan, high SWB adds 4 to 10 years to life compared to low SWB.

Many studies support this research. Stress is associated with a myriad of diseases; optimism lowers disease risk. In short, the evidence pointing to the relationship between happiness and health is clear.

I am making an unscientific leap here by applying the results of this research to chronic hepatitis C virus infection (HCV). In reality, this study does not specifically measure the effects of living with HCV, which to some, is a royal drag in any month, not just February. Nevertheless, since HCV does increase risk of death from many diseases, not just liver-related ones, it leaves me to wonder about factors that would increase mortality.2

Commonsense tells me to connect happiness and health. The bottom line is that I feel better when I am happy. Since hepatitis C is a constant in my life, then my health relies on improving the controllable variables, such as my happiness level. If my happiness depended on freedom from HCV, I would have lived in misery the past 25 years.

For me, living with HCV is a call to action. HCV reminds me that I can surrender to illness or pursue happiness and health. I have been through treatment twice, and since that didn’t work out the way I had hoped, I have explored other avenues to stay well. Cultivating happiness is like taking a daily vitamin – it is cheap insurance. I can’t prove that it helps me, but it sure does feel good.

Most of us probably buy the notion that happiness is good for our health. The problem is that happiness is not something you can just turn on or off. Even worse, if you want to be happy but you aren’t, life can feel extra miserable.

If you don’t feel happy, what can you do? First of all, don’t beat yourself up for not feeling content. Your attitude is a tool to help you, and never to be used against you. The Dalai Lama said, “If you want others to be happy, practice compassion.  If you want to be happy, practice compassion.” Extend this compassion to yourself.  If you are on HCV treatment, it may feel nearly impossible to be happy, but you can be gentle with yourself.

Next, be sure your lack of happiness is related to your attitude and not a psychiatric illness. Mental illness is a medical problem needing professional help. Willpower is a powerful ally, but it doesn’t cure mental illness.  The same is true if you are taking HCV medications, such as peginterferon.  Determination may help you get through treatment, but it may not help you manufacture a better mood.

There are simple ways to improve a sour mood. One strategy is to “act as if.” Deciding or pretending to be happy can actually improve your mood. Try acting like a contented person and you may be surprised by the results.

Another tactic is to stop and smell the roses. Happy people make time to savor moments. In fact, if you aren’t happy, try this: If the weather is nice, go outside and look around you. Spend one to ten minutes paying attention to clouds, rocks, a tree, a puddle, or anything that appeals to you. Don’t think—just be. If weather keeps you inside, look out a window or at the rain on the window.

Practice smiling. Oddly enough, faking a smile or laugh can open the door to joy.  Buddhist monk, Thích Nhất Hạnh suggests a simple mindfulness practice—breathe three times while smiling. This practice is a lovely way to start the day. “There is no way to happiness; happiness is the way,” said Hạnh.

Laughter yoga is another way to practice happiness. I am not a practitioner of this type of yoga, but whenever I watch John Cleese doing Laughter Yoga on YouTube, I always end up laughing.  http://laughteryoga.org/

Moving the body is a good way to perk up. The problem with this strategy is that in order to implement it, you need to overcome inertia. However if you can coax yourself to take a mere five minute walk, the results can be amazing.

Counting your blessings is a rapid attitude-changer. Fyodor Dostoevsky wrote, “Man is fond of counting his troubles, but he does not count his joys.  If he counted them up as he ought to, he would see that every lot has enough happiness provided for it.” I keep a notebook by my bed and write a gratitude list before turning off the light. It paves the way to better dreams.

Take a page from Mark Twain. This American humorist battled despair and depression following the death of his daughter, wife, and other loved ones. “The best way to cheer yourself up is to try to cheer somebody else up,” wrote Twain. Call someone who is having a hard time. Send an encouraging note or email. Volunteer your time, pick up litter around your neighborhood, or practice random acts of kindness.

And then there is my favorite mood adjuster—humor.  Norman Cousins who used humor to heal from two life-threatening illnesses, called laughter, “inner jogging.” Unlike the other kind of jogging, laughter doesn’t require special shoes, good weather, or willpower. In fact, unless your jaw is wired, there is no excuse not to pursue humor.

If you are rolling your eyes at these suggestions, consider this—if happiness means 4 to 10 years of health and longevity, why wouldn’t one pursue joy? Besides, it isn’t like I am suggesting trying something that might make you feel temporarily uncomfortable, such as going on a diet or running a marathon might. Instead I am proposing the pursuit of pleasure, a gift that will be felt by both heart and liver.  Can you think of a better Valentine to give to yourself?

Lucinda K. Porter, RN, author of Free from Hepatitis C is a long-time contributor to the HCV Advocate.  Her blog is http://lucindaporterrn.com

Endnotes

  1. Happy People Live Longer: Subjective Well-Being Contributes to Health and Longevity Ed Diener and Micaela Y. Chan Applied Psychology: Health and Well-Being March 2011 Volume 3, Issue 1, pages 1–43 http://onlinelibrary.wiley.com
    /doi/10.1111/j.1758-0854.2010.01045.x/full
  2. Chronic Hepatitis C Virus Infection Increases Mortality from Hepatic and Extrahepatic Diseases: A Community-Based Long-Term Prospective Study – Lee MH, Yang HI, Lu SN, et al .Journal of Infectious Disease July 2012

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Liver Cancer in People with Hepatitis C: Part 1—Benefits of Antiviral Therapy
—Liz Highleyman

Over years or decades, chronic hepatitis B or C can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC). HCC is the most common type of primary liver cancer, meaning it originates in the liver rather than spreading from elsewhere in the body. Liver cells, known as hepatocytes, normally reproduce in an effort to repair damaged tissue. HCC occurs when cell proliferation gets out of control and produces tumors.

HCC is not a common type of cancer in the U.S., with approximately 28,000 new cases in 2012, according to the National Cancer Institute. Hepatitis C is a leading cause of liver cancer in the U.S., accounting for at least half of all cases. HCC incidence tripled between 1975 and 2005 as people infected with HCV many years ago reached advanced stages of disease. Worldwide, liver cancer is the third leading cause of cancer-related death. Hepatitis B is the most common global cause of liver cancer, but it is decreasing due to widespread HBV vaccination.

HCC Risk Factors
Besides viral hepatitis, other causes and factors contributing to liver cancer include heavy alcohol consumption, exposure to toxins (including aflatoxin and tobacco smoke), genetic disorders, and fatty liver disease.

Many experts think rising rates of obesity, metabolic syndrome, and diabetes help explain the recent increase in HCC. At the 2012 EASL International Liver Congress, Frank Lammert reported new data from Denmark showing that people who are overweight during childhood have a higher likelihood of developing liver cancer as adults.

HCC is about three times more common among men than among women. The risk rises with age overall, with most cases occurring among people 50 years or older. The largest increase in incidence has been seen in the Baby Boomer cohort, born between 1946 and 1964, as they get older.

Less than 5% of people with chronic hepatitis C will develop liver cancer, but it is difficult to predict who these will be. HCC typically develops 20 to 30 years after HBV or HCV infection, though it may occur sooner. People coinfected with both HBV and HCV, and HIV-positive people with hepatitis B or C, are at greater risk. This is also true for people with viral hepatitis who have other contributing factors such as heavy drinking or obesity.

Most people who develop HCC already have liver cirrhosis, or scarring; liver inflammation also plays a role. But researchers at the 2012 AASLD Liver Meeting reported that some people with chronic hepatitis B or C can develop HCC without cirrhosis, and even without significant fibrosis.

Detecting HCC
Liver cancer detection is difficult because most people do not have symptoms during early stages. As cancer progresses they may experience symptoms including fatigue, malaise, fever, loss of appetite, unintended weight loss, nausea, and tenderness in the upper abdomen. But many of these are signs of liver disease in general—or of interferon-based therapy—and not specific to HCC.

People with liver cancer may also have symptoms of cirrhosis and progression toward decompensated disease, including jaundice, ascites (abdominal fluid accumulation), portal hypertension, bleeding varices, and hepatic encephalopathy. In advanced cases the liver may become enlarged and tumors may be felt from outside the body.

The most frequently used screening biomarker for HCC is alpha-fetoprotein (AFP). This test is simple and inexpensive but has a high rate of both false-negatives and false-positives. Some people with liver cancer have normal AFP levels, while some people with elevated AFP have other conditions including testicular cancer or pregnancy. Tests that combine multiple biomarkers may be more accurate than AFP alone.

Imaging tests to detect liver cancer include abdominal ultrasound, computed tomography, and magnetic resonance imaging. Angiography, which shows patterns of blood vessel growth, may also reveal tumors. These methods, however, may not find small, early tumors when they are easiest to treat. Finally, liver biopsies can detect cancerous cells and may be used to distinguish malignant tumors from benign growths.

People with progressive liver disease are advised to undergo regular liver cancer screening. Most experts recommend that individuals with cirrhosis should be screened every six to twelve months. But since some people can develop HCC without advanced fibrosis or cirrhosis, some clinicians advise that chronic hepatitis C or B patients should receive frequent screening regardless of liver disease status.

Once liver cancer is detected, it is staged to determine the size, number, and location of tumors, as well as involvement of blood vessels and metastasis beyond the liver. Several different staging methods are used including the Tumor-Node-Metastasis (TNM), Milan, and Barcelona Clinic Liver Cancer systems.

HCC is usually classified as either localized resectable (a single tumor that can be surgically removed in a person with overall good liver function), localized unresectable (cancer in one part of the liver that cannot be removed due to its location, advanced liver damage, or poor overall health), or advanced (cancer that has spread throughout the liver or to other parts of the body).

Benefits of Hepatitis Treatment
HCC is most likely to occur among people with active HBV or HCV replication, as indicated by detectable viral load (HBV DNA or HCV RNA). Therefore, people who achieve sustained viral suppression with antiviral treatment can reduce their risk of developing liver cancer, though it does not fall to zero.

Studies have shown that interferon-based hepatitis C treatment that results in sustained virological response (SVR)—or continued undetectable HCV RNA 12 or 24 weeks after completion of treatment—dramatically lowers HCC incidence.

Nina Kimer and colleagues from Copenhagen University Hospital performed a systematic review and meta-analysis of eight randomized clinical trials and several observational studies, with more than 2,000 total participants, looking at liver disease progression after interferon-based therapy.

As described in the October 22, 2012, edition of BMJ Open, chronic hepatitis C patients who underwent treatment had about half the likelihood of developing HCC. The protective effect of antiviral therapy was much greater for people with virological response (85% risk reduction), but even non-responders showed some benefit (about 40% reduction). The researchers calculated that eight patients would need to be treated over five years to prevent one case of liver cancer.

Only two of the included trials evaluated pegylated rather than conventional interferon, most did not include ribavirin, and none looked at direct-acting antiviral agents, so the protective effect of more effective modern therapy would probably be even greater.

Although Kimer’s meta-analysis found a protective effect of treatment even for non-responders, longer interferon therapy appears to have no clinically significant benefit. In the HALT-C trial, more than 1,000 chronic hepatitis C patients with advanced fibrosis or cirrhosis who did not achieve sustained response with standard doses of pegylated interferon and ribavirin were randomly assigned to receive low-dose interferon maintenance therapy or no further treatment.

Although an interim analysis showed that maintenance therapy reduced ALT levels, HCV viral load, and necroinflammation, the primary analysis found no significant reduction in liver cancer, decompensation, or death over 3.5 years. Further analysis by Anna Lok and colleagues showed that the cumulative five-year HCC incidence rate was similar in the maintenance therapy and control groups (5.4% and 5.0%, respectively).

Hepatitis C patients who respond well to treatment are not always in the clear when it comes to liver cancer. For example, Justin Sewell from the University of California at San Francisco and colleagues described five chronic hepatitis C patients without cirrhosis at baseline who developed HCC despite achieving SVR; two of the five still did not have cirrhosis at the time of HCC diagnosis.

Similarly, studies have shown that treating chronic hepatitis B with nucleoside/nucleotide analogs can significantly reduce the likelihood of developing HCC. A Japanese study presented at AASLD 2012, for example, found that long-term treatment with entecavir (Baraclude) reduced HCC incidence by 60%. But as with hepatitis C, hepatitis B patients can still develop liver cancer despite treatment, especially if they have pre-existing liver damage.

Taken together, these findings suggest that people who are considered cured of viral hepatitis still require liver cancer screening even if they do not have advanced fibrosis or cirrhosis.

Part 2 of this article in the next issue of HCV Advocate will look at various treatments for HCC, focusing on targeted chemotherapy drugs evaluated in recent clinical trials.

References

  • Berentzen, T. et al. Childhood body size and the risk of hepatocellular carcinoma. 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona, April 18-22, 2012.Abstract 110.
  • Hosaka, T. et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with chronic hepatitis B. 63rd Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9-13, 2012. Abstract 357.
  • Kimer, N. et al. Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials. BMJ Open 2(5):e001313. October 22, 2012.
  • Lok, A. et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136(1):138-148. January 2009.
  • Sewell, J. et al. Hepatocellular carcinoma after sustained virologic response in hepatitis C patients without cirrhosis on a pretreatment liver biopsy. European Journal of Gastroenterology and Hepatology 21(2): 225-229. February 2009.



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New Phase III Interferon-Free Studies
—Alan Franciscus, Editor-in-Chief

Recently new interferon-free Phase 3 studies were announced.  Joining the stellar line-up of HCV drugs in Phase 3 clinical development are Boehringer Ingelheim and Gilead. 

Gilead
ION-1 was launched in October 2012 to test sofosbuvir/GS-5885 with and without ribavirin for a treatment duration of either 12 or 24 weeks. Sofosbuvir/GS-5885 is a fixed dose once-a-day pill.  The trial is recruiting HCV Genotype 1 treatment-naïve patients. 

ION-2 will recruit patients with HCV genotype 1 who did not achieve a sustained virological response or viral cure with a prior course of interferon or interferon plus protease inhibitor therapy. 

  • Fixed-dose of sofosbuvir, GS-5885 plus ribavirin for a treatment duration of 12 weeks, and
  • Fixed-dose of sofosbuvir, GS-5885 with and without ribavirin for a treatment duration of 24 weeks

Gilead now has clinical trials with their lead candidates, sofosbuvir, GS-5885, with and without ribavirin and/or pegylated interferon in HCV genotype 1, 2, 3, and 4 patients.  Gilead expects to file for Food and Drug Administration (FDA) approval mid-2013 for sofosbuvir, and  in 2014 for GS-5885.  Gilead is also studying sofosbuvir/GS-5885 with and without ribavirin for a treatment duration of 8 weeks for HCV genotype 1 treatment-naïve patients and 12 weeks for HCV genotype 1 treatment-experienced patients.  These two Phase 3 studies will mean that Gilead now has 7 Phase 3 studies.

In these trials Gilead is studying a fixed dose which will mean a very low pill burden (possibly 1 combination pill of sofosbuvir/GS-5885—only once a day).  This is compared to today’s current standard of care treatment that requires taking many, many pills every 7 to 9 hours.

Boehringer Ingelheim (BI)
BI already has faldaprevir in combination with pegylated interferon plus ribavirin in Phase 3 studies.  In January BI announced HCVerso 1 and HCVerso 2 clinical trials for HCV genotype 1b patients.  The new studies announced will combine faldaprevir—120 mg (QD-once a day), BI 207127—600 mg (BID-twice a day) plus ribavirin (TID-three times a day). There will be three treatment arms:

HCVerso 1 (Treatment Naïve)

  • Group 1 will be treated for 24 weeks of the study drugs (without placebo)
  • Group 2 will receive 16 weeks of the study drugs and 8 additional weeks of placebo
  • Group 3 will include patients with compensated cirrhosis treated with the same combination and for 24 weeks (without placebo)

HCVerso 2 (Treatment Naïve) 
HCVerso 2 will also include patients who are ineligible for interferon.

  • Group 1—24 weeks of BI 207127, faldaprevir plus ribavirin
  • Group 2—16 weeks of BI 207127, faldaprevir plus ribavirin—the first 8 weeks of treatment will be with a placebo drug
  • Group 3—24 weeks of BI 207127, faldaprevir plus ribavirin—HCV patients with compensated cirrhosis will be recruited for this group

All in all, the future looks very bright for people with hepatitis C since there are now 8 HCV drugs in Phase 3 studies and the promise of an interferon-free therapy is even closer than ever to a realization. 

For more information about how to qualify for these and other studies visit
www.clinicaltrials.gov



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