September 18, 2013

Provided by Healio

September 18, 2013

Patients with hepatocellular carcinoma who experienced dermatologic side effects while treated with sorafenib had improved survival in a study presented at the International Liver Cancer Association Annual Conference in Washington, DC.

Researchers evaluated data from 147 patients with hepatocellular carcinoma treated with sorafenib for a median of 6.7 months between October 2007 and July 2011. Clinical and laboratory evaluations were performed monthly, with tumor staging after 4 weeks followed by every 8 weeks, for a median follow-up of 11.6 months. Ninety-seven percent of participants had cirrhosis, and 46% were HCV-positive.

Overall, the median time to progression (TTP) was 5.1 months for the cohort; median overall survival was 12.7 months. Dermatologic adverse events that occurred within 60 days of treatment (AED60) were observed in 79 patients, 37 of whom required a sorafenib dose modification.

Although dose modifications were significantly more common among AED60 patients (three modifications vs. two; P=.006), median time to progression (8.1 months vs. 3.9 months; P=.02) and overall survival (18.16 months vs. 10.1 months; P=.009) were better among these participants compared with those who did not experience AED60. No other evaluated categories of early adverse events were associated with treatment outcomes.

Multivariate analysis indicated a significant association between improved survival and any grade of AED60 (P=.039). When cases of early death were excluded from analysis, this association was upheld for incidence of AED60 that required sorafenib dose modification (above grade 1in severity) (P=.03).

“Development of dermatologic adverse events within 60 days of sorafenib initiation is associated with better survival,” the researchers concluded. “Therefore, this should not … discourage treatment maintenance. Likewise, second-line clinical trials should be designed and/or evaluated considering this information to avoid significant bias.”

Disclosure: Researchers Maria Reig, MD, and Alejandro Forner, MD, reported serving as consultants for Bayer Pharmaceuticals.

For more information:

Reig M. O-033: Dermatologic Adverse Events Within the First 60 Days of Sorafenib Treatment Are Associated with Better Overall Survival in Patients with Hepatocellular Carcinoma. Presented at: The International Liver Cancer Association Annual Conference 2013; Sept. 13-15, Washington, DC.

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New mouse model for hepatitis C (Nature)

Princeton Journal Watch 

Princeton University

By Catherine Zandonella, Office of the Dean for Research

Hepatitis C affects about three million people in the U.S. and is a leading cause of chronic liver disease, so creating a vaccine and new treatments is an important public health goal. Most research to date has been done in chimpanzees because they are one of a handful of species that become infected and spread the virus.

Now researchers led by Alexander Ploss of Princeton University and Charles Rice of the Rockefeller University have generated a mouse that can become infected with hepatitis C virus (HCV).  They reported the advance in the Sept 12 issue of the journal Nature. “The entire life cycle of the virus — from infection of liver cells to viral replication, assembly of new particles, and release from the infected cell — occurs in these mice,” said Ploss, who joined the Princeton faculty in July 2013 as assistant professor of molecular biology.

Ploss and his colleagues have been working for some time on the challenge of creating a small animal model for studying the disease. Four years ago, while at the Rockefeller University in New York, Ploss and Rice identified two human proteins, known as CD81 and occludin, that enable mouse cells to become infected with HCV (Nature 2009). In a follow up study Ploss and colleagues showed that a mouse engineered to express these human proteins could become infected with HCV, although the animals could not spread the virus (Nature 2011).

In the present study, which included colleagues at Osaka University and the Scripps Research Institute, the researchers bred the human-protein-containing mice with another strain that had a defective immune system – one that could not easily rid the body of viruses. The resulting mice not only become infected, but could potentially pass the virus to other susceptible mice.

The availability of this new way to study HCV could help researchers discover new vaccines and treatments, although Ploss cautioned that more work needs to be done to refine the model.

The study was supported in part by award number RC1DK087193 from the National Institute of Diabetes and Digestive and Kidney Diseases; R01AI072613, R01AI099284, and R01AI079031 from the National Institute for Allergy and Infectious Disease; R01CA057973 from the National Cancer Institute; and several foundations and contributors, as well as the Infectious Disease Society of America and the American Liver Foundation.

Read the abstract

Marcus Dorner, Joshua A. Horwitz, Bridget M. Donovan, Rachael N. Labitt, William C. Budell, Tamar Friling, Alexander Vogt, Maria Teresa Catanese, Takashi Satoh, Taro Kawai, Shizuo Akira, Mansun Law, Charles Rice & Alexander Ploss. 2013. Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature 501, 237–241 (First published online on 31 July 2013)  doi:10.1038/nature12427.

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3 Companies Racing to Transform Hepatitis-C Treatment

Provided by DailyFinance

by Keith Speights, The Motley Fool Sep 18th 2013 7:00PM
Updated Sep 18th 2013 7:02PM

Imagine a line of adults lying on the ground stretching from Los Angeles to the Atlantic coast of Maine. That number of people, around 3.2 million, represents how many Americans are estimated to have chronic hepatitis-C.  

Many individuals affected by chronic hep-C must take antiviral medications via injection that can cause side effects including flu-like symptoms. That could be changing in the not-too-distant future, though. Several companies are racing to develop an all-oral regiment for hepatitis-C that could transform how the disease is treated. Here are three leaders in this race.

1. Gilead Sciences
At this point, Gilead appears to be able to claim front-runner status. The biotech awaits a decision by the U.S. Food and Drug Administration on or before Dec. 8 regarding approval of sofosbuvir in combination with ribavirin as an all-oral treatment for hep-C genotypes 2 and 3. However, the big prize is getting to market with an oral regimen for genotype 1, which accounts for around 75% of all hep-C patients.

Gilead shouldn't be too far off in jumping that hurdle. The biotech has late-stage studies under way, with sofusbuvir combined with both ribavirin and its own ledipasvir. Mid-stage results for the combo were very impressive, with a 95% cure rate after eight weeks of treatment.

Unless unforeseen problems emerge, Gilead seems poised to reach the market first with its all-oral regiment for hep-C genotype 1. The company hopes to market the sofusbuvir/ledipsasvir combo next year.

2. AbbVie
If AbbVie has anything to say about it, though, Gilead won't be the first to market. Scott Brun, the company's VP of pharmaceutical development, recently stated that he thinks AbbVie has "a very good shot at being first."

Brun's optimism stems from success that AbbVie has had with its own all-oral combo. Results from mid-stage studies showed that the company's antiviral combination of drugs achieved a 99% cure rate in treatment-naive patients and a 93% cure rate in all responders after 12 weeks.

Like Gilead, AbbVie currently has late-stage studies under way. Also like Gilead, the company hopes to be on the market with its drug combo in 2014. As Brun noted, "it is a very tight race."

3. Bristol-Myers Squibb
Regardless of which company wins that race, chances are that they won't share the market between just the two of them for long. Bristol-Myers Squibb doesn't trail too far behind with its all-oral regimen including daclatasvir, asunaprevir, and BMS-791325.

In April, Bristol announced positive phase 2 results for the combo. Up to 94% of patients were cured of hepatitis C after 24 weeks of treatment.

Bristol is now in phase 3 testing of the three-drug combo. The likelihood for now appears to be that the big drugmaker will reach the market several months after Gilead and AbbVie.

Winners
It isn't out of the question that all three of these companies could ultimately prove to be marketplace winners. The overall hepatitis-C market size is pegged to be around $20 billion. That pie will be split somehow, although how big each slice is remains to be seen.

Gilead probably stands the best shot at becoming the biggest winner. The biotech should hit the market first with its treatment (even if only barely). More importantly, there's a convenience factor that could help the sofusbuvir/ledipsasvir combo. While AbbVie's regimen requires patients to take three pills in the morning and another pill in the evening, patients taking Gilead's combo will probably only have to take one pill once per day.

This race isn't limited to Gilead, AbbVie, and Bristol. Several of other companies have other drugs a little further behind in the development cycle. Johnson & Johnson , for example, teamed up with Idenix to develop an all-oral regimen. The two companies, along with J&J's partner, Medivir, kicked off a mid-stage study of samatasvir combined with simeprevir in May. 

The intensity of the competition ultimately means that the biggest winner of all won't be any of these companies. That honor belongs to the millions suffering from hepatitis-C -- from Los Angeles to Maine and around the world.

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The article 3 Companies Racing to Transform Hepatitis-C Treatment originally appeared on Fool.com.

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Viral Hepatitis: Patients’ Perspective in Ghana

Provided by GhanaWeb

Feature Article of Thursday, 19 September 2013

Columnist: Owusu-Ansah, Theobald

I am honoured to speak on viral hepatitis from the perspectives of patients in Ghana. Viral hepatitis is a silent and under-estimated public health problem worldwide, and which is particularly endemic in the Sub-Saharan Africa and Ghana. Hepatitis B is a preventable disease.

Thousands of Ghanaians live with viral hepatitis. About a third of Ghanaians living with viral hepatitis are unaware of their status and are not receiving care and treatment for the condition. Raising awareness about hepatitis is crucial to effectively fight stigmas, stem the tide of new infections, and ensure treatment reaches those who need it. On World Hepatitis Day, we join others across Ghana and around the world in promoting strategies that will help save lives and prevent the spread of viral hepatitis.

“Hepatitis” means inflammation of the liver. It refers to a group of viral infections that affect the liver. There are five main hepatitis viruses, referred to as types A, B, C, D, and E. The most common types are the A, B, and C.

Ladies and Gentlemen, nearly one out of every three people in the world (approximately 2 billion people) has been infected by the hepatitis B virus (HBV), and one in twelve (more than 520 million people) live with chronic HBV or/and hepatitis C (HCV) infection. In Ghana, hepatitis is the leading infectious cause of death, claiming the lives of thousands of Ghanaians each year. While we have come thus far in containing the spread of the virus, much more work is still needed to be done in treating and managing the disease.

Viral hepatitis affects Ghanaians of all backgrounds, but certain groups are at a greater risk than others. Before blood was screened for viral hepatitis many who received blood transfusion were infected, infants born to mothers infected with the viral hepatitis, and persons with multiple sex partners or indulge in certain behaviours such as injection of drugs, tattooing and tribal marks have a higher risk of infection.

Carriers of viral hepatitis in Ghana face many social and economic challenges. Ladies and Gentlemen, the social impact of hepatitis on carriers are numerous but because time is not on my side, I will focus on but a few:

Social effects on patients

Sexual Activity: Many viral hepatitis patients in Ghana are fearful of engaging in sexual activities once they are diagnosed with the virus. They are concerned about passing the virus onto their partners, and as a result, many marriages are not consummated and relationships are broken. But research shows that sexual activity can benefit one’s immune system. Sexual activity triggers the release of endorphin, which helps create a more positive attitude. It also helps one to forget about his/her problems. Thus, sexual activity can go a long way to enhance the healing process and creating an environment for a better functioning of one’s immune system. Carriers of the viral hepatitis living with one long-term sexual partner do not need change their sexual habits and practices. However, those with more than one sexual partner should practice safe sex by using condom.

Stigmatization: There is a societal stigma about hepatitis. Infected people are alienated by society. Individuals may also be isolated within their families, hidden away from visitors or made to eat alone. Many carriers are refused access to educational facilities and there is as a result a high prevalence of school dropout and illiteracy. They are looked down upon for contacting the virus, as it is generally to be associated with sexual promiscuity. Because society ignores their plight some carriers choose to revenge on society by spreading the virus through indiscriminate sexual activities.

Difficulties in accessing medical care: Many health centres in Ghana are not well equipped to handle viral hepatitis cases and the technical know-how of some medical doctors and other healthcare professionals in treating the condition is limited. As a result, many patients do not get diagnosed and do not get referred to receive appropriate medical attention that they may need.

Low self-esteem: Many carriers of the virus suffer a great loss of self-esteem once diagnosed. Because of the lack of knowledge about the disease, many away even from close relatives, withdraw from society and can no longer participate in public activities. Low self-esteem can bring depression, which can lead one to commit suicide. Many people living with the chronic viral hepatitis in Ghana become depressed as a result blaming themselves. They find it very difficult to tell their partners or family members because getting infected by the viral hepatitis is usually associated with indulging in sexual activities.

Beliefs: Some people see the viral hepatitis as a curse. There is a traditional belief that viral hepatitis is a spiritual disease. It is also believed that viral hepatitis is hereditary so if one’s parents are infected, it is automatically thought that children will also be infected. Most patients also believe that viral hepatitis is not treatable.

Stress: Carriers of the virus are always stressed up because of the factors I just numerated earlier. Stress can suppress the immune system, which may cause patients to be more vulnerable to other diseases. The stress may be compounded by the fact that one may never know how, when, or where the infection occurred since most people are not diagnosed until well after the initial infection. Asking questions and trying to understand as much as one can about Hepatitis B can also go a long way toward reducing one’s stress level. Without knowledge you run the risk of having your decision controlled by fear and misinformation.

Breastfeeding: Breastfeeding mothers are always fearful of transmitting the virus to their newborn babies. Some mothers will not breastfeeding their babies at all, which is dangerous because the breast milk is good for the baby to grow well. It is always advisable to inform one’s nurse when one is going for antenatal care, the nurse will give your baby a shot called H-BIG and a shot of hepatitis B vaccine within 12 hours after birth. After the baby has been vaccinated on delivery, it is alright to breastfeed the baby. The viral hepatitis is not transmitted through breast milk! It is important to take good care of your nipple areas to prevent cracking and bleeding.

Marriage: Many people are fearful of getting married or telling their partners of their status. Some people also think that they may lose their partners if they tell them so they will not tell. Is advisable to inform your partner before getting married, if he/she gets to know of it? Yes, it is always a good idea to let your partner know of one’s status before marrying so that the would-be partner can get vaccinated

Life Span: There is no life span for hepatitis patients, you can live as many years as God wants you to live when you treat it and monitor it well. Many patients are fearful of death so those who call always want to know the number of years they have on earth or to know the time they will die. “Say no to ignorance.”

Ladies and Gentlemen, I will now focus on the economic impact of hepatitis on individuals, families and the national economic development and growth.

Economic effects on patients

Household Income: The incomes of carriers of the viral hepatitis may also be affected because carriers may not be able to work at their full capacity and/or even holding down permanent job.

Basic Needs: Most carriers have to constantly cut their spending on basic necessities of life .The most likely expenses to be cut are clothing, electricity, food, shelter and other services. The cost of medical treatment means that most of their already reduced income is spent on medical care.

Termination of Employment: People living with chronic viral hepatitis have to visit the hospital regularly, which costs their employers thousands of cedis in medical bills and time away from the workplace. As a result, employments of many carriers are employments of many carriers are often terminated.

The Way Forward

Counseling:
• Counseling should be an integral part of any medical model when treating carriers of viral hepatitis.
• A holistic approach should be adopted by medical doctors and allied healthcare professionals in treating carriers so that their psychological needs can be recognized.
• Adequate support should be given when one is diagnosis or the first time, as patients do experience great stresses due to fear of the disease and of rejection and social stigma that are associated with the disease.

Confidentiality: Confidentiality is as important for viral hepatitis patients as it is for all other patients. All healthcare professionals should treat the cases of their patients with the strictest confidentiality, particularly with regards to:
- Medical records
- Staff confidentiality
- Partner/family notification and disclosure

Screening facilities: Screening facilities should be provided at all local health centres, district polyclinics, and regional government hospitals (e.g. all pregnant women should be tested).

Prevention tools: Precaution should be exercised regarding injection safety, blood safety and immunization of all new born as well as vaccination of all healthcare professionals.

Continuing care: Ensuring that those already infected with the virus have timely access to care, and effective and affordable treatments to delay development of the disease and prevent disability and eventual death.

Disease surveillance: Strengthening disease surveillance, such as establishing national database to monitor spread of the virus in order to establish patterns of progression would be a step in the right direction.

National awareness: Increasing national awareness of viral hepatitis through the commemoration of a World Hepatitis Day on 28 of July every year, as Member States agreed to do at the 63rd World Health Assembly in Geneva on 21 May, 2010.

Ladies and Gentlemen, we must make sure that this "silent epidemic" does not go unnoticed by health professionals or by communities across our country. Our goal is to reduce the number of new infections, increase status awareness among people living with virus, and eliminate the transmission of viral hepatitis from mothers to their children.

The first step toward achieving these goals is to raise public awareness of this life-threatening disease. We must work to reduce the social stigma of the virus, and to ensure that testing, information, counseling, and treatment are available to all who need it. The hard work and dedication of healthcare professionals, researchers, and advocates will help bring us closer to these goals. On this day, we renew our support for those living with the viral hepatitis, and for their families, friends, and communities who are working to create a brighter, healthier future for all!

For counsel and advice on treatment and management, Contact us. Support our work to spread the word but not the virus.

Theobald Owusu-Ansah
President, Theobald Hepatitis B Foundation
President, Hepatitis Coalition of Ghana
Regional Board Member for Africa, World Hepatitis Alliance, UK
Board Member, National Association of Hepatitis C Taskforce, USA
Email: theobald2003@yahoo.com/  president@theobaldhepb.org
Web: www.theobaldhepb.org  . Tel: +233 (24) 709-3893 / +233-26-8269214

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Hepatitis: Understanding the Enemy

By Abdul-Lateef Balogun

Freelance Writer - Malaysia

Wednesday, 18 September 2013 00:00

14314

1 in every 12 people is living with Hepatitis, and the majority of those infected are unaware of their status.

According to the World Hepatitis Alliance, globally, one in every 12 people is living with hepatitis, and the majority of those infected are unaware of their status.

Ironically, despite its higher occurrence rate, not much is known by the general public about this disease when compared with less prevalent diseases such as cancer and AIDS.

For a disease that claims an approximated 1.5 million lives annually, hepatitis certainly deserves much more attention than it is presently getting.

Knowing the Enemy

Hepatitis simply means inflammation of the liver and it can be caused by various types of hepatitis viruses that lead to the destruction of liver tissue. There are seven known types of viral hepatitis, and their causes, symptoms and cures vary. Hepatitis A virus (HAV) is the most common cause of viral hepatitis and can be found in the feces of those infected. (Magee)

Many people become infected with HAV by eating or drinking contaminated food or drink, and it is a popular disease in developing countries where sanitation and sewage infrastructure is poor. Hepatitis A is the cause of approximately 100 deaths perآ year in America (HFI).

Hepatitis B is a type of liver inflammation caused by the hepatitis B virus (HBV) that triggers medical complications such as cirrhosis (scarring of the liver), and in some people liver cancer. If left untreated, this disease can lead to chronic long-term illness.

According to Jodie Walton, the health promotion officer at Queensland's Hepatitis Council in Australia, "Hepatitis B and C are chronic health conditions that can cause long term health problems. Other strains D, E, F are less likely to cause any major health problems."

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People are more likely to get the virus if they receive unsterile body piercings, tattoos or even the increasingly utilized acupuncture

Discussing the forthcoming World Hepatitis Day event, she explained to IslamOnline.net that even Hepatitis A, which is a short-term disease, has the potential to cause severe sickness. While adults who are infected usually recover, most infants infected at birth become chronic carriers and even spread the infection (WHO).

Both HAV and HBV are regarded as sexually transmitted diseases (STD) as they can also be transmitted via unprotected sex with an infected person.

Hepatitis C is perhaps the most worrisome viral hepatitis because there is no known vaccine for it. "Vaccination research is being conducted for hepatitis C, but it is unlikely that we will ever get a vaccination for hepatitis C that is as effective as the hepatitis B vaccine," said Walton.

For a disease that can affect virtually anyone, it is definitely important to be aware of its various modes of transmission in order to avoid it. "Anyone can be affected by hepatitis; we see young and old people, male and female, affected by it from all walks of life," she explained.

Just like AIDS, hepatitis is often spread through blood contact. People are more likely toآ become infected withآ the virus if they receive unsterile body piercings, tattoos or even the increasingly utilized acupuncture. Sharing contaminated needles or other drug injecting paraphernalia can also lead to infection, as can blood and blood product transfusions in countries where blood is not carefully screened for blood-borne viruses.

Apart from such generic causes, hepatitis B can also spread from infected mothers to their children during pregnancy or childbirth. While it is possible to avoid these modes of transmission, it is rather unfortunate that not all types of hepatitis are preventable, although they can still be managed if detected early enough.

Another form of hepatitis that is not caused by a virus is autoimmune hepatitis, a form of hepatitis that occurs when the body's immune system, which is supposed to protect it from pathogens, begins to attack liver cells, thereby, causing inflammation of the liver. The majority of such patients are women, and the disease can last for a long period if not detected and treated early on. (NDDICa)

Tackling the Problem

One major problem with combating hepatitis is that many times, it appears with mild symptoms, which can be easily ignored. In some cases, there are no symptoms at all and this accounts for the large number of people who are infected with the disease rather unknowingly and live normal lives, or so it seems.

However, when symptoms are apparent, they are similar in most types of viral hepatitis. Some of the most common symptoms include: nausea, vomiting, diarrhea, loss of appetite, weight loss, itchy skin, jaundice and abdominal pain. In autoimmune hepatitis, skin rashes, joint pain and the appearance of abnormal blood vessels on the skin may also be observed.

"Prevention is better than cure," is a very popular axiom in medical circles, and this also applies to dealing with hepatitis. By avoiding the common mediums of transmission i.e. exposure to blood or body fluids of infected persons, the chances of infection are drastically reduced. "To prevent hepatitis C, never share blood and never share drug injecting equipment," warned Walton.

Adopting a decent lifestyle, devoid of indiscriminate sex will also lower the chances of infection. It is interesting to note that not all types of hepatitis require serious medical attention.

Hepatitis A and E are likely to resolve on their own without medical intervention within a period of 2-4 months and once the immune system effectively fights off HAV, the person becomes permanently immune to it (NDDICb). This is in addition to the fact that Hepatitis A immunization, administered through a series of injections can prevent an infection for up to 10 years.

hepatitis-c-symptoms-and-progression

"It is unlikely that we will ever get a vaccination for Hepatitis C that is as effective as the Hepatitis B vaccine," said Walton.

Similarly, vaccines are available to protect people against hepatitis B, and it is essential that all newborns of hepatitis B infected mothers be immunized against the virus at the time of birth. There are no vaccines available for hepatitis C, D or E, and limiting exposure to the viruses ultimately provides the best form of protection.

For people who have previously been exposed to any of the likely transmission modes, it is necessary to visit a doctor for comprehensive tests in order to ascertain their condition and if needed to get prompt medical attention before it is too late.

Ignorance Fuelling Hepatitis

It is commonly said that ignorance is a disease of its own, and widespread ignorance regarding hepatitis is one of the major factors militating against the control of this potential time bomb. It is amazing that some people still believe it can be transmitted through physical contact with an infected person. "Hepatitis B or C cannot be spread through touching, hugging, kissing, sharing food, or bathrooms," affirmed Walton.

"Unfortunately, many people tell us they experience stigma. Hepatitis is just a chronic health condition like many others such as diabetes or asthma, not a reason to fear someone or treat them differently," she added. If people are stigmatized they become isolated, irritable, and depressed, so it is very important for people with hepatitis to get appropriate support.

Recently, the Hepatitis Foundation International revealed that the hepatitis B virus is 100 times more infectious than HIV (the AIDS causing virus), and an estimated 350 million people are infected globally. Despite its high prevalence, not much attention is being given to it when compared with less prevalent diseases such as AIDS and cancer that enjoy lots of publicity.

"In Australia, we have had large campaigns surrounding HIV/AIDS and cancer. The community has a good understanding of these health conditions; they have also been well funded by governments around the world," noted Walton.

"Hepatitis is just beginning to change from a stigmatized disease to a chronic health condition needing just as much care and attention," she added.

Speaking further on the issue, she confirmed that the situation is getting brighter as a result of the collective efforts of various international movements, though there is still a long way to go if the present alarming infection rate is to be reduced.

With researchers still working hard to come up with effective treatment options for patients, the best thing people can do is to get educated about hepatitis and learn how to prevent its transmission.

For those already infected, their situation is quite redeemable. "We advise all people affected by hepatitis to avoid contact with alcohol, which is highly toxic to the liver; get regular exercise; eat a healthy diet and avoid stress. If people do these things they can manage their hepatitis and live well," assured Walton.

References

"Autoimmune Hepatitis." National Digestive Diseases Information Clearing House (NDDICHa). April, 2008. Accessed 18 May 2009.

"Hepatitis." World Health Organization (WHO). Accessed 18 May 2009.

Magee, James. "Hepatitis A, Hepatitis B and Hepatitis C." avert.org. 20 Feb. 2009. Accessed 18 May 2009.

"The ABC's of Hepatitis." Hepatitis Foundation International (HFI). 2003. Accessed 18 May 2009.

"Viral Hepatitis: A through E and Beyond." National Digestive Diseases Information Clearing House (NDDICHb). May 2003. Accessed 18 May 2009.

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Provided by NATAP

53rd ICAAC Interscience Conference on
Antimicrobial Agents and Chemotherapy
September 10-13, 2013, Denver CO

53rd ICAAC, September 10-13, 2013, Denver

Mark Mascolini

Two thirds of people with HCV genotype 2 or 3 in an Italian single-center study responded to pegylated interferon plus ribavirin (PegIFN/RBV), and HIV infection did not independently affect chances of a sustained virologic response (SVR) in multivariate analysis [1].But HIV/HCV-coinfected people were more likely than people infected only with HCV to have advanced (F4) fibrosis, and advanced fibrosis independently lowered SVR chances

Infection with HCV genotype 2 or 3 responds to PegIFN/RBV more often than genotype 1 or 2 infection. Because little is known about how HIV coinfection may affect chances of SVR in people with type 2 or 3 infection, researchers at an infectious disease center in Brescia, Italy conducted this retrospective analysis of adults infected with those genotypes and starting a first course of PegIFN/RBV between 2005 and 2010.

Study participants took PegIFN/RBV for 48 weeks, but HIV-negative people could stop at week 24 if they had a rapid virologic response or began treatment with fibrosis stage F0 to F2 or an HCV load below 500,000 IU/mL. All HIV-positive patients could use growth factor, but only cirrhotic HIV-negative people could use growth factor. Ribavirin dose could be reduced in any patient if hemoglobin fell despite erythropoietin, if the white cell count remained below 750 in people without HIV, or if the white count fell in an HIV-positive person taking growth factor. Everyone had a Child-Pugh score at or below A5.

Of the 740 study participants, 113 (15%) had HIV and 627 did not. Of the 113 people with HIV, 5% had genotype 2 and 95% had genotype 3. Proportions with genotype 2 and 3 in the HIV-negative group were 45% and 55%. The HIV group included a lower proportion of women (15% versus 36%, P < 0.0001), had lower average body mass index (23.8 versus 25.1 kg/m(2), P = 0.004), and had lower platelet counts (163,200 versus 208,400, P < 0.0001). A lower proportion of HIV-positive than negative people had a pretreatment HCV load above 500,000 IU/mL (33% versus 51%, P = 0.0004). And a significantly higher proportion of people with HIV had F4 fibrosis (23% versus 5%, P < 0.0001).

A moderately but significantly lower proportion of people with than without HIV attained SVR (58% versus 67%, odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0 to 2.2, P = 0.02). Among HIV-positive nonresponders, 15% never had a virologic response, 50% responded and relapsed, and 35% stopped for any other reason. Respective percentages in the HIV-negative group were similar: 16%, 45%, and 40%. Among all study participants, a significantly higher proportion of people with HCV genotype 2 than genotype 3 attained SVR (71.7% versus 61%, OR 1.6, 95% CI 1.1 to 2.2, P = 0.001).

A significantly higher proportion of people with than without HIV had neutropenia during treatment (42% versus 12%, OR 1.3, 95% CI 1.2 to 2.2, P = 0.04), and a significantly higher proportion used growth factor (41% versus 4%, OR 1.2, 95% CI 1.1 to 3.3, P = 0.0005). A much lower proportion of HIV-positive people interrupted PegIFN (9% versus 68%, OR 0.2, 95% CI 0.1 to 0.3, P < 0.0001). Anemia rates did not differ significantly between people with and without HIV (12% and 10%), but a significantly lower proportion of HIV-positive people used erythropoietin (2% versus 16%, OR 1.5, 95% CI 1.1 to 2.6, P = 0.04).

Logistic regression analysis determined that HIV coinfection did not affect chances of SVR (adjusted odds ratio [aOR] 1.0, 95% CI 0.5 to 1.7). Age over 45, gender, F0 to F2 fibrosis, and genotype 3 versus 2 also had no impact on chances of SVR. Ribavirin dose reduction doubled chances of SVR (aOR 2.2, 95% CI 1.3 to 3.8, P = 0.003). Advanced (F4) fibrosis, high pretreatment HCV load, and PegIFN interruption all lowered chances of SVR at the following adjusted odds ratios (and 95% CIs):

-- F4 fibrosis: aOR 0.4 (0.2 to 0.7), P = 0.004
-- Pretreatment HCV RNA above 500,000: aOR 0.6 (0.4 to 1.0), P = 0.03
-- PegIFN interruption: aOR 0.2 (0.1 to 0.3), P < 0.0001

The Brescia team cautioned that their sample size, especially people with HIV, is small. They suggested that failure of HIV infection to affect chances of SVR in multivariate analysis could reflect (1) longer treatment duration in everyone with HIV and (2) frequent use of growth factor to keep HIV-positive people on treatment at the highest dose. The researchers noted that the HIV group had a higher proportion with F4 fibrosis and that F4 fibrosis cut chances of SVR 60%.

The investigators argued that treating HIV/HCV-coinfected people, particularly those with genotype 2 or 3, "remains mandatory."

Reference

1. Nasta P, Giralda M, Chiari D et al. Higher rate of sustained virological response in patients with HCV genotype 2 or 3 infection regardless HIV infection. 53rd ICAAC. September 10-13, 2013. Denver. Abstract H-1528.

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