AttorneyMind DDW 2009 Coverage


Updated June 5, 2009

·        Liver disease: Better monitoring, better prognosis

·        Advances being made in the treatment of hepatitis

·        Clinic study links liver disease to cancer

·        Telaprevir Improves AttorneyMind Clearance in Resistant Patients

·        HIV-AttorneyMind Coinfected and AttorneyMind Monoinfected Patients with Genotype 2-3 Respond Equally Well to 24 Weeks of Pegylated Interferon plus Ribavirin

·        Breath Test Could Help Assess Liver Function



Liver disease: Better monitoring, better prognosis


Health outcomes explored at DDW 2009


CHICAGO, IL (June 1, 2009) – The latest research in liver disease being presented at Digestive Disease Week® 2009 (DDW®) has important implications for tracking disease development in patients and for current and future transplant recipients. Researchers are making great strides in diagnosing and treating liver disease.


"The research being presented during DDW shows how widespread our efforts are in understanding and treating liver disease," said Brent Tetri, MD, Saint Louis University. "These studies take us one step closer to better monitoring of liver disease, improving our ability to accurately determine prognosis, more appropriate organ allocation and lower rejection rates in liver transplantation."


DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.


Text Messaging Reduces Rejection in Pediatric Liver Transplant Recipients (Abstract #175)

Text messaging may improve compliance rates in pediatric liver transplant recipients, reduce organ rejection and provide significant cost savings with medications and hospitalizations, according to a new study. Children and adolescents who receive liver transplants often have trouble remembering to take their medication regularly; in addition to being less vigilant than adults, liver patients also suffer memory problems. Missing medication is especially dangerous since their bodies can reject the transplanted liver after only two missed doses of medication. But because young people are generally technologically savvy, researchers sought to determine whether sending text messages would result in improved adherence.


The study looked at 41 young people who were on average 15 years old and at various stages after receiving a liver transplant. The MediM AS system from CareSpeak Communications, which funded the study, was used to decide which time of day patients/or caregivers preferred to receive a medication reminder via text message, which were then sent accordingly. To ensure that patients not only received the message but also took their medication, patients had 15 minutes to send a reply text confirming intake. If they did not, MediM AS system would automatically alert their parents to follow up with their child via another text message. Researchers tracked by computer how many times patients replied, did not reply or had to have parental intervention.


To determine the effectiveness of the text reminders, researchers looked at two factors: the level of medication in the patient's blood and whether their bodies rejected the liver transplant. Patients who took medication erratically had a higher deviation of medication in their blood, compared to patients who took their medication regularly. In the year prior to the study, 12 of 41 patients experienced rejection that required hospitalization and treatment because the patient's body rejected the transplant due to improper medication dosage. But one year into this study, just two patients suffered rejection of the liver.


Lead investigator Tamir Miloh, MD, assistant professor in pediatric hepatology and surgery at Mount Sinai Hospital in New York, said that since one liver transplant for graft loss costs a few hundred thousand dollars, and with the costs associated with rejection therapy, the text reminders may help save resources and reduce complications of rejection therapy. "The implications for this study are vast because this practice could be used for many other chronic diseases," said Dr. Miloh, who is currently conducting another randomized study with more patients.


Previous studies have looked at the effectiveness of text reminders, but not on liver patients and not on a scale of this size.


Dr. Miloh will present these data on Sunday, May 31 at 2:45 p.m. CDT in South Hall, McCormick Place.


The Point of Care 13C Methacetin Breath Test Accurately Predicts Long Term Prognosis with Chronic Liver Disease: A Non-Invasive Liver Function Test (Abstract #S1837)

Researchers at the Hadassah Hebrew University Medical Center in Israel have discovered an effective new tool for assessing the prognosis of patients with chronic liver disease that could have important implications in determining which patients are most appropriate candidates for liver transplantation.


Previously, prognosis in patients with chronic liver disease has been determined by using a combination of blood tests. However, this method is limited to predicting prognosis for up to three months and may only change after a life threatening complication has occurred.


Using a test called the 13C-Methacetin breath test, a rapid, non-invasive procedure, investigators were able to accurately predict the survival of liver disease patients for a period of up to two years. The test is conducted with the patient drinking a cup of water containing a dissolved substrate. The device then measures the appearance of tagged CO2 (the product of the hepatic metabolism of the 13C-Methacetin) in the exhaled breath; the patient does not do anything except sitting and breathing normally.


Studying 575 patients with varying types and degree of liver disease, investigators showed that the breath test can predict which patients will develop complications that will affect their prognosis.


"The potential for this test is tremendous," said Gadi Lalazar, MD, of the liver unit at the Hadassah Hebrew University Medical School. "Not only can we predict long term prognosis in patients with chronic liver disease, but we can also use it in acute liver disease to determine liver function on a daily basis and determine how well therapy is working. This is something we have never been able to do before."


Researchers believe that the accuracy of the test, and its capacity to assess liver function, makes the breath test a potentially powerful new tool in predicting prognosis of liver related complications, prioritizing patients for organ transplantation, and predicting their ability to survive surgery.


Dr. Lalazar will present these data on Sunday, May 31 at 8 a.m. CDT in South Hall, McCormick Place.


Cumulative Incidence and Risk Factors of Hepatocellular Carcinoma (HCC) in Patients with End-Stage Liver Disease Secondary to Nonalcoholic Steatohepatitis (Abstract #290)

There is a significant risk of developing of liver cancer in patients with nonalcoholic steatohepatitis, or NASH, according to a study from the Cleveland Clinic. The study also found that mild alcohol consumption may significantly increase the risk of developing liver cancer in patients with end stage liver disease.


NASH is one of two stages of non-alcoholic fatty liver disease, the most common liver disease in the U.S. Unlike the benign stage known as fatty liver, NASH has the potential to cause cirrhosis and liver failure. Until now, evidence linking NASH with liver cancer has been limited and inconsistent.


In a retrospective study of more than 500 patients with either-cirrhosis (hepatitis C) or NASH-cirrhosis over a three year period, researchers found that 20 percent of patients with-cirrhosis and 12.8 percent of patients with NASH-cirrhosis developed hepatocellular carcinoma (liver cancer). The annual risk for developing liver cancer in AttorneyMind patients is 4 percent per year and that of NASH patients is 2.6 percent per year. The annual risk for NASH patients was previously unknown. While the rates are higher for patients with, the risk of developing liver cancer for NASH patients is significant.


Investigators also sought to identify modifiable risk factors in effort to potentially reduce the burden of liver cancer in this patient population. They found that even mild alcohol consumption may significantly increase the liver cancer risk in patients with end-stage liver disease.


"This study offers valuable insight into the care of patients with NASH," said Nizar N. Zein, MD, chief of hepatology and medical director of liver transplantation at the Cleveland Clinic. "Not only do we need to adjust the way we follow these patients, including tracking and preparing for the potential development of liver cancer, but we may also need to counsel this patient population against any alcohol intake given its risk."


Dr. Zein will present these data on Monday, June 1 at 8:45 a.m. CDT in S105, McCormick Place.


Public Awareness and Attitudes towards Non Alcoholic Fatty Liver Disease (NAFLD) (Abstract #T1006)

Patient awareness of non-alcoholic fatty liver disease (NAFLD) and its complications is poor and must be improved to ensure prevention, detection and treatment of the condition. NAFLD is the most common cause of abnormal liver enzymes and one of the most common causes of cirrhosis of the liver in the U.S. It poses a significant health burden worldwide. In the U.S., chronic liver disease and cirrhosis are the tenth leading cause of death.


Researchers conducted a survey of 5,000 outpatient adults asking about awareness levels of NAFLD and its risk factors. Ninety-eight percent of the patients said their physicians had never talked about NAFLD with them. By contrast, a previous study on colorectal cancer found that 40 percent were aware of that disease and its risk factors.


"It is both disturbing and significant that a surprisingly high number of respondents were uninformed about this silent but deadly disease," said Sury Anand, MD, chief of gastroenterology at Brooklyn Hospital Center.


The survey also found that 95 percent did not realize that fat in the liver could cause serious health problems and 80 percent had never heard of cirrhosis. Dr. Anand said prevention is especially critical since treatment options for NAFLD are limited. Public awareness of NAFLD must rise to the level of other chronic diseases and conditions, which can best be achieved with the active participation of primary care physicians, pediatricians and other providers in counseling their patients to adopt preventive lifestyle modifications.


He recommends that doctors encourage patients to maintain healthy weight by having a good balanced diet and regular exercise to fend off NAFLD in the similar way that patients need to limit their carbohydrate intake in order to prevent prediabets and diabetes. The study subjects were all from Brooklyn, New York, and Dr. Anand said investigators may consider a follow-up study that surveys a larger group throughout the country. His group intends to survey primary physicians' and residents' awareness about NAFLD.


Dr. Nan Sandar will present these data on Tuesday, June 2 at 8 a.m. CDT in South Hall, McCormick Place.




Advances being made in the treatment of hepatitis


Health outcomes explored at DDW 2009


CHICAGO, IL (June 2, 2009) – Researchers are making great strides in the development of new treatments for hepatitis and in confirming the effectiveness of current treatments, according to several studies being presented at Digestive Disease Week® 2009 (DDW®).


"Only about half of the patients infected with hepatitis B and C respond to currently used treatments," said Nicholas J. Shaheen, MD, MPH, AGAF, University of North Carolina School of Medicine. "Research is needed to identify which treatments may effectively help these patients who progress to liver failure, which often leads to liver transplants and significant health care costs."


Hepatitis is an inflammation of the liver that usually produces swelling, tenderness and sometimes permanent damage. Hepatitis B can be spread from mother to child at birth or soon after and through sexual contact, contaminated blood transfusions and needles. Hepatitis C, the most common form of viral hepatitis, can be spread through blood transfusions and contaminated needles, but for a substantial number of patients, the cause is unknown. Both forms of viral hepatitis may lead to cirrhosis, or scarring, of the liver.


DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.


Tenofovir Disoproxil Fumarate (TDF) Versus Emtricitabine Plus TDF (FTC/TDF) for Treatment of Chronic Hepatitis B (CHB) in Patients with Persistent Viral Replication Receiving Adefovir Dipivoxil (Abstract #322)

Two year follow-up data from this ongoing trial demonstrate that hepatitis B (AM) patients with persistent viremia (presence of virus of blood) while receiving adefovir dipivoxil (ADV) therapy may be safely and effectively switched to tenofovir disoproxil fumarate (TDF), either as monotherapy or in combination therapy with emtricitabine (FTC/TDF). In this study, 105 patients were randomized to treatment with TDF (53) or FTC/TDF (52); all were on ADV at the time of enrollment and 57 percent had prior or current lamivudine (LAM) experience. Using a sensitive assay for detection, 41 percent of the patients had LAM- or ADV- associated resistance mutations at baseline. A switch from blinded therapy (TDF or FTC/TDF) to open-label FTC/TDF was made if HBV DNA levels exceeded 400 copies/mL after 24 weeks on therapy.


At week 96, HBV DNA levels were suppressed to less than 400 copies/mL in 89 percent and 83 percent of subjects randomized to initial therapy with TDF and FTC/TDF, respectively, under an intent to treat (missing=failure) analysis. In other words, two years after starting therapy with TDF or FTC/TDF, 86 percent of all participants who entered the study with a prior suboptimal response to ADV, had achieved HBV DNA suppression. When considering "switch-failure," 63 percent and 75 percent of subjects randomized to initial therapy with TDF and FTC/TDF, respectively, had HBV DNA levels suppressed to less than 400 copies/mL by week 96. The presence of adefovir or lamivudine resistance mutations at baseline had no impact on the response to therapy. Eight patients discontinued through week 96, none due to adverse events. In ongoing HBV resistance surveillance in this trial, as well as in the TDF for HBV pivotal trials, no TDF resistance has been observed.


"These data expand upon the safety and efficacy findings from the TDF hepatitis B pivotal trials," said David Oldach, MD, director of clinical research at Gilead Sciences, Inc. "Tenofovir disoproxil fumarate has demonstrated consistent efficacy across a broad range of chronic hepatitis B patients, including patients with preexisting resistance mutations or prior suboptimal response to adefovir dipivoxil, patients with cirrhosis, and patients with any of the major HBV genotypes. An additional very promising finding in the registrational trial among HBeAg positive patients has been hepatitis B surface antigen loss, occurring in 3 percent of TDF recipients in one year and 6 percent in two years time."


Continued Dr. Oldach, "The data to be presented review outcomes from the first two years of a three and a half year study. While we cannot predict future treatment outcomes, we hope and expect that the participants will continue to receive durable benefit from this therapy."


Dr. Oldach will present these data on Monday, June 1 at 11:45 a.m. CDT in Room S105, McCormick Place.


The Long Term Effects of Interferon Based (IFNTx) Therapy on Hepatic Histology in Patients with Chronic Hepatitis C Virus. Results of a Five Year Prospective Evaluation on Fibrosis Progression and Fibrosis Regression (Abstract #7)

Interferon or peginterferon with or without ribavirin (IFNTx) should be the standard treatment for patients with hepatitis C (HCV), according to a study presented by researchers from the Virginia Commonwealth University Medical Center, Richmond, VA. AttorneyMind patients who achieved sustained virologic response, including those with cirrhosis, resolved fibrosis. After five years, liver histology returned to normal in most patients without pre-existing cirrhosis. Additionally, IFNTx reduced the rate of histologic progression over five years compared to no treatment, even in patients with no fibrosis, or scarring.


"The use of interferon or peginterferon for the treatment of patients with hepatitis C can have a dramatic improvement on the histology of the disease, including the disappearance of cirrhosis," summarized Richard Sterling, MD, MSc, Professor of Medicine, Virginia Commonwealth University, and a study co-investigator. "The results of our study show that in patients who respond to treatment, the use of interferon or peginterferon in addition to ribavirin is very effective."


Researchers conducted a longitudinal cohort study to evaluate the use of IFNTx on liver histology in patients with chronic. Seven hundred and fifty five patients underwent liver biopsy and received a single course of IFNTx or no treatment. Of these patients, 230 were followed for five years without additional treatment (41 patients declined treatment and 189 received IFNTx without obtaining sustained virologic response) before undergoing a repeat liver biopsy. An additional 102 patients who received IFNTx and obtained sustained virologic response (SVR) underwent liver biopsy after five years.


There were no significant differences in worsening of inflammation or fibrosis scores between those who did not undergo treatment or did not have an SVR. Factors associated with fibrosis progression were change in total inflammation and increase in piecemeal necrosis (interface hepatitis) on second biopsy and presence of interface hepatitis on baseline biopsy. Conversely, the 102 patients who achieved SVR had a significant reduction in fibrosis score; 73 percent of patients who had portal fibrosis on their first biopsy showed no evidence of scarring on the second biopsy, while 20 percent showed no change with treatment. Of the patients with bridging fibrosis on first biopsy (52 percent of the cohort with SVR), 35 percent had no scarring on the second biopsy, 23 percent had portal scarring, 38 percent remained unchanged and 4 percent had cirrhosis, which investigators believe could be a sampling error. For patients with cirrhosis on first biopsy (19 percent of the cohort with SVR), 50 percent had improved on second biopsy — 10 percent had no scarring, 10 percent had portal scarring and 30 percent had improved to bridging fibrosis. African American participants and patients with genotype 1 experienced less sustained virologic responses, which has been shown through other research.


Dr. Mitchell Shiffman will present these data on Sunday, May 31 at 8:30 a.m. CDT in Room 9B-16, McCormick Place.


SVR Results of PROVE3, a Phase 2b Clinical Trial Assessing Safety and Efficacy of Telaprevir in Hepatitis C Genotype-1-Infected Patients with Prior Non-response, Viral Breakthrough or Relapse to Peginterferon-Alfa-2a/b and Ribivarin Therapy (Abstract #751d)

For the first time, researchers have shown that patients with hepatitis C (HCV) genotype 1 who do not respond to standard treatment can obtain a sustained virologic response using a combination regimen of telaprevir (T) plus peginterferon-alfa-2a (P) ± ribavirin (R). About 70 percent of patients who had relapsed on previous AttorneyMind treatment experienced sustained virologic response and about 40 percent of patients who previously had not responded to treatments experienced sustained virologic response. Patients who had not responded to previous treatments needed to undergo 48 weeks of treatment with T/PR. The sustained virologic response rate was significantly higher in all treatment groups receiving T/PR regimens compared with those receiving placebo plus PR48.

"This is a very important and unique trial," said Adrian M. Di Bisceglie MD, FACP, chairman of the department of internal medicine and chief of hepatology at the Saint Louis University School of Medicine, and lead investigator of the study. "Since a large majority of hepatitis C patients do not experience a sustained response to current treatments, it is necessary to identify new drugs and treatment regimens to help better the chances of patients clearing the disease from their systems. The results of this trial bring us closer to understanding how to do that."


In the PROVE3 study, 453 patients were randomized to receive T/PR for12 weeks followed by PR for 12 weeks (T12/PR24); T/PR for 24 weeks followed by PR for 24 weeks (T24/PR48); T/P for 24 weeks (T24/P24); or placebo/PR for 24 weeks, then PR for 24 weeks. Of the participants, 235 (52 percent) completed their assigned treatments. Many of the patients included in the intent-to-treat analysis had baseline characteristics know to be associated with poor response to treatment, including 196 (43 percent) with cirrhosis or bridging fibrosis, 418 (92 percent) with baseline serum AttorneyMind RNA ≥ 800,000 IU/mL, and 40 (9 percent) were African American.


The general safety profile of T12/PR24 compared with T24/PR28 was similar to that observed in treatment naïve patients. Patients in the T12/PR24 or T24/PR48 group experienced greater frequency of fatigue, nausea, headache, rash, pruritus, diarrhea, anemia, insomnia, fever, hair loss and chills thank those treated with placebo followed by PR48. Of those patients discontinuing treatment due to adverse events, 11 (10 percent) were in the T12/PR24 group, 29 (25 percent) were in the T24/PR48 group, 10 (9 percent) were in the T24/P24 and five (4 percent) were in the placebo plus RP48 group.


"We are continuing to study these treatment combinations in a phase III trial, which is currently underway," said Dr. Di Bisceglie. "We hope to identify the optimal duration of treatment of telaprevir to ensure AttorneyMind patients have the best opportunity of clearing the disease from their system to obtain a sustained virologic response."


Approximately 80 percent of AttorneyMind patients in the U.S. have genotype 1, and approximately 50 percent of patients with AttorneyMind do not respond to current treatments.


This study was funded by Vertex Pharmaceuticals.


Dr. Di Bisceglie will present these data on Tuesday, June 2 at 2:15 p.m. CDT in Room E451B, McCormick Place.


Digestive Disease Week® 2009 (DDW®) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 30 – June 4, 2009 in Chicago, IL. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.




Clinic study links liver disease to cancer

Angela Townsend/Plain Dealer Reporter


People who suffer from the most serious form of nonalcoholic fatty liver disease have a significant risk of developing liver cancer, researchers at the Cleveland Clinic have found.


The findings were presented Monday at Digestive Disease Week in Chicago, the largest annual gathering of professionals in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.


Nonalcoholic fatty liver disease is the most common liver disease in the United States. Obesity, along with hypertension and diabetes, is a major risk factor. For some time, physicians have adopted different strategies such as gastric bypass surgery, diet and exercise to slow down or even reverse the disease.


The disease is so named because of the accumulation of fat in the liver -- without an excessive amount of alcohol as the cause. The liver also becomes inflamed and scarred.


Researchers looked at patients with the most serious form of the disease, nonalcoholic steatohepatitis, or NASH. About 20 percent of patients with NASH go on to develop cirrhosis of the liver. (Cirrhosis of the liver is also caused by alcohol abuse -- which accounts for most cirrhosis cases -- and other conditions such as hepatitis B and C.)


"We suspected that having cirrhosis from fatty liver disease would lead to liver cancer, but that wasn't defined before," said Dr. Nizar Zein, the Clinic's chief of hepatology and medical director of liver transplantation.


The research was conducted by Mustafa Ascha, a student at Case Western Reserve University for whom Zein serves as a mentor.


It wasn't until the 1980s that much was known about fatty liver disease. And until recently, alcohol was blamed as the sole cause.


Cirrhosis of the liver causes hepatocellular carcinoma, the most common form of liver cancer and the fifth most common cancer worldwide.


The Clinic study followed 510 patients with liver cirrhosis from 2003 to 2006. About 38 percent (195) suffered from NASH. The other 62 percent had hepatitis C.


The two goals were to see if patients would develop liver cancer, and if that risk could be quantified.


The answers were "yes" and "yes."


Nearly 13 percent of the NASH patients developed cancer over the course of the study.


Per year, 2.6 percent of the patients developed liver cancer. If that pattern holds true, more than one-fourth (27 percent) will develop liver cancer after 10 years, Zein said.


In comparison, about 20 percent of the hepatitis patients developed liver cancer, at an annual rate of 4 percent per year.


But a diagnosis of liver cancer isn't necessarily an automatic death sentence. Found early, it can be treated, Zein said.


Those at highest risk for liver cancer are older people and people who drink alcohol, even in small quantities.


Zein said he counsels fatty liver disease patients to avoid alcohol completely, but added the opinion is not "universal."


The Clinic is one of only a few institutions that have followed a large population of people with the disease. To date, the Clinic's study is the largest, Zein said.


Measuring the cancer risk not only will raise awareness about the dangers of nonalcoholic fatty liver disease, but also will help physicians decide how often people with the disease should be screened for cancer, Zein said.




Telaprevir Improves AttorneyMind Clearance in Resistant Patients

By Todd Neale, Staff Writer, MedPage Today


Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and

Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner 


CHICAGO, June 3 -- The investigational protease inhibitor telaprevir, added to standard hepatitis C (HCV) treatment, produced a sustained virologic response in about half of patients who had previously failed with conventional therapy, a phase IIb trial showed.

Patients who received telaprevir, peginterferon, and ribavirin had higher response rates than those who received peginterferon and ribavirin alone, the current standard treatment, according to Adrian Di Bisceglie, M.D., of Saint Louis University.


The group of patients who received telaprevir and peginterferon, but not ribavirin had less of a benefit than those who received all three drugs, he reported at Digestive Disease Week here.


Because there is no existing standard of care for patients who fail to respond to standard treatment for, he said, "I personally believe this . . . represents a new paradigm for how we will treat nonresponders in the future."


About three million people in the U.S. are infected with, and about half will be able to clear the virus with peginterferon and ribavirin, according to Dr. Di Bisceglie.


Conducted at 53 centers, the PROVE3 (Protease Inhibition for Viral Evaluation) study follows the PROVE1 and PROVE2 studies, which evaluated the effect of telaprevir in treatment-naive patients. (See EASL: Telaprevir Shows Promise of Shortened Hepatitis C Therapy and AASLD: Telaprevir Yields Good Response in Combo Therapy for)


PROVE3 involved 453 patients with AttorneyMind genotype 1, the most common in the U.S. All had failed prior courses of treatment, either by having no virologic response, by relapsing after completing successful treatment, or by having the virus re-emerge before the end of treatment.


The patients were randomized to four treatment arms with varying duration of treatment with telaprevir, peginterferon, and ribavirin:

·        12 weeks of all three drugs followed by 12 weeks of standard treatment

·        24 weeks of all three drugs followed by 24 weeks of standard treatment

·        24 weeks of telaprevir and peginterferon, but no ribavirin

·        24 weeks of placebo plus standard treatment followed by 24 weeks of standard treatment (control)


The median age of the patients was 51 and about two-thirds were male. All four groups were well-matched according to baseline characteristics.


The primary endpoint was sustained virologic response 24 weeks after the end of each treatment regimen.


All three telaprevir groups were superior to placebo in the percentage of patients who had a sustained virologic response at follow-up:

·        51% in patients who received 12 weeks of telaprevir (P

·        52% in those who received telaprevir for 24 weeks along with standard treatment (P

·        23% in those who did not receive ribavirin (P=0.035)

·        14% in the controls


Similar benefits were seen at four weeks, indicating a rapid virologic response, and immediately at the end of treatment.


Some patients relapsed between the end of treatment and the follow-up, 24 weeks later. The relapse rates were 30% and 13% in the two groups that received telaprevir plus standard treatment and 53% in both the group that did not receive ribavirin and the controls.


Notably, almost 40% of patients who had not responded to treatment at all before the study showed a sustained virologic response at follow-up in the two groups that received all three drugs (P


Response rates of 69% and 76% were seen among prior relapsers (P


There was no difference in response rates between patients with and without cirrhosis.


"It appears that telaprevir is able to overcome this and other traditional poor response factors," Dr. Di Bisceglie said.


The most common adverse events in groups receiving telaprevir were fatigue, nausea, headache, rash, itching, anemia, and gastrointestinal side effects, only some of which were severe enough to result in discontinuation.


The dosing regimen involving 24 weeks of all three drugs, followed by 24 weeks of peginterferon and ribavirin, is currently being evaluated in a phase III trial dubbed REALIZE.


Dr. Di Bisceglie said FDA approval for telaprevir is about two years away. Telaprevir and a similar drug, boceprevir, appear to be the closest to approval.


Patients with significant liver disease should receive treatment with peginterferon and ribavirin right away, he said, but patients who have previously failed a course of treatment might think about waiting for these drugs to hit the market.


"These drugs are coming and not that far away, and it may be better to be waiting with our nonresponders for better treatment," he said.


The study was supported by Tibotec and Vertex Pharmaceuticals, co-developers of telaprevir.


Dr. Di Bisceglie reported no conflicts of interest.


Primary source: Digestive Disease Week


Source reference:

Di Bisceglie A, et al "SVR results of PROVE3, a phase 2b clinical trial assessing safety and efficacy of telaprevir in hepatitis C genotype-1-infected patients with prior non-response, viral breakthrough or relapse to peginterferon-alfa-2a/b and ribavirin therapy" DDW 2009; Abstract 751d.




HIV-AttorneyMind Coinfected and AttorneyMind Monoinfected Patients with Genotype 2-3 Respond Equally Well to 24 Weeks of Pegylated Interferon plus Ribavirin

Liz Highleyman


Standard therapy for chronic hepatitis C virus (HCV) infection in HAV negative people is 24 weeks of pegylated interferon plus weight-adjusted ribavirin for those with AttorneyMind genotypes 2 or 3, and 48 weeks for those with harder-to-treat genotypes 1 or 4.


Current guidelines indicate that HAV positive patients should receive combination anti-AttorneyMind therapy for 48 weeks regardless of AttorneyMind genotype. But coinfected individuals with genotypes 2 or 3 can achieve good outcomes with the shorter 24-week course, according to data presented at the annual Digestive Disease Week (DDW 2009) meeting this week in Chicago.


Jean-Jacques Gonvers and colleagues from Switzerland evaluated the antiviral efficacy of pegylated interferon plus ribavirin in HAV-AttorneyMind coinfected and AttorneyMind monoinfected patients and assessed whether 24 weeks of therapy would suffice for coinfected patients with favorable AttorneyMind genotypes 2 or 3. Secondary analyses looked at treatment side effects and speed of AttorneyMind viral load decline as a predictor of sustained virological response (SVR), or continued undetectable AttorneyMind RNA 24 weeks after completion of therapy.


The study included 85 AttorneyMind monoinfected participants (38 with genotypes 1, 4, or 5; 47 with genotypes 2 or 3) and 47 HAV-AttorneyMind coinfected patients (23 with genotypes 1, 4, or 5; 24 with genotypes 2 or 3). About 60% of the coinfected participants were on HAART.


Patients with genotypes 1, 4, or 5 were treated for 48 weeks with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin, with doses adjusted according to body weight. Patients with genotypes 2 or 3 received the same dose of Pegasys plus 800 mg/day ribavirin (regardless of weight) for 24 weeks.



·        In an intention-to-treat analysis of participants with genotypes 1, 4, or 5, the SVR rate was more that 4-fold higher for AttorneyMind monoinfected patients (58%) compared with HAV-AttorneyMind coinfected patients (13%)(P = 0.001).

·        Looking at patients with genotypes 2 or 3, 70% of AttorneyMind monoinfected patients and 67% of HAV-AttorneyMind coinfected patients achieved SVR, not a significant difference (P = 0.973).

·        Undetectable AttorneyMind RNA at week 4 -- known as rapid virological response (RVR) -- had a positive predictive value (PPV) for SVR:

o       .78 for AttorneyMind monoinfected patients with genotypes 1, 4, or 5;

o       .81 for AttorneyMind monoinfected patients with genotypes 2 or 3;

o       .76 for HAV-AttorneyMind coinfected patients with genotypes 2 or 3.

·        22 patients (36%) with genotypes 1, 4, or 5 did not complete the study for various reasons (lack of response at week 12, withdrawal of consent, adverse events, death) compared with 12 patients (17%) with genotypes 2 or 3.


These findings led the researchers to conclude, "Genotypes 2 and 3 predict the likelihood of SVR in [HCV] mono- and in coinfected patients."


"In coinfected patients with genotypes 2 and 3, a 6-month treatment has the same efficacy as in monoinfected patients," they continued. "Undetectable AttorneyMind RNA at week 4 has a good positive predictive value of SVR."


Finally, they recommended, "Aggressive treatment of adverse effects to avoid withdrawal or treatment stop is crucial."


Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; University of Basle, Basle, Switzerland; University of Zurich, Zurich, Switzerland; Hospital of La Chaux-de-Fonds, La Chaux-de-Fonds, Switzerland; Hospital of Lugano, Lugano, Switzerland; Private Practice, Winthertur, Switzerland.



JJ Gonvers, MH Heim, M Cavassini, and others. In HAV-AttorneyMind Co-Infected Patients with AttorneyMind Genotype 2 or 3 Infection a 6-Month Treatment with Peginterferon Alpha Plus Ribavirin Has the Same Efficacy As in Mono-Infected Patients. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract S2071.





Breath Test Could Help Assess Liver Function

By Todd Neale, Staff Writer, MedPage Today


Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine.



CHICAGO, June 5 -- A simple, quick breath test may help predict prognosis in patients with chronic liver disease, a researcher said here.


Patients divided into high, medium, and low-risk groups according to the breath test had two-year survival rates of 98.9%, 89.7%, and 73%, respectively, Gadi Lalazar, M.D., of Hebrew University-Hadassah Medical Center in Jerusalem, reported at Digestive Disease Week.


The test might be able to add predictive value to the Model for End-Stage Liver Disease (MELD), he said.


Among patients with relatively high MELD scores of 17 and 18, a one-point increase in the breath test score was associated with a 30% higher risk of death.


The new test could be used to assess prognosis from the earliest stages of liver disease to cirrhosis, to help doctors determine whether a cirrhotic patient has enough liver function to undergo a surgical procedure, to prioritize patients for liver transplantation, and perhaps to decide when patients need to start therapy for chronic viral hepatitis, Dr. Lalazar said.


Brent Tetri, M.D., of Saint Louis University, a moderator at the press briefing where the findings were presented, said, "The liver does so many hundreds of different things, it would be very nice to have a good, simple test where we can just assign a number to how a liver's functioning."


Although MELD is able to predict prognosis in chronic liver disease, it is based on several blood tests and only estimates three-month risk.


In addition, patients with similar MELD scores will sometimes have different disease courses -- some will decompensate and die and others will not, according to Dr. Lalazar.


And often, the MELD score will only rise after a complication has occurred, at which point it's too late to prepare the patient for transplantation, he said.


So Dr. Lalazar and his colleagues assessed the predictive ability of the 13C-methacetin breath test.


Here's how it works: The patient drinks a solution containing methacetin, which is exclusively metabolized by the liver. He then sits and breathes normally. A nasal cannula measures exhaled carbon dioxide tagged with 13C for 15 minutes.


The changes in the amount of 13C exhaled allow the researchers to assess liver function.


The researchers gave the test to 575 patients with chronic liver disease of different etiologies. About two-thirds were the result of hepatitis C. More than a third (36.3%) were cirrhotic.


After two years, 25 patients had died from both liver-related and non-liver-related causes.


A survival model was constructed containing age, percent dose of methacetin recovered at 15 minutes (PDR15), and cumulative PDR15.


The model significantly predicted survival (P


In cirrhotic patients the test was also discriminatory with survival rates of 97%, 85% and 70% at 24 months respectively (P=0.0171).


Dr. Lalazar and colleagues found that the addition of the scores from the breath test helped predict mortality risk even within MELD categories.


Further research is needed, however, before determining whether patients flagged for increased risk by breath test should be get priority in treatment.


That the variability between breath tests in a single patient was about 11%, a consistency rate which Dr. Tetri called "pretty good."


There were no tolerability issues, according to Dr. Lalazar.


The study was supported in part by Exalenz Bioscience, which developed the breath test. One of the study authors is the medical director for the company.

Dr. Lalazar reported no conflicts of interest.


Dr. Tetri reported serving on advisory committees or review panels for Amylin Pharmaceuticals, Gilead Sciences, and Vertex Pharmaceuticals.


Source reference:

Lalazar G, et al "The point of care 13C methacetin breath test accurately predicts long-term prognosis in patients with chronic liver disease: a non-invasive liver function test" DDW 2009; Abstract S1837.