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-         May 16th, 2004  -

 

 

 

 

 

Calendar 1

48-Week Regimen May be Too Short For Genotype 1 Hepatitis. 1

Communicating with Your Doctor 2

Liver Regeneration Is Slower in Living Donors Than in Their Recipients  3

Pennsylvania Hepatitis A Outbreak Claims 4th Victim.. 3

Help Wanted. 4

Amantadine of No Benefit in Hepatitis C Infection. 4

Rising Death Rates From Hepatitis C-Related Chronic Liver Disease  4

Medical Research Opportunity for Hepatitis-C Patients. 5

Love Your Liver Walk. 5

 

48-Week Regimen May be Too Short For Genotype 1 Hepatitis

by John C. Martin
March 31, 2004

Though there have been major advances in hepatitis treatment over the years, patients infected with genotype 1 strains have a much poorer prognosis compared to their counterparts infected with other strains of the virus. And that’s the case even if they receive treatment with high-dose pegylated interferon plus ribavirin.

According to statistics, therapy with pegylated interferon/ribavirin combination is associated with a response rate of approximately 50% among patients infected with the genotype 1 strain of hepatitis C (HCV). The regimen is also associated with a number of predictable toxicities. Side effects are not uncommon either. Flu-like syndrome, depression, and alternations in hemoglobin levels and white blood cell counts are among the adverse events that occur when patients take the combination treatment over long periods of time.

The prognoses for patients with non-genotype 1 strains of HCV are better, according to estimates. Patients with strains other than genotype 1 face about an 80% chance

of clearing the virus. As a result, doctors have been attempting over the past several years to improve response rates among this group of patients in order to “level the playing field”, so to speak.

Is 48 Weeks Enough?

Based on that notion, researchers who published a study recently wanted to determine if the conventional treatment regimen of 48 weeks was truly optimal for patients with genotype 1.

To make that evaluation, doctors at the Ordway Research Institute in Albany, New York evaluated the findings of a 2001 clinical trial that tested the efficacy of the pegylated interferon, PEG-Intron (Schering-Plough) combined with ribavirin versus a standard interferon, (interferon alfa-2b) and ribavirin.

The objective of the most recent study was to develop a model predicting SVR using the patient data from the 2001 trial, and to examine the effect of therapeutic response duration on outcome. The researchers believed they could prove that there was an association between the length of time that a particular patient has a response to therapy during that treatment (an undetectable viral load for a certain number of weeks continuously), and the probability of achieving a long-term response after therapy ended, known better as a sustained virologic response, or SVR.

"We hypothesized that the longer the duration that the virus was rendered undetectable in serum, the better would be the probability of a sustained viral response (SVR)," wrote the research team headed by George Drusano, M.D., co-director of the Ordway Research Institute.

SVR is defined as undetectable levels of virus in a patient’s bloodstream for at least 6 months after therapy concludes.

The SVR model that Drusano and his team built was based on three key influential factors: duration of non-detectable hepatitis C virus in the bloodstream, estimated creatinine clearance, and whether patient had contracted the genotype 1 strain of the virus.

Continuous Non-Detectable Viral Levels

In the end, the model predicted that patients infected with genotype 1 must have continuous non-detectable viral loads during treatment for at least 32 weeks to achieve an 80% SVR. To achieve a 90% SVR, patients must have non-detectable viral levels in their blood for a minimum of 36 weeks.

But in the clinical trial that the investigators analyzed, it took, on average, about 30.4 weeks for patients with the genotype 1 strain to initially clear the virus. Based on the model, therefore, a patient who cleared the virus after 30.4 weeks of treatment would have to remain on treatment for an additional 32 weeks—a total of 62.4 weeks—to achieve an 80% SVR.

Obviously, that estimate doesn’t coincide with the recommended 48-week treatment regimen currently advised for patients with any HCV strain.

Despite the fact the researchers deemed the findings as significant, they’re urging a prospective clinical trial to confirm the results. "This hypothesis requires prospective validation," they wrote.

Reference
G. L. Drusano and S. L. Preston.  A 48-Week Duration of Therapy with Pegylated Interferon 2b plus Ribavirin May Be Too Short to Maximize Long-Term Response among Patients Infected with Genotype-1 Hepatitis C Virus. The Journal of Infectious Diseases 189(6): 964-970. March 15, 2004. http://www.hepatitisneighborhood

Communicating with Your Doctor

Chinweike Ukomadu, M.D., Ph.D.

Instructor in Medicine, Harvard Medical School

04/09/2004 - Veritas Medicine Viewpoint

Communication between doctors and HCV-infected patients is an important aspect of the disease’s management. There is little doubt that a patient is more likely to be compliant with treatment, and thus more likely to attain sustained virologic response (SVR), if the physician is attentive and supportive.

Recent evidence suggests that physicians are not doing well in this aspect of medical care. In a report in the recent issue of Hepatology, investigators evaluated 322 HCV patients treated at a tertiary hospital’s liver clinic.  41% of the patients reported communication difficulties with their physician. Among these, 28% were felt to be due to poor communication skills, 23% due to incompetence, 16 % felt misled or abandoned by their doctor, and 9% felt stigmatized. Interestingly, sub-specialists were two times more likely to have communication problems than generalists.

While non-response to medical therapy and a history of psychosocial problems were associated with perceived communication difficulties, a past history of substance abuse was not.

Regardless of the reason, these communication deficiencies, even if only perceived by patients, are troubling. Physicians who treat HCV-infected patients function like primary care doctors, dealing with a plethora of side effects from skin rashes to headaches. It is thus troubling that despite this intimacy over the treatment period, sub-specialists are still felt to have problems in communicating with their patients

What should one do? Doctors should take time in talking to patients. Every question, concern or issue should never be approached in a dismissive manner. Because the physician’s time is often limited in most practices, the additional use of other personnel (physician assistants, nurse practitioners, etc.) dedicated to caring for HCV-infected patients can be critical, helping decompress the physician’s schedule and providing easier access to patients. Patients should make their feelings known to the physician as such dialogue can often lead to an improvement in relations.

Reference: Zickmund S, et al. Hepatitis C virus-infected patients report communication problems with physicians. Hepatology 2004;39:999-1006.

Liver Regeneration Is Slower in Living Donors Than in Their Recipients

NEW YORK (Reuters Health) Mar 17, 2004 - Living donor liver transplantation is possible because near-complete regeneration occurs within weeks in the transplanted graft as well as in the donor's residual liver. Now, researchers have discovered that liver regeneration is slower in the donors than in the recipients of partial grafts.

At the University of Minnesota in Minneapolis, Minnesota, Dr. Abhinav Humar and colleagues used computed tomography volumetrics to analyze liver volume at three months after transplant in patients who had received either a right lobe from a living donor, or a right or left lobe from a cadaver donor in a split liver transplant. The researchers also analyzed liver volume at three months in the living donors.

Their findings are published in the March issue of Liver Transplantation.

When the investigators used a standard formula to calculate subjects' ideal liver volume, they discovered that at three months, living donors had attained an average of 78% of their ideal volume, compared to 103.9% for recipients of right lobes from living donors, 113.6% for recipients of right lobes from cadavers, and 121.4% for recipients of cadaveric left lobes.

The researchers admit that the reasons for their findings remain unclear. They point out, however, that while the donors' livers appeared to regenerate "at a less vigorous pace," this may not have great clinical significance. "Synthetic function was usually completely normal in living donors by 1 week" after their surgery, according to the paper.

"Patients who undergo a partial-liver transplant or a partial hepatectomy offer ideal clinical models for the in vivo study of liver regeneration," the investigators comment. "Studies such as this are important to help solve the mystery of liver regeneration and to ultimately make partial-liver transplants safer for donors and more effective for recipients."

Liver Transpl 2004; 10:374-378

Pennsylvania Hepatitis A Outbreak Claims 4th Victim

By Joe Mandak

Associated Press

PITTSBURGH (AP) April 03, 2004  - A fourth person has died from last year's hepatitis A outbreak at a Chi-Chi's Mexican restaurant, the man's attorney said Saturday.

Frank Rossi, 50, died Thursday at a Pittsburgh hospital. Results of an autopsy performed Saturday weren't complete, but the death certificate lists the cause as "complications from hepatitis A," attorney Richard Urick said.

Rossi was one of at least 660 people sickened in an outbreak last fall traced to green onions served at the restaurant, at a mall about 25 miles northwest of Pittsburgh. Three others died shortly after the outbreak became known in early November.

The Food and Drug Administration said tainted green onions from four Mexican farms caused the Pennsylvania outbreak and others that sickened at least 300 people in Georgia, North Carolina and Tennessee last fall. The farms have been shut down.

Rossi was still recovering from a heart valve replacement in February 2003 when he contracted hepatitis A. He was in and out of hospitals in November and had been an inpatient since December for various ailments stemming from hepatitis A, a virus that affects the liver, Urick said.

Editor’s Note: Important reminder – Get vaccinated for hepatitis A if you have hepatitis C.

 

Amantadine of No Benefit in Hepatitis C Infection

NEW YORK (Reuters Health) Jan 13, 2004 - The addition of amantadine to a regimen of interferon alfa-2b and ribavirin does not improve outcomes in patients with chronic hepatitis C viral (HCV) infection, researchers in the U.S. report.

Amantadine is an antiviral drug with activity against the flaviviridae family, but clinical trials of the agent used to treat HCV have yielded conflicting results. A sustained response is achieved in fewer than half of patients with HCV treated with interferon plus ribavirin, they note in their paper.

In fact, lead author Dr. P. J. Thuluvath and colleagues write in the January issue of Gut, "We believe that amantadine should be abandoned as a potential agent for the treatment of HCV."

In their prospective study, Dr. Thuluvath, at Johns Hopkins University in Baltimore, and his team treated 171 patients with interferon alfa-2b 3 million units s.c. three times a week and ribavirin 1000 to 1200 mg daily for 24 weeks, with treatment continuing for 48 weeks if HCV RNA clearance was noted by PCR after 24 weeks. Eighty-five were randomly assigned to co-treatment with amantadine hydrochloride 100 mg b.i.d. and 86 were assigned to placebo.

Adverse event profiles were similar in the two groups, and withdrawal rates did not differ significantly. After 48 weeks of treatment, HCV RNA clearance rates were 40.6% among 28 patients remaining in the amantadine group and 47.8% of 33 in the placebo group. At 72 weeks, only 21 patients in the amantadine group and 24 in the placebo group were available for evaluation; response rates were 30.4% and 34.8%, respectively.

"We assumed that our study had the power to show a moderate difference if it existed," the investigators write, "but we did not find even a trend favoring triple therapy."

Gut 2004;53:130-135.

Rising Death Rates From Hepatitis C-Related Chronic Liver Disease

NEW YORK (Reuters Health) Feb 27 - Though chronic liver disease mortality declined slightly, the mortality rates for hepatitis C-related chronic liver disease more than doubled during the 1990s, according to a report in the February issue of Hepatology.

Chronic liver disease (CLD) is the 10th most frequent cause of death in the United States, the authors explain, but the contribution of viral hepatitis to CLD-related mortality has been elusive.

Dr. Sirenda Vong and Dr. Beth P. Bell from Centers for Disease Control and Prevention (CDC), Atlanta, Georgia used an expanded definition of CLD deaths that included death certificates where CLD, viral hepatitis, or CLD-related sequelae were reported to calculate overall age-specific and age-adjusted mortality rates from 1990 through 1998.

The age-adjusted death rate for CLD declined 4.5% (from 12.1 to 11.6/100,000) between 1990 and 1998, the authors report, though rates were stable from 1995 through 1998.

Between 1993 and 1998, hepatitis C-related CLD deaths increased 220%, the report indicates, along with a 45% increase in deaths from unspecified viral hepatitis. Hepatitis B-related CLD deaths remained unchanged from 1990 through 1998.

During this period, deaths from alcohol-related CLD fell by 10.5%, the researchers note, whereas death rates from primary biliary cirrhosis increased by 12.8%.

Age-adjusted death rates in 1998 were highest among American Indians/Alaska Natives (28.7/100,000), the results indicate, followed by African Americans (12.9/100,000), whites (11.5/100,000), and Asians/Pacific Islanders (4.1/100,000). Age-adjusted death rates were more than 1.5 times higher among Hispanics than among non-Hispanics.

"In contrast to reported trends," the investigators write, "the decline in CLD mortality observed during previous decades and sustained through the early 1990s did not continue after 1994, largely because of increases in hepatitis C-related deaths."

"This analysis highlights large disparities in CLD mortality, demonstrating the need for social and public health interventions that target high-risk groups such as American Indians/Alaska Natives and Hispanic Americans," the authors conclude. "Further studies are needed to evaluate the validity of estimates of the mortality burden from CLD generated from national mortality data and to characterize better the causes of CLD deaths."

Hepatology 2004;39:476-483.

Medical Research Opportunity for Hepatitis-C Patients

Orman Guidance Research is a medical marketing research firm in Bloomington, MN, that is working with a pharmaceutical company on the subject of Hepatitis-C.  This marketing research study involves interviewing Hepatitis-C patients that meet the following parameters:

 

·         Diagnosed with Hepatitis-C

·         First-time and current treatment with injectable Pegasys for less than 13 weeks

·         Patients do not have HIV, cancer, alcoholism or drug addiction

 

If you meet the above criteria, you may be invited to share your perspectives in a one-time, 45 minute interview, which will take place in mid-May, at their offices in Bloomington, MN.  You will be compensated with $100 cash for your participation.

 

This research does not involve any clinical blood tests or dispensing of placebos/prescriptions.

 

For more information, contact Orman Guidance Research at 952-831-7198.

 

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