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HCV ADVOCATE WEEKLY NEWS REVIEW: A Review of HCV, HBV and HIV/HCV Coinfection Related News and Highlights

Week Ending: November 13th, 2004

Alan Franciscus
Editor-in-Chief

In This Issue:

• Hepatitis B Vaccination Is Advisable

• Tainted Blood: How Safe Is the U.S. Blood Supply?

• Studies Demonstrate Positive Data in Treatment of Hepatitis C

• Risk Factors for Gynaecomastia include Hepatitis C, Fat Loss, and Low Testosterone

• State Extends Workers' Comp Coverage for Court Workers

• Pegasys (R) Receives New Indication in Europe Allowing Hepatitis C Patients with 'Normal' Liver Enzyme Levels to Be Treated

• HIV-Positive Former Idus Have Poorer Immune Response to HAART

• Chronic Liver Failure to Be Treated Using Stem Cell Therapy

• Hepatitis C at 'Epidemic Levels'

• Response to Hepatitis C Therapy Can Last for Years

• Report: State Has Highest Rate of Infectious Diseases: But NYC May Skew Results

• Think B: Hepatitis B in Asian Americans

• Where Does the Blood Go?

• Hepatitis C Epidemic Hits London Drug Users: Study

November 8th, 2004

JEHANABAD: As many as 175 million people across the world, including 12.5 million Indians, are infected with Hepatitis C virus.

The number is about three times the number of HIV infected Indians. But awareness about the disease is low despite the fact that there is no protective vaccine available.

This was stated by noted urologist and executive member of the Medical Council of India Dr Ajay Kumar while delivering a talk under Popular Science Lecture series organised by "Science for Masses" here on Saturday.

Kumar said that it is liver disease caused by the Hepatitis C virus (HCV). HCV is spread by blood contact with an infected person. A distinct characteristic of Hepatitis C is chronic liver disease with symptoms like tiredness, lethargy, nausea and discomfort in the upper abdomen area. If it is not diagnosed and treated at the right time, it can lead to cirrhosis, liver failure and liver cancer.

According to Kumar, for most of the patients, the illness begins suddenly like flu which does not seen to completely go away. Many other symptoms may also be present varying from patient to patient. The urine may become yellow to dark brown and the stools may be pale. In severe acute infections, some people may develop jaundice in which the skin and whites of the eyes become yellow.

Kumar stated that the major factors promoting progression of chronic Hepatitis C include alcohol consumption and coexisting HBV/HIV infection. Since the virus mutates frequently, creating slightly different versions every time it replicates, it easily evades the body's immune system.

Concluding his speech, Kumar said that the disease must be treated early because research reveals that response to treatment is better at an early age. "There is no better protection against Hepatitis C or for that matter, any other disease than awareness of the disease itself," he added.

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Reported by Susan Aldridge, PhD, medical journalist

It is time that Britain followed the example of over 150 countries around the world and adopted universal immunisation against hepatitis B.

There is effective and safe vaccination against hepatitis B virus (HBV) which can protect against acute and chronic liver infection and even liver cancer. In Britain, it's been the policy to vaccinate people at risk, such as health care workers and homosexual men. But researchers at the University of Liverpool say that it's time to vaccinate everybody.

In the UK, there are 4,500 acute cases of HBV every year and 7,500 infections, plus 430 cases of related liver cancer. These figures could be brought down by vaccination. Universal vaccination against HBV is practised in 150 countries already and its effectiveness lasts for ten years.

Source: British Medical Journal 6th November 2004 Volume 329 pages 1059-1060

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Ryan White, suffering from the blood disorder hemophilia, was just 13 in 1984 when he received a blood transfusion tainted with the AIDS virus. He became a symbol of the epidemic as it crossed demographic lines, but his case also brought to light the need for methods to test donated blood for HIV and other diseases that could be transmitted to unsuspecting recipients. Back then, up to 1 percent of all blood units in the United States contained either HIV or hepatitis C. New screening techniques have been introduced since then, and two separate studies from the American Red Cross update the safety statistics on the blood supply and donated human tissue

What the researchers wanted to know: How safe is the U.S. blood supply from viral infections and what is the rate of infection from donated human tissues?

What they did: In the first study, on blood supplies, the researchers compiled data from more than 40 million blood donations and analyzed whether a recently developed and almost universally used test, known as a nucleic acid-amplification test, was better at detecting HIV and hepatitis C than older tests. In the second study, to assess the safety of tissues such as heart valves, veins, or bones (but not organs), the researchers used data from tissue donation centers from around the country to estimate the rate of viral infection in tissue donors. They analyzed 11,391 tissue samples that were tested for HIV, hepatitis C, hepatitis B, and human T-lymphotropic virus, which causes a disease of the immune system, at centers around the country. Because tissue samples are tested using a technique that may not capture viral infection in its earlier, latent stages, the researchers also used demographic data to estimate the rate of disease among donors unaccounted for in reports from tissue donation centers. Since tissue donors are almost always dead, they can't be asked all the questions that blood donors have to answer about their potential for exposure to different diseases.

What they found: The blood supply has become much safer in the past 20 years; with new testing techniques, the risk of infection with either HIV or hepatitis C is 1 for every 2 million units. The authors estimate that nucleic acid-amplification screening catches about five cases of HIV-infected blood that would not otherwise be caught and 56 cases of hepatitis C that would be transfused into someone else each year. The second study, on infection from tissue transplants, is not as encouraging. Tissue donors are less likely than the general population to be infected with the viral infections but more likely to be infected than blood donors. The researchers estimated that the probability that a tissue will be infected but undetected is 1 out of 55,ooo donations for HIV, 1 out of 34,000 for hepatitis B, 1 out of 42,000 for hepatitis C, and 1 out of 128,000 for human T-lymphotropic virus. In other words, at the highest, one donor per year has a viral infection that passes through the system without detection. However, because tissue products can be used on multiple patients, the average is 50, one donor could affect a good number of people.

What it means to you: The odds of receiving blood tainted with hepatitis C or HIV are now about the same as the odds of being killed by a large meteor impact (at least according to NASA's calculations)--so it's probably not something you should lose sleep over. Similarly, the odds of receiving infected tissue, while greater, are still quite small. The authors say that the same test that has improved blood safety should also be used for human tissues but acknowledge it would cost millions of additional dollars for the chance of eliminating one infected sample per year.

Caveats: These risks only pertain to those diseases listed above; some rare viruses can still slip through the screeners. Some other viruses, such as West Nile, are being kept out of the blood supply, but screening is relatively new and more research needs to be done to determine the reduction in risk from these programs.

Find out more: The American Association of Blood Banks has a very long Web page with all you've ever wanted to know about blood donation and more.

The American Red Cross also has information about donating blood and tissue, linked from their home page.

Read the articles:

Stramer, S.L. et al. "Detection of HIV-1 and HCV Infection Among Antibody-Negative Blood Donors by Nucleic Acid-Amplification Testing." New England Journal of Medicine. Aug. 19, 2004. Vol. 351, No. 8, pp. 760-768.

Abstract online: http://content.nejm.org

Zou, S. et al. "Probability of Viremia With HBV, HCV, HIV, and HTLV Among Tissue Donors in the United States." New England Journal of Medicine. Aug. 19, 2004. Vol. 351, No. 8, pp. 751-759

Abstract online: http://content.nejm.org

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BOSTON -- Data from two ongoing studies testing new approaches for the treatment of chronic hepatitis C will be presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) this afternoon.

Presented by principal investigator Nezam Afdhal, M.D., Chief of Hepatology at Beth Israel Deaconess Medical Center (BIDMC) and Associate Professor of Medicine at Harvard Medical School, the new findings provide researchers with sufficient evidence to demonstrate promising results for hepatitis C patients who have not responded to existing therapies.

A viral infection, hepatitis C is transmitted through exposure to infected blood. The virus, which affects an estimated 4 million individuals nationwide, is able to survive and flourish inside the body by taking up residence in the liver cells, and subsequently using the cells' inner machinery to make more copies of the virus. These in turn, infect other healthy cells.

The standard treatment for hepatitis C is a combination of interferon alfa and ribavirin, which act as anti-viral agents to eradicate the virus. According to Afdhal, the most recent advance in treatment has been the pegylation of interferon, which enables a once- a- week administration of the protein by injection and improves the ability to clear the virus. Combination therapy with pegylated interferon plus ribavirin for 24 to 48 weeks can result in eradication of the virus in about 50 percent of patients, he adds.

"When the hepatitis C virus doesn't respond -- as occurs in about half of all patients who are treated -- those patients who already have cirrhosis are at a far greater risk for developing liver cancer or suffering liver failure," notes Afdhal. In fact, he says, hepatitis C is the leading cause of liver transplants in the U.S. Until now, no treatment has been available for these patients.

In his first presentation, Afdhal will describe results from the COPILOT [Colchicine versus PEG-INTRON Long-Term] study, which was designed by Afdhal and colleagues at BIDMC to test the long-term use of low-dose interferon among hepatitis C patients. Conducted at 40 sites nationwide, the findings are the first to demonstrate that the progression of hepatitis C can be prevented or delayed through long-term maintenance therapy with peginterferon alfa-2b.

According to Afdhal, researchers found that peginterferon alfa-2B reduced by 50 percent the risk of patients reaching a clinical endpoint (variceal bleeding, liver failure, liver transplantation, hepatocellular carcinoma or death) and reported the results as part of a planned two-year interim analysis of the data.

"This is a new treatment paradigm, showing for the first time that we can prevent the serious complications of liver disease," he explains. "The results found that when used in this way, the therapy reduced by half the risk of the virus advancing to cause liver damage."

The COPILOT study tested weight-based low-dose peginterferon alfa-2b (0.5 mcg/kg/wk, injected subcutaneously) against colchicine (0.6 mg orally, twice daily), an anti-inflammatory and antifibrotic medication, in 550 chronic hepatitis C patients with advanced fibrosis who had previously failed interferon-based therapies. A total of 59 patients reached a clinical verified endpoint: 39 in the colchicine group versus 20 in the peginterferon alfa-2b group (p=0.003). The annual clinical event rate was approximately five percent (7.0 percent vs. 3.5 percent for colchicine and peginterferon alfa-2b, respectively), underscoring the need for better treatments to prevent disease progression.

Afdhal noted that the low 0.5 mcg/kg weekly dose of peginterferon alfa-2b used in the study -- one-third the dose used in standard combination therapy --was well tolerated by patients and spared them the side effect of developing hemolytic anemia, which is often associated with ribavirin use.

"Patient adherence to their prescribed regimen is critical to success in hepatitis treatment and is an important consideration for long-term maintenance therapy," he said.

The COPILOT study was supported by Schering-Plough Corporation, manufacturer of peginterferon alfa-2b.

Afdhal's second presentation will describe results from a Phase II clinical trial of a new antiviral agent, NM283, being tested in humans for the first time.

The new drug shows activity against hepatitis C genotype 1 (HCV). One of six genotypes in existence, genotype 1 is the most predominant strain in the U.S., Japan and Western Europe, and is particularly difficult to treat.

Unlike existing therapies, which are administered by injection, NM283 is taken orally, says Afdhal, adding that it also has fewer side effects than existing agents. NM283 is the first in a new class of designer drugs, a polymerase inhibitor, specifically designed to block a step in HCV viral replication.

"This drug is a new class of treatment for HCV and represents significant hope for future therapies," he noted. "Data from these clinical trials are encouraging and suggest that NM283 may prove to be another treatment option [for hepatitis C patients]." NM283 was shown to have direct and significant antiviral activity against HCV as a single agent in both Phase I and Phase II clinical trials. Combining NM283 with interferon also showed promising activity, according to Afdhal.

NM283 was developed by Idenix Pharmaceuticals, Inc., which sponsored the Phase II clinical trial.

Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information visit http://www.bidmc.harvard.edu.

Editor's Note: The original news release can be found here. (http://www.bidmc.harvard.edu
/tools/newsnow/pr_out.asp?pr_id=622)

This story has been adapted from a news release issued by Beth Israel Deaconess Medical Center.

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Low levels of testosterone have been identified as a risk factor for the development of gynaecomastia (breast enlargement) in HIV-positive men taking highly active antiretroviral therapy (HAART) in a Spanish study published in the November 15th edition of Clinical Infectious Diseases. The investigators from Barcelona also found that gynaecomastia was rare, and that coinfection with hepatitis C virus and lipoatrophy were independent risk factors for the development of the condition.

Gynaecomastia affects less than 1% of HIV-negative adult males. Although cases have been reported in HIV-positive men taking HAART, studies have been limited to small case series which often lacked data on participants' hormonal levels.

Accordingly, investigators in Barcelona conducted a case-control study of the prevalence, risk factors and potential hormonal abnormalities associated with the condition. Data were gathered in early 2003 from a total of 2275 adult male HIV-positive patients. Gynaecomastia was diagnosed by physical examination and ultrasound, and case-controls were randomly selected.

In total, 44 cases of breast enlargement were detected and forty of these were confirmed as gynaecomastia using ultrasound examination. This provided an overall prevalence of gynaecomastia in the clinic population of 1.8%.

Compared to controls, individuals were significantly more likely to be coinfected with hepatitis C virus (p = 0.02), and to have fat loss (lipoatrophy; p = 0.03). Patients with gynaecomastia were also significantly more likely to currently be taking d4T (stavudine, Zerit; p = 0.004), efavirenz (Sustiva; p = 0.04), and AZT (zidovudine, Retrovir; p = 0.008). However, total exposure to these drugs did not differ significantly between individuals with gynaecomastia and control patients.

In multivariate logistic regression analysis, co-infection with hepatitis C virus (p = 0.003), lipoatrophy (p = 0.005), and current use of d4T (p = 0.05) and efavirenz (p = 0.008) remained independently associated with gynaecomastia.

When the investigators looked at levels of hormones in both patients with gynaecomastia and controls, they found that 67% of patients with breast enlargement had hypogonadism (low levels of testosterone) compared to 38% of controls (p = 0.008).

The investigators then included hypogonadism as a variable in their multivariate logistic regression model and found that hypogonadism (p = 0.003), hepatitis C virus coinfection (p = 0.003), and lipoatrophy (p = 0.005) were all significantly related to gynaecomastia.

"We found that 1.8% of HIV-infected men in our cohort had gynaecomastia", write the investigators.

Regarding risk factors they note that "lipoatrophy and chronic hepatitis C were independently associated" with the side-effect. However, they add that gynaecomastia has been more commonly reported with fat gain than fat loss in the literature, and that none of the patients with hepatitis C had end-stage liver disease.

Although the investigators also found that hypogonadism was associated with gynaecomastia, it was also "not unusual among control subjects," and they call for further study of this.

In many cases gynaecomastia improved or resolved in a significant number of patients without treatment, and testosterone patches and injections were safely used to treat the condition.

Reference
Biglia A et al. Gynecomastia among HIV-infected patients is associated with hypogonadism: a case-control study. Clin Infect Dis 39: 1514-1519, 2004.

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(Albany, NY) AP 11/11/04 - New York state is extending workers' comp benefits to court reporters and interpreters who contract a disease through exposure to tainted blood or bodily fluids.

Governor Pataki signed a bill last month changing the workers' comp statute so that if court reporters get hepatitis C or HIV,

it can be legally presumed that they contracted it through on-the-job contact with infected people.

Union officials say court reporters and interpreters are often close to witnesses or defendants testifying at trials and could be exposed to bodily fluids.

State and local corrections workers, as well as uniformed court officers and clerks, are already covered in such cases.

The Association of Surrogate's and Supreme Court Reporters in New York City, a union that represents 389 people, lobbied for the change.

The new law covers all blood-borne diseases. Workers must report possible exposure to their employer within 24 hours in order to be eligible for workers' comp.

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BASEL, Switzerland, November 11 / / --- A Large Number of Hepatitis C Patients Gain Access to Therapy

Roche announced today that the European Medicines Agency (EMEA) has approved PEGASYS(R) for the treatment of hepatitis C patients with persistently 'normal' liver enzymes. This extension of the current label is based on the results of a pioneering study(i) that showed that combination therapy with PEGASYS eradicated the virus (sustained virological response) in more than half of this patient group. Under current treatment guidelines, hepatitis C patients with normal liver enzymes would not normally be eligible for treatment.

As a result of this breakthrough study, the EMEA has recognised that patients who have 'normal' alanine aminotransferase (ALT) levels should be assessed for treatment in the same way as other chronic hepatitis C patients and that normal ALT status per se should no longer be considered a barrier to treatment. PEGASYS is the only pegylated interferon that has an indication in the EU for these patients, who account for approximately 30% of the total hepatitis C patient population(ii).

'Normal' ALT Patients Traditionally Untreated

It has become apparent, however, that having 'normal' levels of ALT does not necessarily mean that the liver is undamaged; studies have shown that about 80% of these patients have some degree of liver damage and one third have significant liver damage(v). Unfortunately, since these patients were routinely excluded from treatment, they were not included in clinical trials assessing the safety and efficacy of new pegylated interferons and therefore the risk:benefit of treatment remained unclear - until now.

"By removing the stipulation that patients must have elevated levels of this biochemical marker before being considered for treatment, the EMEA is facilitating a positive change in how physicians make decisions and offering more patients the chance of a cure," said Professor Stefan Zeuzem, Director of the Department of Internal Medicine at the University Hospital in Homburg, Germany, and the lead investigator of the study on which the approval was based. "It marks a new era in our understanding of how best to treat patients and underscores that the decision to treat should be based on multiple factors rather than simply on ALT."

Revised PEGASYS Labelling Information

In 2002, the EMEA approved PEGASYS for the treatment of chronic hepatitis C in adult patients with elevated transaminases and who are positive for serum HCV-RNA, including patients with compensated cirrhosis. In the EU, this criterion for elevated ALT has now been removed only from the PEGASYS label, marking another distinction for this compound.

The Research that Informed the EMEA Decision

The approval was based on the first and only large, randomised, multinational study examining the benefit of treatment in this under-served patient population. The study involved 514 patients that were randomised into one of three arms; one arm included patients selected to continue with observation but no treatment, since this approach was considered the current standard of care at that time. The other two arms randomised patients to treatment with PEGASYS (180 mcg/weekly) and COPEGUS(R) (800 mg/daily) for either 24 or 48 weeks.

The following summarises the research findings:

• Nearly 30% of patients of patients were found to have some degree of liver scarring (fibrosis) and/or evidence of hepatic inflammation, despite a 'normal' ALT reading.

• Overall, 52% of the treated patients achieved a sustained virological response (SVR - or cure), while no patient spontaneously eradicated their virus in the untreated group.

• Consistent with findings from studies involving patients with elevated ALT levels(vi), 72% of patients infected with genotype 2 or 3 treated with PEGASYS combination therapy achieved an SVR after just 24 weeks of treatment and 40% of difficult-to-treat genotype 1 patients achieved an SVR after 48 weeks of therapy.

• The incidence of the most common interferon-related side effects was lower than in previous studies with this population and similar to those seen in HCV patients with elevated ALT levels treated with PEGASYS combination therapy.

"The question of whether or not persistently 'normal' ALT patients should be treated has been a long-standing issue in the hepatitis C community," said William M. Burns, Head of Roche's Pharmaceutical Division. "As a company, we are proud to bring this issue to resolution and delighted that PEGASYS combination therapy is the treatment that will be of benefit to these patients."

About PEGASYS

PEGASYS, the market leader worldwide in hepatitis C therapy, provides significant benefit over conventional combination interferon therapy in HCV patients of all genotypes. The benefits of PEGASYS are derived from its large 40 kilodalton (KD) branched-chain polyethylene glycol (PEG) construction, which allows for sustained drug levels over the course of a full week. PEGASYS also distributes more readily to the liver (the primary site of infection) than conventional interferon. PEGASYS is the only pegylated interferon available as a ready-to-administer solution. Each weekly subcutaneous injection contains 180 mcg of pegylated interferon alfa-2a (40KD), which is the approved dose for all patients, regardless of body weight.

Roche in hepatitis

Roche is committed to the viral hepatitis disease area, having introduced Roferon-A for hepatitis B and C, followed by PEGASYS in hepatitis C and a full development program in hepatitis B. Roche has its own brand of ribavirin, COPEGUS, which is used in conjunction with Roferon A or PEGASYS for HCV. In addition, Roche manufactures HBV and HCV diagnostic and monitoring systems: The COBAS AMPLICOR(TM) Test, and the AMPLICOR MONITOR(TM) Test, two testing systems used to detect the presence of, and quantity of, HBV DNA or HCV RNA in a person's blood. Roche has filed a new indication for PEGASYS and COPEGUS as a treatment for patients co-infected with HIV-HCV and for PEGASYS as a treatment for chronic hepatitis B. More than 40,000 patients worldwide continue to participate in trials with PEGASYS and COPEGUS as Roche examines the unmet medical needs of hepatitis C patients. Roche's commitment to viral hepatitis also extends to its pursuit of strategic alliances and partnerships to develop new compounds for the future.

Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is number one in the global diagnostics market, the leading supplier of pharmaceuticals for cancer and transplantation and a market leader in virology. In 2003 the Pharmaceuticals Division generated 19.8 billion Swiss francs in prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

All trademarks used or mentioned in this release are legally protected.

Further information:

About Hepatitis C: http://www.health-kiosk.ch/start_hepa

(i) Zeuzem, S. et al. International, multicentre, randomised controlled study for the treatment of patients with chronic hepatitis C and persistently normal ALT levels with pegInterferon alfa2a and ribavirin. AASLD 2003 Boston.

(ii) Conry-Cantilena C. et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med. 1996;334(26):1691-6.

(iii) Kaplan MM. Alanine aminotransferase levels: what's normal? Ann Intern Med. 2002;137(1):346-355.

(iv) NIH. NIH Consensus Statement. Management of hepatitis C. National Institutes of Health. 1997.

(v) Puoti, C. et al. Histological and virological features and follow up of hepatitis C virus carriers with normal aminotransferase levels: The Italian prospective study of the asymptomatic C carriers (ISACC). J Hepatol. 2002;37(1):117-23.

(vi) Hadziyannis, S.J. Peginterferon-alfa2a and ribavirin combination therapy in chronic hepatitis C: A randomised study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346-355.

Sheila Gies, Roche, +1-973-687-0188, Joanne Galea, Axon Communications, +44-208-822-6779

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Former injecting drug users are significantly less likely to experience a good immunological response to highly active antiretroviral therapy (HAART), even with sustained suppression of HIV, than other HIV risk groups, according to a Spanish study published in the November 5th edition of AIDS. Although almost all the former injecting drug users were also coinfected with hepatitis C virus, the investigators believe that the suppressive effect of opiate and cocaine use on the immune system is the reason for the poor immune response to HAART rather than hepatitis coinfection.

Several studies have found that former or current injecting drug users have a poorer immunological recovery after starting HAART than other HIV risk groups. Two explanations for this have been offered: coinfection with hepatitis C virus, or the immunosuppressive effects of some drugs.

Investigators in Madrid conducted a retrospective analysis of 288 treatment-naive patients who started HAART after 1996 to establish if injecting drug users did indeed have a poorer immunological response to HAART and if they did, the possible causes.

A total of 176 patients (61%) were former injecting drug users. To be included in the study individuals were required to have maintained a viral load below 50 copies/ml for at least two years and to have baseline, pre-treatment CD4 cell count data available.

Immunological recovery was assessed in both the short-term and long-term by measuring CD4 cell count six months and 24 months after starting HAART. The main outcome of the study was the proportion of patients with a CD4 cell count increase of at least 50 cells/mm3 after 24 months of HAART.

At baseline, the former injecting drug users were significantly younger (34 vs. 38 years, p = 0. 003) than other HIV risk groups, and were more likely to be male (78 vs. 68%, p = 0.046). A total of 95% of former injecting drug users were coinfected with hepatitis C virus compared to 16% of patients in other HIV risk categories. Median CD4 cell count was lower at baseline amongst former injecting drug users (214 vs. 258 cells/mm3), but not significantly so (p = 0.4), and viral load was comparable (former injecting drug users, 80,000 copies/ml vs. 100,000 copies/ml for other HIV risk groups, p = 0.1).

After six, twelve and 18 months of HAART, former injecting drug users had significantly lower CD4 cell counts than other HIV risk groups. At six months the median CD4 cell count for former injecting drug users was only 346 cells/mm3 compared to 456 cells/mm3 for other HIV risk groups (p = 0.037).

After two years of HAART and complete viral suppression, the median CD4 cell count for former injecting drug users was 472 cells/mm3 compared to 588 cells/mm3 for all other HIV risk groups (p = 0.013).

Multivariate analysis showed that injecting drug users were significantly less likely than other HIV risk groups to achieve a CD4 cell gain of 50 cells/mm3 after two years of HAART (odds ratio 0.23).

A total of six patients died during the study, five of them former injecting drug users. However, the difference in death rate between groups was not statistically significant (p = 0.41).

"Intravenous drug use and not hepatitis C virus coinfection determined the amount and speed of the increase in CD4 cell count," the investigators argue. However a limitation of this study is that virtually all former injecting drug users were also hepatitis C virus-positive (95%), making it difficult to determine the contribution of hepatitis C virus infection to a poorer immune response.

The investigators note that both opiates and cocaine can suppress immune function, therefore "blunting" CD4 cell count recovery after the initiation of HAART. The authors note that opiate use has been shown to cause long-term impairment of the capacity of T-lymphocytes to repair DNA damage, leading to a higher rate of cell apoptosis, and also reduces host defences against opportunistic infections.

Reference

Dronda F et al. CD4 cell count recovery during successful antiretroviral therapy in naive HIV-infected patients: the role of intravenous drug use. AIDS 18: 2210-2212, 2004.

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Scientists believe it may be possible to use stem cell therapy to help patients with chronic liver failure. The team from Imperial College London and Hammersmith Hospital believe that by injecting patients with their own stem cells their liver function may improve. By injecting the patient's own stem cells, or blood derived stem cells, directly into the bloodstream, the researchers hope they may be able to improve the function of the liver by getting the stem cells to repopulate the liver.

From Imperial College London: “Chronic liver failure to be treated using stem cell therapy”

Scientists believe it may be possible to use stem cell therapy to help patients with chronic liver failure.

The team from Imperial College London and Hammersmith Hospital believe that by injecting patients with their own stem cells their liver function may improve.

By injecting the patient's own stem cells, or blood derived stem cells, directly into the bloodstream, the researchers hope they may be able to improve the function of the liver by getting the stem cells to repopulate the liver. In patients with chronic liver failure, the liver has lost cells reducing the effectiveness of the liver, and leading to disease and ill health.

Professor Nagy Habib, from Imperial College London and Hammersmith Hospital, and trial leader comments: ''Although this is still very early days for the trial, it could be a first step to providing a new treatment option for those suffering from chronic liver failure.''

The researchers are currently looking for patients suffering from chronic liver failure to take part in the trial. This will involve 13 hospital visits over a period of two months for various procedures, including scans and a procedure called leukapheris.

Leukapheris is a procedure in which blood is taken from the patient, and separated into its component parts. The white blood cells are taken and the stem cells separated from them. The red blood cells are then returned to the body through the arm, while the stem cells are injected into the hepatic artery, an artery in the liver.

Patients will have to visit the hospital every two weeks to test the function of their liver, kidneys and how well the blood is clotting.

For further information please contact:

Tony Stephenson
Imperial College London Press Office
Tel: +44 (0)20 7594 6712
Mobile: +44 (0)7753 739766
E-mail: at.stephenson@imperial.ac.uk

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Hepatitis C among young drug users in London is reaching epidemic levels while HIV cases are "worryingly high", researchers have warned.

A study in the British Medical Journal found two in five new drug users have hepatitis C, which damages the liver.

It also showed 3% of injecting drug users have HIV.

Researchers blamed the government's drug policy. But a government spokesman said it was committed to driving down cases of hepatitis C.

'New programmes needed'

Researcher Dr Ali Judd, of Charing Cross Hospital, west London, said: "Hepatitis C is now spreading at epidemic levels across London and HIV incidence is worryingly high, which if unchecked will lead to an increase in the total number of HIV infections.

"There is an urgent need for new and comprehensive programmes to tackle this growing number," she added.

There is a need now to reinvigorate harm reduction policies that prevent transmission of hepatitis C and HIV Dr Matthew Hickman, Imperial College London The research was conducted by a team from Imperial College London, the Health Protection Agency and the London School of Hygiene and Tropical Medicine.

Tests were carried out on 428 drug users who had been injecting for up to six years.

It was found one in four reported sharing a needle in the past four weeks. Both hepatitis C and HIV can be spread in this way.

'Successful treatment'

Dr Matthew Hickman, from Imperial College London, said government drug policy has focused on drugs and crime for the past six years.

"There is a need now to reinvigorate harm reduction policies that prevent transmission of hepatitis C and HIV," he said.

A Department of Health spokeswoman said almost £500m will be spent on drug treatment from 2004 to 2005 .

She said: "The extra funding in the last few years has led to many more drug users engaging in treatment and an increase in the numbers successfully completing treatment."

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NEW YORK (Reuters Health) - A sustained response to successful treatment with interferon for hepatitis C virus (HCV) infection can persist for up to 12 years, according to a report in the November issue of the Journal of Medical Virology.

Previous studies have shown remission for up to 5 years after successful treatment with interferon, the authors explain, but HCV eradication from the liver has not been well validated in longer follow-up.

Dr. Natsuko Tsuda from Osaka National Hospital, Osaka, Japan and colleagues monitored 38 patients who had a virological response to interferon therapy, defined as clearance of HCV from the blood after 6 months.

Thirty-seven patients who had a biochemical response were also monitored. These patients were defined as having normal liver function test results after 6 months of therapy, but detectable levels of virus in the blood.

The subjects were followed for 4.4 years to 12 years after interferon therapy.

All sustained virological responders remained persistently negative for HCV in the blood during the entire follow-up period, the authors report. The biochemical responders continued to have HCV detected in the blood and nearly half (46 percent) experienced flared ups.

Four sustained virological responders (but no biochemical responders) developed liver cancer (between 6 months and 5.5 years after treatment), the report indicates. However, all four patients had advanced liver disease before treatment.

HCV was not detected in biopsy samples from 15 sustained virological responders taken 5.9 to 12.5 years after pretreatment biopsies, the researchers note. However, all but one of the 15 biochemical responders who had repeat biopsies had HCV detected in the liver.

In evaluations of liver tissue samples, all measures improved significantly in the sustained virological responders, whereas only partial improvements were observed the biochemical responders. In both groups, evidence of at least mild inflammation remained in the biopsy tissue samples after treatment.

The results suggest that clearance of HCV by 6 months after interferon therapy indicates a "virological cure," the authors conclude. "Although further studies with a larger number of patients are necessary, control of biochemical disease activity to near-normal levels may also confer favorable long-term...outcomes," they add.

SOURCE: Journal of Medical Virology, November 2004

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New York state has an infectious disease problem, according to a report released Monday, but New York City skews the results for the rest of the state.

Lumping New York City health statistics with those of the rest of the state can be problematic, two public health officials said Wednesday.

"It’s so different from the rural communities," said Bonnie Hamilton, public health director in Delaware County.

For two years in a row, New York has ranked 50th in the nation for infectious disease, according to the report from the United Health Foundation and the American Public Health Association.

That means the state has the highest rate of infectious diseases nationwide.

There wasn’t a breakdown between New York City and upstate New York, however.

"We just summed the whole state together," said Tom Eckstein, a principal with Arundel Street Consulting. Eckstein was an author of the report.

The infectious disease rankings came from determining how many cases per 100,000 each state had for hepatitis, HIV and tuberculosis, Eckstein said.

New York City, in those diseases, has more of an issue than the upstate area," he said.

Although the state Department of Health website said chlamydia had the highest rate for communicable disease in New York -- and in Chenango, Delaware, Otsego and Schoharie counties -- Eckstein said that didn’t play a role in New York’s national ranking.

The group picked the three diseases, Eckstein said, because all states kept good records on those.

"We used the ones that are easy to report," he said.

There were 4,384 cases of HIV/AIDS in New York City in 2003, but only 5,007 in the state as a whole.

Chenango County had a rate of 7.7 cases per 100,000; there were only four actual cases in the county in 2003.

Delaware County had a rate of 6.4 cases per 100,000; that represents three cases in the county.

"We know New York City has a very high HIV rate," Hamilton said. "Delaware County has a very low HIV rate."

In 2003, there was a rate of 4.8 cases per 100,000 in Otsego County, which equals three cases.

The rate in Otsego County is comparable to other areas, said Diane Cusworth, public health director.

Both counties are seeing a slight increase in hepatitis cases, Hamilton and Cusworth said.

But that’s also happening across the state and the nation, Cusworth said.

"We are seeing more hepatitis C, but that’s because we have new ways to diagnose and treat it," Hamilton said. "It’s probably in people who had it before."

There are 282 combined cases of hepatitis A, B and C in New York, excluding New York City.

New York City has 650 combined cases of hepatitis A and B, according to the Department of Health.

For the United Health Foundation report, Eckstein said, the cases were combined.

Nationwide, infectious disease cases dropped 36 percent between 1990 and 2004, the report said. New York only had a 14 percent decrease. Between 2003, when the last report was issued, and 2004, the rate dropped 2 percent.

Overall, New York is the 31st healthiest state in the country. Minnesota, where the United Health Foundation is based, was the healthiest state.

Louisiana was the least healthy state.

Data for the report were collected over three years and came from the federal Centers for Disease Control and Prevention, Eckstein said.

General rankings were based on personal behaviors, such as smoking, motor vehicle accidents, prenatal care, public health spending, high school graduation rates and the number of people with health insurance.

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You have probably heard of hepatitis B infection, a liver infection caused by the hepatitis B virus (HBV). But Asian Americans in particular should be concerned.

“Asian Americans are more frequently infected with hepatitis B than any other ethnic group in the United States,” explained Dr. Anna Lok, a hepatitis expert from the University of Michigan. “Chronic infection with hepatitis B can cause serious consequences, such as liver cirrhosis (scarring), liver cancer and liver failure.

“Complications of hepatitis B are more common among Asian Americans. Chinese and Vietnamese American men, for instance, have much higher rates of liver cancer, caused by hepatitis B infection, than white, black or Hispanic men. And many of these men will die young,” she added.

Approximately 1 of every 10 Asian Americans is chronically infected with HBV. In the case of chronic infection, the virus remains in a person’s blood and liver for his or her lifetime and can be passed to others who do not have immunity to the virus.

Hepatitis B is spread through contact with infected body fluids. It can be transmitted through the sharing of something as everyday as a toothbrush, or, as in the case of many Asian Americans, unknowingly spread from mother to child at birth.

Vaccination can prevent hepatitis B infection and its consequences. But what about those who already have hepatitis B or who don’t know if they were vaccinated?

“Anyone who is not sure of his or her hepatitis B status should be screened by a doctor. If anyone in your family has been diagnosed with liver disease or hepatitis B, other family members should be screened. It only requires a basic blood test,” said Dr. Eddie Cheung, a liver specialist from the University of California at Davis.

Those who test positive should be evaluated to see if they have liver disease, how serious it is and if the patient will benefit from treatment.

“Some patients have inactive infection and minimal liver disease,” Lok said. “Whether they are receiving treatment or not, all people with chronic hepatitis B should visit their doctor regularly,” she emphasized.

Hepatitis B is not a disease that is unique to Asians, but the way they tend to become infected contributes to the staggering rates in this population.

“Asians tend to get infected at birth or when they are very young,” Cheung explained. “At those ages, their bodies cannot fight the infection as an adult’s would and they are likely to become long-term carriers --with the ability to spread the virus and a higher likelihood of suffering serious complications. In contrast, in many other groups, people are infected later in life and can fight off the infection,” he said.

“We hear of so many patients who did not know they had hepatitis B until it was too late. ... They show up with advanced liver cancer, cirrhosis or liver failure. If they had known the risk and come in for a screening, perhaps they could have been treated earlier and saved,” Cheung said.

New programs like the American Liver Foundation’s national THINK B Asian outreach campaign and established ones like Stanford’s Jade Ribbon Campaign are helping to raise awareness of the disease among both patients and physicians.

“There have been a lot of great hepatitis B efforts reaching Asian Americans around the country. We need to keep the momentum going and make it even stronger to reach those who are unaware of their risk,” said Dr. James Boyer, chairman of the board of directors of the American Liver Foundation.

The American Liver Foundation’s “THINK B Leadership Conference: Hepatitis B Prevention and Management in Asian Americans,” Nov. 12 - 14, in New York City, brings together experts to help prevent hepatitis B and its complications in Asian Americans. For more information and conference updates, go to ALF’s website at www.liverfoundation.org or call (888) 4HEP-USA.

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From donor to recipient: It's further than you think: Donated blood has quite a journey in just a short period of time

The laboratory at St. Francis Medical Center is a cubicle-free zone with all tests being done in full view of everyone else -- except in one department.

"In the world of the laboratory, blood is one of the most important things we work on," said Mary Lou Emanuel, director of pathology for the lab. "We shield it from other areas so they (medical technicians) can focus on their work."

The laboratory is the last stop for donated blood on a journey that starts and ends in a human body. It's impossible to replicate and impossible to do without, Emanuel said. Blood, for lack of a better term, is the lifeblood of much of the work in the hospital, and the technicians treat it as such.

Unfortunately, blood donations locally are not only down in terms of goals at the Central Plains Chapter of the American Red Cross, but are down across the board. The Red Cross is charged with a congressional mandate to collect and provide blood, and has an infrastructure in place to do so.

The process begins, obviously enough, when a donor rolls up his or her sleeve and donates a unit of blood. Lisa Kustka, chief operations officer for Midwest Regional Blood Services, said after the donation has taken place, the clock starts ticking.

"The thing I don't think many people necessarily understand is that blood is a very perishable product," she said. "It lasts 42 days and any days needed for testing or processing that's needed is part of that time frame."

Once collected, the donation is sent in two directions. The bulk of the donation, known as "whole blood," is sent to a production center where a centrifuge is used to separate the donation into two different transfusable products -- plasma and what is known as packed blood.

The blood is further refined to remove white blood cells, as they can lead to adverse reactions when transfused. From there it is put into a storage location until it is deemed safe, labeled using a computerized labeling process and shipped to fill orders of different medical facilities.

During the donation, blood is also collected for testing. That blood is shipped simultaneously to testing facilities in St. Paul, Minn., or St. Louis, where it is tested for such diseases as HIV, West Nile virus and hepatitis. The local chapter is then electronically notified when the blood is deemed ready to use.

The entire process usually takes several days before the medical facilities receive the blood products, which are then used in a variety of situations. Emanuel said a majority of blood at St. Francis goes to treat various types of trauma and to the oncology department. In either case, she said, it's a vitally important thing because there's nothing else that will do.

"They haven't found a good substitute. There is no substitute," she said. "There's no other way. It's life-saving medicine and we understand someone gave that blood and it deserves to be used correctly."

The Red Cross not only fills orders for medical organizations, but also works with them to try to determine the best types to keep on hand and in what quantity. Emanuel said A positive and O are the most used types of blood.

The reverence for the process goes beyond not wasting donations, with lab workers donating blod themselves. Emanuel said there are four blood drives a year in the lab, and they are the most consistent donors in the hospital.

That's good, Kustka said, and also indicative of the area. Statistically, urban areas donate far less than rural areas, with rural areas providing a majority of the nation's blood supply. Still, only 20 percent of eligible donors in some of the best rural areas take the time to donate regularly, and supplies are starting to be affected. Nationally, 60 percent of adults are eligible to donate, but roughly 5 percent actually do.

The problem, she said, is while those who donate might fluctuate, the need never goes away.

"The need never stops," she said. "It doesn't follow routine business hours. It doesn't stop for holidays or weekends. We need to be ready in the case of an emergency and donors is how that happens."

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An epidemic of the deadly disease hepatitis C is spreading unchecked amongst London's drug users, researchers said on Friday.

London now has higher rates of hepatitis C infection among injecting drug users than Sydney and New York, and a greater incidence of HIV infection than Amsterdam, they said.

"Hepatitis C is now spreading at epidemic levels across London and HIV incidence is worryingly high," Ali Judd and colleagues at London's Imperial College said in the study published online by the British Medical Journal.

"There is an urgent need for new and comprehensive programmes to tackle this growing problem," she said.

Judd and her colleagues tracked 428 drug users, who were under 30 years old or who had been injecting drugs for less than six years, for one year.

Over 40 per cent of those who did not have hepatitis C at the beginning of the study developed it a year later, and 3.4 percent of those who initially did not have HIV tested positive.

The hepatitis C virus is a major cause of liver diseases including cirrhosis and cancer. About 170 million people globally are infected with virus, according to the World Health Organisation.

It is spread by mostly by sharing needles, or in developing countries through unscreened blood transfusions. Symptoms such as jaundice and night sweats can develop up even up to 40 years after infection.

The authors blamed inadequate government drug policies for the hepatitis C epidemic.

"It was a great surprise to us. When we started the study we did it in order, we thought, to find a low incident rate," Matthew Hickman, a co-author of the study, told Reuters.

The researchers urged the government to provide better education and healthcare, including more free syringes, for injecting drug users.

"What we need is the government to make a commitment," Hickman said.

No one at Britain's Department of Health was immediately available to comment on the research.

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