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France: Is more frequent monitoring for liver cancer among co-infected people needed?
10 January 2012 - In high-income countries such as Canada, Australia and in Western Europe,
the widespread availability of potent combination therapy for HIV (commonly called ART or HAART) has greatly
reduced deaths from AIDS-related infections. Furthermore, the benefit of ART is so profound that researchers
in the UK recently estimated that HIV-positive people who have minimal co-existing health conditions and
who are diagnosed and receive treatment early in the course of HIV disease are very likely to have
near-normal life spans.
Many possible factors can affect access to and engagement in care and treatment-and thus survival;
addiction is one such factor. Some HIV-positive people may not be able to seek and receive the help
and support needed to break free from addiction to substances-including alcohol, street drugs and
tobacco-and their associated risks. Such risks can include serious bacterial infections,
overdose, cardiovascular disease, liver and kidney damage, accidents, suicide and violence.
Even among some HIV-positive people who have been able to successfully overcome their addiction,
past engagement in substance use or unprotected sex may have also exposed them to co-infections
such as hepatitis B virus (HBV) and hepatitis C virus (HCV). These viruses attack the liver,
injuring this vital organ. Chronic hepatitis caused by these viruses degrades the liver,
causing it to lose healthy tissue and have scar tissue build up. In the absence of
treatment, over time the liver becomes increasingly dysfunctional and serious
complications including liver failure, liver cancer and death can occur.
Treatment
In high-income countries, treatment for HBV co-infection is usually one of the following combinations:
- 3TC (lamivudine) + tenofovir (Viread)
- tenofovir + FTC (sold as a fixed-dose combination called Truvada)
In the case of HCV mono-infection (HCV alone), a combination of the following three drugs is used:
- ribavirin
- interferon-alpha
- boceprevir (Victrelis) or telaprevir (Incivik)
Note that neither boceprevir nor telaprevir are approved in Canada for the treatment of HIV-HCV
co-infection.
Viral hepatitis and liver cancer
French researchers have found that while ART can greatly reduce deaths due to AIDS-related infections,
complications from liver disease are increasingly taking their toll. One complication of infection with
HBV or HCV is liver cancer, and researchers in France continue to study this cancer both in people with
either HBV or HCV or HIV co-infection. Their most recent study results suggest that liver cancer
occurs earlier and is more extensive in some co-infected people who are at high risk for liver
cancer. If the French findings are confirmed, increased medical monitoring of co-infected
people at high risk for liver cancer may be necessary.
Study details
The French team reviewed data collected from 2,256 participants who were being monitored as part of
research on viral hepatitis. They selected 32 people from this group for further analysis. All 32
participants had cirrhosis-extensive liver damage arising from chronic infection with HBV or HCV,
whereby healthy tissue is replaced by scar tissue. Additionally, all participants had liver
cancer. The diagnosis of cirrhosis was made using one or more of the following methods:
- analyzing a tiny sample of the liver
- specialized blood tests (Fibrotest)
- specialized ultrasound scans of the liver (Fibroscan)
The distribution of viral infections among the 32 participants was as follows:
- HIV-HCV co-infection - 16 participants
- HCV mono-infection - 16 participants
As people with cirrhosis are at heightened risk for the development of liver cancer, all participants
underwent ultrasound scans of the liver every six months, along with medical monitoring.
On average, participants were monitored for 30 months.
All participants had tumours in their liver that arose from abnormal liver cells (primary liver
cancer); none of the tumours had migrated to the liver from another part of the body.
Results
The researchers found that co-infected people were generally younger (48 years) than mono-infected
people (60 years)-a statistically significant difference. Additionally, there was a trend that
approached statistical significance: Co-infected people (56%) drank more alcohol than HCV
mono-infected people (20%).
In reviewing the medical records, the research team found that all mono-infected participants had
previously received treatment for HCV while 67% of co-infected people received this treatment. This
difference was also statistically significant. The reasons for this difference were not clear to the
research team.
The researchers also found that 87% of co-infected people were taking ART; of these, 69% had low
levels of HIV in their blood (less than 40 copies/ml).
Cure vs. palliative therapy
Treatment for liver cancer can vary depending on several factors, including the following:
- the health of the liver
- the size and number of tumours
- whether or not the tumours have spread (metastasized) beyond the liver
In cases where doctors decide that a person does not have a good chance of recovery from cancer,
palliative care-measures to minimize discomfort and complications in the short term-may be
provided. In the case of the current report, when French oncologists judged that recovery
was likely they choose from several options, including surgery, attacking the tumour
with an electrical current (radiofrequency ablation), or surgery followed by a liver transplant.
Oncologists gave the 32 study participants either palliative or curative therapy, distributed as follows:
- HIV-HCV co-infection - 25% received therapy with the intention to cure cancer
- HCV mono-infection - 69% received therapy with the intention to cure cancer
This difference was statistically significant.
As cancer patients were assessed and treated outside of the study by oncologists, the research team is
not certain why there was a difference in who received curative therapy. However, the researchers found
that when liver cancer was diagnosed within the study, it was generally more severe (more and larger
tumours) in co-infected people. Also, some co-infected participants had higher-than-normal levels
of a protein called AFP (alpha-fetoprotein). Past studies have suggested that high levels of
AFP are sometimes associated with liver cancer and that elevated AFP at liver cancer
diagnosis may indicate a poor outcome. Thus it was possible that because liver
cancer was more "advanced" when diagnosed in co-infected people, oncologists
may have decided that the prospects of recovery in this group were poor.
Over an average of 30 months of monitoring, deaths due to complications from liver cancer were distributed
as follows:
- HIV-HCV co-infection - 10 out of 16 people died
- HCV alone (mono-infection) - one out of 16 people died
Monitoring
International liver cancer management guidelines suggest that people with cirrhosis (who are at high risk
for liver cancer) should undergo ultrasound scans of their liver and have AFP tests to help their doctors
detect tumours. According to the researchers, these guidelines were followed in the French study.
Therefore, the French team suggests that the worse pattern of liver cancer among co-infected
people did not arise due to lack of monitoring.
The precise cause for the more rapid appearance of liver cancer among co-infected people in this study
is not clear but it may be due to a weakened immune system caused by HIV infection. While most
participants with HIV in the study were taking combination therapy, ART can only partially
restore the immune system; residual immune dysfunction continues.
The French study had a major weakness: A relatively small number of participants (32). A larger study is
necessary to confirm its findings.
If another team confirms the French results, more frequent monitoring of HIV-HCV co-infected people at
high risk for liver cancer may be deemed necessary. For instance, the French team suggests that
ultrasound scans and other tests could be done every three months. This shorter time span
might allow technicians and doctors to detect liver cancer when it is at an early stage.
This could make a difference to the prospects of surviving liver cancer for co-infected people.
-Sean R. Hosein
REFERENCES:
- May M, Gompels M, Delpech V, et al. Impact of late diagnosis and treatment on life expectancy in people
with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study. BMJ . 2011 Oct 11;343:d6016.
- Larsen MV, Omland LH, Gerstoft J, et al. Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population-based cohort study. Addiction . 2010 Mar;105(3):529-35.
- Hser YI, Kagihara J, Huang D, et al. Mortality among substance-using mothers in California: a 10-year prospective study. Addiction . 2012 Jan;107(1):215-22.
- Ferreros I, Lumbreras B, Hurtado I, et al. The shifting pattern of cause-specific mortality in a cohort of human immunodeficiency virus-infected and non-infected injecting drug users. Addiction . 2008 Apr;103(4):651-9.
- Smit C, van den Berg C, Geskus R, et al. Risk of hepatitis-related mortality increased among hepatitis C virus/HIV-coinfected drug users compared with drug users infected only with hepatitis C virus: a 20-year prospective study. Journal of Acquired Immune Deficiency Syndromes . 2008 Feb 1;47(2):221-5.
- Bonacini M. Alcohol use among patients with HIV infection. Annals of Hepatology . 2011 Oct-Dec;10(4):502-7.
- Downey JS, Attaf M, Moyle G, et al. T-cell signalling in antiretroviral-treated, aviraemic HIV-1-positive individuals is present in a raised state of basal activation that contributes to T-cell hyporesponsiveness. AIDS . 2011 Oct 23;25(16):1981-6.
- Appay V, Almeida JR, Sauce D, et al. Accelerated immune senescence and HIV-1 infection. Experimental Gerontology . 2007 May;42(5):432-7.
- Herbeuval JP, Nilsson J, Boasso A, et al. HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques. AIDS . 2009 Jan 2;23(1):35-40.
- Boasso A, Royle CM, Doumazos S, et al. Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood . 2011 Nov 10;118(19):5152-62.
- Grebely J, Dore GJ. What is killing people with hepatitis C virus infection? Seminars in Liver Disease . 2011 Nov;31(4):331-9.
- El-Serag HB. Hepatocellular carcinoma. New England Journal of Medicine . 2011 Sep 22;365(12):1118-27.
- Tyson GL, Duan Z, Kramer JR, et al. Level of a-fetoprotein predicts mortality among patients with hepatitis C-related hepatocellular carcinoma. Clinical Gastroenterology and Hepatology . 2011 Nov;9(11):989-94.
- Davila JA, Morgan RO, Richardson PA, et al. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology . 2010 Jul;52(1):132-41.
- Bourcier V, Winnock M, Ait Ahmed M, et al. Primary liver cancer is more aggressive in HIV-HCV coinfection than in HCV infection. A prospective study (ANRS CO13 Hepavih and CO12 Cirvir). Clinics and Research in Hepatology and Gastroenterology. 2012; in press .
CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian
AIDS Treatment Information Exchange, in Toronto.
From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information
Network at http://www.catie.ca
Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE
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