- Global prevalence of HIV infection is rising
since persons on anti-retroviral treatment are living longer.
- Incidence of non-Hodgkin's lymphoma in persons
with HIV infection is nearly ten times higher compared to normal
- Certain infections such as hepatitis B (HBV)
and hepatitis C (HCV) infections are also associated with an increased
risk of non-Hodgkin's lymphoma in immunocompromised persons.
- Risk of non-Hodgkin's lymphoma shown to be
higher in HIV persons co-infected with HBV or HCV compared to non-infected
infected persons on anti-retroviral
, who have co-infection with hepatitis B
or C have a higher risk of developing non-Hodgkin's
, indicates a recent study.
Findings of the Study
The investigators analyzed 18 out of 33 cohorts from the Collaboration of
Observational HIV Epidemiological Research Europe (COHERE) to determine if
chronic HBV and HCV co- infection are associated with a higher occurrence of
non-Hodgkin's lymphoma. The study initially
included 52,479 ART-naïve patients, 40,219 of whom later began ART.
‘It is critical that early diagnosis of HIV is also combined with routine screening for chronic hepatitis B and C infections, to further reduce the risk of non-Hodgkin’s lymphoma (NHL).’
Some patients had associated HBV or HCV co-infection, while others had
dual infection at the time of inclusion into cohorts. A few others acquired
infection during the follow up phase. The authors found that the ART-treated
patients having chronic HBV or HCV
infection was at more risk of developing non-Hodgkin's lymphoma
compared with those who were not infected
Proposed Mechanisms of NHL in HIV infections
therapy (ART), survival of HIV infected persons has considerably improved.
Additionally, with restoration of immunity following ART, the incidence of
opportunistic infections and Kaposi sarcoma
has also come down. Unfortunately,
the expected decrease in AIDS related lymphomas has not decreased, and
currently, HIV associated cancers, including NHL's are becoming the leading
causes of death in AIDS patients.
Currently, it is
hypothesized that majority of AIDS-associated lymphomas (NHL) are caused by human
γ-herpes viruses, mainly Kaposi sarcoma-herpes virus (KSHV) and to a lesser
extent by Epstein-Barr virus
infections. The growth of these cancers is
attributed to loss of immunoregulation due to immunosuppression induced by HIV
A lot of recent studies
have evaluated the role of anti-herpes treatment in the prevention and
treatment of AIDS-related lymphomas. Other modalities of treatment emerging
include therapies targeting viral latency to kill infected tumor cells.
Proposed Mechanisms of NHL
in HBV and HCV infections
Hepatitis B and C are hepatotropic
(tendency to infect
liver) viruses, and are associated with an increased risk of development of
NHL, compared to the general population.
Three mechanisms have
been suggested for hepatitis virus induced non-Hodgkin's lymphoma.
- Chronic antigenic stimulation of B cells by
the viruses, followed by uncontrolled B-cell proliferation.
- Interaction between the HCV-E2 receptor
and CD 81 on B cells leading to polyclonal activation of naïve B cells.
- Direct infection
of B cells by the virus.
Whether these mechanisms
act singly or in cohesion is not known, but researchers have suggested the
importance of evaluating the efficacy of HBV and HCV vaccination
in reducing the risk of NHL and other blood-related malignancies.
Lessons from the Study
It is probable that the
mechanisms elaborated in the above paragraphs may exist and act in synergy in
HIV patients co-infected with HBV and/or HCV, contributing to a much higher
risk of development of NHL in this population.
The researchers conclude that early diagnosis and treatment of HIV
infection should be combined with routine screening for chronic HBV an HCV
infection. This is critical to further decrease non-Hodgkin's lymphoma
associated morbidity and death in HIV-infected persons.
- Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities - (http://www.bloodjournal.org/content/117/6/1792?sso-checked=true)
- Newly Emerging Therapies Targeting Viral-related Lymphomas - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041592/)
- The Need for Investigations of Prophylactic Regimens to Prevent AIDS-Associated Non-Hodgkin's Lymphoma - (http://cid.oxfordjournals.org/content/30/5/762.full)