Liver and biliary tract

Liver and biliary tract Jetra i bilijarni trakt ARCH GASTROENTEROHEPATOL 2001; 20 ( No 3 – 4 ): We read it for You

Journal:The New England Journal of Medicine

September 6th, 2001 ( N Engl J Med, 2001; 345: 707-14 )

Title: Effect of coinfection with GB virus C on

survival among patients with HIV infection

Efekat koinfekcije sa GB vurusom C na

prezivljavanje pacijenata sa HIV infekcijom

Authors: Xiang J, Wunschman S, Diekema D, Klinzman D, Patrick KD,

George SL, Stapleton JT.

Institutions: Department of Internal Medicine and Research, Iowa City,

Veterans Affairs Medical Center, University College

of Medicine,Iowa City,

and the Helen C. Lewitt Center for Viral Pathogenesis and

Disease, Iowa City, USA.

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ABSTRACT

Background: Previous studies have suggested that people with HIV infection who are coinfected with GB virus C (GBV-C, HGV, or hepatitis G virus) have delayed progression of HIV disease. GBV-C is related with C-virus (HCV) but does not appear to cause liver disease.

Methods: We examined the effect of coinfection with GB-C virus on the survival of patients with HIV infection. We also evaluated cultures of peripherial-blood.mononuclear cells infected with both viruses to determine whether GBV-C infection alters replication in vitro.

Results: Of 362 HIV- infected patients, 144 (39.8%) had GBV-C viremia. Forty-one of the patients with GBV-C viremia (28.5%) died during the follow-up period, as compared with 123 of the 218 patients who tested negative for GBV-C RNA positive (56.4%; p<0.001). The mean duration of the follow-up for the entire cohort was 4.1 years. In Cox regression analysis adjusted for HIV treatment, baseline CD4+ T-cell count, age, sex, race among the 218 HIV infected patients without

GBV-C coinfection was significantly higher than than among the 144 patients with GBV-C coinfection (relative risk, 3.7; 95% confidence interval, 2.5 to 5.4). HIV replication, as measured by the detection of p24 antigen in cultures of supernatants, was reproducibly inhibited in culture of peripheral-blood mononuclear cells by GBV-C coinfection.

Coinfection did not alter the surface expression of HIV cellular receptors on peripheral-blood mononuclear cells, as determined by flow citometry.

Conclusions: GBV-C coinfection is common in people with HIV infection and is associated with significantly improved survival.

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EDITOR^,S DIGEST

Infection with HIV virus is associated with conditions ranging from asymptomatic infection to severe impairment of the immune system and the development of AIDS. The usual course of events for infected persons is depletion of the CD4+ T- cells and the development of AIDS 8 – 10 years after the initial infection. In some rare cases, AIDS do not develop, and the infected persons have normal CD4+ T-cell count 10 – 20 years later.

The rate of progression of HIV disease correlates with the level of active viral replication, and is related to a variety of factors specific to the virus, the host, and host ^, s immune system. Qantitative difference in the cell-mediated immune reponse to HIV correlate with the course and outcome of the disease in many infected persons. Slower rate of progression have been observed in patients with a more vigorous response of the HIV specific helper CD4+ T-cells and the cytotoxic CD8+ T-cells.

Coinfection with common opportunistic organism, such as Mycobacterium tuberculosis, Mycobacterium avium, herpes simplex virus type, increase the rate of HIV replication and worsen the prognosis of HIV disease. It is therefore unexpected that the patients who are infected with bot HIV and GBV-C virus ( HGV ) have more favorable prognosis and delayed development of AIDS.

Hepatitis G virus ( HGV, GBV-C ) do not appear to replicate primarily in hepatocytes or to cause acute or chronic liver disease. Transmission of HGV principally occurs by the parenteral route. Beside its ability to replicate in various types of cells in vitro, including blood mononuclear cells, the site of HGV replication is firmly established.

Infection with HGV is especially common in persons infected with HIV and hepatitis C virus (HCV ). Approximately 1 – 2 %of volunteer blood donors and 15 – 20% of I.V. drug users in US are HGV RNA positive. Yet, the aetiological role HGV infection in human disease and the long-term consequences of persistent HGV infection have not been established. Notably, HGV infection does not alter the severity of chronic liver disease caused by HCV.

In early reports it was published that there is beneficial effect of HGV infection on the course of HIV disease. In this article from the New England Journal of Medicine the authors provide additional evidence that patients coinfected with HGV and HIV have delayed progression of HIV disease and prolonged survival. The plasma level of HGV RNA inversely correlated with the plasma level of HIV RNA, but not with CD4+ T-cell count. Interestingly there are reports that plasma HGV RNA level is increased in patients who are receiving antiretroviral therapy. In this study it is reported that the presence of HGV inhibits the replication of HIV. But the mechanism by which HGV might influence the replication of HIV and delay the development of AIDS is still enigmatic.

The clinical significance of the relation between HGV and prolonged survival is intriguing. It may implicate the development of new treatment. But any suggestion that the iatrogenic, intentional infection of AIDS patients with HGV has to be explored is premature. But the clarification of the relation between HGV and HIV may have practical implications for the development of new treatment of HIV infection.

Neda Svirtlih

Vojislav N. Perisic