Discordance between CD4 cell count and percentage associated with markers of liver disease in HIV/hepatitis C co-infected people

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Discordance between CD4 cell count and CD4 cell percentage in people co-infected with HIV and hepatitis C is associated with markers of liver fibrosis and other indicators of liver dysfunction, Canadian investigators report in the online edition of Clinical Infectious Diseases. The research also showed that discordance between CD4 cell count and percentage was present in almost two-thirds of co-infected patients.  

The investigators believe their findings could have clinical applications and help to identify patients with significant liver damage, “and thus may have clinical utility for identifying patients for whom further liver disease staging using non-invasive methods or liver biopsy is indicated”.

CD4 cell count is a key test in the care of HIV-positive people. Overall, the percentage of total lymphocyte cells which are CD4 cells can be correlated to the absolute CD4 cell count. For instance, a CD4 cell percentage for a CD4 cell of 500 cells/mm3 would be 35%, and the CD4 cell percentage for a CD4 cell count of 200 cells/mm3 would be 14%.

Glossary

CD4 cell percentage

The CD4 cell percentage measures the proportion of all white blood cells that are CD4 cells.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

discordant

A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

end-stage disease

Final period or phase in the course of a disease leading to a person's death.

Studies conducted in HIV-negative people who are infected with hepatitis C have shown that a significant proportion have a discordance between their CD4 cell count and CD4 cell percentage.

Canadian investigators wished to see if this was also the case for co-infected people. They therefore designed a prospective study involving 908 co-infected patients who received care after 2003.

If someone had a CD4 cell percentage lower than expected for their CD4 cell count they were classified as “low discordant”. A higher than expected CD4 cell percentage for a CD4 cell count was categorised as “high discordant”.

The investigators were especially eager to see if discordance was associated with liver fibrosis, an AST-to-platelet ratio (APRI) score above 1.5, and the presence of a detectable hepatitis C viral load.

Most of the patients were men (74%) and their median age was 45% years. A third were current injecting drug users. The majority of participants (80%) were taking antiretroviral therapy and median CD4 cell count was 373 cells/mm3.

Hepatitis C infection was spontaneously cleared by 11% of patients, and a similar proportion had a history of end-stage liver disease. Just under a fifth had a APRI score above 1.5.

Only 35% of participants had a concordant CD4 cell count and percentage. A third of those taking part in the study were low discordant and 31% were high discordant.

“Discordance between values of absolute CD4 cell count and CD4 percentage was common in our cohort of co-infected patients,” comment the authors.

A history of end-stage liver disease was associated with the presence of high discordance (adjusted odds ratio [aOR] = 2.76; 95% CI, 1.14-6.67) as was an APRI score above 1.5 (aOR = 2.48; 95% CI, 1.19-5.15).

“The association between progressive liver disease and discordance observed here supports the findings of other studies in HCV mono-infection, and the hypothesis that the development of portal hypertension and splenomegaly may lead to a degree of sequestration of lymphocytes and other cell lines,” note the investigators.

They also found that patients who spontaneously cleared their hepatitis C infection were significantly less likely to have high discordance than those with ongoing hepatitis C replication (aOR = 0.08; 95% CI, 0.008-0.87).

“Further study is required to determine whether regression of inflammation and fibrosis following successful HCV eradication may lead to more concordant absolute CD4 cell counts and CD4 cell percentage,” conclude the authors. They also believe further research is needed to see if discordance is “associated with adverse clinical outcomes”.

References

Hull MW et al. Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in HIV/hepatitis C co-infected patients. Clin Infect Dis, online edition, 2012.