Use of CD4 cell percentages to assess immunological condition of HIV/HCV coinfected patients, says study

HIV-negative patients with cirrhosis have low CD4 cell counts, but normal CD4 cell percentages, American researchers report in a study published in the February 1^st edition of Clinical Infectious Diseases. The investigators believe that this finding could have important implications for the use of CD4 cell counts to monitor HIV disease status in HIV-positive patients coinfected with hepatitis C virus, and the author of an accompanying editorial suggests “the examination of CD4 T cell percentage and hepatic fibrosis may better reveal the relationship between HIV-induced immunosuppression and liver disease.”

Accelerated liver fibrosis has been observed in hepatitis C virus-infected individuals who are coinfected with HIV, particularly if CD4 cell counts are low. It has therefore been concluded by many investigators and clinicians that advanced HIV disease, indicated by a low CD4 cell count, is associated with cirrhosis.

However, investigators from the Tufts-New England Medical Center in Boston, believed that it was plausible that cirrhosis by itself could cause the loss of CD4 cells, even if there was no concomitant HIV infection.

To test this hypothesis they designed a cross-sectional study involving HIV-negative patients with cirrhosis. Their study had four aims:

• To determine the CD4 cell counts of patients with cirrhosis, and to establish what relationship CD4 cell counts had with CD4 cell percentages.
• To determine if viral versus non-viral causes of cirrhosis had differing effects on CD4 cell count.
• To examine the relationship between low CD4 cell count and factors including demographics, liver dysfunction, and portal hypertension.
• To compare CD4 cell counts in patients with cirrhosis to healthy controls.

A total of 60 patients were enrolled in the study between 2001 and 2003. Most of the patients (54, 90%) were white, 38 (63%) were male and the mean age was 50 years. The majority of patients had underlying viral causes for cirrhosis, with hepatitis C virus being the cause in 31 patients, with an additional patient infected with hepatitis B.

CD4 cell counts ranged between 52 and 1,269 cells/mm³, with the median count being 384 cells/mm³. Just under two-thirds of patients were found to have an abnormally low CD4 cell count (defined in the study protocol as a CD4 cell count below 550 cells/mm³, with a sub-analysis of counts below 350 cells/mm³), with 43% (26) having a CD4 cell count below 350 cells/mm³ and a further 7% (4) a CD4 cell count below 200 cells/mm³.

The investigators found, however, that 95% of patients with an abnormally low CD4 cell count had a normal CD4 cell percentage.

Next they looked to see if there were any risk-factors for an abnormally low CD4 cell count. No demographic factors were found to be significant. Nor did having viral versus non-viral causes of cirrhosis affect the likelihood of having a low CD4 cell count.

A low CD4 cell count was, however, associated with certain clinical and laboratory features, including an enlarged spleen (p = 0.03), decreased white blood count (p = 0.014), low platelet count (p = 0.002), and absolute CD8 T-cell count (p = 0.002). The investigators also found that a low albumin level was significantly associated with a CD4 cell count below 350 cells/mm³.

Clinical markers of portal hypertension were also associated with a low CD4 cell count, including dilated blood vessels in the wall of the oesophagus (p = 0.02) and an enlarged spleen (p = 0.04).

Finally, the investigators conducted a literature search to identify CD4 cell counts of healthy controls to compare to patients with cirrhosis. They found that patients with cirrhosis had significantly lower mean CD4 cell counts (492 versus 925 cells/mm³, p

“Our study has highlighted a previously unreported association between low absolute CD4 T cell counts and cirrhosis in the absence of HIV infection”, write the investigators. They add, “we believe that low CD4 T cell counts are the result of global sequestration of blood cell lines related to portal hypertension.”

They suggest that their findings could have implications for the management of patients coinfected with HIV and hepatitis C. Absolute CD4 cell counts may not, they believe, fully reflect the stage of HIV infection in patients with advanced liver disease. This finding is particularly important for coinfected patients in need of liver transplants. Protocols for liver transplants demand an assessment of a candidate’s immunological status. Therefore, the investigators suggest that "the use of CD4 T cell percentages should be incorporated into liver transplant protocols to assure a more precise assessment of the host’s immunological status.”

An accompanying editorial says that the study makes a “convincing case” and provides “a fresh perspective on how cirrhosis affects absolute CD4 T cell count.”