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Antiretrovirals at CD4 Counts Above 350 May Quell HCV-Related Liver Inflammation
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48th ICAAC, October 25-28, 2008, Washington, DC
Mark Mascolini
Antiretrovirals taken by people with a CD4 above 350 lowered the risk of high-level liver inflammation in a Spanish study of patients coinfected with hepatitis C virus (HCV) [1]. But the mechanism behind this lower inflammation risk with antiretrovirals may not to be tighter control of HIV. Results of this single-center study must be interpreted with caution because the investigators measured liver inflammation at only a single point and did not study a comparison group, such as HIV/HCV-coinfected people with a CD4 count above 350 who never took antiretrovirals.
The researchers noted that cohort studies suggest immune recovery after antiretroviral therapy begins can ease necroinflamatory activity. But antiretrovirals may also threaten the liver through drug-induced steatosis, immune reconstitution syndrome, or drug-induced hepatotoxicity. They planned this study to evaluate the impact of antiretroviral therapy on liver inflammation in people with a current CD4 count above the 350-cell threshold for starting antiretrovirals.
Clinicians at Madrid's Hospital La Paz studied 119 HIV/HCV-coinfected people, all of whom had a CD4 count above 350 at the time of their liver biopsy. Most people, though, had a lower CD4 count before starting antiretrovirals (median nadir 210, interquartile range [IQR] 113 to 336). No one had hepatitis B virus infection, prior anti-HCV therapy, an unknown date of HCV infection, or poor adherence to antiretroviral therapy. A single pathologist blinded to patients' clinical status evaluated samples for necroinflammatory activity (by the Scherer system), fibrosis (by the Scherer system), and steatosis.
All 119 study participants were Caucasian and 93 (78%) were men. Median age stood at 38 years (IQR 35 to 41), median duration of HCV infection at 20 years (IQR 15 to 22), median alanine aminotransferase (ALT) at 87 U/L (IQR 54 to 131), median CD4 count at liver biopsy at 549 (IQR 456 to 675), and median antiretroviral duration at 1444 days (IQR 1152 to 1913). Sixty people (48%) had AIDS, 29 (24%) were current alcohol abusers, 58 (49%) had an HCV load above 800,000 copies, 85 (71%) had HCV genotype 1 or 4, 41 (60%) had an HIV load under 400 copies, and 93 (78%) were taking antiretrovirals at the time of their biopsy.
While 30 people (25%) had a necroinflammatory activity score of 3 or more, 89 (75%) had a score under 3. Twenty-three people (19%) had F3 fibrosis and 4 (3%) had F4 fibrosis. Twenty-three of 27 people (85%) with F3 or F4 fibrosis had a necroinflammation score of 3 or more. In multivariate analysis neither steatosis grade nor alcohol abuse predicted a high necroinflammation score. Nadir CD4 count, CD4 count at biopsy, and HIV load below 400 also had no impact on necroinflammation score.
Current antiretroviral use lowered the risk of a 3+ necroinflammation score 84% (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.03 to 0.7, P = 0.024). A fibrosis score at or above F3 independently raised the risk of high-grade necroinflammation more than 100-fold (OR 131.9, 95% CI 24.8 to 700.8, P < 0.001). Higher ALT also independently raised the risk of worse necroinflammation (median 137 U/L for necroinflammation score of 3 or more versus 92 U/L for a lower necroinflammation score, P = 0.022).
Antiretrovirals may help control liver inflammation, the La Paz team suggested, by inhibiting HIV replication in the liver. If so, however, HIV replication in blood did not mirror replication in liver cells among these patients, because equivalent proportions with a high and a low necroinflammation score had a plasma HIV load below 400 copies (53% versus 62%). The researchers noted, though, that this comparison rests on HIV loads measured at a single point--upon liver biopsy. Effective antiretroviral therapy may also protect the liver, the investigators surmised, by lowering levels of proinflammatory cytokines in HIV/HCV-coinfected people.
Reference
1. Pascual J, Pareja, A. Caminoa A, et al. HAART is associated with a lower level of hepatic necroinflamatory activity in HIV-HCV coinfected patients with CD4 > 350 at the time of liver biopsy. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-2319.
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