HIV/HCV Coinfected Patients with Persistently Normal ALT Can Develop Advanced Fibrosis, but Respond Better to Interferon-based Therapy

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HIV/HCV Coinfected Patients with Persistently Normal ALT Can Develop Advanced Fibrosis, but Respond Better to Interferon-based Therapy

SUMMARY: HIV/HCV coinfected people can develop advanced liver fibrosis despite persistently normal alanine transaminase (ALT) levels, though this is less common compared to patients with elevated ALT. Those with persistently normal ALT are also significantly more likely than those with elevated ALT to achieve sustained response to pegylated interferon plus ribavirin, according to a study published in the January 18, 2010 advance online edition of the Journal of Viral Hepatitis.

By Liz HighleymanALT is a liver enzyme released during liver injury. It is a biomarker for liver inflammation, but does not necessarily reflect fibrosis. Studies have shown that hepatitis C patients with persistently normal ALT (PNALT) can nevertheless develop advanced liver fibrosis or cirrhosis, but this has not been as extensively studied in HIV/HCV coinfected people.Ivana Maida from Hospital III in Madrid, Spain, and colleagues analyzed all HIV/HCV coinfected patients who were evaluated for liver fibrosis using transient elastometry (FibroScan) at their clinic during 2005.People who had at

least 1 year of follow-up with 3 prior consecutive ALT measurements below the upper limit of normal were considered to have PNALT. The researchers compared characteristics and outcomes in 87 patients with PNALT and 122 people with elevated ALT. A subset of 22 patients with PNALT and 45 with elevated ALT received treatment with pegylated interferon plus ribavirin. Results

Participants with PNALT were significantly more likely to be women than those with elevated ALT (42% vs 26%).

Patients with PNALT had a higher mean CD4 cell count than those with elevated ALT (565 vs 420 cells/mm3).

People with PNALT had a mean HCV RNA level of 5.8 logs, compared with 6.2 for patients with elevated ALT.

Patients with PNALT were more likely than those with elevated ALT to have HCV genotype 4 (33% vs 6%).

Based on liver stiffness measurements, 10% of patients with PNALT had severe fibrosis (Metavir stage F3) and another 4% had cirrhosis.

Advanced liver disease was more common among people with elevated ALT, however, with 16% having stage F3 fibrosis and 35% having cirrhosis.

Among treated participants, sustained virological response rates were 50% for patients with PNALT and 29% for those with elevated ALT.

In a multivariate analysis, PNALT was independently associated with higher likelihood of treatment response (odds ratio [OR] 7.9; P = 0.02).

Based on these findings, the researchers conclude, "Nearly 15% of HIV/HCV coinfected patients with PNALT showed advanced liver fibrosis (Metavir F3-F4 estimates by elastometry)."In summary, they concluded, "response to [pegylated interferon plus ribavirin] is higher in patients with PNALT than in those with elevated ALT. Therefore, treatment should not be denied in HIV/HCV-coinfected patients with PNALT."Infectious Diseases Department, Hospital III, Madrid, Spain; University of Sassari, Sassari, Italy.1/26/10

ReferenceI Maida, L -Carbonero, G Sotgiu, and others. Differences in liver fibrosis and response to pegylated interferon plus ribavirin in HIV/HCV-coinfected patients with normal vs elevated liver enzymes. Journal of Viral Hepatitis (Abstract). January 18, 2010 (Epub ahead of print).

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