[pronut-hiv] Liver damage linked to ddI exposure in small series of Spanish patients

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Liver damage linked to ddI exposure in small series of Spanish
patients

Prolonged exposure to ddI (didanosine, Videx / VidexEC) can lead to
liver damage, according to a Spanish case-control study published in the
June edition of The Journal of Acquired Immune Deficiency Syndromes.
However, most cases of liver damage in people with HIV are caused by
other factors, such as hepatitis, alcohol or other diseases. 

Liver disease is seen frequently in people with HIV, but its cause is
unclear in a minority of patients. Accordingly, doctors from two large
HIV clinics in Seville and Madrid set out to determine how many of the
patients in their clinics had liver disease that could not be explained
by traditional risk factors, such as co-infection with hepatitis B or C,
or alcohol abuse. 

Of 3200 patients seen at their clinics in the year 2004, only 17 (0.5%)
had liver disease that was not caused by hepatitis, alcohol, or other
inherited or infectious diseases. Fourteen of these patients were male,
with 13 having caught HIV through gay sex. The mean time since HIV
infection was over 15 years, and all of the patients had taken
antiretroviral therapy. 

The investigators compared these patients to a similar group of
patients who were matched according to CD4 cell counts, age and gender,
but who had healthy livers. 

After comparing the two groups, the only factor linked to liver disease
was ddI exposure. The patients with liver damage had taken the drug for
longer than those without liver damage (47 vs. 25 months; p = 0.009).
Exposure to nevirapine (Viramune), d4T (stavudine, Zerit) and ritonavir
(Norvir), as well as age, duration of HIV infection, CD4 cell count and
viral load were similar in the two groups. 

"Antiretroviral therapy, and in particular prolonged ddI exposure,
might be involved in the pathogenesis of [serious liver
complications]," write the doctors. "Thus, although
antiretroviral therapy may overall ameliorate liver disease progression
in most patients co-infected with hepatitis C virus or hepatitis B
virus, prolonged exposure to some antiretrovirals might be detrimental
for the liver in a different subset of individuals." 

The doctors diagnosed liver disease by elevated liver enzyme levels in
the blood, and they established its severity by examining small liver
samples or 'biopsies' or by a new non-invasive technique called
elastography. Ten of the patients had advanced liver disease, with a
Metavir score of F3 or F4. 

Nine patients also had symptoms of liver complications, including fluid
retention in the abdomen, blood clots in the vein supplying the liver,
bleeding from blood vessels in the gullet and effects on the brain.
However, none of the patients died before the end of the study in
December 2005. 

Although this study found a link between ddI use and liver damage, its
results should be interpreted cautiously, since only 17 cases of
unexplained liver disease were found. Comparing these patients'
treatment histories to those of a set of patients without liver disease
has provided some evidence that ddI may be linked to liver damage. 

However, further studies are needed to establish how common this effect
is, and which factors increase a patient's risk of developing liver
disease when taking ddI. 

Reference 

Maida I et al. Severe liver damage associated with prolonged exposure
to antiretroviral drugs. J Acquir Immune Defic Syndr 42: 177-182, 2006.