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

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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.


traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.

case-control study

An observational study in which a group of people with an infection or condition (called ‘cases’) are compared with a group of people without the infection or condition (called ‘controls’). The past events and behaviour of the two groups are compared. Case-control studies can help us understand the risk factors for having an infection or a condition. However, it is difficult both to accurately collect information about past events and to eliminate bias from case-control studies.

retention in care

A patient’s regular and ongoing engagement with medical care at a health care facility. 


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 


A procedure to remove a small sample of tissue so that it can be examined for signs of disease.

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.


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