The value of screening HIV-infected individuals for didanosine-related liver disease?

Didanosine (ddI) use has been consistently associated with the development of non-cirrhotic portal hypertension (NCPH) [1–5]. We read with interest the recent article by Merchante et al. [6] showing an association of ddI use and abnormal liver stiffness (>7.2 kPa) determined by transient elastography (TE). This article raised the important question as to whether there would be benefit from screening individuals exposed to ddI with TE. We performed a retrospective analysis of all individuals within our HIV cohort who had ever received ddI in order to identify the risk of developing this condition with cumulative ddI use and suitability of screening. A case notes review was performed for each individual and those with radiological or endoscopic features of portal hypertension were identified. Individuals with a recognized cause of liver disease were excluded. A χ2 test with trend analysis was performed to assess risk of developing portal hypertension with cumulative ddI in this cohort. A timeline was created to see the time after initiation of ddI to two consecutive pathology results outside the normal range (those with abnormal results at time of initiation of ddI were excluded) or features of portal hypertension on radiology or endoscopy. Within our cohort, 2,070 individuals had been exposed to ddI. Of these, 26 subjects had idiopathic portal hypertension. A χ2 test with trend analysis revealed the development of portal hypertension was significantly associated with cumulative ddI exposure (P=0.0001; Table 1). There were no identifiable cases of portal hypertension in those exposed for <2 years to ddI. Of 26 subjects, 24 had complete data for dates of commencing and stopping ddI. This timeline revealed the median duration of ddI exposure in this group was 66 months (IQR 47–90). Alanine aminotransferase (ALT) was the first parameter to become abnormal after median 32 months of ddI exposure (IQR 18–55) in 22/23 subjects, then alkaline phosphatase (ALP) at median 44 months (IQR 30–62) in 22/23. Platelets fell below the Letter