Valproic acid-induced liver injury: A case-control study from a
prospective pharmacovigilance program in a tertiary hospital
Abstract
Introduction: Valproic acid (VPA) is an antiepileptic drug extensively
used for treating partial and generalised seizures, acute mania and as
prophylaxis for bipolar disorder. Drug-induced liver injury (DILI)
persists as a significant issue related to fatal outcomes by VPA. The
aim of this study was to increase our knowledge about this condition and
to better identify patients affected. Methods: We conducted an
observational retrospective case-control study that identified cases of
DILI by VPA from the Pharmacovigilance Programme from our Laboratory
Signals at La Paz University Hospital from January 2007 to December
2019. Two control groups were assigned, VPA-tolerant patients and the
other with patients who developed mild VPA-related hepatitis but who did
not meet the DILI criteria. Results: A total of 15 cases of DILI by VPA
were found, 3(20%) of them fatal. Mean age was 45.7 years, 4(26.7%)
were women and 5(33.34%) were children under 18 years. Polytherapy with
other antiepileptic drugs (p=0.047) and alcohol consumption
(p<0.001) were associated with a greater risk of developing
DILI by VPA. A diagnosis of epileptic seizure was more frequently
related to DILI when compared with the VPA-tolerant controls
(p<0.001). The cases developed hepatocellular hepatitis
(p<0.001), while the mild hepatitis controls had a higher rate
of cholestatic hepatitis (p<0.001). The laboratory lactate
dehydrogenase values were statistically higher (even at baseline) in
patients with DILI than in both control groups (p= 0.033 and p=0.039).
Conclusions: VPA hepatotoxicity remains a considerable problem. This
study offers interesting findings for characterising VPA-induced liver
injury and at-risk patients.