Adverse events of nucleos(t)ide analogues for chronic hepatitis B: a systematic review

Abstract

Nucleos(t)ide analogues (NAs) are the main drug category used in chronic hepatitis B (CHB) treatment. Despite the fact that NAs have a favourable safety profile, undesired adverse events (AEs) may occur during the treatment of CHB. Given the eminent number of patients currently receiving NAs, even a small risk of any of these toxicities can represent a major medical issue. The main objective of this review was to analyse information available on AEs associated with the use of NAs in published studies. We choose the following MesH terms for this systematic review: chronic hepatitis B, side effects and treatment. All articles published from 1 January 1990 up to 19 February 2018 in MEDLINE of PubMed, EMBASE, the Cochrane Library and LILACS databases were searched. A total of 120 articles were selected for analysis, comprising 6419 patients treated with lamivudine (LAM), 5947 with entecavir (ETV), 3566 with tenofovir disoproxil fumarate (TDF), 3096 with telbivudine (LdT), 1178 with adefovir dipivoxil (ADV) and 876 with tenofovir alafenamide (TAF). The most common AEs in all NAs assessed were abdominal pain/discomfort, nasopharyngitis/upper respiratory tract infections, fatigue, and headache. TAF displays the highest density of AEs per patient treated among NAs (1.14 AE/treated patient). In conclusion, treatment of CHB with NAs is safe, with a low incidence of AEs. Despite the general understanding TAF being safer than TDF, the number of patients treated with TAF still is too small in comparison to other NAs to consolidate an accurate safety profile. PROSPERO Registration No. CRD42018086471

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“…Moreover, drug resistance mutations were not observed after a 2-year treatment of tenofovir alafenamide 25 mg [ 36 ]. The most common adverse events of tenofovir disoproxil fumarate include laboratory abnormalities (19%), gastrointestinal disorders (15%), infestations and infections (13%), and nervous system disorders (8%) [ 37 ]. Similarly, the most frequent adverse events of tenofovir alafenamide are gastrointestinal disorders (23%), laboratory abnormalities (20%), infestations and infections (18%), renal and urinary disorders (11%), and nervous system disorders (9%) [ 37 ].…”

“…The most common adverse events of tenofovir disoproxil fumarate include laboratory abnormalities (19%), gastrointestinal disorders (15%), infestations and infections (13%), and nervous system disorders (8%) [ 37 ]. Similarly, the most frequent adverse events of tenofovir alafenamide are gastrointestinal disorders (23%), laboratory abnormalities (20%), infestations and infections (18%), renal and urinary disorders (11%), and nervous system disorders (9%) [ 37 ]. Compared with tenofovir alafenamide, tenofovir disoproxil fumarate caused a higher risk of bone loss in the hip and spine [ 37 ].…”

“…Similarly, the most frequent adverse events of tenofovir alafenamide are gastrointestinal disorders (23%), laboratory abnormalities (20%), infestations and infections (18%), renal and urinary disorders (11%), and nervous system disorders (9%) [ 37 ]. Compared with tenofovir alafenamide, tenofovir disoproxil fumarate caused a higher risk of bone loss in the hip and spine [ 37 ].…”

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“…The most commonly reported AEs were nausea (2.1%), tiredness (1.4%), and headache (1.4%) [ 26 , 27 ]. In a recent review, the following AEs have been reported: nasopharyngitis (10.2%), occult blood stool (7.1%), elevated ALT (8.6%), elevated LDL cholesterol (4.0%), urine erythrocytes (7.8%), urine glucose (4.9%), and increased creatine kinase (2.6%) [ 43 ]. Although TAF is considered a well-tolerated treatment, 1% of patients discontinued treatment with TAF due to AEs in international phase III trials [ 26 , 27 ].…”

Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

“…Because of the high rates of drug-resistant mutations as well as common treatment emergent adverse events [44], these three NAs with low genetic barrier to resistance are no longer being recommended as the first-line antiviral treatment by the latest international treatment guidelines [8,10].…”