Incident hepatocellular carcinoma developing during tenofovir alafenamide treatment as a rescue therapy for multi-drug resistant hepatitis B virus infection: A case report and review of the literature

Abstract

Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue with high barrier to resistance, which is recommended for multi-drug resistant hepatitis B virus (HBV) infection. However, nephrotoxicity has been reported during TDF treatment, and tenofovir alafenamide (TAF), which has comparable efficacy to TDF and improves bone and renal safety, can be used as a replacement strategy. Herein, we describe a clinical case concerning a 60-year-old individual suffering liver cirrhosis and renal dysfunction, and being infected with multidrug-resistant HBV. When failing treatment with TDF, he received TAF as a rescue therapy. TAF effectively inhibited HBV replication without worsening renal function or serum phosphorus abnormality. Furthermore, hepatocellular carcinoma (HCC) occurred during TAF treatment despite controlling the viral load. The risk of HCC could not be eliminated and should be monitored during TAF treatment.

Hepatitis B virus resistance to tenofovir: fact or fiction? A synthesis of the evidence to date

“…Seven studies were case reports (15,16,(32)(33)(34)(35)(36), four were in vitro studies (37)(38)(39) and four were longitudinal studies of CHB (with or without HIV coinfection) (40)(41)(42)(43). Studies were from Asia (15,16,32,34,39), Australia (43), Europe (33,36,38,(40)(41)(42) and USA (35,37,44). Eight studies reported HBV genotypes, representing genotypes A-G (16,32,(35)(36)(37)(40)(41)(42)44).…”

“…Among the case reports, three were of high quality as they clearly described patients' characteristics, clinical history, current clinical condition, diagnostic tests or assessment methods, interventions or treatment procedures, post-intervention clinical condition, and concluded with take away lessons (32)(33)(34). Three further case reports did not describe diagnostic test or assessment methods (15,35,36), and one study did not describe postintervention clinical condition of the participant (16).…”

“…A sequencing approach to identifying possible RAMs in HBV sequence isolated from individuals in whom viremia was not suppressed by TFV therapy, undertaken in seven studies (15,32,(34)(35)(36)40,43);…”

“…In 12/15 studies, HBV mutations were reported in association with TFV resistance or reduced TFV susceptibility (16,32,33,(36)(37)(38)(39)(40)(41)(42)44). In the remaining three studies, persistent viraemia was reported among individuals with chronic HBV infection while on TFV but either no RAMs were identified (35,43) or viral sequencing was not performed due to low viral load (34).…”

Hepatitis B virus‐related hepatocellular carcinoma in the era of antiviral therapy: The emerging role of non‐viral risk factors

“…Long‐term NAs therapy could effectively relieve liver inflammation, reverse fibrosis and reduce the incidence of HCC 5‐7 . Nevertheless, treatment with current potent NAs, including entecavir (ETV), tenofovir disoproxil fumarate and tenofovir alafenamide, cannot eliminate the risks of HCC 8‐10 . This indicates that in addition to the viral risk factors, other non‐viral risk factors may also have a significant impact on HCC occurrence.…”