Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience

Abstract

AIMTo evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODSWe performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent’s Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time.RESULTSNinety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of non-compliance. Tenofovir therapy was well tolerated.CONCLUSIONTenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials.

Chronic hepatitis B genotype E in African migrants: response to nucleos(t)ide treatment in real clinical practice

“…This proportion increases to 100% in both groups at month 18. In other studies conducted in real clinical practice with chronic hepatitis B patients, overall viral load negativization rates at 12 months in patients treated with tenofovir ranged from 59.2 to 91.9% [ 24 , 25 , 47 , 49 – 51 ]; and with entecavir, from 41 to 89.4% [ 21 – 23 , 51 – 62 ]. These differences between the studies are possibly due to the diverse populations studied in each case, the different sensitivity of the PCR used to detect viral load, and to the fact that, in many studies, patients previously treated with other treatments for HBV are included.…”

“…These percentages reached 55.6% in HBeAg-negative and 100% in HBeAg-positive patients at 18 months of follow up. In other studies of actual clinical practice, the percentage of patients with normal transaminases at 12 months ranged from 34.6–95.5% [ 21 – 25 , 47 , 49 – 53 , 56 – 60 , 62 ]. These discrepant results may be explained by the different cutoff points taken for normal ALT in the different studies, and by the different stages of hepatopathy of the included patients, since in some cases they include patients with established cirrhosis and even with hepatocarcinoma.…”

“…HBV genotype may influence disease progression and antiviral response [ 5 ] and there are numerous studies related to such aspects: evolution of the disease according to genotype or risk of chronicity [ 6 – 9 ]; percentage of HBeAg or HBsAg loss [ 10 , 11 ]; HBV DNA levels [ 12 – 15 ]; risk of progression of liver disease [ 16 , 17 ] and risk of hepatocellular carcinoma [ 18 – 20 ]; and response to treatment [ 21 – 25 ]. However, most studies are performed on genotypes A, B, C, and D.…”

Real-world single-center experience with entecavir and tenofovir disoproxil fumarate in treatment-naïve and experienced patients with chronic hepatitis B

“…There have been some real-world data reported on the efficacy of ETV and TDF. [ 18 19 ] However, there have been no real-world single-center data on the predictors of complete virological response (CVR) and on complications and HCC developed during ETV and TDF treatment.…”

Complex genetic encoding of the hepatitis B virus on-drug persistence

“…Nevertheless, TDF treatment results in a variable duration of HBV replication in different patients. Some patients experience a rapid HBV clearance, while others have detectable HBV after almost 2 years of TDF treatment 21,22 . While treatment response depends on a variety of host and viral factors, such differences could also be a result of genetic mechanisms that reduce TDF efficacy for some HBV strains without affording actual resistance.…”