By Reuters Staff
NEW YORK (Reuters Health) - 4/3/2019
A new analysis provides insight into what happens after stopping tenofovir disoproxil fumarate (TDF) in chronic hepatitis B patients with persistent viral suppression who took the drug for at least eight years.
During 24 weeks off TDF, half of the patients experienced a grade 3 or higher laboratory abnormality, and continued virological suppression was seen in a small subgroup of hepatitis B e antigen (HBeAg)-negative patients.
"This study adds to the body of evidence showing that nucleotide analogue withdrawal is successful in a subgroup of HBeAg-negative patients without cirrhosis who are willing to adhere to close follow-up," the study team notes in The Lancet Gastroenterology & Hepatology, online February 19.
"Stopping long-term nucleotide analogue therapy in HBeAg-negative patients might be considered an effective strategy for a subgroup of individuals, although reliable predictors of when and in which patients to withdraw therapy and criteria for monitoring and restarting treatment are yet to be determined. Furthermore, long-term outcomes after stopping therapy remain largely uncharacterized," add Dr. Maria Buti of Hospital Universitari Vall d'Hebron, in Barcelona, Spain, and colleagues.
They analyzed the outcomes of patients with persistent viral suppression who discontinued TDF after extended treatment in a prespecified analysis of patients from two completed randomized controlled studies (GS-US-174-0102 and GS-US-174-0103).
In both studies, patients who had completed eight years or more of TDF, were hepatitis B surface antigen (HBsAg)-positive with hepatitis B virus (HBV) DNA concentration < 29 IU/mL, and were unwilling or unable to continue treatment entered a 24-week treatment-free follow-up (TFFU) phase.
Only a small proportion (5%) of HBeAg-negative patients lost HBsAg during follow-up; the disease remained inactive in about a third (35%) of patients, defined as HBV DNA < 2,000 IU/mL and alanine aminotransferase below the upper limit of normal at TFFU week 24. About half of patients who entered the TFFU phase experienced ALT flare.
Overall, 26% of patients reported an adverse event, but most adverse events were mild and only 8% were grade 3 or higher. Owing to the small number of patients with HBsAg seroclearance at TFFU week 24 (five patients only), the researchers could not identify predictors of this endpoint.
In a comment published with the study, Dr. Grace Lai-Hung Wong and two colleagues from The Chinese University of Hong Kong say this "important study provided valuable data on what happens after stopping nucleos(t)ide analogue therapy in a cohort of patients who had received a sufficiently long period of nucleos(t)ide analogue treatment. This study echoed the findings of a systematic review of studies predominantly done in Asia, which showed that the weighted probability of HBsAg seroclearance was only 2%."
"HBsAg seroclearance is regarded as the functional cure of chronic hepatitis B," they add. "However, HBsAg seroclearance is uncommon in patients, particularly Asian patients, treated with nucleos(t)ide analogues. Cessation of nucleos(t)ide analogues might lead to high rate of viral relapse and occasionally fatal outcome. Nonetheless, hepatitis flare in the absence of hepatic decompensation increases the rate of HBsAg seroclearance. Data support the use of serum HBsAg and HBcrAg levels to predict the success rate of nucleos(t)ide analogue cessation. More prospective studies, preferably randomised trials, are warranted to provide the definitive answer to this important clinical question," the authors conclude.
Dr. Buti did not respond to a request for comment by press time.
This research was funded by Gilead Sciences. The study authors and comment writers have indicated financial relationships with Gilead.
Lancet Gastroenterol Hepatol 2019.