Most people with hepatitis B virus (HBV) who stopped taking tenofovir
(Viread) after more than three years
on treatment had good outcomes, according to a presentation at the recent European
Association for the Study of the Liver (EASL) 50th International
Liver Congress in Vienna, Austria. Although everyone who stopped tenofovir saw their HBV
viral load rise, most maintained normal ALT (alanine aminotransferase) levels and only a few needed to
restart therapy.
Antiviral therapy using nucleoside/nucleotide analogues
such as lamivudine, entecavir or tenofovir is the mainstay of chronic hepatitis
B treatment. While antiviral drugs can
effectively suppress HBV replication long-term during therapy, they
usually do not lead to a cure as indicated by hepatitis B surface antigen
(HBsAg) loss. The optimal duration of antiviral treatment is still not defined.
Thomas Berg of University Medical Centre Leipzig and
colleagues looked at outcomes after controlled discontinuation of prolonged
tenofovir treatment.
Prior research indicates that long-term effective
antiviral therapy may lead to partial restoration of HBV-specific T-cell
function, the researchers noted as background. Stopping therapy usually results
in disease reactivation with HBV DNA viral load rebound and sometimes hepatic
flares, or sudden ALT increases due to inflammation
as the immune system attacks the resurgent virus. In some cases, however, this
may be followed by HBsAg clearance.
The Finite CHB study included 45 people with chronic hepatitis B at 13 sites in Germany who had been on effective tenofovir treatment
for at least four years, with HBV DNA <400 copies/ml for at least 3.5 years.
A majority were men, most were white and the median age was 45 years. At
baseline, all were HBsAg-positive, hepatitis B 'e' antigen (HBeAg)-negative, had
normal ALT (median 22 IU/ml; 40 IU/ml is considered the upper limit of normal),
did not have liver cirrhosis and had no history of decompensated liver disease.
Participants in this open-label study were randomly
assigned to either stop tenofovir or continue therapy for 144 weeks. Tenofovir
could be restarted if clinically significant hepatitis B flares occurred.
The primary endpoint was HBsAg loss at week 144,
considered the closest approximation to a cure. Berg presented interim 48-week
findings; 21 participants in the stop-tenofovir group and 21 in the
continuous-tenofovir group completed 48 weeks and were included in this
analysis.
At 48 weeks, people who remained on tenofovir
maintained viral suppression, had stable ALT levels and none experienced HBsAg
loss.
Three people (14%) who stopped tenofovir restarted
therapy by week 48 – two due to early hepatitis B flares and one due to
persistent high-level viraemia. All returned to undetectable HBV DNA and normal
ALT levels.
All participants who stopped tenofovir experienced HBV
rebound, mostly within the first 12 weeks after discontinuation. By 48 weeks,
among the 18 people who stopped and stayed off tenofovir, 16 (89%) had a
viral load below 20,000 IU/ml, including 14 (78%) with HBV DNA <2000 IU/ml.
Most people who stopped tenofovir also experienced ALT
elevations, with 12 (57%) reaching levels more than twice the upper limit of
normal. But by 48 weeks, among the 18 who stayed off tenofovir, all had ALT
less than twice the upper limit of normal, including 15 (83%) with normal ALT.
Several people who stopped tenofovir experienced
substantial reductions in HBsAg. The median reduction was -0.28 log10
in this group compared with just -0.09 log10 in the
continuous-tenofovir group.
Two people who stopped tenofovir experienced HBsAg
loss, one at week 20 and one after week 40. Participants who experienced the
largest HBsAg reductions – including the two with HBsAg loss – started out with
lower baseline HBsAg levels (<25,000 IU/ml) than those with smaller or no
HBsAg reductions.
The proportion of people with both low HBV DNA and
near-normal ALT increased with longer time off tenofovir, while the proportion
with both higher HBV viral load and elevated ALT decreased.
"Stopping [tenofovir] in HBeAg-negative patients
with undetectable HBV DNA for at least 3.5 years appears to be safe," the
researchers concluded, noting that tenofovir can be restarted if necessary.
"Stopping [tenofovir] was associated with a more
profound decline in HBsAg levels compared with continuous [tenofovir],"
they continued. "These data support the concept of stopping antiviral
therapy in long-term HBV DNA-suppressed subjects without cirrhosis."