Stopping tenofovir is safe for people with hepatitis B on long-term therapy

Liz Highleyman
Published:
02 June 2015
Thomas Berg of University Medical Centre Leipzig. Photo by Liz Highleyman, hivandhepatitis.com

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."

Reference

Berg T et al. Stopping tenofovir disoproxil fumarate (TDF) treatment after long-term virologic suppression in HBeAg-negative CHB: week 48 interim results from an ongoing randomized, controlled trial ('Finite CHB'). EASL 50th International Liver Congress, Vienna, abstract O119, 2015.