EASL 2015: Stopping Tenofovir is Safe for Hepatitis B Patients on Long-term Therapy

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Most hepatitis B patients who stopped taking tenofovir (Viread) after more than 3 years on treatment had good outcomes, according to a presentation at the European Association for the Study of the Liver (EASL) 50th International Liver Congress last month in Vienna. Although all patients who stopped tenofovir saw their HBV viral load rise, most maintained normal ALT levels and only a few needed to restart therapy.

Antiviral therapy using nucleoside/nucleotide analogs 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 nucleoside/nucleotide treatment is still not defined.

Thomas Berg from University Medical Center 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 (alanine aminotransferase) 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 chronic hepatitis B patients at 13 sites in Germany who had been on effective tenofovir treatment for at least 4 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 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.

Results

"Stopping [tenofovir] in HBeAg-negative patients with undetectable HBV DNA for at least 3.5 years appears to be safe," the researchers concluded, and tenofovir can be restarted if necessary.

"Stopping [tenofovir] was associated with a more profound decline in HBsAg levels compared to with continuous [tenofovir]," they continued. "These data support the concept of stopping antiviral therapy in long-term HBV DNA-suppressed subjects without cirrhosis."

5/28/15

Reference

T Berg, K-G Simon, S Mauss, 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"). 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract O119.