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

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

• At 48 weeks, patients who remained on tenofovir maintained viral suppression, had stable ALT levels, and none experienced HBsAg loss.
• 3 people (14%) who stopped tenofovir restarted therapy by week 48 -- 2 due to early hepatitis B flares and 1 due to persistent high-level viremia; all returned to undetectable HBV DNA and normal ALT.
• All patients who stopped tenofovir experienced HBV rebound, mostly within the first 12 weeks after discontinuation.
• By 48 weeks, among the 18 patients 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 patients who stopped tenofovir experienced substantial reductions in HBsAg; the median reduction was -0.28 log, compared with just -0.09 log in the continuous-tenofovir group.
• 2 patients who stopped tenofovir experienced HBsAg loss, 1 at week 20 and 1 after week 40.
• Participants who experienced the largest HBsAg reductions -- including the 2 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.

"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.