DDW 2014: Some Hepatitis B Patients Can Stop Antiviral Treatment without Relapse

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Stopping antiviral therapy after several years appears generally safe for people with HBeAg negative chronic hepatitis B without liver cirrhosis, and a substantial proportion do not experience viral relapse or worsening liver inflammation while off treatment, according to a pair of posters presented at the Digestive Disease Week (DDW 2014) meeting this week in Chicago.

Nucleoside/nucleotide analog antivirals including adefovir (Hepsera), entecavir (Baraclude), and tenofovir (Viread) can fully suppress hepatitis B virus (HBV) replication long-term. But they typically do not eradicate the virus, so treatment may be continued indefinitely and there are no definitive guidelines about if and when to stop.

Neil Sengupta and Nezam Afdhal from Beth Israel Deaconess Medical Center in Boston and colleagues retrospectively evaluated outcomes among 33 non-cirrhotic hepatitis B "e" antigen (HBeAg) negative patients who had viral suppression for 4-5 years and subsequently stopped treatment. Most (73%) were men and the median age was 41 years.

Most had been treated with adefovir or tenofovir, with a few taking entecavir or lamivudine (Epivir). The mean treatment duration prior to stopping was just over 5 years. At the time of treatment discontinuation they had well-controlled disease, with undetectable HBV DNA viral load (<40 IU/mL), normal alanine aminotransferase (ALT) indicating minimal liver inflammation (median 25 IU/L), and a history of mild liver fibrosis (median stage F1 prior to treatment).

The primary endpoint was a composite of virological and biochemical relapse, indicated by an increase in HBV DNA to >2000 IU/mL and ALT elevation above 1.25 times the upper limit of normal (ULN) or doubling the level at the time of treatment cessation. Patients who reached this combined endpoint restarted antiviral therapy.

Eleven patients (33%) met the composite endpoint of virological and biochemical relapse. Looking at individual endpoints, 21 patients had viral relapse, 16 had biochemical relapse, and 16 restarted treatment. The median time to relapse was 3 months. No ALT increases or "flares" were associated with jaundice or liver failure.

The remaining 17 patients stayed off treatment without relapse for a median of 24 months of follow-up. There were 2 people who lost hepatitis B surface antigen (HBsAg) and remained negative following treatment discontinuation -- the closest thing to a cure for hepatitis B.

"HBV non-cirrhotic [HBeAg negative] patients can safely stop treatment after 5 years of suppressive therapy with nucleosides/nucleotides with more than 50% staying off treatment without significant biochemical or virological relapse," the researchers concluded.

However, they were not able to identify any variables -- including HBV viral load, ALT level, extent of liver damage, treatment duration, or demographic factors such as age or sex -- that predicted who would relapse.

In related research, Spilios Manolakopoulos, George Papatheodoris, and colleagues from the University of Athens carried out a prospective study to investigate outcomes among HBeAg negative chronic hepatitis B patients after stopping antivirals.

This analysis also included about 30 patients without cirrhosis who maintained undetectable HBV DNA for at least 5 years on nucleoside/nucleotide analogs. Most (90%) were men, the median age was 56 years, and they had been on treatment for a median of 7.5 years.

Participants consented to stop treatment and were followed closely -- including monthly at the beginning of the study -- for up to 12 months. Treatment was restarted if they relapsed, defined as: ALT >2 x ULN with bilirubin >2 mg/dL, ALT >10 x ULN at any time, ALT > 5 x ULN on 2 monthly tests, ALT > 3 x ULN with HBV DNA >100,000 IU/mL, HBV DNA >20,000 IU/mL increasing on 2 monthly tests, or ALT >ULN with HBV DNA >2000 IU/mL for 6 months or more.

After treatment discontinuation, all participants had detectable HBV DNA on at least 1 test, and half had ALT above the upper limit of normal at least once. However, none develop jaundice or symptoms of liver decompensation.

One-quarter of participants required retreatment, starting at a median of 12 weeks (range 4-24) after stopping. This left 75% of patients who remained off treatment during a median follow-up of 11 months -- including 58% who stayed off treatment for more than 48 weeks. At the last visit, 55% had normal ALT and 42% had HBV DNA <2000 IU/mL.

"Discontinuation of effective long-term [nucleoside/nucleotide analog] therapy in non-cirrhotic [HBeAg negative] patients seems to be feasible and to be associated with off-treatment remission in a substantial proportion of patients," the investigators concluded.

Here again, they found that baseline characteristics were not significantly different between patients who relapsed and those who were able to remain off treatment, leading them to add that "[m]ore data are required to determine predictors of post-[nucleoside/nucleotide analog] relapses."

5/6/14

References

N Sengupta, VR Patwardhan, A Bonder, et al. Treatment Cessation Is Safe and Effective After Prolonged Suppression With Nucleosides/ Nucleotides in Hepatitis B E-Antigen Negative, Non-Cirrhotic Patients. Digestive Disease Week (DDW 2014). Chicago, May 3-6, 2014. Abstract Su1017.

S Manolakopoulos, H Kranidioti, M Deutsch, et al. Discontinuation of Long-Term Nucleos(T)Ide Analogue(S) [Na(S)] Therapy in HBeAg-Negative Chronic Hepatitis B (Chbe-) Patients Without Cirrhosis: a Prospective Study. Digestive Disease Week (DDW 2014). Chicago, May 3-6, 2014. Abstract Su1018.