Patients with HBV who discontinue tenofovir relapse sooner

Patients with chronic hepatitis B virus infection who discontinued the antiviral tenofovir faced a significantly earlier relapse compared with those who discontinued entecavir, researchers in Taiwan reported.

Jia-Horng Kao, MD, PhD, FAASLD, distinguished professor at National Taiwan University College of Medicine, and colleagues wrote that HBV often requires lifelong treatment, but nucleotide analogue therapies have raised growing renal and bone safety concerns, as well as concerns about lactic acidosis.

“Although patients with chronic hepatitis B are advised to receive prolonged nucleotide analogues therapy, sustained viral responses after a finite duration may be an optimal treatment goal,” Tung-Hung Su, MD, also of National Taiwan University, told Infectious Disease News. “However, identifying those who can stop nucleotide analogue therapies with a minimal risk of relapse still remains an unmet clinical need.”

The researchers conducted a prospective cohort study of patients with chronic HBV who were discontinuing nucleotide analogue therapy at National Taiwan University Hospital between October 2012 and August 2017 (n = 172). Kao and colleagues evaluated viral and host predictors of relapse, such as HBsAg, hepatitis B core antibodies and single nucleotide polymorphisms of NTCP, CTLA4, HLA-DPA1 and HLA-DPB1, as well as post-therapy predictors.

A total of 100 patients discontinued 3-year courses of either tenofovir or entecavir. The median age was 51 years, and most patients (72%) were male. Those who discontinued tenofovir experienced a significantly higher rate of viral relapse at 3 months, the researchers reported (52.9% vs. 6.1%; P < .001), as well as a higher rate of clinical relapse (15.2% vs. 1.5%; P = .007). Kao and colleagues reported that both groups had similar relapse rates at 1 year, however.

HbsAg levels at the end of therapy were predictive of viral relapse (HR = 1.62; 95% CI, 1.19-2.21), as well as clinical relapse (HR = 1.78; 95% CI, 1.13-2.81) and sustained clinical response (HR = 0.57; 95% CI, 0.35-0.94), Kao and colleagues wrote. The CTLA4 non-GG genotype was also predictive of both viral (1.74; 95% CI, 1.01-3) and clinical relapse (HR = 2.06; 95% CI, 1.04-4.11), whereas the HLA-DPA1 AA genotype was predictive of sustained clinical response (OR = 10.84; 95% CI, 1.12-105).

The researchers reported that HBV DNA levels at 1 month after ceasing nucleotide analogue therapy served as an early predictor of relapse.

Kao and colleagues acknowledged that the study was limited by its small sample size.

“These results suggest a nucleotide analogue therapy-specific monitoring plan after therapy discontinuation is clinically warranted,” Su said.– by Andy Polhamus

Disclosures: Kao reports consulting and speaking fees for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck, Novartis and Roche. No other authors report any relevant financial disclosures.