Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B

Abstract

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) has the advantages of low price, quick onset, good efficacy, and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks, followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM-TDF groups died or received liver transplantation (P = 0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24, and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE. (This study has been registered at ClinicalTrials.gov under identifier NCT01848743).

Keywords: acute exacerbation; exacerbation; hepatitis B virus; lamivudine; tenofovir disoproxil fumarate.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIG 1

Flow of study participants who received TDF or LAM followed by TDF.

FIG 2

Cumulative rates of overall mortality or liver transplantation by week 24 in patients treated with tenofovir disoproxil fumarate and lamivudine.

FIG 3

Two-log reduction in HBV DNA levels at 1 and 2 weeks and mortality or liver transplantation in TDF or lamivudine/TDF group.

FIG 4

Virological responses at 12, 24, and 48 weeks in CHB patients with SAE who received TDF or lamivudine for 24 weeks followed by TDF.

FIG 5

Biochemical responses at 12, 24, and 48 weeks in CHB patients with SAE who received TDF or lamivudine for 24 weeks followed by TDF.