Tenofovir versus lamivudine followed by tenofovir in severe exacerbation of hepatitis B: a randomized controlled study

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) had 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.

Download Full-text

Tenofovir versus Entecavir in Treatment of Chronic Hepatitis B Virus with Severe Acute Exacerbation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00261-15 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3168-3173 ◽

Cited By ~ 15

Author(s):

Chao-Hung Hung ◽

Tsung-Hui Hu ◽

Sheng-Nan Lu ◽

Chuan-Mo Lee ◽

Chih-Hung Chen ◽

...

Keyword(s):

Liver Transplantation ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Acute Exacerbation ◽

Chronic Hepatitis B ◽

Cox Regression ◽

Similar Treatment ◽

Cox Regression Analysis ◽

Severe Acute Exacerbation ◽

Chronic Hepatitis B Virus

ABSTRACTTenofovir disoproxil fumarate (TDF) and entecavir (ETV) are effective antivirals recommended as first-line monotherapies for treatment of chronic hepatitis B (CHB) infection. This study aimed to compare the short-term efficacies of TDF and ETV in the treatment of CHB with severe acute exacerbation. From 2008 to 2013, 189 consecutive treatment-naive CHB patients receiving TDF (n= 41) or ETV (n= 148) for severe acute exacerbation were enrolled. The primary endpoint was overall mortality or receipt of liver transplantation by week 24. The baseline characteristics were comparable between these two groups. By week 24, 8 (19% [95% confidence interval {CI}, 7% to 32%]) patients in the TDF group and 26 (18% [95% CI, 11 to 24%]) patients in the ETV group died (n= 30) or received liver transplantation (n= 4) (P= 0.749). The two groups of patients developed similar rates of liver-related complications and achieved comparable biochemical and virological responses at week 24. Cox regression analysis showed that baseline viral DNA level (P= 0.002), hypertension (P= 0.002), model for end-stage liver disease (MELD) score (P= 0.01), platelet count (P= 0.005), early presence (within 4 weeks) of ascites (P= 0.005), hepatic encephalopathy (P= 0.002), and hepatorenal syndrome (P< 0.001) were independent factors for mortality or liver transplantation. Among the patients who survived by week 24, there was no difference between the two groups in the percentage of patients who had a serum creatinine increase of ≥0.5 mg/dl from baseline (6.7% [95% CI, 0% to 16%] versus 2.0% [95% CI, 0% to 4.8%] in the TDF and ETV groups, respectively;P= 0.231), whereas a significant reduction in the estimated glomerular filtration rate (eGFR) was found in the two groups (P= 0.001 for both). In conclusion, TDF and ETV produce a similar treatment response and clinical outcome in patients with severe acute exacerbation of CHB.

Download Full-text