Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients

<div><p>Background</p><p>The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.</p><p>Methods</p><p>In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.</p><p>Results</p><p>Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m², p = 0.000)</p><p>Conclusions</p><p>Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01732367" target="_blank">NCT01732367</a></p></div

LAM-resistance mutation profiles and previous treatment period.

<p>LAM-resistance mutation profiles and previous treatment period.</p

Baseline characteristics of patients.

<p>Baseline characteristics of patients.</p

Comparison between two groups after 96-week follow-up.

<p>Comparison between two groups after 96-week follow-up.</p

Details of the 25 patients with transient virologic rebound or withdrawal from the trial.

<p>Details of the 25 patients with transient virologic rebound or withdrawal from the trial.</p

Role of endoscopic biliary drainage in advanced hepatocellular carcinoma with jaundice

<div><p>Background</p><p>Patients with advanced hepatocellular carcinoma (HCC) with jaundice have an extremely poor prognosis. Although biliary drainage can resolve obstructive jaundice, signs of obstruction may not be evident. This study evaluated the role of endoscopic biliary drainage in patients with advanced HCC and obstructive jaundice.</p><p>Methods</p><p>From 2010 to 2015, 74 patients underwent endoscopic biliary drainage for obstructive jaundice due to advanced HCC. Jaundice resolution was defined as complete response and total bilirubin concentration below 3 mg/dl.</p><p>Results</p><p>The technical success rate in the 74 patients was 92.1% (70/76). Of the 70 patients who underwent successful biliary drainage, 48 (68.6%) and 22 (31.4%) were Child-Pugh classes B and C, respectively, and 10 (14.3%) and 60 (85.7%) were BCLC stages B and C, respectively. Intrahepatic bile duct (IHD) dilatation was observed in 35 patients (50%). After drainage, the complete response rate was 35.7% (25/70). The mean time to resolution was 17.4 ±8.5 days. However, jaundice was re-aggravated in 74.3% (15/25) after a mean 103.5 ±96.4 days. Multivariate analysis showed that the absence of ascites, presence of IHD dilatation, normal range of prothrombin time, and lower MELD score were significantly associated with complete response. The overall survival rate was 15.7% (11/70) and the median survival time is 28 days (95% confidence interval 2.6–563 days). Complete response and HCC treatment after drainage were significantly associated with survival.</p><p>Conclusion</p><p>Effective endoscopic biliary drainage is an important palliative treatment in patients with advanced HCC and obstructive jaundice, especially those with IHD dilatation and preserved liver function, as determined by ascites, prothrombin time, and MELD score.</p></div

Baseline characteristics.

<p>Baseline characteristics.</p

Study flow chart.

<p>Study flow chart.</p

Clinical factors associated with survival.

<p>Clinical factors associated with survival.</p

Clinical factors associated with complete response after biliary drainage.

<p>Clinical factors associated with complete response after biliary drainage.</p