Model Output.

<p>(A) Simulation of No treatment vs. treatment with entecavir for a Korean CHB population: Model simulation of patient outcomes at year 30 in two hypothetical Korean cohorts of patients with chronic hepatitis B, 60% of whom were HBeAg-positive. A total of 1000 patients were untreated and 1000 patients received entecavir treatment for 5 years (B) Weighted value differentiations between entecavir versus lamivudine or telbivudine: Daily cost savings per patient with chronic hepatitis B (60% with HBeAg-positive CHB) in Korea over a 30-year period by use of entecavir instead of lamivudine or telbivudine assuming an average patient lifespan of 65 years and an average initiation age of 35 years and 5 years of treatment with 74% compliance (histological reversal stops when treatment stops). Sensitivity analysis was conducted within 95% Confidence Interval. (C) Weighted value differentiations between switching to entecavir versus maintaining on lamivudine of suboptimal responders for lamivudine: Daily cost savings per patient with chronic hepatitis B (60% with HBeAg-positive CHB) in Korea over a 30-year period by use of entecavir instead of maintain on lamivudine assuming an average patient lifespan of 65 years and an average initiation age of 35 years and 5 years of treatment with 74% compliance (histological reversal stops when treatment stops). Sensitivity analysis was conducted within 95% Confidence Interval.</p

Model Cost Input.

a<p>Antiviral drug cost not included</p>b<p>Calculated from fibrosis total cost, assuming F0F1/∶F2F3F4 = 1∶1.1 based on guidance of Korean advisory board, In addition, patient ratio is assumed to 1∶1</p>c<p>Calculated from cirrhosis total cost, assuming compensated∶ decompensated  = 1∶2.1 and patient ratio is assumed to be 1∶1.61 based on Yang et al. 2004</p>d<p>Calculated & updated liver transplant surgery cost & post liver transplant cost with Korea organ sharing networks database & Seoul national university organ transfer center data base</p>e<p>Assume about 50% of F0/F1 based on EASL guideline</p>f<p>Only consider direct medical cost of caring disease state</p

Model Assumption.

a<p>No patients entered the model in Ishak fibrosis stages F0/F1 or decompensated cirrhosis/HCC/liver transplant/post-liver transplant.</p>b<p>Sensitivity analysis input range for compliance rate 70%∼90%, for annual discount rate 3%∼7%, and for all other variables ±10% standard deviation.</p>c<p>Patients with uncontrolled viral load (HBV DNA level>300 copies/ml).</p>d<p>Patients with controlled viral load (HBV DNA level <300 copies/ml).</p>e<p>Assumptions for the population as a whole. The probability of death was linked to liver histology and not to viral load.</p><p>HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen, HBV = hepatitis B virus, HCC = hepatocellular carcinoma; CHB = chronic hepatitis B; HIRA = Health Insurance Review & Assessment Service in Korea</p

Radioembolization Is a Safe and Effective Treatment for Hepatocellular Carcinoma with Portal Vein Thrombosis: A Propensity Score Analysis

<div><p>Background/Aims</p><p>Limited treatment options are available for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Transarterial radioembolization using Yttrium-90 microspheres is a new treatment modality for HCC with PVT. For this analysis, we compared responses to treatment with radioembolization and with sorafenib.</p><p>Methods</p><p>We evaluated 32 patients who were part of a multicenter retrospective cohort. All patients had PVT without extrahepatic metastasis and were treated with radioembolization in one of six tertiary referral hospitals in Korea. We retrospectively enrolled another 31 consecutive PVT patients without extrahepatic metastasis from a single center who received sorafenib treatment to serve as the control group. We used inverse probability weighting (IPW) using propensity scores to adjust for the between-group differences in baseline characteristics.</p><p>Results</p><p>At 3 months, the response rate and disease control rate were 32.1% (9/32) and 57.1% (16/32), respectively, in the radioembolization group and 3.2% (1/31) and 41.9% (13/31) in the sorafenib group. Median overall survival (OS) and time to progression (TTP) were not significantly different between the radioembolization group and the sorafenib group (13.8 months and 10.0 months, P = 0.22; and 6.0 months and 6.0 months, P = 0.08; respectively). No differences in OS (P = 0.97) or TTP (P = 0.34) were observed after IPW was applied to balance the population characteristics. The sorafenib group showed significantly more grade 3/4 adverse effects than the radioembolization group (P < 0.01).</p><p>Conclusion</p><p>HCC patients with PVT who underwent radioembolization achieved comparable survival to patients who received sorafenib, even after application of IPW. The radioembolization group also experienced fewer severe adverse effects. Radioembolization can be considered a new treatment option for patients with HCC with PVT.</p></div

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

Adverse effects according to CTCAE ver 4.03.

<p>Adverse effects according to CTCAE ver 4.03.</p

Patient selection.

<p>Patient selection.</p

Survival analysis of balanced population after inverse probability weighting.

<p>(A) Overall survival and (B) Time to progression of patients treated with sorafenib and radioembolization.</p

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

Radioembolization treatment characteristics.

<p>Radioembolization treatment characteristics.</p