Sung-Jo Bang

Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels

Summary.  Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on‐treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty‐two patients with HBeAg‐positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on‐treatment factors, on‐treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log10 IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940–1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On‐treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut‐off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log10 PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on‐treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg‐positive CHB patients with entecavir treatment.

Clinical course of patients with insufficient viral suppression during entecavir therapy in genotype C chronic hepatitis B

BACKGROUND/AIMS The clinical course of patients with insufficient virologic suppression diagnosed with chronic hepatitis B undergoing entecavir therapy is unclear. METHODS We retrospectively investigated the long-term clinical outcomes of entecavir treatment for more than 12 months in 355 nucleos(t)ide-naïve chronic hepatitis B patients, particularly those with primary non-response or partial virologic response. RESULTS The median duration of entecavir therapy was 40 months (range, 12-64 months). Virologic response was achieved in 315 patients (88.7%). One hundred forty-four (96.6%) of 149 HBeAg-negative patients achieved virologic response. Among 206 HBeAg-positive patients, 52 (25.2%) achieved HBeAg seroconversion. Virologic breakthrough was observed in 7 patients (2.0%). Of these 7 patients, 5 (1.4%) had genotypic resistance to entecavir. Primary non-response and partial virologic response were evident in 6 (1.7%) and 63 (17.7%) patients, respectively. During continuous prolonged entecavir therapy, virologic response of patients with primary non-response and partial virologic response was achieved in 6 (100%) and 28 (44.4%) patients, respectively. CONCLUSION The vast majority of chronic hepatitis B patients in this study achieved virologic response through prolonged entecavir therapy, with only 1.4% chance of viral resistance. Furthermore, all patients with primary non-response were able to achieve virologic response without adjustment of antiviral therapy.

Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine, adefovir, and entecavir

In the past decade, many chronic hepatitis B (CHB) patients have undergone sequential treatment with lamivudine (LAM), adefovir (ADV), and entecavir (ETV) to manage antiviral resistance or insufficient suppression of HBV‐DNA. Very limited data are available on the efficacy of tenofovir (TDF) rescue regimens in patients with multidrug resistance (MDR).

Successful outcomes of endoscopic resection for gastric adenomas and early cancers located on the pyloric ring (with video)

BACKGROUND Endoscopic resection is difficult to perform in patients who have gastric neoplasms located on the pyloric ring, especially for lesions that extend from the pyloric area to the duodenal bulb, where it is difficult to retroflex the endoscope, and the risk of perforation is increased. OBJECTIVE To assess the results of endoscopic resection of early gastric neoplasms located on the pyloric ring. DESIGN Case series. SETTING Tertiary-care referral center. PATIENTS This study involved 16 patients with 5 gastric adenomas and 11 early cancers that were located on the pyloric ring. INTERVENTIONS After a retroflexion trial within the duodenum for evaluation of tumor extension from the pyloric area to the duodenal bulb, en bloc resection was attempted. Endoscopic submucosal dissection was attempted at the duodenal bulb with an endoscope retroflexed for cases of duodenal invasion. MAIN OUTCOME MEASUREMENTS The curative resection rate, en bloc resection rate, and complications were determined. RESULTS The success rate of retroflexion within the duodenum was 88% (14 of 16). The curative resection rate was 81.3% (13 of 16), and the en bloc resection rate was 75% (12 of 16). En bloc resection was possible for 3 of 4 (75%) cases of duodenal bulb extension. Major procedure-related complications were not encountered. LIMITATIONS Small number of patients. CONCLUSION Endoscopic resection appears to be a feasible and effective treatment for early gastric neoplasms located on the pyloric ring, including lesions that extend from the pyloric area to the duodenal bulb.

High Pallidal T1 Signal is Rarely Observed in Obstructive Jaundice, but is Frequently Observed in Liver Cirrhosis

High Pallidal T1 Signal is Rarely Observed in Obstructive Jaundice, but is Frequently Observed in Liver Cirrhosis: Sung‐Jo Bang, et al. Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, South Korea—Although high signal intensities in the globus pallidus are frequently observed in T1‐weighted magnetic resonance images (MRI) of patients with liver cirrhosis, it is unclear whether these increases are due to portal‐systemic shunt or obstruction of biliary excretion. We therefore studied pallidal signals in 18 cancer patients with bile duct obstruction and marked jaundice (>10 mg/dl). Patients who had fever, leukocytosis or liver cirrhosis were excluded to ensure that jaundice was due to bile duct obstruction. All patients showed a dilated intrahepatic duct on computed tomography (CT) scan. A high pallidal signal was observed in one of 18 biliary obstructive patients whereas high signals were highly prevalent in liver cirrhosis. A portal‐systemic shunt rather than an obstruction of biliary excretion may be responsible for the increased blood manganese concentrations and pallidal T1 signals in chronic liver diseases.

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B.

Summary.  The efficacy of lamivudine re‐treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re‐treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty‐three relapsed patients received lamivudine re‐treatment for at least 6 months. The mean duration of lamivudine re‐treatment was 16 months and the follow‐up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re‐treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re‐treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re‐treatment. In conclusion, lamivudine re‐treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re‐treatment was not durable.

Efficacy of Tenofovir-based Rescue Therapy in Lamivudine-resistant Chronic Hepatitis B Patients With Failure of Lamivudine and Adefovir Combination

PURPOSE In chronic hepatitis B patients, lamivudine (LAM) and adefovir (ADV) combination therapy is commonly used as a rescue therapy for LAM resistance, but it often results in incomplete viral suppression. We investigated the antiviral efficacy of tenofovir (TDF)/LAM combination therapy versus TDF monotherapy in LAM-resistant chronic hepatitis B (CHB) patients who failed to respond to LAM plus ADV rescue therapy. METHODS Among 108 patients with LAM-resistant CHB who had a partial virologic response (VR) to LAM and ADV combination therapy, Eighty one patients were finally included in this study. FINDINGS Resistance to ADV (ADV-R) was present in 32 patients (39.5%), and the remaining 49 patients (60.5%) had a partial virologic response to LAM/ADV combination (ADV-P). The study subjects were treated with TDF alone (n=15) or TDF/LAM combination (n=66). VR was achieved in 61 patients (75.3%). The rates of VR at 6 and 12 months were not significantly different between TDF monotherapy and TDF/LAM combination therapy groups (46.7 vs. 68.2% at 6 months, and 66.7 vs. 75.9% at 12 months, log-rank P=0.357). Treatment efficacy of TDF alone or TDF/LAM combination was not statistically different according to pre-existing ADV or LAM resistant strains. In multivariate analysis, absolute HBV DNA levels at the start of TDF rescue treatment (P<0.001; OR, 0.556; 95% CI, 0.422-0.731) were the only significantly associated with VR. IMPLICATIONS TDF monotherapy was as effective as TDF/LAM combination therapy in maintaining viral suppression in patients with LAM-resistant patients who failed to respond to LAM/ADV combination therapy.

The expression kinetics of CD137 in chronic hepatitis C patients treated with pegylated-interferon and ribavirin

Abstract Objective. CD137, a member of the tumor necrosis factor receptor family, generates co-stimulatory signals leading to T-cell activation and proliferation for viral eradication. We examined the expression kinetics of CD137 to validate whether it can affect treatment outcomes of chronic hepatitis C (CHC) patients. Methods. The expression of CD137 on peripheral blood mononuclear cells (PBMC) from 50 CHC patients and 20 healthy controls was analyzed by flow cytometry. CD137 expression levels were examined before treatment, and every 4 weeks during treatment until week 24 or 48, and at the 24-week follow-up. Results. CD137 expression on PBMC was significantly lower in CHC patients than controls (15.5 ± 7.8% vs 23.4 ± 5.2%; p < 0.05). Patients with sustained virological response (SVR) showed higher level of CD137 expression on PBMC than treatment failures at week 4 (20.11% vs 10.97%; p < 0.05) and week 12 (15.48% vs 5.74%; p < 0.01). CD137 expression on CD4 T cells was also higher in patients with SVR at week 8 (7.75% vs 3.29%; p < 0.05). CD137 expression on PBMC from patients with SVR recovered to the control level at the 24-week follow-up. In multivariate analysis, the increased expression of CD137 at week 4 and genotype non-1 were significantly associated with SVR. Conclusions. The increased expression of CD137 within 12 weeks after the initiation of interferon therapy might be associated with a successful treatment outcome. Modulation to improve expression of CD137 might improve efficacy of CHC treatment.

The risk of hepatocellular carcinoma within and beyond the first 5 years of entecavir in Korean patients with chronic hepatitis B

The development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) has decreased due to potent antiviral agents. However, it remains uncertain whether the risk of HCC will diminish after long‐term antiviral therapy in Asia, where CHB is endemic and vertical transmission is common. This study aimed to compare the incidence of HCC within and beyond the first 5 years of entecavir (ETV) in treatment‐naïve Korean patients with CHB.

Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study

BACKGROUND & AIMS There are limited data on the association between non-alcoholic fatty liver disease (NAFLD) and subclinical coronary atherosclerosis. This study investigated the influence of NAFLD on subclinical coronary atherosclerosis as detected by coronary computed tomography angiography (CCTA) in an asymptomatic population. METHODS A total of 5,121 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake voluntarily underwent abdominal ultrasonography and CCTA as part of a general health examination. Fatty liver was assessed by ultrasonography examination. The fatty liver index and NAFLD fibrosis score were also calculated. Coronary atherosclerotic plaques on CCTA were evaluated. The association between NAFLD and subclinical coronary atherosclerosis was determined by logistic regression analysis. RESULTS Of the study participants, 1,979 (38.6%) had ultrasonography-diagnosed NAFLD. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of NAFLD for calcified plaque (1.03; 95% CI 0.89-1.20; p = 0.673) and mixed plaque (1.15; 95% CI 0.93-1.42; p = 0.214). However, adjusted odds ratios for any atherosclerotic plaque (1.18; 95% CI 1.03-1.35; p = 0.016) and non-calcified plaque (1.27; 95% CI 1.08-1.48; p = 0.003) were significantly higher in NAFLD. In addition, there was a significant association of fatty liver index ≥30 with non-calcified plaque (1.37; 95% CI 1.14-1.65; p = 0.001) and NAFLD fibrosis score ≥-1.455 with non-calcified plaque (1.20; 95% CI 1.08-1.42; p = 0.030). CONCLUSIONS In this large cross-sectional study of asymptomatic individuals undergoing CCTA, NAFLD was consistently associated with non-calcified plaque, suggesting an increased cardiovascular risk. LAY SUMMARY In asymptomatic individuals, non-alcoholic fatty liver disease (NAFLD) was an independent risk factor for non-calcified plaque, which has been known as a vulnerable plaque associated with sudden and unexpected cardiac events. Therefore, appropriate medical therapy for NAFLD was required to reduce future cardiac events.