A randomized, open-label study comparing low-dose clevudine plus adefovir combination therapy with clevudine monotherapy in naïve chronic hepatitis B patients

PURPOSE: Clevudine 30 mg showed potent antiviral activity with a marked post-treatment antiviral effect. However, long-term treatment with clevudine monotherapy induced resistance and myopathy in some cases. The objective of this study is to evaluate the preliminary efficacy and safety of the combination of clevudine 20 mg and adefovir compared to clevudine monotherapy. METHODS: Seventy-four patients were randomized to either a combination of clevudine 20 mg and adefovir or clevudine 20 or 30 mg and were treated for 2 years. The viral kinetics for 24 weeks, virological response [VR; hepatitis B virus (HBV) DNA less than 300 copies/ml], and the biochemical response [BR; normal alanine aminotransferase (ALT)] were assessed. RESULTS: There was no difference in baseline characteristics among the three groups. Viral kinetics study showed no statistically significant difference among them during 24 weeks. The combination group showed 95 % virological response with a statistically significant difference compared to the clevudine 30 mg (67 %) and 20 mg (71 %) groups (p = 0.0376). Biochemical response rates were similar in all groups (78–94 %). No resistance was reported in the combination group, while 20 % of patients treated with clevudine 30 mg or 20 mg reported resistance during 2 years. Muscle-related symptoms such as myalgia (1 in clevudine 30 mg, 1 in the combination group) and muscle weakness (1 in clevudine 30 mg, 2 in clevudine 20 mg) were reported in five patients (7 %); of these, three patients discontinued the study. CONCLUSION: We concluded that the combination of clevudine 20 mg and adefovir produced a potent antiviral response together with a good resistance profile compared to clevudine monotherapy at 96 weeks in this pilot study

Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials

BACKGROUND & AIMS: The effect of race on routinely available noninvasive tests of fibrosis is incompletely under stood. This study evaluated the performance of noninvasive tests among white and Asian pa tients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH). METHODS: Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross validation repeated 100 times. RESULTS: Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years. CONCLUSIONS: In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients

Advanced fibrosis is not a negative pretreatment predictive factor for genotype 2 or 3 chronic hepatitis C patients

Background/AimsChronic hepatitis C patients with advanced fibrosis have unsatisfactory sustained virological response (SVR) rates. Few data demonstrating the efficacy of combination therapy in chronic hepatitis C patients with advanced fibrosis in South Korea are available. The purpose of this study was to assess whether the stage of fibrosis impacts the efficacy of combination therapy for chronic hepatitis C.MethodsWe retrospectively reviewed data for a total of 109 patients with chronic hepatitis C, treated with peginterferon alfa and ribavirin. SVR according to the stage of liver fibrosis assessed by pretreatment liver biopsy and genotype results were analyzed.ResultsData from 66 genotype 1 patients (60.6%) and 43 genotype 2 or 3 patients (39.4%) among the 109 patients were analyzed. SVR rates for the genotype 1 patients were significantly lower for the stage 3-4 group (32.1%) than the stage 0-2 group (78.9%; P<0.001). SVR rates (92.0% for stage 0-2, 77.8% for stage 3-4, P=0.184) of genotype 2 or 3 patients were not significantly different according to fibrosis stage. Likewise, the frequency of adverse events was not significantly different according to fibrosis stage.ConclusionsCompared to patients without advanced fibrosis, we can anticipate good SVR rates for genotype 2 or 3 patients with advanced fibrosis and they did not show an inferior tolerability for peginterferon and ribavirin combination therpy. Our results suggest that active treatment is needed for genotype 2 or 3 patients with advanced fibrosis

A case of hemocholecyst associated with hemobilia following radiofrequency ablation therapy for hepatocellular carcinoma

Radiofrequency ablation (RFA) is performed as an alternative to surgical resection for primary or secondary liver malignancies. Although RFA can be performed safely in most patients, early and late complications related to mechanical or thermal damage occur in 8-9.5% cases. Hemocholecyst, which refers to hemorrhage of the gallbladder, has been reported with primary gallbladder disease or as a secondary event associated with hemobilia. Hemobilia, defined as hemorrhage in the biliary tract and most commonly associated with accidental or iatrogenic trauma, is a rare complication of RFA. Here we report a case of hemocholecyst associated with hemobilia after RFA for hepatocellular carcinoma that was successfully managed by laparoscopic cholecystectomy

An artificial neural-network approach to identify motor hotspot for upper-limb based on electroencephalography: a proof-of-concept study

Abstract Background To apply transcranial electrical stimulation (tES) to the motor cortex, motor hotspots are generally identified using motor evoked potentials by transcranial magnetic stimulation (TMS). The objective of this study is to validate the feasibility of a novel electroencephalography (EEG)-based motor-hotspot-identification approach using a machine learning technique as a potential alternative to TMS. Methods EEG data were measured using 63 channels from thirty subjects as they performed a simple finger tapping task. Power spectral densities of the EEG data were extracted from six frequency bands (delta, theta, alpha, beta, gamma, and full) and were independently used to train and test an artificial neural network for motor hotspot identification. The 3D coordinate information of individual motor hotspots identified by TMS were quantitatively compared with those estimated by our EEG-based motor-hotspot-identification approach to assess its feasibility. Results The minimum mean error distance between the motor hotspot locations identified by TMS and our proposed motor-hotspot-identification approach was 0.22 ± 0.03cm, demonstrating the proof-of-concept of our proposed EEG-based approach. A mean error distance of 1.32 ± 0.15cm was measured when using only nine channels attached to the middle of the motor cortex, showing the possibility of practically using the proposed motor-hotspot-identification approach based on a relatively small number of EEG channels. Conclusion We demonstrated the feasibility of our novel EEG-based motor-hotspot-identification method. It is expected that our approach can be used as an alternative to TMS for motor hotspot identification. In particular, its usability would significantly increase when using a recently developed portable tES device integrated with an EEG device