Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Does whey protein supplementation during resistance exercise have additional benefits for decreasing hepatic fat content?

BACKGROUND: Exercise and diet have positive effects on hepatic fat reduction, and protein supplementation is known to lower hepatic fat accumulation. However, the effect of a combination of exercise and whey protein supplementation (WPS) on hepatic fat content (HFC) is unknown. METHODS: We investigated the effect of WPS on HFC during resistance exercise and diet control intervention for four weeks. A total of 34 sedentary males participated and were randomly assigned to two groups: a protein supplement group (PSG, n = 18) and a control group (CG, n = 16). The PSG took 60 g of WPS per day, and the CG took 60 g of an isocaloric placebo per day. All participants were fed a calorie-controlled diet throughout the study period, with their daily caloric intake determined by their resting metabolic rate and physical activity level. Both groups performed resistance exercises supervised by experts at 60-70% of their maximum efforts for 60 min/day, 6 days/week for 4 weeks. HFC was assessed using the controlled attenuation parameter (CAP) after an 8 h fast, at pre-, mid-, and post-intervention. Liver enzymes and lipid profile were also analyzed after an 8 h fast and pre- and post-intervention. RESULTS: The CAP was significantly reduced after 4 weeks of intervention in both groups (PSG, p < .001; CG, p = .002). However, there was no significant interaction between the group and changes in CAP. Interestingly, when comparing the pre- and mid-tests, both groups also had significantly reduced CAP (PSG, p = .027; CG, p = .028), but there was a significant difference in the amount of change in CAP between the two groups (PSG, -47.2 ± 25.4 dB/m; CG, -19.5 ± 15.1 dB/m; p = .042). For liver enzymes, there was a significant interaction between the two groups and a change in aspartate transaminase (AST) (p = .038). However, alanine aminotransferase (ALT) levels were significantly decreased only in the PSG group (p = .002). In lipids, both groups showed significantly decreased total cholesterol (p < .001) and low-density lipoprotein cholesterol (p < .001) after the intervention. CONCLUSION: Our data showed that WPS may not enhance the overall effects of resistance exercise on HFC and lipid profiles. However, in part, WPS may have a beneficial effect on liver enzymatic changes and rapid response to resistance exercise-induced HFC reduction.

Response-Guided Therapy With Cefotaxime, Ceftriaxone, or Ciprofloxacin for Spontaneous Bacterial Peritonitis: A Randomized Trial: A Validation Study of 2021 AASLD Practice Guidance for SBP.

INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.

Stereotactic body radiotherapy versus radiofrequency ablation as initial treatment of small hepatocellular carcinoma.

BACKGROUND/AIM: Stereotactic body radiotherapy (SBRT) may be an alternative treatment for patients with small (≤3 cm) hepatocellular carcinomas (HCCs) who were not indicated for resection or local ablation therapy. This study compared the therapeutic effects of radiofrequency ablation (RFA) and SBRT in patients with small (≤3 cm) HCCs. METHODS: Data of HCC patients who underwent SBRT or RFA as an initial treatment at four tertiary referral hospitals between March 2011 and February 2017 were reviewed. The patient inclusion criteria were a single nodule measuring ≤3 cm in size and not suitable for resection. RESULTS: SBRT and RFA were performed for 72 (SBRT group) and 134 (RFA group) patients, respectively. The 1-, 3-, and 5-year overall survival (OS) rates were 97.0%, 80.3%, and 80.3%, respectively, in the SBRT group compared with 98.5%, 83.9%, and 80.8%, respectively, in the RFA group, with no significant differences between the groups (P = 0.81). The estimated five-year local control (LC) rate was 68.1% in the SBRT group and 73.1% in the RFA group (P = 0.81). In the SBRT group analysis, both SBRT alone (n = 34) and SBRT combined with transarterial chemoembolization (n = 38) showed no difference with RFA in OS (P = 0.72 and P = 0.90) or LC rate (P = 0.95 and P = 0.68), respectively. CONCLUSION: SBRT is an effective and safe treatment method for small HCCs, with survival and tumor recurrence rates similar to those of RFA.

Effect of Nutrition Education in NAFLD Patients Undergoing Simultaneous Hyperlipidemia Pharmacotherapy: A Randomized Controlled Trial.

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) have a high prevalence of combined hyperlipidemia. The importance of nutritional education is well-known in NAFLD, but the impact of medical nutrition therapy (MNT) is unclear in patients with NAFLD with hyperlipidemia. The purpose of this study is to investigate the effect of MNT on the improvement of steatohepatitis in patients with NAFLD taking antihyperlipidemic medications. METHODS: Nondiabetic patients with dyslipidemia were prospectively randomized (1:1) either to the MNT group or the control group with standard advice for 48 weeks with simultaneous statin/ezetimibe combination pharmacotherapy at three tertiary centers in Korea. RESULTS: Sixty-six patients were enrolled. Among them, 18 patients dropped out and, overall, 48 patients (MNT group 27, control group 21) were prospectively analyzed in the study. The serum ALT level at 48 weeks between the two groups was not significantly different (66.6 ± 37.7 IU/L vs. 57.4 ± 36.7 IU/L, p = 0.40). Serum liver enzymes, controlled attenuation parameter and fibrosis-4 index were significantly improved within the MNT group after 48 weeks compared to baseline. There was no significant difference between the two groups other than the NAFLD fibrosis score (p = 0.017). CONCLUSIONS: Although there were no significant differences between the two groups in terms of steatosis, metabolic and fibrosis surrogate indicators after 48 weeks, MNT groups showed significant improvement within patient analysis over time. Future studies with a larger number of subjects and a longer study period regarding the effect of MNT are warranted.

Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study.

BACKGROUND/AIM: We aimed to demonstrate the efficacy and safety of tenofovir disoproxilorotate (TDO) compared with that of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B. METHODS: This multicenter, open-label, prospective clinical trial (KCT0004185) was conducted to evaluate the efficacy and safety of TDO on switching from TDF for 24 weeks in virologically suppressed chronic hepatitis B patients. The primary efficacy endpoint was the maintenance of virologic response. Safety was assessed by evaluating major adverse events, changes in renal function, and occurrence of hepatocellular carcinoma (HCC). RESULTS: TDO treatment was not inferior in terms of virological response when compared with that on TDF treatment, with a noninferiority margin of -10% (risk difference, -3.17%; 95% confidence interval, -7.5%-1.15%). The biological response of TDO was also comparable to that of TDF, with no significant difference in the proportion of patients with normalized alanine transaminase levels. After 24 weeks of treatment, hepatitis B core-related antigen (HBcrAg) significantly decreased to a mean titer of 3.91 log U/mL from 4.15 log U/mL at baseline (p = 0.01). There were no cases of grade 3 or higher adverse events and HCC. The mean estimated glomerular filtration rate increased from 91.09 mL/min to 93.34 mL/min (p = 0.056), and the mean serum level of phosphorus increased from 3.33 mg/dL to 3.44 mg/dL (p = 0.045), suggesting improvement in renal function with TDO treatment. CONCLUSION: In patients with chronic hepatitis B, the efficacy of TDO was noninferior to that of TDF, with a significant decrease in the HBcrAg titer and improved renal function.

Clinical impact of serum exosomal microRNA in liver fibrosis.

BACKGROUND/AIM: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. METHODS: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. RESULTS: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. CONCLUSION: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.

Adverse outcomes after surgeries in patients with liver cirrhosis among Korean population: A population-based study.

BACKGROUND: Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years. METHODS AND FINDINGS: We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56-1.79, P<0.001], especially in-hospital mortality. In liver cirrhosis group, presence of decompensation or varices showed significantly increased postoperative complication or mortality. Adverse outcomes in patients with cirrhosis was the highest in patients who underwent otorhinolaryngology surgery (aOR 1.86), followed by neurosurgery (aOR 1.72), thoracic and cardiovascular surgery (aOR 1.56), and plastic surgery (aOR 1.36). CONCLUSION: The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment.

Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma.

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial.

BACKGROUND/AIMS: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. METHODS: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). RESULTS: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. CONCLUSION: BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Application of Hepatic Venous Pressure Gradient to Predict Prognosis in Cirrhotic Patients with a Low Model for End-Stage Liver Disease Score.

: Background/aim: We aimed to derive a model representing the dynamic status of cirrhosis and to discriminate patients with poor prognosis even if the Model for End-Stage Liver Disease (MELD) score is low. METHODS: This study retrospectively enrolled 700 cirrhotic patients with a MELD score of less than 20 who underwent hepatic venous pressure gradient (HVPG) measurement. A model named H6C score (= HVPG + 6 × CTP score) to predict overall survival was derived and internal and external validations were conducted with the derivation and validation cohorts. RESULTS: The H6C score using the HVPG was developed based on a multivariate Cox regression analysis. The H6C score showed a great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas, patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort. CONCLUSION: This new model using the HVPG provides an excellent predictive power in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation to positively impact long-term survival, even when the MELD score is low.

C-14 powered dye-sensitized betavoltaic cells.

A dye-sensitized betavoltaic cell is developed for the first time, which utilizes radioisotopic carbon, composed of nano-sized quantum dots, and ruthenium-based dye sensitized TiO2 as electrodes. In this cell, emitted beta radiations are absorbed by the dye rather than TiO2, which resulted in enhanced performance compared to the pristine betavoltaic cell.

Besifovir Dipivoxil Maleate 144-Week Treatment of Chronic Hepatitis B: An Open-Label Extensional Study of a Phase 3 Trial.

INTRODUCTION: Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV). METHODS: After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL). RESULTS: Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients. DISCUSSION: This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.

Prevalence, incidence and risk factors of tamoxifen-related non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Tamoxifen is associated with an increased risk of developing fatty liver. The aim of this systematic review and meta-analysis was to evaluate the prevalence and incidence of fatty liver developed after tamoxifen treatment in breast cancer patients. METHODS: A systematic search of PubMed (Medline), EMBASE, OVID Medline, the Cochrane Library and other databases was performed for this review. The abstracts obtained from the search were reviewed by two investigators who chose manuscripts for full-text review. The event rates were calculated with a random-effects model and quality-effects model. RESULTS: The search yielded 165 references. Of these, 24 were included in the quantitative summary. We analysed the data of a total of 6,962 patients treated with tamoxifen and 975 patients not treated with tamoxifen. The prevalence of fatty liver among patients with breast cancer taking tamoxifen was 40.25 per 100 patients and the incidence rate was 12.37 per 100 person-years. The incidence of fatty liver was much higher in the tamoxifen group than in the control group [incidence rate ratio: 3.12, 95% CI (confidence interval): 2.05-4.75, I2  = 61%], regardless of region. The main risk factors were body mass index (BMI) [hazard ratio (HR): 1.15, 95% CI: 1.09-1.22] and hypercholesterolaemia (HR: 1.01, 95% CI: 1.00-1.02). CONCLUSION: The use of tamoxifen was associated with increased risks in the incidence and prevalence of fatty liver, especially in patients with high BMI and hypercholesterolaemia.

Change in Portal Pressure and Clinical Outcome in Cirrhotic Patients with Gastric Varices after Plug-Assisted Retrograde Transvenous Obliteration.

Background/Aims: Plug-assisted retrograde transvenous obliteration (PARTO) is widely used to manage gastric varices with a portosystemic shunt. It is not clear whether portal pressure and the incidence of complications increase after PARTO. The aim of this study was to determine the changes in portal pressure and the associated changes in liver function, ascites, hepatic encephalopathy, and especially esophageal varix (EV) after PARTO. Methods: From March 2012 to February 2018, 54 patients who underwent PARTO were analyzed retrospectively. The parameters collected included liver function and episodes of cirrhotic complications before and at 1 and 6 months after PARTO. Results: The analysis of 54 patients showed improvement in liver function during the 6-month follow-up period (Model for End-Stage Liver Disease score: change from 11.46±4.35 to 10.33±2.96, p=0.021). Among these 54 patients, 25 patients were evaluated for their hepatic venous pressure gradient (HVPG) before and after PARTO (change from 12.52±3.83 to 14.68±5.03 mm Hg; p<0.001). Twenty-five patients with portal pressure measured before and after PARTO were evaluated for risk factors affecting liver function improvement and EV deterioration. No factor associated with portal pressure was affected by liver function improvement. Post-PARTO portal pressure was a risk factor affecting EV deterioration (HVPG-post: odds ratio, 1.341; 95% confidence interval, 1.017 to 1.767; p=0.037). Conclusions: The artificial blockade of the portosystemic shunt evidently leads to an increase in HVPG. Liver function was improved over the 6-month follow-up period. Portal pressure after PARTO was a significant risk factor for EV deterioration. Portal pressure measurement is helpful for predicting the patient's clinical outcome.

Propranolol plus endoscopic ligation for variceal bleeding in patients with significant ascites: Propensity score matching analysis.

The use of beta-blockers in decompensated cirrhosis accompanying ascites is still under debate. The aim of this study was to compare overall survival (OS) and incidence of cirrhotic complications between endoscopic variceal ligation (EVL) only and EVL + non-selective beta-blocker (NSBB) combination therapy in cirrhotic patients with significant ascites (≥grade 2).This retrospective study included 271 consecutive cirrhotic patients with ascites who were treated with EVL only or EVL + NSBB combination therapy as a primary prophylaxis of esophageal varices. The primary outcome was all-cause mortality. Propensity score matching was performed between the 2 groups to minimize baseline difference.Median observation period was 42.1 months (interquartile range, 18.4-75.1 months). All patients had deteriorated liver function: 81.1% Child-Pugh class B and 18.9% Child-Pugh class C. All-cause mortality was significantly higher in the EVL + NSBB group than in the EVL only group not only in non-matched cohort, but also in matched cohort (48.9% vs 31.2%; P = .039). More people died from hepatic failure in the EVL + NSBB group than that in the EVL only group (40.5% vs 20.0%; P = .020). However, the incidence of variceal bleeding, hepatorenal syndrome (HRS), or spontaneous bacterial peritonitis (SBP) was not significantly different between the 2 groups.The use of NSBB might worsen the prognosis of cirrhotic patients with significant ascites. These results suggest that EVL alone is a more appropriate treatment option for prophylaxis of esophageal varices than propranolol combination therapy when patients have significant ascites.

Relation of fibroblast growth factor receptor 2 expression to hepatocellular carcinoma recurrence after liver resection.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after liver resection depends upon the stage and histological grade of the tumor and the expression of certain biomarkers. However, it remains unclear which of these factors has the highest predictive value regarding HCC recurrence after surgical resection. METHODS: This study investigated the associations among clinicopathological characteristics, expression of biomarkers, and HCC recurrence after liver resection. Fifty-four patients having undergone liver resection for HCC were enrolled prospectively, and their data were analyzed retrospectively. Evaluated variables were clinical data, laboratory findings, modified Union for International Cancer Control (UICC) stage, vascular invasion, histological differentiation, and immunohistochemical staining for fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor, and tumor-necrosis-factor-related apoptosis-inducing ligand receptors 1 and 2. RESULTS: Mean patient age was 58.6 years (range, 30-71), and the mean and SD for follow-up duration were 51.2 ± 34.8 months. Cumulative 1-, 3-, and 5-year recurrence rates were 32.9%, 53.6%, and 68.1%, respectively. In univariate analysis, FGFR2 (p = 0.026) and Edmonson-Steiner grade (E-S grade) (p = 0.030) were associated with recurrence after resection in HCC patients. In multivariate analyses, increased FGFR2 expression (p = 0.017) was the only significant predictor of HCC recurrence. CONCLUSIONS: High FGFR2 expression had marginal association with poor E-S grade (p = 0.056). More intensive surveillance of HCC recurrence is warranted in HCC patients with increased FGFR2 expression.

Noble metal sensitized invasive porous bioelectrodes: advanced medical device for enhanced neuronal activity and chronic alcohol treatment.

Invasive bioelectrodes are widely used as an effective treatment for several acute and chronic diseases. In earlier work using high surface area invasive porous bioelectrodes evaluated in an animal model of alcoholism withdrawal, we demonstrated significantly improved electrophysiological and behavioral responses. In this study, we further modify the surface of these invasive porous bioelectrodes with noble metal (Ag, Au, Pt) nanoparticles. Compared to both conventional and porous bioelectrodes, noble metal sensitized invasive porous bioelectrodes show markedly increased low threshold (LT) and wide dynamic range (WDR) neuronal activity. In particular, Pt-sensitized invasive porous bioelectrodes show the highest WDR neuronal activity only upon insertion. In addition, Ag-sensitized invasive porous bioelectrodes, whose surface area is about 37 times greater than that of conventional bioelectrodes, show improved electrochemical properties with higher LT and WDR neuronal activity when stimulated. In an animal model of chronic alcoholism, using normal and alcohol-treated Sprague-Dawley (SD) rats evaluated with the elevated plus maze (EPM) test, the Ag-sensitized invasive porous bioelectrodes show about 20% higher open arms time. These results suggest that these noble metal-sensitized invasive bioelectrodes may offer improved therapeutic outcomes for the treatment of chronic alcoholism, and given these enhanced electrophysiological properties, for other conditions as well.

Physiological impact of nanoporous acupuncture needles: Laser Doppler perfusion imaging in healthy volunteers.

BACKGROUND: Recently, porous acupuncture (PA), which is anodized to increase its surface area for higher stimulation intensity, was developed and showed significantly improved therapeutic effects with more comfort as compared with original acupuncture (OA) in vivo. However, the impact of PA on the change of local blood flow as well as its efficacy and acceptability has not yet been confirmed in a clinical trial. In a randomized, controlled crossover clinical trial, we investigated the effects of PA on the change in local blood flow using laser Doppler perfusion imaging and considered the sensation of pain intensity and discomfort severity using a visual analogue scale (VAS) to explore its physiological impact and the possibility of PA in clinical use. METHODS: Twenty-one healthy participants were randomly treated with PA or OA on one side of Zusanli (ST36) and each participant served as his or her own control. Baseline local blood flow and galvanic skin response (GSR) were obtained for 5 min and acupuncture interventions were subsequently performed. Next, local blood flow and GSR were subsequently obtained for 10 min after insertion, 10 min after manipulation, and 5 min after the withdrawal of acupuncture. At the end of the experiment, participants were asked to indicate the sensation of pain intensity at each session of insertion, retention, manipulation, and withdrawal as well as the overall pain intensity and discomfort severity. RESULTS: PA significantly increased the local blood flow as compared with OA and there was no significant difference in GSR between patients treated with PA versus OA in each phase of insertion and manipulation. No significant difference in pain intensity or discomfort severity was found during manipulation, retention, or withdrawal of acupuncture. CONCLUSIONS: These results indicate that PA increases local blood flow, which can be closely related to the observed enhanced performance, without any associated discomfort or pain, suggesting its applicability in clinical practice.

Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices.

BACKGROUND: The aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE). METHODS: Between January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE. RESULTS: The area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701-0.810) and 0.813 (95% CI, 0.763-.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621-0.738) and 0.834 (95% CI, 0.785-0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed. CONCLUSIONS: The diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs.