Effects of direct anti-viral agents on the gut microbiota in patients with chronic hepatitis C.

BACKGROUND/PURPOSE: Gut microbiology is associated with liver disease due to gut-liver circulation via the gut microbial-liver axis. There is a paucity of data regarding the effects of treatment to cure hepatitis C virus (HCV) infection on the gut microbiota. The aim of this study was to evaluate the fecal microbiota before and after treatment with direct antiviral agents (DAA) in patients with HCV infection. METHODS: This prospective study was conducted at Kaohsiung Chung-Gung Memorial Hospital, Taiwan, between December 2019 and November 2020. We recruited patients with chronic hepatitis C (CHC) receiving DAA treatment. Fecal samples were collected twice: at baseline (before DAA treatment; CHC group) and 24 weeks after the end of treatment (EOT; SVR24 group), and once from healthy controls at baseline (control group). The taxonomic composition of the gut microbiota was determined using 16 S ribosomal RNA gene sequencing of stool samples. RESULTS: A total of 60 patients with CHC and 60 healthy controls matched by age and gender were enrolled. All patients achieved a sustained virologic response (SVR). Alpha diversity was not significantly difference between any groups. Analysis of similarities (ANOSIM) revealed minor differences in the microbial community structure between the control group and CHC group (R = 0.0146, P = 0.098) and less significant differences between the CHC group and SVR24 group (R = -0.0139; P = 0.94). Three phyla and eight genera were differentially abundant between the control group and CHC group. CONCLUSION: Individuals with CHC do not exhibit significant gut microbiota alterations and eradication of HCV by DAA is not associated with significant modification of the gut microbiota.

The Impact of Direct-Acting Antiviral Therapy on the Risk of Recurrence after Curative Resection in Patients with Hepatitis-C-Virus-Related Early Stage Hepatocellular Carcinoma.

Background and Objectives: The impact of direct-acting antiviral (DAA)-based regimens on the recurrence of hepatocellular carcinoma (HCC) after successful curative hepatectomy is controversial. Aims: This study aimed to assess the association between DAAs treatment and recurrence risk in HCC after resection. Materials and Methods: We retrospectively assessed 152 cases of early stage (BCLC stage 0/A) hepatitis C virus (HCV)-related HCC (HCV-HCC) that underwent resection with curative intent between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital; 48 cases achieved a sustained virological response (SVR) by DAA, and 104 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative resection was analyzed by using the log-rank test and Kaplan-Meier method. A Cox proportional hazards model was used to analyze the factors that impacted RFS and OS. Results: Five patients (10.4%) experienced HCC recurrence after DAA therapy. The cumulative HCC recurrence rate was significantly lower in the DAA group than the non-treatment group (p < 0.001). Multivariate analysis revealed a significant difference in RFS between the non-treatment group and DAA group (p = 0.001; hazard ratio (HR), 4.978; 95% CI, 1.976-12.542); liver cirrhosis (p = 0.005; HR, 2.062; 95% CI, 1.247-3.410), microvascular invasion (p = 0.001; HR, 2.331; 95% CI, 1.408-3.860) and AFP > 15 ng/mL (p = 0.022; HR, 1.799; 95% CI, 1.089-2.970) were also independent factors for HCC recurrence. ALBI stage II/III (p = 0.005; HR, 3.249; 95% CI, 1.418-7.443) and microvascular invasion (p < 0.001; HR, 4.037 95% CI, 2.071-7.869) were independent factors for OS; no significant difference in OS was observed between the DAA and no DAA treatment groups. Conclusions: DAA treatment could reduce the risk of recurrence after curative treatment for early stage HCC.

Statin use is associated with a lower risk of recurrence after curative resection in BCLC stage 0-A hepatocellular carcinoma.

BACKGROUND: Use of statins is associated with a reduced risk of hepatocellular carcinoma (HCC). However, the effect of statin use on HCC recurrence is unclear. This study aimed to evaluate the effect of statin use on recurrence after curative resection among patients with HCC. METHODS: We retrospectively assessed 820 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statins was defined as use of a statin for at least 3 months before HCC recurrence. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. RESULTS: Of the 820 patients, 46 (5.6%) used statins (statin group) and 774 (94.4%) did not (non-statin group). During the mean follow-up of 76.5 months, 440 (53.7%) patients experienced recurrence and 146 (17.8%) patients died. The cumulative incidence of HCC recurrence was significantly lower in the statin group than the non-statin group (p = 0.001); OS was not significantly different between groups. In multivariate analysis, age (hazard ratio [HR]: 1.291; p = 0.010), liver cirrhosis (HR: 1.743; p < 0.001), diabetes (HR:1.418; p = 0.001), number of tumors (HR: 1.750; p < 0.001), tumor size (HR: 1.406; p = 0.004) and vascular invasion (HR: 1.659; p < 0.001) were independent risk factors for HCC recurrence, whereas statin use (HR: 0.354; p < 0.001) and antiviral therapy (HR: 0.613; p < 0.001) significantly reduced the risk of HCC recurrence. The statin group still had lower RFS than the non-statin group after one-to-four propensity score matching. CONCLUSION: Statins may exert a chemo-preventive effect on HCC recurrence after curative resection.

Risks of adverse events for users of proton-pump inhibitors plus aspirin or clopidogrel in patients with aspirin-related ulcer bleeding.

BACKGROUND AND AIM: Clopidogrel is widely prescribed for patients with of aspirin-related upper gastrointestinal bleeding (UGIB) history. This study aimed to compare the risk of a major adverse cardiovascular event (MACE), UGIB, and mortality between aspirin and clopidogrel in patients at risk of bleeding. METHODS: We analyzed adult patients at high risk of UGIB following aspirin-related bleeding for secondary MACE prevention between 2000 and 2012. Secondary prevention was for those patients who had ever been hospitalized for cardiovascular disease and reused aspirin or changed to clopidogrel after discharge. Study endpoints were recurrence of MACE, UGIB, and death in 90 days of follow-up. The associations between study outcomes and the use of clopidogrel (vs aspirin) were analyzed. RESULTS: Among 947 eligible patients, 653 reused aspirin (in combination with a proton-pump inhibitor), and 294 were treated with clopidogrel (in combination with a proton-pump inhibitor) after discharge for UGIB. Compared with aspirin treatment, clopidogrel showed an increased risk of MACE (adjusted hazard ratio [aHR] 1.65; 95% confidence interval [CI] 0.87-3.12) and UGIB (aHR 1.25; 95% CI 0.66-2.36), but without statistical significance in 90 days' follow-up. Clopidogrel use was associated with greater than four times the risk of any cause of mortality (aHR 4.84; 95% CI 1.59-14.75), but the significance did not hold in propensity score-matched cohort analysis (P = 0.06). CONCLUSIONS: A nonsignificant difference between clopidogrel and aspirin for short-term MACE prevention as well as UGIB recurrence was found in the present study. Further research to assess 90-day mortality would assist clinical decision making.

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy.

Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

Effect of extracorporeal low-energy shock wave on diabetic gastroparesis in a rat model.

BACKGROUND AND AIM: Delayed gastric emptying occurs in more than 50% of chronic diabetic patients, and this is associated with significant impairments in quality of life. Traditional therapy for delayed gastric emptying has focused on supportive treatment, and there is no significant effective therapy. The effect of low-energy shock wave on gastric motility is never studied. We investigated low-energy shock wave on gastric motility in a diabetic rat model. METHODS: Twenty-eight male Wistar rats were studied and separated in three groups in randomized order as control, diabetic rats received shock wave, and diabetic rats received the sham procedure. Antral area and motility were recorded using the transabdominal ultrasound. Blood was taken for measurement of gastric motility peptides. Subjects were killed for immunohistochemical stain analysis of enteric plexus of the stomach. RESULTS: We successfully induced 20 diabetic rats and set ultrasound for measuring rat gastric contract and emptying model and demonstrated that 6 weeks of low-energy shock wave could promote gastric contraction and emptying in diabetic rats. Moreover, we demonstrated that shock wave could increase defecation and feces and decrease serum cholesterol and triglycerol. However, no effect on glycohemoglobin and gastric motility peptides was recorded. In the immunohistochemical staining, shock wave increased expression of gastric myenteric neuron plexus. CONCLUSION: Low-energy shock wave can increase gastric contraction and emptying by activating axonal regeneration and increasing myenteric plexus, but not related with motility peptides.

The effect of dietary carbohydrate on gastroesophageal reflux disease.

BACKGROUND: Acid changes in gastroesophageal reflux with vary component in the food have less been studied, especially carbohydrate. We plan to clarify the effect of different carbohydrate density on low esophageal acid and reflux symptoms of patients with gastroesophgeal reflux disease. METHODS: Twelve patients (52 ± 12 years old; five female) with gastroesophageal reflux disease were recruited for the prospective crossover study. Each patient was invited for panendoscope, manometry and 24 h pH monitor. The two formulated liquid meal, test meal A: 500 ml liquid meal (containing 84.8 g carbohydrate) and B: same volume liquid meal (but 178.8 g carbohydrate) were randomized supplied as lunch or dinner. Reflux symptoms were recorded. RESULTS: There are significant statistic differences in more Johnson-DeMeester score (p = 0.019), total reflux time (%) (p = 0.028), number of reflux periods (p = 0.026) and longest reflux (p = 0.015) after high carbohydrate diet than low carbohydrate. Total reflux time and number of long reflux periods more than 5 min are significant more after high carbohydrate diet. CONCLUSION: More acid reflux symptoms are found after high carbohydrate diet. High carbohydrate diet could induce more acid reflux in low esophagus and more reflux symptoms in patients with gastroesophageal reflux disease.

Liver stiffness-based score in hepatoma risk assessment for chronic hepatitis C patients after successful antiviral therapy.

BACKGROUND & AIMS: Patients with chronic hepatitis C (CHC) after successful antiviral therapy remain at risk of hepatocellular carcinoma (HCC). This study was to determine whether liver stiffness measurement (LSM) was useful in HCC risk assessment and to develop a risk-score system for clinical use. METHODS: This retrospective study enrolled patients with CHC achieving sustained virological response (SVR) after interferon-based therapy with LSM at/after SVR determination. The demographics, clinical characteristics and HCC development were obtained from medical chart reviews. The diagnosis of HCC was based on recommended criteria. RESULTS: A total of 376 (M/F: 185/191, mean age: 54.1 years) patients, including 278 with pretreatment liver biopsy specimens, with a median follow-up period of 7.6 years were enrolled. Twenty-one patients developed HCC. The 5- and 10-year cumulative HCC incidences were 1.4% and 7.8%, respectively. Multivariate analysis showed advanced fibrosis/cirrhosis, diabetes and LSM were associated with HCC developments with odds ratio (OR) of 12.38, 2.80 and 1.01, respectively. For LSM in HCC prediction, the performance and cut-off were 0.783 and 12 kilopascal (kPa), respectively. For 278 patients with pretreatment biopsy, a risk-score system (score 0-4) combining advanced fibrosis/cirrhosis, diabetes and LSM >12 kPa was developed. With the low-risk group as a reference, patients in intermediate- (OR: 12.57) and high-risk (OR: 197.33) groups carried higher risk of HCC development. CONCLUSIONS: For patients with CHC achieving SVR, liver stiffness value at/after SVR determination was associated with HCC development independently. Patients with pretreatment advanced fibrosis/cirrhosis, diabetes and LSM >12 kPa after SVR were at high risk of HCC development.

Combining age and HBsAg level predicts post-treatment durability of nucleos(t)ide analogue-induced HBeAg seroconversion.

BACKGROUND AND AIMS: Previous studies have indicated that lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion may not be durable in the Asian population. We investigated the useful predictors of post-treatment hepatitis B virus (HBV) relapse in patients with nucleos(t)ide analogue (NA)-induced HBeAg loss/seroconversion. METHODS: A total of 157 non-cirrhotic patients with NA-induced HBeAg loss/seroconversion (78, lamivudine; 68, entecavir; 11, telbivudine) were retrospectively analyzed. All patients had at least 12 months of post-treatment follow-up and consolidation therapy duration. RESULTS: The cumulative rate of post-treatment HBV relapse at 5 years was 57.1%. Multivariate analysis revealed that age and baseline hepatitis B surface antigen (HBsAg) levels independently predicted post-treatment HBV relapse. The post-treatment HBV relapse rate was significantly higher in patients aged > 40 years than in those < 40 years (P < 0.001). A baseline HBsAg level of 2000 IU/mL was the optimal cut-off value for predicting post-treatment HBV relapse (P = 0.002). The post-treatment HBV relapse risk further increased with the presence of both risk factors (age ≥ 40 years and baseline HBsAg level ≥ 2000 IU/mL; P < 0.001). A prolonged consolidation therapy period of ≥ 18 or 24 months had no positive effect on sustained viral suppression. There was no significant difference in post-treatment HBV relapse rates between patients with lamivudine- and entecavir-induced HBeAg loss/seroconversion during the off-treatment follow-up (P = 0.31). CONCLUSION: The combination of an age of 40 years and a baseline HBsAg level of 2000 IU/mL was a useful marker for predicting post-treatment HBV relapse in patients with NA-induced HBeAg loss/seroconversion.

Similar survival after endoscopic submucosal dissection and esophagectomy in early esophageal cancer and synchronous or metachronous head and neck cancer.

BACKGROUND: Early-stage esophageal cancer is treated using endoscopic submucosal dissection and esophagectomy. Field cancerization in patients with early-stage esophageal cancer affects treatment outcomes and causes synchronous or metachronous head and neck cancers. We hypothesized that esophagectomy could provide better overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer. METHODS: We retrospectively identified patients with early esophageal squamous cell carcinoma and synchronous or metachronous head and neck cancers. We separated the patients into endoscopic submucosal dissection and esophagectomy groups to compare overall and relapse-free survivals. RESULTS: The study included 106 patients, 25 of whom underwent endoscopic submucosal dissection and 81 underwent esophagectomy. Overall and relapse-free survivals did not show significant differences between the two groups for both synchronous and metachronous head and neck cancers. CONCLUSIONS: Endoscopic submucosal dissection could provide similar overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer.

The multicenter real-world report of the efficacies of 14-day esomeprazole-based and rabeprazole-based high-dose dual therapy in first-line Helicobacter pylori eradication in Taiwan.

BACKGROUND: High-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes. METHODS: A retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173). RESULTS: Five patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071). The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%). CONCLUSIONS: Esomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed.

Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma.

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.

Efficacy and Safety of 7-Day Non-Bismuth Concomitant Quadruple Therapy for First-Line Helicobacter pylori Eradication in the Elderly.

BACKGROUND: Aging may affect the efficacy of Helicobacter pylori eradication. The aim of our study was to assess the efficacy and safety of 7-day non-bismuth concomitant quadruple therapy as a first-line H. pylori infection eradication regimen in elderly individuals. METHODS: We retrospectively analyzed a cohort with prospectively collected data from January 2013 to December 2019 at Chang Gung Memorial Hospital in Kaohsiung. There were 408 naive infected subjects aged 20 years or older who were treated with 7 days of concomitant therapy as a first-line H. pylori eradication regimen. We divided the patients into an elderly group (aged ≥ 65 years) and a control group (aged < 65 years). Two patients were lost during follow-up in the elderly group and 29 patients were lost in the control group, resulting in 56 in the ≥ 65-year age group and 321 in the control group. The patients were asked to perform urea breath tests 8 weeks later. RESULTS: The eradication rates for the elderly and control groups were 93.1% (95% confidence interval (CI): 83.3-98.1) and 84.0% (95% CI 79.7-87.7) (p = 0.070), respectively, in the intention-to-treat analysis, and 96.4% (95% CI 87.6-99.6) and 91.6% (95% CI 88.0-94.4) (p = 0.210), respectively, in the per-protocol (PP) analysis. The adverse event rates were 8.9% in the elderly group and 12.8% in the control group (p = 0.417). The compliance was 100% in both groups. No significant difference was seen in antibiotic resistance in either group. Multivariate analysis revealed that metronidazole resistance (odds ratio (OR) 6.870, 95% CI 1.182-39.919, p = 0.032) and dual-therapy resistance (OR 7.188, 95% CI 1.326-38.952, p = 0.022) were independent factors for eradication failure. CONCLUSIONS: The efficacy of non-bismuth concomitant quadruple therapy in the elderly cohort was comparable with that in the non-elderly cohort for first-line H. pylori eradication with acceptable adverse effects.

Short Half-Life of Des-γ-Carboxy Prothrombin Is a Superior Factor for Early Prediction of Outcomes of Hepatocellular Carcinoma Treated with Radiofrequency Ablation.

BACKGROUND: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. MATERIALS AND METHODS: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. RESULTS: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). CONCLUSIONS: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.

The Efficacy and Safety of 14-day Rabeprazole Plus Amoxicillin High Dose Dual Therapy by Comparing to 14-day Rabeprazole-Containing Hybrid Therapy for the Naïve Helicobacter pylori Infection in Taiwan: A Randomized Controlled Trial.

INTRODUCTION: High-dose dual therapy (HDDT) can attain acceptable eradication rates provided that the optimal doses, timing and treatment duration are applied. The existing evidence still shows inconsistent reports (< 90%) on HDDT therapy except in some Asian countries. We aimed to assess and compare the efficacy of 14-day HDDT by comparing it to 14-day rabeprazole-containing hybrid therapy (HT) and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies. METHODS: In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori-infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later. RESULTS: The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) (P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] (P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group (P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis. CONCLUSION: This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004.

Correlation between Psychosomatic Assessment, Heart Rate Variability, and Refractory GERD: A Prospective Study in Patients with Acid Reflux Esophagitis.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD. METHODS: A prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment. RESULTS: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively). CONCLUSIONS: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial.

Metabolic Risks Are Increasing in Non-B Non-C Early-Stage Hepatocellular Carcinoma: A 10-Year Follow-Up Study.

BACKGROUND: Non-B, non-C hepatocellular carcinoma (NBNC-HCC) may be related to metabolic syndrome, and the incidence of this tumor type is increasing annually. The definition of metabolic-associated fatty liver disease (MAFLD) proposed in 2020 may help to more accuratelyassess the association between metabolic syndrome and NBNC-HCC. However, this new concept has not yet been applied in NBNC-HCC research. Therefore, this study aimed to compare the clinicopathological characteristics of patients with NBNC-HCC and CHB-HCC diagnosed between 2009-13 and 2014-18, focusing on metabolic risk factors and the new concept of MAFLD. METHOD: Patients with BCLC-0/A-HCC who received curative hepatectomy between January 2009 and December 2018 were retrospectively assessed; the associations between clinicopathological characteristics and clinical outcomes of NBNC-HCC and CHB-HCC were analyzed by multivariate analysis. RESULT: Compared to patients diagnosed in 2009-13, the frequency of metabolic disorders in NBNC-HCC was significantly higher in 2014-18 [DM (p=0.049), HTN (p=0.004), BMI (p=0.017) and MAFLD (p=0.003)]; there was no significant change in patients with CHB-HCC. Moreover, CHB-HCC was an independent risk factor for HCC recurrence (HR, 1.339; 95% CI, 1.010-1.775, p=0.043) and death (HR, 1.700; 95% CI, 1.017-2.842, p=0.043) compared to NBNC-HCC. CONCLUSIONS: Therisk of MAFLD, obesity, DM, and hypertension in patients with early-stage NBNC have significantly increased in recent years, thus metabolic syndrome should be monitored in this special population. Moreover, NBNC-HCC tend to had a better prognosis than CHB-HCC, probably due to their distinct clinicopathological features.

Clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms: A single-center experience in Southern Taiwan.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) as an advanced endoscopic procedure can be considered for the removal of colorectal lesions with high suspicion of limited submucosal invasion or cannot be optimally removed by snare-based techniques. We aimed to analyze the clinical outcomes of ESD for colorectal neoplasms in our hospital. METHODS: We retrospectively enrolled 230 patients with 244 colorectal neoplasms who received ESD procedures from April 2012 to October 2020 at Kaohsiung Chang Gung Memorial Hospital. Clinicopathological data were collected by chart review. We also recorded ESD-related complications and clinical outcomes. RESULTS: The average age was 64 years old, with a mean follow-up time of 22.59 months. There was a loss of follow-up in 34 lesions. Most lesions were lateral spreading tumors of the non-granular type. The average ESD time was 51.9 minutes. Nine cases (3.7%) had procedure-related complications, including two intra-procedure perforations (0.8%) and seven delayed bleeding (2.9%) without procedure-related mortality. 241 lesions (98.8%) achieved en-bloc resection, while 207 lesions (84.8%) achieved R0 resection. Most lesions were tubulo-(villous) adenoma. Malignancy included 35 adenocarcinomas and 5 neuroendocrine tumors. No local recurrence was developed during follow-up. Multivariate analysis for long ESD time revealed significance in size ≥ 10 cm2 and endoscopist's experience < 3 years. Pre-ESD endoscopic ultrasound revealed good prediction in discrimination of mucosal (sensitivity: 0.90) and submucosal lesion (specificity: 0.67). CONCLUSIONS: ESD for colorectal neoplasms is an effective and safe technique. Size ≥ 10 cm2 and endoscopist's experience < 3 years were significantly associated with long procedure time. Pre-ESD EUS provided a good prediction for colorectal neoplasms in invasion depth.

Eradication Rates for Esomeprazole and Lansoprazole-Based 7-Day Non-Bismuth Concomitant Quadruple Therapy for First-Line Anti-Helicobacter pylori Treatment in Real World Clinical Practice.

PURPOSE: Non-bismuth concomitant quadruple therapy is commonly administered in Taiwan, achieving an acceptable efficacy as a first-line anti-Helicobacter pylori treatment. This study compared the eradication rates between esomeprazole- and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line anti-H. pylori treatment. PATIENTS AND METHODS: This study included 206 H. pylori-infected naïve patients between July 2016 and February 2019. The patients were prescribed with either a 7-day non-bismuth containing quadruple therapy (esomeprazole, 40 mg twice daily; amoxicillin, 1 g twice daily; and metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily for 7 days [EACM group]; lansoprazole, 30 mg twice daily; amoxicillin, 1 g twice daily; metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily [LACM group]). Then, the patients were asked to perform urea breath tests 8 weeks later. RESULTS: The eradication rates in the EACM group were 86.1% (95% confidence interval [CI], 77.8%-92.2%) and 90.6% (95% CI, 82.9%-95.6%) in the intention-to-treat (ITT) and the per-protocol (PP) analyses, respectively. Moreover, the eradication rates in the LACM group were 90.1% (95% CI, 82.6%-95.2%) and 92.6% (95% CI, 85.5%-96.9%) in the ITT and the PP analyses, respectively. Consequently, the LACM group exhibited more diarrhea patients than the EACM group (7.1% versus 1.0%, p = 0.029), but all symptoms were mild. Univariate analysis in this study showed that metronidazole-resistant strains were the clinical factor affecting the eradications (95.3% versus 78.9%, p = 0.044). Moreover, a trend was observed in dual clarithromycin- and metronidazole-resistant strains (91.5% versus 66.7%, p = 0.155). CONCLUSION: The eradication rates between esomeprazole and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line H. pylori treatment were similar in this study. Both could achieve a > 90% report card in the PP analysis.

Concurrent Cholecystectomy Is Associated with a Lower Risk of Recurrence after Curative Resection in Early-Stage Hepatocellular Carcinoma: A 10 Year Observational Single-Center Study.

BACKGROUND: Cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC). However, there is little information about the impact of cholecystectomy on the outcome of HCC. AIMS: To evaluate the long-term effect of concurrent cholecystectomy on recurrence and overall survival in HCC after curative hepatectomy. PATIENTS AND METHODS: We retrospectively enrolled 857 patients with BCLC stage 0 or A HCC who underwent primary resection from January 2001 to June 2016. The impact of concurrent cholecystectomy on overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox's proportional hazards models after one-to-one propensity score matching (PSM). RESULTS: Of the 857 patients, 539 (62.9%) received concurrent cholecystectomy (cholecystectomy group) and 318 (37.1%) did not (non-cholecystectomy group). During the mean follow-up period of 75.0 months, 471 (55.0%) patients experienced recurrence, and 321 (37.5%) died. RFS and OS were not significantly different between the groups. After PSM, a total of 298 patients were enrolled in each group. RFS was significantly higher in the cholecystectomy than non-cholecystectomy group (p = 0.044). In multivariate analysis, age (p = 0.022), serum AFP (p = 0.008), liver cirrhosis (p < 0.001), diabetes (p = 0.004), tumor number (p = 0.005), tumor size (p = 0.002), histological grade (p = 0.001), microvascular invasion (p < 0.001) and cholecystectomy (p = 0.021) were independent risk factors for HCC recurrence. However, there were no significant differences in OS between the cholecystectomy and non-cholecystectomy groups. CONCLUSIONS: Concurrent cholecystectomy may reduce recurrence in early-stage HCC after curative resection. Further studies are needed to validate our results.