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.

Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naïve and nucleos(t)ide analog-experienced chronic hepatitis B patients.

BACKGROUND AND AIMS: This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3 years of innucleos(t)ide analog (NA)-naïve and NA-experienced chronic hepatitis B (CHB) patients. METHODS: Tenofovir disoproxil fumarate-treated NA-naïve and NA-experienced CHB patients were retrospectively analyzed. RESULTS: After 3 years of TDF therapy, 97.7%, 71%, and 45.5% NA-naïve patients achieved a virological response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion, respectively. Compared with NA-naïve patients, NA-experienced patients without drug resistance and infected with lamivudine/telbivudine-resistant mutants showed similar results. In contrast, patients previously infected with adefovir-resistant mutants and with a suboptimal entecavir response showed significantly lower rates of virological response and hepatitis B e antigen loss/seroconverion than NA-naïve patients. Mean estimated glomerular filtration rate markedly reduced within 12 months of TDF therapy; however, it did not decrease significantly during 12-36 months of treatment. Diabetes mellitus was an independent predictor of a ≥ 0.5 mg/dL increase above baseline in serum creatinine level, and age, hypertension, diabetes mellitus, and baseline creatinine level were independent factors for > 20% decline in estimated glomerular filtration rate from baseline. Liver stiffness measurements improved significantly, but bone mineral density did not change significantly during treatment. Hepatocellular carcinoma incidence was low at 36 months. Age of > 60 years, cirrhosis, a low baseline platelet count and a high α-fetoprotein level at 12 months were significant predictors of hepatocellular carcinoma development. CONCLUSIONS: Tenofovir disoproxil fumarate is effective and safe for NA-naïve and NA-experienced CHB patients and should be used cautiously in patients with comorbidities because of a renal dysfunction risk.

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.

Liver stiffness measurement as an alternative to fibrotic stage in risk assessment of hepatocellular carcinoma incidence for chronic hepatitis C patients.

BACKGROUND: Hepatic fibrosis stage is useful in assessing risk of hepatocellular carcinoma (HCC) occurrence. AIM: To evaluate liver stiffness measurement (LSM), in addition to fibrosis stage, in risk assessment of long-term HCC occurrence for patients with chronic hepatitis C. PATIENTS AND METHODS: Consecutive patients with chronic hepatitis C, without past history and presence of HCC, with concomitant liver biopsy and LSM were enrolled in this study. All patients attended regular surveillance for HCC development every 3-12 months. The medical records were reviewed. Follow-up LSM was performed at least 1 year later. RESULTS: One hundred and ninety-eight patients (M/F: 112/86) with reliable LSM results were enrolled. Ten patients developed HCC in a median follow-up period of 47.8 months. For patients with initial LSM >24 kPa, 12-24 kPa, and <12 kPa, 5- year HCC incidence was 45.1%, 9.5% and 0.9% respectively. Multivariate analysis showed patients with LSM>24 kPa and patients with LSM 12-24 kPa had higher risks of HCC development (HR: 24.6, CI: 2.7-220.4 and HR:11.7, CI:1.3-105.2). Patients without sustained virological response after treatment also had higher risk of HCC occurrence (HR: 9.7, CI: 1.1-82.2). Among 106 patients with follow-up LSM, there was a higher risk of HCC development for patients with LSM>12 kPa in the initial and follow-up LSM. CONCLUSION: As an alternative of fibrosis stage, initial LSM is useful as a non-invasive method in risk assessment of HCC occurrence for patients with chronic hepatitis C. Serial follow-up LSM>12 kPa carries higher risk of HCC development.

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.

The Pre- and Postoperative FIB-4 Indexes Are Good Predictors to the Outcomes of HBV-Related HCC Patients after Resection.

BACKGROUND AND AIM: Liver fibrosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after resection. The fibrosis-4 (FIB-4) index is an accurate and noninvasive marker to determine the degree of liver fibrosis. Here, we evaluated the effect of pre- and postoperative FIB-4 index in predicting the outcomes after resection of HCC in patients who have chronic hepatitis B (CHB) infection. METHODS: A total of 534 CHB patients with HCC who received curative hepatectomy between 2001 and 2016 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were enrolled in this study. The impact of the FIB-4 index (preoperative and the 1st year after operation) on overall survival (OS) and recurrence-free survival (RFS) was evaluated. RESULTS: There was a significant association between the preoperative FIB-4 index and Metavir fibrosis stage (p < 0.01). The multivariate analysis showed that preoperative FIB-4 > 2 is an independent risk factor for RFS and OS after HCC curative resection [hazard ratio (HR), 1.902; 95% CI, 1.491-2.460; p < 0.001, and HR, 2.207; 95% CI, 1.420-3.429; p < 0.001, respectively]. Notably, preoperative FIB-4 is also an independent risk factor for RFS (HR, 1.219; p = 0.035) in noncirrhotic patients. Furthermore, patients had deteriorated FIB-4 1 year after operation [definition: the value (the 1st year FIB-4 after operation minus preoperative FIB-4) > 1] and had an adverse outcome in RFS and OS (p < 0.001, both). CONCLUSION: The pre and postoperative FIB-4 indexes are useful clinical markers to predict the prognosis in HBV-HCC patients after curative hepatectomy.

Efficacy of a 14-day quadruple-therapy regimen for third-line Helicobacter pylori eradication.

PURPOSE: To assess the efficacy of amoxicillin, tetracycline, high-dose metronidazole, and a proton-pump inhibitor for third-line Helicobacter pylori eradication. METHODS: We enrolled 70 consecutive patients who had registered, failed to respond to two rounds of H. pylori eradication, and undergone endoscopy for H. pylori culture. Seven patients were lost to follow-up. Patients were treated according to the results of antibiotic-susceptibility testing reports (cultured group, n=39). Those who failed the H. pylori culture were prescribed 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three times daily (empirical group, n=24). A follow-up urea breath test was performed 8 weeks later. RESULTS: Antibiotic-resistance rates were 79.5% (clarithromycin), 94.9% (levofloxacin), 66.7% (metronidazole), 2.6% (amoxicillin), and 0 (tetracycline). Eradication rates attained by the cultured and empirical group were 89.7% (95% CI 72.7%-97.1%) and 58.3% (95% CI 36.6%-77.9%) in per-protocol analysis (P=0.004) and 81.4% (95% CI 66.6%-91.6%) and 51.8% (95% CI 31.9%-71.3%) in intention-to-treat analysis (P=0.014), respectively. Culture-guided therapy was the only clinical factor influencing the efficacy of H. pylori eradication (OR 0.16, 95% CI 0.04-0.60; P=0.006). Despite the high metronidazole-resistance rate (66.7%) after two treatment failures, the eradication rate in patients with this condition was 84%. CONCLUSION: Empirical 14-day modified quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment. The success rate of third-line susceptibility-guided treatment was near 90%. This report is valuable as a reminder to medical practitioners that rather than a try-and-see approach, susceptibility-guided therapy should always be considered whenever possible for patients who have undergone several treatment failures.

Associated factors in Streptococcus bovis bacteremia and colorectal cancer.

Reports suggest that between 25% and 80% of patients with Streptococcus bovis/gallolyticus bacteremia have concomitant colorectal tumors. This retrospective study was aimed to identify associations between clinical characteristics and a finding of colorectal neoplasm in patients with S. bovis bacteremia who had colonoscopy examination. We retrospectively reviewed the records of patients with S. bovis bacteremia from Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, between January 2004 and January 2014. Clinical data including age, sex, comorbidities, blood culture, and colonoscopy findings were collected and their relationship to a finding of colorectal cancer was examined. A total of 107 patients with S. bovis bacteremia were identified, of whom 49 (72% male; age 65 ± 12 years) were investigated with colonoscopy; 15 of these patients (30.6%) had colorectal adenocarcinoma. Female sex (p = 0.014) and a history of noncolorectal malignancy (p = 0.004) were associated with a finding of colorectal adenocarcinoma. There were no associations with age, percentage of blood cultures, or the presence of diabetes mellitus, chronic liver disease, heart disease, or end-stage renal disease. Our results show that S. bovis bacteremia is associated with the presence of colorectal adenocarcinoma, especially in female patients, and concomitant existence of other malignancies.

Comparison of treatment outcomes of endoscope-guided pneumatic dilation and laparoscopic Heller myotomy.

The debate on which is the better choice between laparoscopic Heller myotomy (LHM) and endoscopic pneumatic dilation (PD) for esophageal achalasia has been ongoing for decades. This study aims to compare the results of endoscope-guided PD and LHM in 42 patients with achalasia between May 1996 and August 2011. Twenty-one patients who had received PD and 21 who had received LHM were enrolled. The cumulative remission rate was analyzed using the Kaplan-Meier method with the assessment of symptom scores between grades before and after PD or LHM done at 6 weeks, 6 months, 1 year, and then every year thereafter. Possible confounding factors related to the remissions were analyzed by Cox's proportional hazard model. For PD, the cumulative remission rates were 81.0% (1 year), 76.2% (2), 66.7% (3), 61.9% (4), and 47.6% (5). For LHM, the cumulative remission rates were 90.5% every year from the 1(st) to the 5(th). The LHM patients had significantly better remission rates than the PD patients (p = 0.033, by log-rank test). The LHM group had a longer hospital stay than the PD group [median (interquartile range): 8 (6.5-10) days vs. 3 (2-3) days, p < 0.001) and had more reflux complications (52.4% vs. 19.0%, p = 0.024). No perforation occurred in either group. In conclusion, the 5-year cumulative effectiveness of LHM is better than that of PD despite the association of LHM with more reflux events (52.4%).