Leisure-Time Physical Activity as a Pathway to Sustainable Living: Insights on Health, Environment, and Green Consumerism.

In the aftermath of the COVID-19 pandemic, the intricate relationship between health and the environment has emerged with unparalleled significance. This investigation examines the effect of leisure-time physical activity (LTPA) on health and environmental consciousness and its influence on attitudes towards green/sustainable products among 533 individuals. Utilizing linear structural modeling and regression analysis, the findings reveal that participation in sports and leisure activities significantly mediates the connection between individual well-being and eco-responsible consumer behaviors. Highlighting LTPA's crucial role in enhancing environmental awareness, this study offers invaluable perspectives for the green product sector. It advocates for the development of strategies that align with consumers' environmental values, underscoring the essential function of sports and leisure in fostering sustainable consumer practices. Crucially, this underscores the intertwined nature of environmental sustainability and individual health, highlighting their mutual dependence.

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.

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.

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.

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.

Early and Direct Endoscopic Stone Removal in the Moderate Grade of Acute Cholangitis with Choledocholithiasis Was Safe and Effective: A Prospective Study.

BACKGROUND: Evidence supporting the feasibility of single-stage stone removal in patients with a moderate grade of acute cholangitis remains insufficient. The maximal size of a common bile-duct stone suitable for removal during a single-stage ERCP in a moderate grade of acute cholangitis is unknown. METHODS: We prospectively enrolled 196 endoscopic retrograde cholangiopancreatography (ERCP)-naïve patients diagnosed with acute cholangitis and choledocholithiasis. For eligible patients, single-stage treatment involved stone removal at initial ERCP. RESULTS: A total of 123 patients were included in the final analysis. The success rate of complete stone extraction was similar between patients with mild and moderate grades of acute cholangitis (89.2% vs. 95.9%; p = 0. 181). Complication rates were comparable between the two groups. In the moderate grade of the cholangitis group, among patients who underwent early single-stage ERCP, the length of hospitalization declined as short as the patients in the mild grade of cholangitis (10.6 ± 6.2 vs. 10.1 ± 5.1 days; p = 0.408). In the multivariate analysis, early ERCP indicated shorter hospitalization times (≤10 days) (odds ratio (OR), 3.981; p = 0.001). A stone size less than 1.5 cm presented a high success rate (98.0%) for complete stone removal. CONCLUSIONS: Single-stage retrograde endoscopic stone removal in mild and moderate grades of acute cholangitis may be safe and effective, which can obviate the requirement for a second session, thus reducing medical expenses. CLINICALTRIALS: gov: NCT03754491.

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.

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.

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.

Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection.

BACKGROUND: The albumin-bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. AIM: This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. METHOD: From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. RESULTS: There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child-Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS. CONCLUSION: The preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.

Impact of MAFLD on HBV-Related Stage 0/A Hepatocellular Carcinoma after Curative Resection.

BACKGROUNDS AND AIM: Metabolic-associated fatty liver dis-ease (MAFLD) is a novel term proposed in 2020 to avoid the exclusion of certain subpopulations, though the application of this term in the real world is very limited. Here, we aimed to evaluate the impact of MAFLD on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. METHODS: Patients with chronic hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and December 2019 were consecutively selected. The association between histologically proven concurrent MAFLD and clinical outcomes were retrospectively analyzed. RESULTS: Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients (37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver transplantation. Although no differences in the incidences of HCC recurrence (HR: 0.902, 95% CI: 0.719-1.131, p = 0.370) and death or liver transplantation (HR: 0.743, 95% CI: 0.518-1.006, p = 0.107) were observed between patients with and without MAFLD in multivariate analysis, the patients with MAFLD tended to achieve better recurrent-free survival compared to patients without MAFLD. Notably, lean MAFLD (BMI < 23 kg/m2) was a relative risk factor for tumor recurrence (HR: 2.030, 95% CI: 1.117-3.690, p = 0.020) among patients with MAFLD. CONCLUSIONS: The overall prognosis in HBV-related early-stage HCC, in terms of HCC recurrence and death or liver transplantation, was not significantly different between patients with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for HCC recurrence. Further studies are warranted to validate these results.

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.

The role of hepatitis B virus core-related antigen in predicting hepatitis B virus relapse after cessation of entecavir in hepatitis B e antigen-negative patients.

This study investigated the ability of hepatitis B core-related antigen (HBcrAg) to predict hepatitis B virus (HBV) relapse in HBeAg-negative patients after cessation of entecavir therapy. A total of 301 HBeAg-negative patients without cirrhosis who had stopped entecavir therapy for at least 12 months were recruited. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines. The five-year cumulative rates of virological relapse, clinical relapse and HBsAg loss were 71.6%, 57.3% and 18.7%, respectively. Serum HBsAg at end of treatment (EOT) was an independent predictor of virological relapse, clinical relapse and HBsAg loss; an EOT HBsAg of 150 IU/ml was the optimal cut-off value. The 5-year virological relapse rates for patients with <150 and ≥150 IU/ml HBsAg at EOT were 43.3% and 82.2% (p < 0.001), clinical relapse rates were 32.3% and 66.3% (p < 0.001), and HBsAg loss rates were 46.1% and 5.2% (p < 0.001), respectively. A baseline HBcrAg of 4 IU/ml was the optimal cut-off value for predicting HBV relapse. Among patients with an EOT HBsAg <150 IU/ml, the five-year virological relapse rates for patients with baseline HBcrAg levels ≤4 and >4 log U/ml were 27.9% and 59.1% (p = 0.006) and the clinical relapse rates were 18% and 48.1% (p = 0.014), respectively. EOT HBcrAg was not a significant predictor of virological or clinical relapse after cessation of entecavir. In conclusion, the combination of an EOT HBsAg of 150 IU/ml and baseline HBcrAg of 4 log U/ml can effectively predict the risk of HBV relapse after stopping entecavir therapy.

A novel evidence of serial changes of bone mineral density in chronic hepatitis B patients treated with entecavir.

BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) and Entecavir (ETV) are commonly used for patients with chronic hepatitis B (CHB), and renal or bone toxicity are possible concerns. This study is to evaluate the renal and bone effect of TDF compared with ETV in CHB patients. METHODS: This is a retrospective study at Kaohsiung Chung-Gung memorial hospital, Taiwan, from June 2013 to December 2018. Patients with CHB were prescribed with TDF or ETV for 3 years or above. Renal function was assessed at 12-week intervals. Dual-energy X-ray absorptiometry scans of the spine and femurs were performed at 48-week intervals. The propensity score analysis was conducted to balance the baseline characteristics of patients in both treatment groups. RESULTS: A total of 258 patients were included in this study: TDF (n = 135) and ETV (n = 123). The prevalence of osteopenia was much higher in the TDF group at week 48 and week 96. The TDF group showed significant mean percentage decrease from baseline in bone mineral density throughout the treatment course. Logistic regression analysis adjusted for the propensity score demonstrated that the use of TDF was the only predictive factor of significant bone density loss at week 144. The mean percentage decline of estimated glomerular filtration rate was significant in the TDF group at all time points. Renal threshold phosphate concentration was similar among both treatment groups. CONCLUSIONS: This study suggested CHB patients treated with TDF may experience increased risks of bone loss and renal deficits compared to those treated with ETV.

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

BACKGROUND: Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. METHODS: We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. RESULTS: During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan.

The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus Ruminococcaceae UCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.

The ALBI Grade is a Good Predictive Model for Very Late Recurrence in Patients with Hepatocellular Carcinoma Undergoing Primary Resection.

BACKGROUND: Hepatocellular carcinoma (HCC) patients still have risk for very late recurrence after curative resection. This study assesses prognostic factors in HCC patients with recurrence-free survival (RFS) for 5 years after primary resection. METHODS: We enrolled 383 HCC patients who received primary tumor resection and achieved more than 5 years without recurrence after resection between January 2001 and April 2013. Predictive factors, including albumin-bilirubin (ALBI) grade, for RFS and overall survival (OS) were analyzed. RESULTS: After a median follow-up of 103 months, 57 patients (14.9%) had recurrent HCC, and 14 (3.7%) died. Independent predictors for HCC recurrence were male sex (p = 0.035), pre-operative liver cirrhosis (LC) (p = 0.025), serum creatinine > 1.5 mg/dL (p = 0.045), post-operative 5th-year alpha-fetoprotein (AFP) > 15 ng/ml (p < 0.001), LC (p = 0.004), and ALBI grades 2 and 3 (p < 0.001). I ndependent risk factors for poor survival were age >70 years (p = 0.002), post-operative 5th-year AFP > 15 ng/ml (p = 0.003), and ALBI grades 2 and 3 (p = 0.002). Patients whose deteriorated ALBI grades 5 years after resection had adverse RFS outcomes compared to those with constant (p = 0.056) and improved ALBI grades (p = 0.008). In subgroup analysis, patients with post-operative 5th-year ALBI grades 2 and 3 had significantly poorer RFS and OS (both p < 0.001) than those with grade 1 among patients with low post-operative 5th-year AFP (<15 ng/mL). CONCLUSION: In HCC patients without recurrence for 5 years after curative resection, post-operative 5th-year ALBI grade is useful for predicting outcomes, even with low AFP during follow-up.

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.

Predictive Effects of Inflammatory Scores in Patients with BCLC 0-A Hepatocellular Carcinoma after Hepatectomy.

BACKGROUND: Inflammatory markers are regarded as prognostic factors of the outcomes of hepatocellular carcinoma (HCC). Examples include the neutrophil-to-lymphocyte ratio (NLR); platelet to lymphocyte ratio (PLR); the albumin and lymphocyte counts used in the prognostic nutritional index (PNI); and the neutrophil, lymphocyte, and platelet counts used in the systemic immune-inflammation index (SII). This study evaluates the effects of PNI, NLR, PLR, and SII to predict recurrence and survival in patients with Barcelona Clinic Liver Cancer (BCLC) stages 0-A of HCC after hepatectomy. METHODS: This retrospective study was conducted at Kaohsiung Chung-Gung Memorial Hospital, Taiwan. The study enrolled 891 patients (77.9% males; mean age 58.53 ± 11.60 years) with BCLC stage 0/A HCC undergoing hepatectomy between 2001 and 2016. PNI, NLR, PLR and SII were measured before hepatectomy. RESULTS: High NLR (>1.8) was adversely associated with overall survival (p = 0.032). Low PNI (≤45) was adversely associated with overall survival and disease-free survival (p < 0.001). Low SII (≤45) also had an adverse association with overall survival (p = 0.008) and disease-free survival (p < 0.001). Diabetes mellitus, cirrhosis, microvascular invasion, low PNI (≤45), and low SII (≤160) were independently associated with poor overall survival in a multivariate analysis. HCV infection, diabetes mellitus, cirrhosis, microvascular invasion, low PNI, and low SII were independent prognostic factors of recurrent HCC. The combined use of PNI and SII provided improved prognostic information. CONCLUSIONS: Low PNI and low SII are significantly poor prognostic factors for overall survival and recurrence in patients with BCLC 0-A hepatocellular carcinoma after hepatectomy.

A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-Helicobacter pylori treatment in Taiwan: a prospective randomized trial.

BACKGROUND: The first-line eradication rate of standard triple therapy for Helicobacter pylori infection has declined to <80%, and alternative therapies with >90% success rates are needed. Inconsistent eradication rates were reported for proton pump inhibitor- and amoxicillin-containing high-dose dual therapy. OBJECTIVES: We performed a prospective, randomized controlled study to assess the efficacy of esomeprazole- and amoxicillin-containing high-dose dual therapy and investigated the influencing clinical factors. PATIENTS AND METHODS: We recruited 240/278 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 14 day high-dose dual therapy (esomeprazole 40 mg three times daily and amoxicillin 750 mg four times daily for 14 days; EA group) or 7 day non-bismuth quadruple therapy (esomeprazole 40 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily for 7 days; EACM group). Urea breath tests were followed up 8 weeks later. RESULTS: The eradication rates for the EA and EACM groups were 91.7% (95% CI = 85.3%-96.0%) and 86.7% (95% CI = 79.3%-92.2%) (P = 0.21) in ITT analysis; and 95.7% (95% CI = 90.2%-98.6%) and 92.0% (95% CI = 85.4%-96.3%) (P = 0.26) in PP analysis. The adverse event rates were 9.6% versus 23.0% in the two groups (P = 0.01). The H. pylori culture positivity rate was 91.8%. The antibiotic resistance rates were amoxicillin, 0%; clarithromycin, 14.6%; and metronidazole, 33.7%. CONCLUSIONS: A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy achieves a high eradication rate as first-line anti-H. pylori therapy, comparable to that with 7 day non-bismuth quadruple therapy but with fewer adverse events.