Validating the Baveno Elastography Criteria of Advanced Liver Fibrosis in Two-Dimensional Shear Wave Elastography: A Prospective Pathology-Based Study.

INTRODUCTION: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE. METHOD: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cutoff value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis. RESULTS: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0-63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cutoffs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively. CONCLUSION: This study establishes the compatibility of the Baveno dual cutoff criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

Advances in the Era of Direct-Acting Antivirals for Hepatitis C in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: In patients with unresectable hepatocellular carcinoma (HCC), the advances in direct-acting antiviral (DAA) therapy for chronic hepatitis C remain unclear. We aimed to investigate the characteristics of DAA therapy, when compared to interferon (IFN) therapy. METHODS: In this hospital-based study, all HCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received pegylated IFN or DAA, were retrospectively screened from 2009 to 2020. Patients without viremia, without HCC, or with HCC in BCLC stage 0, A, or D prior to antiviral therapy were excluded. Rates of and odds ratio (OR) for sustained virological response (SVR) achievement were analyzed. RESULTS: Nineteen and 78 patients were recruited into the IFN and DAA groups, respectively. The median age was significantly older in the DAA group (DAA vs. IFN: 69.5 [25-75% IQR: 62.8-77.3] vs. 64.0 [25-75% IQR: 61.0-68.0]; p < 0.05). The SVR rates were higher in the DAA group as per protocol (DAA vs. IFN: 94.5% vs. 76.5%; p < 0.05) and in BCLC stage B (DAA vs. IFN: 95.2% vs. 76.5%; p < 0.05). All patients in BCLC stage C received DAA therapy, with the SVR rate being 90.9%. In multivariable regression analysis, the 4-week virological response (OR 5.6, 95% CI: 1.3-25.4) and HCC within the up-to-7 criteria (OR 3.7, 95% CI: 1.1-12.9) were independent factors associated with SVR (all p < 0.05). CONCLUSIONS: Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

Distinct Physiological Characteristics of Isolated Laryngopharyngeal Reflux Symptoms.

BACKGROUND & AIMS: Patients with isolated laryngopharyngeal reflux symptoms (LPRS) defined as those without concomitant typical reflux symptoms (CTRS) are clinically challenging to manage due to unclear pathophysiology. We investigated esophageal physiology in patients with isolated LPRS and their response to proton-pump inhibitors (PPI) therapy. METHODS: This is a multi-center observational study conducted in referral hospitals in Taiwan. Patients with predominant LPRS, but without common non-reflux causes, underwent esophageal manometry, 24-hr ambulatory esophagopharyngeal pH testing, and Bernstein test, followed by a 12-week esomeprazole 40 mg twice-daily treatment. Participants with pathological reflux were divided into the isolated LPRS group (ie, LPRS without CTRS, n = 40) and the CTRS group (ie, LPRS with CTRS, n = 66). Participants without pathological reflux or esophagitis (n = 132) served as the nonreflux controls. RESULTS: The PPI-responsiveness was similar between the isolated LPRS group and CTRS group (63% vs 57%, P = .8), but lower in the nonreflux controls (32%, P = .005). Despite similar distal esophageal acid exposure time (P = .7) when compared to those with CTRS, the isolated LPRS group had a lower prevalence of both positive Bernstein test (P = .001) and ineffective esophageal motility disorder (P = .03), and fewer pharyngeal acid reflux episodes (P < .0001). CONCLUSIONS: Our findings indicate similar distal esophageal acid exposure and PPI-responsiveness between LPRS patients with and without CTRS. The lack of CTRS in the isolated LPRS group is likely due to esophageal acid hyposensitivity and fewer pharyngeal acid reflux episodes, thus implicating distinct pathophysiology of isolated LPRS from those with CTRS.

Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease: Either non-obese or obese Chinese population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese population. METHODS: Data collected from subjects registered at Taichung Veterans General Hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver (normal or NAFLD), and body mass index (BMI) levels (non-obese if BMI < 25 kg/m2 or obese if BMI ≥ 25 kg/m2). RESULTS: There were 745, 208, 770 and 285 patients enrolled in four groups labeled non-obese normal liver (group A), non-obese NAFLD (group B), obese normal liver (group C) and obese NAFLD (group D), respectively. The highest ratio of metabolic syndrome existed in the group B (26.9%), followed by group A (11.7%), group D (10.9%) and finally the group C (5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride (OR = 1.01; 95% CI: 1.01-1.02) and glucose (OR = 1.02; 95% CI: 1.01-1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride (OR = 1.01; 95% CI: 1.01-1.02). The positive association was most significant in all cases (adjusted OR = 2.41; 95% CI: 1.78-3.24), especially in non-obese individuals (OR = 2.81; 95% CI: 1.92-4.12). CONCLUSIONS: Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.

The association of non-alcoholic fatty liver disease and metabolic syndrome in a Chinese population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with features of metabolic syndrome. The aim of this study was to investigate the association between NAFLD and metabolic syndrome in a Chinese population. METHODS: Data from subjects were retrospectively collected from 2006 to 2009. The exclusion criteria included significant consumption of alcohol and chronic hepatitis B and C. The patients were assigned to two groups according to ultrasound findings: normal group and fatty liver group. The liver function of patients was determined by assessing serum alanine aminotransferase (ALT). Metabolic syndrome was diagnosed based on the 2005 International Diabetes Federation criteria. RESULTS: A total of 7568 subjects were enrolled and 5736 (75.8%) and 1832 (24.2%) patients were assigned to the normal and fatty liver groups, respectively. The fatty liver group had significant male predominance (69.7% vs 56.0%), higher body mass index (mean, 26.67 vs 23.55 kg/m2) compared with the normal group. There were 441 (7.7%) and 377 (20.6%) cases with metabolic syndrome in the normal and fatty liver groups, respectively, with significant difference (P=0.001), and the subgroup of 385 cases with fatty liver and elevated ALT had higher prevalence (28.8%) of metabolic syndrome. The strongest association of an individual component of metabolic syndrome with NAFLD was hyperlipidemia (adjusted OR=2.55, 95% CI: 2.22-2.94). CONCLUSION: The individuals with NAFLD had a higher ratio of metabolic syndrome. Hyperlipidemia had the strongest positive association with NAFLD.

Responder Definition of a Patient-Reported Outcome Instrument for Laryngopharyngeal Reflux Based on the US FDA Guidance.

BACKGROUND: Different end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms. OBJECTIVES: We aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance. METHODS: Patients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis. RESULTS: The mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (-11.0 ± 7.8 vs. -3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70. CONCLUSIONS: We propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.

Impact of Overlapping Functional Gastrointestinal Disorders on the Presentation and Quality of Life of Patients with Erosive Esophagitis and Nonerosive Reflux Disease.

OBJECTIVE: The aim of this study was to investigate the impact of overlapping functional gastrointestinal disorder (FGID) on the quality of life of patients with nonerosive reflux disease (NERD) and erosive esophagitis (EE). MATERIALS AND METHODS: Data from patients with NERD and EE were collected between January 2009 and March 2010. These cases were further stratified into the subgroups of overlapping NERD-functional dyspepsia (FD), NERD-irritable bowel syndrome (IBS), EE-FD, EE-IBS, and NERD or EE alone according to the symptoms. All patients completed the modified Chinese GERDQ and the SF-36 questionnaires. RESULTS: Of the 222 enrolled patients, 96 (43.2%) had NERD and 126 (56.8%) had EE. Overlap of FGID occurred in 43.8-45.8% of the NERD patients, and in 41.3-44.4% of EE cases. The impact of overlapping FGID on patient quality of life was greater in the patients with overlapping NERD-FD compared to those with NERD alone (mean SF-36 total scores 59 vs. 72, adjusted p = 0.025) and the cases with overlapping EE-FD compared to those with EE alone (mean SF-36 total scores 53.19 vs. 73.11, adjusted p = 0.047). There were no significant differences between the individuals with overlapping NERD/EE-IBS and those with NERD/EE alone. CONCLUSIONS: There was a high prevalence of overlapping FGID, with both FD and IBS, among the GERD patients. The individuals with overlapping GERD and FD had lower quality of life scores than those with GERD alone.

The impact of acid-suppressing drugs to the patients with chronic obstructive pulmonary disease: A nationwide, population-based, cohort study.

BACKGROUND: A high prevalence of gastroesophageal reflux disease symptoms has observed among chronic obstructive pulmonary disease (COPD) patients, and proton-pump inhibitors (PPIs) are the main medication in clinical practices. The aim of this study is to analyze the impact of PPIs to the risk of pneumonia in the cases with COPD. MATERIALS AND METHODS: This was a nationwide, population-based, cohort study using National Health Insurance Program in Taiwan. The enrolled cases were newly-diagnosed COPD, older than 30 years, between 2001 and 2005. Patients' prescriptions with PPIs and histamine receptor 2 antagonists (HR2As), >2 months, were identified. The appearance of pneumonia and mortality of these enrolled patients was recorded. Multivariate Cox's regression was used to examine the influence of acid-suppressing drugs to pneumonia on individuals with COPD. RESULTS: A total of 17,498 patients were included, of whom 109 (0.6%) and 526 (3%) cases had used PPIs and HR2As respectively. The risk of pneumonia existed when patients had used concurrent PPIs (adjusted hazard ratio [HR] = 1.76; 95% confidence interval [CI] = 1.33-2.34) or HR2As (adjusted HR = 1.25; 95% CI = 1.07-1.47). The positive association was lost in the cases over 70 years. The ratio of mortality also increased in those with PPIs or HR2As. CONCLUSION: Acid-suppressing drugs, especially PPIs, are attributed to more pneumonia happening in COPD patients compare with nonusers. The association was lost in elderly cases. Use acid-suppressing drugs should be careful about a higher possibility of pneumonia in younger individuals with COPD.

Characteristics of symptom presentation and risk factors in patients with erosive esophagitis and nonerosive reflux disease.

OBJECTIVE: The aim of this study was to investigate the effect of gender on symptom presentation and quality of life of patients with erosive esophagitis (EE) and nonerosive reflux disorder (NERD). SUBJECTS AND METHODS: Medical records from patients with gastroesophageal reflux disease (GERD) between January and December 2009 were reviewed. The patients were assigned to either the EE or the NERD group. The general demographic data, the modified Chinese GERDQ scores and the Short Form (SF)-36 life quality questionnaire scores of the two groups of patients were compared. RESULTS: Of the 261 patients, 87 (33.3%), 86 (33.0%) and 88 (33.7%) patients were classified into the EE, the NERD and the control groups, respectively. The patients in the EE group were significantly older (48.94 ± 17.38 vs. 43.34 ± 12.67 years), were predominately male (58.6 vs. 39.5%), had more frequently hiatal hernia (34.5 vs 17.4%), had a higher body weight (67.57 ± 15.13 vs. 61.06 ± 11.08 kg) and a higher body mass index (24.09 ± 4.61 vs. 22.68 ± 3.12) than those in the NERD group. The GERD-specific symptom scores and the general life quality scores of the EE and the NERD groups were similar, and both groups had lower life quality scores than the control group did. The female patients with NERD had a higher frequency of GERD symptoms and lower quality of life scores. Gender had no effect on symptom scores or life quality scores in the EE group. CONCLUSION: The GERD-specific symptom severity and general quality of life scores of the EE and the NERD patients were similar. Gender had a great influence on symptom presentation and quality of life in patients with NERD, but not in those with EE.

A Real-World Experience on a Chinese Population of Patients With Unresectable Hepatocellular Carcinoma Treated With Nivolumab.

Background: For unresectable hepatocellular carcinoma (HCC), nivolumab (anti-programmed death receptor-1 (PD-1)) is used as non-curative interventions. The aim of the study was to focus on the real-world experience of nivolumab applied to patients with HCC. Methods: Unresectable HCC patients receiving nivolumab treatments at Taichung Veterans General Hospital, from June 2018 to May 2020, were recruited. Exclusion criteria were Child-Pugh stage C, poor performance status, a lack of compliance or intolerable to drug treatments. The tumor radiological responses and survival outcomes of enrolled patients were collected and analyzed. Results: Among a total of 57 patients, most of them were classified as Child-Pugh stage A (70.2%) and Barcelona Clinic Liver Cancer (BCLC) stage C (66.7%). Nivolumab was given to 14 (24.6%) as the primary-line, and 43 patients (75.4%) as the secondary-line systemic treatments. The mean therapeutic duration was 6.5 months. Objective response rate (ORR) was 24.6%, and disease control rate (DCR) was 42.1%. The overall median progression-free survival (PFS) was 5.8 months (95% confidence interval (CI): 1.1 - 10.6), and overall survival (OS) was 11.5 months (95% CI: 4.3 - 17.8). Immune-related adverse event (IRAE) was 8.8%. Presence of alpha-fetoprotein (AFP) response (a decline in AFP ≥ 10% from baseline) during therapy predicted the tumor radiological response (to objective response: hazard ratio (HR): 4.89, 95% CI: 1.14 - 21.00; to disease control: HR: 4.71, 95% CI: 1.32 - 16.81). Those with tumor radiological responses showed longer PFS and OS. Conclusions: Decline in AFP during therapy has a predicting role on HCC radiological responses to nivolumab. Achieving radiological responses had better survival outcomes.

The Impact of Sequential Therapies after First-Line Systemic Therapies in Unresectable Hepatocellular Carcinoma.

Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p = 0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC.

Hepatitis Flares or Hepatic Decompensation after Discontinuation of Tenofovir Disoproxil Fumarate and Entecavir in Non-Cirrhotic Hepatitis B e Antigen-Negative Patients.

Hepatic events can occur after discontinuing antiviral therapy. We investigated factors associated with hepatitis flares and hepatic decompensation after discontinuing tenofovir disoproxil fumarate (TDF) and entecavir (ETV). Hepatitis flares within 6 months and hepatic decompensation were compared between non-cirrhotic hepatitis B e antigen-negative patients after discontinuing TDF or ETV by using the Cox proportional hazard model. The cumulative rates of hepatitis flare at 6 months after discontinuing ETV and TDF were 2% and 19%, respectively (p < 0.001). The respective rates of hepatic decompensation at 6 months were 0% and 7% (p = 0.009). Higher alanine aminotransferase (ALT) (AASLD criteria) at the end of treatment (EOT) (HR = 4.93; p = 0.001), an off-therapy dynamic change in HBV DNA (rapid rebound of HBV DNA from the nadir, ≥1 log10 IU/mL per month) (HR = 10.7; p < 0.001), and the discontinuation of TDF (HR = 6.44; p = 0.006) were independently associated with hepatitis flares within 6 months. Older age (HR = 1.06; p < 0.001) and an off-therapy dynamic change in HBV DNA (HR = 3.26; p = 0.028) were independently associated with hepatic decompensation after the discontinuation of antiviral therapy. In summary, we demonstrated several factors associated with hepatitis flares and hepatic decompensation after discontinuing antiviral therapy in non-cirrhotic hepatitis B e antigen-negative patients.

The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08-5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.

Direct-Acting Antiviral Therapy for Hepatitis C Virus in Patients with BCLC Stage B/C Hepatocellular Carcinoma.

BACKGROUND: The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. METHODS: In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to March 2021 were retrospectively screened, with 97 patients who had completed direct-acting antiviral (DAA) therapy being enrolled for final analysis. RESULTS: In total, the sustained virological response (SVR) rate was 90.7%. In logistic regression analysis, progressive disease (PD) to prior tumor treatments was significantly associated with SVR failure (odds ratio 5.59, 95% CI 1.30-24.06, p = 0.021). Furthermore, the overall survival (OS) rate was significantly higher in the SVR group than that in the non-SVR group (1-year OS: 87.5% vs. 57.1%, p = 0.001). SVR was found to be an independent factor related to OS (hazard ratio 8.42, 95% CI 2.93-24.19, p = 0.001). However, even upon achieving SVR, the OS rates in BCLC stage C or Child-Pugh stage B patients remained poor. CONCLUSIONS: In BCLC stage B/C HCC, DAA could achieve a high SVR rate except in those patients with PD to prior HCC treatments. SVR was related to improvements in OS; therefore, DAA therapy should be encouraged for patients diagnosed without a short life expectancy.

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population.

AIM: Currently, atezolizumab combined with bevacizumab is the standard first-line treatment for unresectable hepatocellular carcinoma (HCC), but lenvatinib or sorafenib are still recommended for these patients for some reasons. The aim of the study was to determine the outcomes of Taiwanese patients with advanced-stage HCC who received lenvatinib or sorafenib. METHODS: Data on patients with BCLC stage C HCC who were receiving lenvatinib or sorafenib as the first-line therapy from May 2018 to August 2020 was collected. The individuals with lenvatinib and sorafenib were propensity score-matched at a ratio of 1:2. RESULTS: A total of 22 patients with lenvatinib and 44 patients with sorafenib were enrolled. The ORR (36.4% vs. 11.4%, p = 0.023) and DCR (81.9% vs. 56.9%, p = 0.039) were both higher in the lenvatinib group compared with the sorafenib group. The median overall survival (OS) of the lenvatinib group and the sorafenib group was 9.36 months and 8.36 months, respectively. The best median OS was detected in patients receiving lenvatinib and having an objective tumor response (11.29 months), with a significant difference (p = 0.031) compared with the other groups. CONCLUSION: Lenvatinib, compared to sorafenib, had better ORR and DCR, but similar OS, in Taiwanese patients with advanced-stage HCC. The patients with an objective tumor response had a better OS.

The Combining of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors as First-Line Treatment for Advanced Stage Hepatocellular Carcinoma.

AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers. Tyrosine kinase inhibitors (TKIs), including sorafenib (SOR) and lenvatinib (LEN), as well as immune checkpoint inhibitors (ICIs), including nivolumab (NIVO) and pembrolizumab (PEMBRO), have been approved for the treatment of advanced HCC. The aim of the study is to determine whether advanced-stage HCC patients should receive a combination of TKI and ICI as first-line therapy. METHODS: Data for subjects with BCLC stage C HCC, who were receiving combining TKI and ICI as first-line therapy at Taichung Veterans General Hospital from April 2019 to July 2021, were evaluated. The general and therapeutic outcome data were collected and analyzed. RESULTS: A total of 33 patients were enrolled (8 SOR/NIVO, 4 SOR/PEMBRO, 11 LEN/NIVO, and 10 LEN/PEMBRO). All cases belonged to Child-Pugh class A. The objective response rate was 48.5%, and disease control rate was 72.7%. The average progression-free survival (PFS) and overall survival (OS) of all patients was 9.2 and 17.0 months, respectively. The use of PEMBRO, when compared with NIVO, had a significantly positive impact towards achieving an objective response, defined as either complete response or partial response (OR 5.54, p = 0.045). PFS and OS between the different TKIs or ICIs had no differences. The most adverse event was fatigue (36.4%), and most cases were mild and manageable. CONCLUSION: Combining TKI and ICI provides an acceptable antitumor efficacy in first-line therapy for advanced-stage HCC patients. The survival outcomes between different TKIs or ICIs display no differences.

Clinical values of Barcelona Clinic Liver Cancer subgroup and up-to-7 criteria in intermediate stage hepatocellular carcinoma with transcatheter arterial chemoembolization.

BACKGROUND: Transarterial chemoembolization (TACE) is a recommended treatment for patients with intermediate stage hepatocellular carcinoma (HCC) but with variable treatment outcomes. AIM: To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC. METHODS: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. Patients were assigned to either the objective responder (OR) group or the non-OR group according to mRECIST criteria. Clinical and radiological characteristics were compared between the 2 groups. The overall survival of enrolled subjects was analyzed. RESULTS: In 128 enrolled patients, 66 (51.6%) were in the OR group and 62 (48.4%) in the non-OR group. Compared with the non-OR group, the OR group had a significantly smaller HCC size (6.55 cm vs 9.50 cm, P = 0.001) and was within the up-to-7 criteria (50% vs 26.7%, P = 0.001). After multivariable analyses, these significant associations still existed. Overall survival rate of all the subjects averaged 20.65 ± 13.26 mo. The survival rate at 1-year was 64.8%, 2-year was 46.9%, and 3-year was 31.2%. For those patients with OR to TACE, smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival. Those patients with subgroup B1 had the highest OR ratio (75%) and better overall survival (26.70 ± 12.07 mo) after TACE. CONCLUSION: BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE. BCLC stage B subgroup is useful to predict refractoriness to TACE.

Safety of Nonagenarians Receiving Therapeutic ERCP, Single Center Experience.

(1) Background: The complication rates for nonagenarians receiving therapeutic endoscopic retrograde cholangiopancreatography (ERCP) remain poorly understood. We aimed to determine whether nonagenarians were at an increased risk of ERCP-related complications. (2) Methods: We performed a retrospective study on therapeutic ERCP in nonagenarians from 2011 to 2016 at Taichung Veterans General Hospital. A control group comprising patients aged 65 to 89 years was used to compare demographic data and the outcomes of therapeutic ERCP with the nonagenarians. The risk factors for complications were determined by logistic regression model. (3) Results: There were 35 nonagenarians and 111 patients in the control group. Overall, complication rates were not statistically different between the two groups. However, advanced age was an independent predictor of complications in the multivariate analysis (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.01-1.12; p = 0.049). End stage renal disease (ESRD) was another independent predictor of complications (OR = 4.87; 95% CI = 1.11-21.36; p = 0.036). Post-ERCP pancreatitis and bleeding were more common in ESRD patients than patients without ESRD. (4) Conclusions: Although nonagenarians receiving ERCP did not have more complications compared to elderly patients younger than 90 years, advanced age and comorbidity still affect the outcome of therapeutic ERCP in the elderly patients.

Prevalence of non-Alcoholic Fatty Liver Disease and Associated Factors in Patients with Moderate or Severe Hemophilia: A Multicenter-Based Study.

INTRODUCTION: Liver health is essential for persons with hemophilia (PWH) in order to maintain access to new therapies, such as gene therapy. Non-alcoholic fatty liver disease (NAFLD) is seldom reported in the hemophilia population. The study aimed to investigate the prevalence of NAFLD and associated factors in PWH. METHODS: Data of this cross-sectional study were obtained from a multicenter collaborative registry database. RESULTS: A total of 163 moderate or severe PWH with a complete data of liver examination were analyzed. There were 77 (47.2%) PWH diagnosed with NAFLD. The multivariate analysis showed that overweight/obesity was associated with NAFLD (OR, 4.31, P < .001). In comparison with hemophilia B patients, hemophilia A patients showed a weaker correlation with NAFLD, (OR, 0.30, P = .009). A total of 17 (25.8%) PWH with NAFLD had an elevated level of alanine transaminase (ALT). Both overweight/obesity and presence of inhibitor to clotting factor were independently associated with elevated ALT in PWH with NAFLD. CONCLUSIONS: The study indicated that a high prevalence of NAFLD existed in the hemophilia population. Overweight/obesity was an independent factor for NAFLD and elevated ALT.

Impact of Overlapping Functional Gastrointestinal Disorders on the Quality of Life in Patients With Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) and functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome and functional dyspepsia, are common afflictions within the general population. Both conditions have a considerable impact on the daily health related quality of life (HRQoL) of affected individuals. Risk factors surrounding any impaired HRQoL in patients with GERD involve those of younger age, obesity, an increase in reflux symptom frequency, and overlapping FGIDs. The risk factors for subjects experiencing an overlap in FGIDs and GERD involve those who are female, younger age, cigarette smoking, non-erosive reflux disease, more GERD symptoms, and psychological performances including anxiety, somatization, and more frequent healthcareseeking behavior. The overlap of GERD and FGIDs is associated with a worsening of both physical and mental health, an increase in bothersome symptoms, impaired functional capacity, and a higher likelihood of consulting a physician. Acid secretion suppressors could offer therapeutic efficacy to some patients experiencing overlapping GERD and FGIDs.