Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS: From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS: The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION: The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).

Similarities and differences between IBS-C and FC with regards to symptomatology, sleep quality and psychological attributes.

BACKGROUND: Irritable bowel syndrome (IBS) and functional constipation (FC) are highly prevalent in the general population and have significant symptom overlap, while the clinical associations and psychological links between IBS and FC remains poorly understood. We aimed to compare the clinical, metabolic and psychological factors between patients with FC patients and constipation predominated IBS. METHODS: We consecutively enrolled 360 patients from the outpatient clinics of Hualien Tzu Chi medical center. Constipation-predominant IBS (IBS-C) and FC were diagnosed based on Rome III criteria. All participants completed the Pittsburg Sleep Quality Index (PSQI) score, the State Trait Anxiety Inventory (STAI) score and the Taiwanese Depression Questionnaire (TDQ) score. RESULTS: Fifty-four patients had FC and twenty-three patients had IBS-C. Compared to asymptomatic controls, FC/IBS-C groups had female predominance (p < 0.001), FC as well as more GI discomforts and inferior psychosocial characteristics (p < 0.05). Compared to FC, IBS-C had higher severity scores of abdominal distention (4.52 ± 1.90 vs. 3.07 ± 1.88) and heartburn (2.17 ± 1.50 vs. 1.46 ± 1.14). However, FC was independently associated with poor sleep quality [adjusted OR: 1.19 (1.08-1.31), p < 0.001] and IBS-C with depression [adjusted OR: 1.07 (1.02-1.12), p = 0.005]. CONCLUSION: Patients with FC and IBS-C shared many similar GI complaints and psychosocial characteristics, however IBS-C had more severe bloating, heartburn and depression and FC had worse sleeping quality.

Hepatitis C virus genotypes 1-3 infections regulate lipogenic signaling and suppress cholesterol biosynthesis in hepatocytes.

BACKGROUND: Patients with different hepatitis C virus (HCV) genotype infections are associated with varying metabolic disorders. Although alteration of lipid metabolism has been confirmed as a virus-induced metabolic derangement in chronic hepatitis C patients, the impact of various HCV genotypes on hepatic cholesterol metabolism remains elusive. In this study, we thus investigated the HCV genotype-specific lipogenic and cholesterol metabolism profiles in an in vitro cell culture system. METHODS: We first conducted HCV cell culture system (HCVcc) assays by infecting Huh7.5.1 cells with multiple infection-competent HCV strains, including the genotype 2a JFH1 and JFH1-based intergenotypic recombinants 1b and 3a. We then examined the expression levels of various lipid and cholesterol-related genes. RESULTS: The data showed that infection with individual HCV genotypes exerted unique gene expression regulatory effects on lipoproteins and cholesterol metabolism genes. Of note, all HCV strains suppressed cholesterol biosynthesis in hepatocytes through downregulating the expression of HMG-CoA reductase (HMGCR) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - two essential enzymes for cholesterol biosynthesis. These HCV-mediated inhibitory effects could be reversed by treatment with sofosbuvir, a pangenotypic NS5B inhibitor. In addition, overexpression of HCV genotype 1b, 2a or 3a core protein significantly suppressed HMGCR mRNA transcription and translation, thus diminished cellular cholesterol biosynthesis. Nonetheless, the core protein had no effect on FDFT1 expression. CONCLUSION: Although HCV infection regulates host lipid metabolism in a genotype-specific manner, its inhibition on hepatocellular cholesterogenic gene expression and total cholesterol biosynthesis is a common effect among HCV genotype 1b, 2a and 3a.

Clinical and psychological characteristics in gastroesophageal reflux disease patients overlapping with laryngopharyngeal reflux symptoms.

BACKGROUND AND AIM: Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms. METHODS: This study enrolled 303 consecutive patients with proton pump inhibitor treatment-naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non-dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances. RESULTS: There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms. CONCLUSIONS: Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms.

Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity.

BACKGROUND/AIMS: We aimed to investigate gastrointestinal symptoms, clinical characteristics, and psychological factors in subjects with and without sleep disturbance (SD) in a health screening cohort. METHODS: We enrolled 2,752 consecutive subjects during their health checkups. All participants underwent an evaluation with questionnaires. Demographic characteristics and biochemical data were recorded. SD was confirmed when Pittsburgh Sleep Quality Index score was greater than 5. RESULTS: Among the study population (n = 2,674), 956 (36%) individuals had SD. SD was associated with female gender, older age, lower level of education, higher systolic blood pressure, higher serum high-density lipoprotein levels and higher prevalence of functional dyspepsia and irritable bowel syndrome (IBS). SD subjects also had more depression, more anxiety, more severe gastrointestinal reflux disease symptoms and higher prevalence of non-erosive reflux disease (NERD; p < 0.001). SD was -independently associated with female gender (OR 1.75, p < 0.001), older age (OR 1.03, p < 0.001), NERD (OR 1.88, p = 0.004), IBS (OR 1.51, p = 0.043), and depression (OR 1.16, p < 0.001) by multivariate analysis. CONCLUSIONS: Future studies will be needed to clarify the interrelationships among SD, psychological stress, and functional gastrointestinal disorders.

Pegylated IFN-α suppresses hepatitis C virus by promoting the DAPK-mTOR pathway.

Death-associated protein kinase (DAPK) has been found to be induced by IFN, but its antiviral activity remains elusive. Therefore, we investigated whether DAPK plays a role in the pegylated IFN-α (peg-IFN-α)-induced antiviral activity against hepatitis C virus (HCV) replication. Primary human hepatocytes, Huh-7, and infectious HCV cell culture were used to study the relationship between peg-IFN-α and the DAPK-mammalian target of rapamycin (mTOR) pathways. The activation of DAPK and signaling pathways were determined using immunoblotting. By silencing DAPK and mTOR, we further assessed the role of DAPK and mTOR in the peg-IFN-α-induced suppression of HCV replication. Peg-IFN-α up-regulated the expression of DAPK and mTOR, which was associated with the suppression of HCV replication. Overexpression of DAPK enhanced mTOR expression and then inhibited HCV replication. In addition, knockdown of DAPK reduced the expression of mTOR in peg-IFN-α-treated cells, whereas silencing of mTOR had no effect on DAPK expression, suggesting mTOR may be a downstream effector of DAPK. More importantly, knockdown of DAPK or mTOR significantly mitigated the inhibitory effects of peg-IFN-α on HCV replication. In conclusion, our data suggest that the DAPK-mTOR pathway is critical for anti-HCV effects of peg-IFN-α.

Association of coffee consumption and liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B: A 5-year population-based cohort study.

BACKGROUND/PURPOSE: Although coffee consumption has been associated with decreased risk of liver fibrosis progression, cirrhosis or hepatocellular carcinoma in patients with HCV infection or fatty liver diseases, its effect on hepatitis B patients remains unclear. We aimed to examine the effect of coffee consumption on liver fibrosis progression and cirrhosis-related complications in patients with chronic HBV infection. METHODS: Coffee consumption was assessed in 2604 participants who were previously recruited from a population-based GERD survey. The primary endpoints of this study were the impact of coffee consumption on the development of cirrhosis-related complications, including liver cirrhosis, esophageal varices, or hepatocellular carcinoma at the end of 5-year follow-up. The secondary endpoints were the declines of serum predicting indices of liver fibrosis (AST/ALT, APRI, FIB-4, Hui score) or liver function tests (AST, ALT). RESULTS: 328 patients with chronic HBV infection were enrolled into this study. At baseline, coffee consumption was associated with higher education level, more frequent tobacco use and normal blood pressure (p < 0.05 for all). Patients with higher coffee consumption had a significant lower serum AST, APRI and FIB-4 index value than non-coffee drinkers [adjusted HR 0.30, 95% CI(0.11-0.82) for AST; 0.30, 95% CI (0.11-0.84) for APRI; 0.30, 95% CI (0.13-0.69) for FIB-4]. However, higher coffee consumption didn't change serum AST levels, APRI, FIB-4 index values or incidences of cirrhosis-related complications at the end of 5-year follow-up. CONCLUSION: Coffee consumption was not associated with fibrosis progression or HCC risk in chronic hepatitis B patients over the 5-year observation period.

Impact of concomitant dyspepsia and irritable bowel syndrome on symptom burden in patients with gastroesophageal reflux disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) frequently report symptoms like dyspepsia or/and irritable bowel syndrome (IBS). The aim of the study was to investigate the impact of symptom overlap on GERD symptom burden. We also investigate whether GERD overlapping dyspepsia or/and IBS would have different clinical and psychological features as compared with GERD alone. METHODS: A total of 2752 subjects were screened from a health check-up population. We compared the clinical and psychological factors among subjects with GERD alone and with overlap of two or all three diseases. All participants underwent an evaluation with questionnaires including Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory before receiving endoscopic exam. RESULTS: Among the GERD population, we identified 26 with IBS (GERD-IBS), 60 with dyspepsia (GERD-D), and 25 subjects with overlap of all three conditions (GERD-D-IBS). GERD-D and GERD-D-IBS subjects had more severe GERD symptoms as compared subjects with GERD alone (p < 0.001). Subjects with overlapping dyspepsia or/and IBS showed a significant increase in the severity of depression and poorer sleep quality than subjects with GERD alone. Notably, anxiety scores did not differ significantly between subjects with overlapping diseases and GERD alone. CONCLUSION: Our study demonstrates that disease overlap in GERD population is associated with greater symptom burden, higher depression and poorer sleep quality, but not with anxiety. This study highlights the importance of identifying overlapping conditions as a therapeutic strategy for better management of GERD.

Overlap of Dyspepsia in Patients with Gastroesophageal Reflux Disease: Impact of Clinical, Metabolic, and Psychosocial Characteristics.

BACKGROUND: Gastroesophageal reflux disease (GERD) and dyspepsia are highly prevalent in the general population with significant symptom overlap, while the interaction between both remains poorly understood. AIM: To examine whether GERD overlapping dyspepsia would have an impact on clinical and psychological features as compared with GERD alone. METHODS: We performed a cross-sectional study in a GERD cohort (n = 868) that was previously recruited from a population-based GERD survey (n = 2752). We compared the clinical and psychological factors between patients with and without dyspeptic symptoms "epigastric pain or burning." All participants were evaluated with Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index score, Taiwanese Depression Questionnaire score, and State-Trait Anxiety Inventory score. Endoscopic findings were classified according to the Los Angeles classification. RESULTS: Among the GERD population, 107 subjects had overlapping "epigastric pain or burning" (GERD-D), and 761 did not have these symptoms (GERD alone). GERD-D subjects had more severe GERD symptoms and were more often associated with irritable bowel syndrome (IBS) (OR 3.54, 95% CI 1.92-6.52) as compared subjects with GERD alone. In addition, GERD-D subjects had lower quality of sleep (OR 1.11, 95% CI 1.01-1.21), higher depression (OR 1.06, 95% CI 1.02-1.10), lower blood pressure (OR 0.45, 95% CI 0.22-0.95), and higher serum total cholesterol levels (OR 2.78, 95% CI 1.36-5.67) than GERD alone. CONCLUSIONS: GERD-D subjects are characterized with worsening clinical symptoms as well as higher psychosocial, IBS, and metabolic comorbidities, but less erosive esophagitis. Our results indicate that clinical awareness of such overlapping condition would help optimize the management of GERD in clinical practice.

Clinical characteristics and psychosocial impact of different reflux time in gastroesophageal reflux disease patients.

BACKGROUND/PURPOSE: Gastroesophageal reflux disease (GERD) is an emerging disease, and can impair quality of life and sleep. This study aimed to investigate whether GERD patients with different timings of reflux symptoms have different clinical characteristics. METHODS: This study prospectively enrolled individuals who underwent upper gastrointestinal endoscopy during a health checkup. Each participant completed all questionnaires including Reflux Disease Questionnaire, Nighttime GERD questionnaire, Pittsburg Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory. Combined reflux was defined as the timing of reflux symptoms occurring at both daytime and nighttime. RESULTS: A total of 2604 participants were enrolled. Of them, 651 symptomatic GERD patients, according to the Reflux Disease Questionnaire score, were recruited for final analysis. Of them, 224 (34.4%) had erosive esophagitis on endoscopy. According to the timing of reflux symptoms, 184 (28.3%) were assigned to the daytime reflux group, 71 (10.9%) to the nighttime reflux group, and 396 (60.8%) to the combined reflux group. In post hoc analysis, the combined reflux group had a significantly higher Reflux Disease Questionnaire score than the daytime reflux group (p < 0.0001). Combined and nighttime reflux groups had higher body mass index and longer duration (> 12 years) of education than the daytime reflux group (p < 0.05). There was no difference in Pittsburg Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory scores among three groups. CONCLUSION: GERD patients with combined daytime and nighttime reflux of have more troublesome symptoms than those with daytime reflux. GERD patients with different timings of reflux symptoms have different clinical characteristics in terms of body mass index and duration of education, but not in terms of esophageal inflammation, quality of sleep, and psychosocial status.

Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection.

The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3' untranslated region (UTR), leading to the activation of IKK-α and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3'UTR interacts with DDX3X and IKK-α, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-α, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-α, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3'UTR, activating IKK-α and cellular lipogenesis to facilitate viral assembly (Q. Li et al., Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). Here, we report associations of DDX3X with various cellular compartments and viral elements that mediate its multiple functions in the HCV life cycle. Upon infection, the HCV 3'UTR redistributes DDX3X and IKK-α to speckle-like cytoplasmic structures shown to be SGs. Subsequently, interactions between DDX3X, SG, and HCV proteins facilitate the translocation of DDX3X-SG complexes to the LD surface. HCV nonstructural proteins are shown to colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the HCV replication complex and assembly site at the LD surface. Our data demonstrate that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV elements, IKK-α, SGs, and LDs for its critical role in HCV infection.

Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host dependencies yields novel insights into viral infection, pathogenesis and potential therapeutic targets.

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy.

Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day(-1), mean ± SD) but lower daily viral production rate (P = 10(6)-10(12)) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients.

A pilot study of add-on oral hypoglycemic agents in treatment-naïve genotype-1 chronic hepatitis C patients receiving peginterferon alfa-2b plus ribavirin.

BACKGROUND/PURPOSE: Insulin resistance (IR) affects sustained virological response (SVR) to peginterferon alfa plus ribavirin (PR) in patients with chronic hepatitis C (CHC). Whether add-on oral hypoglycemic agents (OHAs) to PR improve SVR remains unclear; therefore, we conducted a prospective, randomized pilot trial on 23 consecutive patients with genotype 1 CHC and IR in Taiwan. METHODS: Patients were randomized to receive acarbose (Arm A; n = 7) or metformin (Arm B; n = 6) or pioglitazone (Arm C; n = 5) in addition to peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (1000-1200 mg/day) or just PR (Arm D; n = 5). The primary end point was SVR, and secondary end points were viral clearance at Weeks 17, 29, and 53. There were no differences among all arms at baseline. RESULTS: Using intent-to-treat analysis, SVR was observed in 66.7% (4/6), 83.3% (5/6), 66.7% (4/6), and 60% (3/5) in Arms A, B, C, and D, respectively. SVR was higher in female patients receiving OHA [90% (9/10)] than in male patients [50% (4/8)]. Results of per protocol analysis showed that SVR was 80.0% (4/5) in Arm A, 100% (5/5) in Arm B, 66.7% (4/6) in Arm C, and 60% (3/5) in Arm D. Patients receiving OHA had a higher rapid virologic response: 11/18 (61%) versus 2/5 (40%). Complete early virologic response was comparable between patients receiving OHA and PR [15/18 (83%) vs. 4/5 (80%)]. CONCLUSION: Our preliminary data show add-on OHAs to PR might achieve better early viral kinetics and SVR. However, further larger studies are needed to confirm these findings.

Factors affecting the diagnostic accuracy of ultrasonography in assessing the severity of hepatic steatosis.

BACKGROUND/PURPOSE: Ultrasonography has long been recognized as a useful tool for detecting hepatic steatosis in clinical practice. However, whether it can assess the severity of hepatic steatosis and which factors affect its diagnostic accuracy remain unclear. METHODS: A total of 171 patients with various causes of hepatitis undergoing liver biopsies were retrospectively reviewed. The clinical, serologic data and ultrasonographical findings were recorded. Hepatic steatosis was graded as negative, mild, moderate, or severe by ultrasonography and histology. Histology was used as gold standard and the agreement rates were calculated. RESULTS: Our data showed that the agreement rate of ultrasonography was 61.4% in assessing the severity of hepatic steatosis and 74.3% in diagnosing hepatic steatosis compared with histology (crude kappa=0.46 vs. 0.46). Using univariate analyses, body mass index and histology activity index score were associated with the agreement in assessing the severity of hepatic steatosis (p=0.008 and 0.035), whereas Ishak fibrosis score had a trend association (p=0.066). Multivariate analyses indicated that age, body mass index, and Ishak fibrosis score could affect the agreement (odds ratio=0.72, 0.89, and 1.41; 95% confidence interval=0.54-0.97, 0.83-0.97, and 1.1-1.8). CONCLUSION: Ultrasonography could assess the severity of hepatic steatosis with moderate accuracy. Obese patients are difficult ultrasonographically. In addition, age and hepatic fibrosis could affect the performance of ultrasonography in assessing the severity of hepatic steatosis.

Efficacy and Safety of Sorafenib or Lenvatinib for Advanced Hepatocellular Carcinoma after Failure of First-Line Atezolizumab Plus Bevacizumab: A Systematic Review and Meta-Analysis.

BACKGROUND: Although atezolizumab plus bevacizumab (hereinafter, atezolizumab-bevacizumab) is the standard first-line treatment for patients with advanced HCC, the optimal second-line regimen remains unknown. This study evaluated the efficacy and safety of sorafenib and lenvatinib in patients with advanced HCC that progressed under atezolizumab-bevacizumab treatment. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase, and the Cochrane Library for articles published before November 2023. Random-effects meta-analysis was performed to determine the pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), comparing patients who received sorafenib versus lenvatinib. RESULTS: Seven studies involving 387 patients were included. The pooled ORR, DCR, OS, and PFS for sorafenib and lenvatinib together were 26% (95% CI: 14-43%), 63% (95% CI: 47-77%), 11.45 months (95% CI: 7.12-15.77, I2 = 92%, p < 0.01), and 3.78 months (95% CI: 2.34-5.23, I2 = 67%, p = 0.02), respectively. Although lenvatinib users had a longer median OS (12.42 vs. 10.75 months) and PFS (5.15 vs. 2.58 months) than sorafenib users, the pooled ORR, DCR, median OS, and PFS for these medications were comparable. Additionally, the distributions of all-grade and grade ≥ 3 adverse events for sorafenib and lenvatinib were comparable to those for these two medications when used as first-line therapies. CONCLUSIONS: Sorafenib or lenvatinib can provide effective treatment with manageable toxicity in patients with advanced HCC after disease progression under atezolizumab-bevacizumab.

Impact of Low Muscle Mass on Hepatocellular Carcinoma Patients Undergoing Transcatheter Liver-Directed Therapies: Systematic Review & Meta-Analysis.

BACKGROUND AND AIM: Transcatheter liver-directed intra-arterial therapies are mainstream treatment options for intermediate-stage hepatocellular carcinoma (HCC). However, the effect of low skeletal muscle mass (LSMM) on overall survival (OS) in these patients remains uncertain. We aimed to ascertain the prevalence and prognostic effect of LSMM in this population. METHOD: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search was performed in the PubMed and Embase databases until Oct 2023. Random-effects meta-analysis was performed to determine the pooled prevalence of LSMM and calculate the hazard ratio (HR) for OS with a 95% confidence interval (CI) in patients with intermediate-stage HCC undergoing various transarterial therapies, comparing those with and without LSMM. RESULTS: Twelve studies involving 2450 patients were included. The pooled prevalence of LSMM was 46% (95% CI, 38-55%), and the results were consistent across different treatments, regions, and age subgroups. The meta-analysis indicated that LSMM was significantly associated with decreased OS (HR, 1.78; 95% CI, 1.36-2.33; I2, 75%). Subgroup analyses reassured the main findings across various therapies, including transarterial chemoembolization (TACE) (HR, 1.68; 95% CI, 1.23-2.30; I2, 81%), transarterial embolization (TAE) (HR, 2.45; 95% CI, 1.42-4.22; I2, 0%), and transarterial radioembolization (TARE) (HR, 1.94; 95% CI, 1.01-3.73; I2, 0%). CONCLUSIONS: In intermediate-stage HCC, LSMM is common and associated with reduced OS. To achieve an optimal prognosis, clinicians should incorporate routine LSMM measurement into practice, while caring for patients with intermediate-stage HCC, irrespective of TACE, TAE, and TARE.

Characterization of esophageal pressure-flow abnormalities in patients with non-obstructive dysphagia and normal manometry findings.

BACKGROUND AND AIM: Patients with non-obstructive dysphagia (NOD) report symptoms of impaired esophageal bolus transit without evidence of bolus stasis. In such patients, manometric investigation may diagnose esophageal motility disorders; however, many have normal motor patterns. We hypothesized that patients with NOD would demonstrate evidence of high flow-resistance during bolus passage which in turn would relate to the reporting of bolus hold up perception. METHODS: Esophageal pressure-impedance recordings of 5 mL liquid and viscous swallows from 18 NOD patients (11 male; 19-71 years) and 17 control subjects (9 male; 25-60 years) were analyzed. The relationship between intrabolus pressure and bolus flow timing in the esophagus was assessed using the pressure flow index (PFI). Bolus perception was assessed swallow by swallow using standardized descriptors. RESULTS: NOD patients were characterized by a higher PFI than controls. The PFI defined a pressure-flow abnormality in all patients who appeared normal based on the assessment esophageal motor patterns and bolus clearance. The PFI was higher for individual swallows during which subjects reported perception of bolus passage. CONCLUSION: Bolus flow-resistance is higher in NOD patients compared with controls as well as higher in relation to perception of bolus transit, suggesting the presence of an esophageal motility disorder despite normal findings on conventional analysis.

Viral load and alanine aminotransferase correlate with serologic response in chronic hepatitis B patients treated with entecavir.

BACKGROUND AND AIM: Although entecavir has been shown to have good efficacy and low resistance for the treatment of chronic hepatitis B (CHB), factors associated with a favorable response remain unknown. METHODS: This was a retrospective, multicenter study of 248 treatment-naïve hepatitis B e antigen (HBeAg)-positive patients (69.4% male; median age, 39.4 years) treated with entecavir for more than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints were HBeAg loss and/or seroconversion. RESULTS: The median baseline levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA were 201 U/L (range, 27-2415 U/L) and 7.6 log(10) IU/mL (range, 2.2-13.18), respectively. The median treatment period was 25.3 months (range, 12-69.6). The rates of ALT normalization at years 1, 2, and 3 were 83.1%, 87.9%, and 94.9%, respectively. The cumulative rates of HBeAg loss at years 1, 2, and 3 were 20.3%, 38.0%, and 48.9%, respectively. The rates of undetectable HBV-DNA at years 1, 2, and 3 were 52.1%, 78.9%, and 82.5%, respectively. Using Cox proportional hazards model, multivariate analysis showed that baseline ALT greater than five times the upper limit of normal, and viral load were independent factors associated with HBeAg loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062-3.085; 0.7-0.942, respectively). CONCLUSION: Entecavir treatment for 3 years can achieve good biochemical and virologic responses in HBeAg-positive CHB patients, but has a modest effect on HBeAg loss and/or seroconversion. In addition, baseline serum ALT and HBV-DNA levels are independent factors associated with favorable treatment responses.