Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

A Noninferiority Trial Comparing 2 Days vs 5 Days of Terlipressin and Ceftriaxone in Terms of 5-Day Rebleeding for Patients With Acute Gastroesophageal Variceal Hemorrhage.

INTRODUCTION: This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage. METHODS: After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days. RESULTS: Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B ( P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B ( P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B ( P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B ( P < 0.001). DISCUSSION: After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

BACKGROUND: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking. OBJECTIVE: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population. DESIGN: Multicenter randomized controlled study. (ClinicalTrials.gov: NCT03373136). SETTING: 6 sites in Taiwan, July 2018 through July 2020. PARTICIPANTS: Participants aged 40 years or older with polyps of 4 to 10 mm. INTERVENTION: CSP or HSP to remove polyps of 4 to 10 mm. MEASUREMENTS: The primary outcome was the delayed bleeding rate within 14 days after polypectomy. Severe bleeding was defined as a decrease in hemoglobin concentration of 20 g/L or more, requiring transfusion or hemostasis. Secondary outcomes included mean polypectomy time, successful tissue retrieval, en bloc resection, complete histologic resection, and emergency service visits. RESULTS: A total of 4270 participants were randomly assigned (2137 to CSP and 2133 to HSP). Eight patients (0.4%) in the CSP group and 31 (1.5%) in the HSP group had delayed bleeding (risk difference, -1.1% [95% CI, -1.7% to -0.5%]). Severe delayed bleeding was also lower in the CSP group (1 [0.05%] vs. 8 [0.4%] events; risk difference, -0.3% [CI, -0.6% to -0.05%]). Mean polypectomy time (119.0 vs. 162.9 seconds; difference in mean, -44.0 seconds [CI, -53.1 to -34.9 seconds]) was shorter in the CSP group, although successful tissue retrieval, en bloc resection, and complete histologic resection did not differ. The CSP group had fewer emergency service visits than the HSP group (4 [0.2%] vs. 13 [0.6%] visits; risk difference, -0.4% [CI, -0.8% to -0.04%]). LIMITATION: An open-label, single-blind trial. CONCLUSION: Compared with HSP, CSP for small colorectal polyps significantly reduces the risk for delayed postpolypectomy bleeding, including severe events. PRIMARY FUNDING SOURCE: Boston Scientific Corporation.

Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations With Implications on Host Gene Dysregulation.

BACKGROUND & AIMS: Hepatocellular carcinogenesis of hepatitis B virus (HBV) infection may arise from integration of viral DNA into the host genome. We aimed to gauge the effect of viral inhibition on transcriptionally active HBV-host integration events and explore the correlation of viral integrations with host gene dysregulation. METHODS: We leveraged data and biospecimens from an interventional trial, in which patients with HBV viremia above 2000 IU/mL and minimally raised serum liver enzyme were randomized to receive tenofovir disoproxil fumarate (TDF) or placebo for 3 years. Total RNA-sequencing was performed on paired liver biopsies taken before and after the 3-year intervention in 119 patients. Virus-host chimeric reads were captured to quantify the number of distinct viral integrations. Dysregulation of a host gene disrupted by viral integration was defined by aberrant expression >2 standard deviations away from samples without viral integration. RESULTS: The TDF (n = 64) and placebo groups (n = 55) were comparable at baseline. Expressed viral integrations were detected in all pre- and posttreatment samples. The number of distinct viral integrations significantly correlated with circulatory biomarkers indicative of viral activities including HBV DNA, RNA, and viral antigens (P < .0003 for all correlations). Moreover, TDF vs placebo achieved a significantly greater reduction in distinct viral integrations, with 3.28-fold and 1.81-fold decreases in the expressed integrations per million reads, respectively (analysis of covariance, P = .037). Besides, viral integrations significantly correlated with host gene dysregulation. CONCLUSION: Inhibition of viral replication reduces the number of transcriptionally active distinct HBV-host DNA integrations in patients with substantial viremia. Given the mutagenic potentials of viral integrations, such treatment effects should be considered in patient management.

Severe Acute Exacerbation After Cessation of Nucleos(t)ide Analog for Chronic Hepatitis B: A Real-World Study of Routine Practice.

There is an ongoing debate as to whether patients with chronic hepatitis B (CHB) may discontinue nucleos(t)ide analogue (NA) therapy before seroclearance of hepatitis B surface antigen (HBsAg).1 Whereas treatment discontinuation may facilitate HBsAg seroclearance and avoid indefinite drug exposure,2 reactivation of viral replication almost always follows treatment cessation and frequently leads to clinical flares.3 In patients who encounter withdrawal flares, severe acute exacerbation (SAE) could occur with fatal consequences.4 Quantitative knowledge about the risk of SAE is imperative to inform the debate and also the practice.

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.

BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

Novel Colorectal Endoscopic Submucosal Dissection With Double-Endoscope and Snare-Based Traction.

BACKGROUND: Colorectal endoscopic submucosal dissection is technically demanding, and the traction offered by gravity, cap, or clip-with-line during conventional endoscopic submucosal dissection remains unsatisfactory. Robotic systems are still under development and are expensive. We proposed double-scope endoscopic submucosal dissection with strong and adjustable traction offered by snaring the lesion with additional scope. OBJECTIVE: This study aimed to test the novel double-scope endoscopic submucosal dissection with snare-based traction. DESIGN: This was a retrospective study that reviewed double-scope endoscopic submucosal dissection compared with matched conventional endoscopic submucosal dissection, and size, location, morphology, and pathology between groups were compared. SETTINGS: This study was conducted in a referral endoscopy center in a local hospital. PATIENTS: This study included patients with colorectal lesions receiving double-scope endoscopic submucosal dissection and matched conventional endoscopic submucosal dissection. MAIN OUTCOME MEASURES: The pathological completeness, procedure time, and complications were analyzed. RESULTS: Fifteen double-scope endoscopic submucosal dissection procedures, with 11 lesions located in the proximal colon with a median size of 40 mm, were performed. The median procedure time of double-scope endoscopic submucosal dissection was 32.45 (interquartile range, 16.03-38.20) minutes. The time required for second scope insertion was 2.57 (interquartile range, 0.95-6.75) minutes; for snaring, 3.03 (interquartile range, 2.12-6.62) minutes; and for actual endoscopic submucosal dissection, 28.23 (interquartile range, 7.90-37.00) minutes. All lesions were resected completely. No major complication was encountered. The procedure time was significantly shorter than that of 14 matched conventional endoscopic submucosal dissections (54.61 [interquartile range, 33.11-97.25] min; p = 0.021). LIMITATIONS: This was a single-center, single-operator, retrospective case-controlled study with limited cases. CONCLUSIONS: This study confirmed the feasibility of double-scope endoscopic submucosal dissection with snare-based traction to shorten procedure time and to simplify endoscopic submucosal dissection. Additional trials are required.

Application of Risk Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: Current Status and Future Perspective.

Accurate risk prediction for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) may guide treatment strategies including initiation of antiviral therapy and also inform implementation of HCC surveillance. There have been 26 risk scores developed to predict HCC in CHB patients with (n = 14) or without (n = 12) receiving antiviral treatment; all of them invariably include age in the scoring formula. Virological biomarkers of replicative activities (i.e., hepatitis B virus DNA level or hepatitis B envelope antigen status) are frequently included in the scores derived from patients with untreated CHB, whereas measurements that gauge severity of liver fibrosis and/or reserve of hepatic function (i.e., cirrhosis diagnosis, liver stiffness measurement, platelet count, or albumin) are essential components in the scores developed from treated patients. External validation is a prerequisite for clinical application but not yet performed for all scores. For the future, higher predictive accuracy may be achieved with machine learning based on more comprehensive data.

Outcomes of Sequential Therapy With Tenofovir Alafenamide After Long-term Entecavir.

INTRODUCTION: Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch. METHODS: ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA <20 IU/mL). RESULTS: We analyzed 425 eligible patients (mean age 60.7 ± 13.2 years, 60% men, 90.8% Asian, 20.7% with diabetes, 27% with hypertension, 14.8% with cirrhosis, 8.3% with hepatocellular carcinoma, and mean ETV duration before switch 6.16 ± 3.17 years). The mean baseline estimated glomerular filtration rate (eGFR) was 89 ± 19 (chronic kidney disease [CKD] stages: 55.6% stage 1, 35.7% stage 2, and 8.8% stages 3-5). CVS rate increased from 91.90% at switch (from 90.46% 24 weeks before switch) to 95.57% and 97.21% at 48 and 96 weeks after (P = 0.03 and 0.02, respectively). Over the 96 weeks after switch, mean HBV DNA (P < 0.001) but not alanine aminotransferase or CKD stage decreased. Between switch and 96-week follow-up, 11% (26/235) of CKD stage 1 patients migrated to stage 2 and 8% (12/151) of stage 2 patients to stages 3-5, whereas 18% (27/151) from stage 2 to 1, and 19% (7/37) from stages 3-5 to 2. On multivariable generalized estimated equation analysis adjusted for age, sex, hypertension, diabetes, and cirrhosis, baseline eGFR, age (P < 0.001), and CKD stages 2 and 3-5 (vs 1) (both P < 0.001) were associated with lower follow-up eGFR. DISCUSSION: After an average of 6 years on ETV, CVS increased from 91.9% at TAF switch to 97.2% at 96 weeks later.

A clinically interpretable convolutional neural network for the real-time prediction of early squamous cell cancer of the esophagus: comparing diagnostic performance with a panel of expert European and Asian endoscopists.

BACKGROUND AND AIMS: Intrapapillary capillary loops (IPCLs) are microvascular structures that correlate with the invasion depth of early squamous cell neoplasia and allow accurate prediction of histology. Artificial intelligence may improve human recognition of IPCL patterns and prediction of histology to allow prompt access to endoscopic therapy for early squamous cell neoplasia where appropriate. METHODS: One hundred fifteen patients were recruited at 2 academic Taiwanese hospitals. Magnification endoscopy narrow-band imaging videos of squamous mucosa were labeled as dysplastic or normal according to their histology, and IPCL patterns were classified by consensus of 3 experienced clinicians. A convolutional neural network (CNN) was trained to classify IPCLs, using 67,742 high-quality magnification endoscopy narrow-band images by 5-fold cross validation. Performance measures were calculated to give an average F1 score, accuracy, sensitivity, and specificity. A panel of 5 Asian and 4 European experts predicted the histology of a random selection of 158 images using the Japanese Endoscopic Society IPCL classification; accuracy, sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Expert European Union (EU) and Asian endoscopists attained F1 scores (a measure of binary classification accuracy) of 97.0% and 98%, respectively. Sensitivity and accuracy of the EU and Asian clinicians were 97%, 98% and 96.9%, 97.1%, respectively. The CNN average F1 score was 94%, sensitivity 93.7%, and accuracy 91.7%. Our CNN operates at video rate and generates class activation maps that can be used to visually validate CNN predictions. CONCLUSIONS: We report a clinically interpretable CNN developed to predict histology based on IPCL patterns, in real time, using the largest reported dataset of images for this purpose. Our CNN achieved diagnostic performance comparable with an expert panel of endoscopists.

Increasing Age and Nonliver Comorbidities in Patients with Chronic Hepatitis B in Taiwan: A Nationwide Population-Based Analysis.

BACKGROUND: Data from the USA suggest that chronic hepatitis B (CHB) patients have aged in the past decade. However, the burden of nonliver comorbidities has not been well characterized in Taiwan, where CHB is very prevalent. AIM: Our study examined this issue as it presented between 2001 and 2011 in Taiwan. METHODS: This study identified adult patients (≥18 years) who were diagnosed with CHB in 2001, 2006, and 2011, from the Taiwan National Health Insurance Research Database (NHIRD). Changes in demographic characteristics, prevalence of nonliver comorbidities, and medication usage over the decade were examined. Non-CHB controls were adults without CHB diagnosis from the Longitudinal Health Insurance Database 2000 (LHID2000). RESULTS: A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The mean age significantly advanced from 45.4 to 52.3 years over the decade (p < 0.001). The prevalence of comorbidities, including diabetes mellitus, hypertension, stroke, chronic kidney disease, and bone fracture, significantly increased between 2001 and 2011 (all p < 0.001), as so were medication usage (all p < 0.001). Moreover, within each study period, compared to non-CHB controls, CHB patients were also older and more likely to have metabolic and cardiovascular comorbidities (all p < 0.001). In addition, the annual nonliver mortality in the CHB population significantly increased from 2001 to 2011. CONCLUSIONS: Over a decade, the CHB population in Taiwan has aged with a higher nonliver comorbidity burden and increasing nonliver mortality. These findings may provide information to care providers in the monitoring and management of CHB patients.

Hepatitis C Virus Cure Rates Are Reduced in Patients With Active but Not Inactive Hepatocellular Carcinoma: A Practice Implication.

BACKGROUND: Cure rates of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared with HCV/non-HCC patients. METHODS: Using data from the Real-World Evidence from the Asia Liver Consortium (REAL-C) registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin levels to evaluate DAA treatment outcomes in a large population of HCV/HCC compared with HCV/non-HCC patients. RESULTS: We included 6081 patients (HCC, n = 465; non-HCC, n = 5 616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs 93.7%; P = .03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR, 0.28; P = .01) when compared with non-HCC. CONCLUSIONS: Active HCC but not inactive HCC was independently associated with lower SVR compared with non-HCC patients undergoing DAA therapy, although cure rate was still relatively high (85%) in active HCC patients.

Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: There is controversy over the best therapeutic approach for T1 colorectal cancer. We performed a systematic review and meta-analysis of long-term outcomes of endoscopic resection (ER) vs those of primary or additional surgery. METHODS: We performed a systematic review of the PubMed, Embase, and Cochrane databases through October 2019 for studies that reported outcomes (overall survival, disease-specific survival, recurrence-free survival at 5 years, recurrence, and metastasis) of ER vs surgery in patients with colorectal neoplasms. Hazard ratios (HR) were calculated based on time to events. RESULTS: In total, 17 published studies with 19,979 patients were included. The median follow-up time among the studies was 36 months. The meta-analysis found no significant differences between primary ER and primary surgery in overall survival (79.6% vs 82.1%, HR, 1.10; 95% CI, 0.84-1.45), recurrence-free survival (96.0% vs 96.7%, HR, 1.28; 95% CI, 0.87-1.88), or disease-specific survival (94.8% vs 96.5%; HR, 1.09; 95% CI, 0.67-1.78). Additional surgery and primary surgery did not produce significant differences in recurrence-free survival (HR, 1.27; 95% CI, 0.85-1.89). A significantly lower proportion of patients who underwent primary ER had procedure-related adverse events (2.3%) than patients who underwent primary surgery (10.9%) (P < .001). Lymphovascular invasion and rectal cancer, but not depth of submucosal invasion, were independently associated with recurrence for all T1 colorectal cancers. CONCLUSIONS: In a systematic review and meta-analysis, we found that ER should be considered as the first-line treatment for endoscopically resectable T1 colorectal cancers. In cases of noncurative resection, additional surgery can have comparable outcomes to primary surgery.

Magnitude of and prediction for risk of hepatocellular carcinoma in patients with chronic hepatitis B taking entecavir or tenofovir therapy: A systematic review.

BACKGROUND AND AIM: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been shown to reduce incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This systematic review aims to evaluate the magnitude, change over time, and prediction of residual HCC risks in CHB patients treated with ETV/TDF therapy. METHODS: Available literature was systematically reviewed through searches of PubMed and EMBASE databases from January 1, 2006 to September 1, 2019, to identify cohort studies that reported HCC incidence in CHB patients during ETV/TDF therapy. Studies were screened by title and abstract and then evaluated for eligibility in terms of full text. RESULTS: We identified 141 studies for full-text review, and 34 were eligible for analysis. From 19 studies with data separated by cirrhosis status, the 5-year cumulative incidence of HCC was 0.5-6.9% in patients without cirrhosis, 4.5-21.6% in compensated cirrhosis, and 36.3-46.5% in decompensated cirrhosis. All four studies that addressed temporal changes in HCC risks consistently found the incidence rate decreased over time in patients with cirrhosis, although the findings were inconsistent in patients without cirrhosis. Six predictive scores were developed and validated to predict incident HCC during ETV/TDF therapy in CHB patients. Common scoring variables included age, sex, cirrhosis (fibrosis grade), and hepatic function. Conflicting results were reported in seven individual studies and two meta-analyses that compared ETV versus TDF. CONCLUSIONS: The residual risk of HCC remains during ETV/TDF treatment in CHB patients with cirrhosis but declines over time. Risk stratification is attainable by validated predictive scores.

Prognostic Impact of Diabetes Mellitus on Overall Survival in a Nationwide Population-Based Cohort of Patients With Pancreatic Cancer.

OBJECTIVE: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality. METHODS: This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed. RESULTS: Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P<.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P<.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P<.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.20 to 1.33; P<.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment. CONCLUSION: After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer. ABBREVIATIONS: CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database.

14 day sequential therapy versus 10 day bismuth quadruple therapy containing high-dose esomeprazole in the first-line and second-line treatment of Helicobacter pylori: a multicentre, non-inferiority, randomized trial.

Background: Whether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown. Objectives: To compare the efficacy and tolerability of optimized 14 day sequential therapy and 10 day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy. Methods: We recruited 620 adult patients (≥20 years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14 day sequential therapy or 10 day bismuth quadruple therapy, both containing esomeprazole 40 mg twice daily. Those who failed after 14 day sequential therapy received rescue therapy with 10 day bismuth quadruple therapy and vice versa. Our primary outcome was the eradication rate in the first-line therapy. Antibiotic susceptibility was determined. ClinicalTrials.gov: NCT03156855. Results: The eradication rates of 14 day sequential therapy and 10 day bismuth quadruple therapy were 91.3% (283 of 310, 95% CI 87.4%-94.1%) and 91.6% (284 of 310, 95% CI 87.8%-94.3%) in the ITT analysis, respectively (difference -0.3%, 95% CI -4.7% to 4.4%, P = 0.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10 day bismuth quadruple therapy than those treated with 14 day sequential therapy (74.4% versus 36.7% P < 0.0001). The eradication rate of 14 day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (P < 0.0001). Conclusions: Optimized 14 day sequential therapy was non-inferior to, but better tolerated than 10 day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Lessons from pathological analysis of recurrent early esophageal squamous cell neoplasia after complete endoscopic radiofrequency ablation.

BACKGROUND: Endoscopic radiofrequency ablation (RFA) is a treatment option for early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up studies are lacking. The risks of local recurrence and "buried cancer" are also uncertain. METHODS: Patients with flat-type ESCN who were treated with balloon-type ± focal-type RFA were consecutively enrolled. Follow-up endoscopy was performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic resection was performed for persistent and recurrent ESCN, and the histopathology of resected specimens was assessed. RESULTS: A total of 35 patients were treated with RFA, of whom 30 (86 %) achieved a complete response, three were lost to follow-up, and five (14 %) developed post-RFA stenosis. Two patients had persistent ESCN and received further endoscopic resection, in which the resected specimens all revealed superficial submucosal invasive cancer. Six of the 30 patients with successful RFA (20 %) developed a total of seven episodes of local recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all of which were successfully resected endoscopically without adverse events. Histological analysis of the resected specimens revealed that six (86 %) had esophageal glandular ductal involvement, all of which extended deeper than the muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67 suggested a clonal relationship between the ductal involvement and epithelial cells. None of the tumors extended out of the ductal structure; no cases of cancer buried beneath the normal neosquamous epithelium were found. CONCLUSIONS: Because ductal involvement is not uncommon and may be related to recurrence, the use of RFA should be conservative and may not be the preferred primary treatment for early ESCN.

A training program of a new simplified classification of magnified narrow band imaging for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS: A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS: The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P < 0.05). CONCLUSIONS: A well-designed training program can improve the diagnostic accuracy in evaluating cancer invasion depth, with substantial agreement.