Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–negative, antibody to hepatitis B core antigen (anti‐HBc)–positive patients after allogeneic hematopoietic stem cell ...transplantation (HSCT) has not been prospectively studied. HBsAg‐negative, anti‐HBc–positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg‐negative, anti‐HBc–positive, of whom 62 were recruited and monitored for a median of 48 (4‐104) weeks. The 2‐year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8‐100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft‐versus‐host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft‐versus‐host disease, compared with the remaining patient cohort, had a significantly lower 2‐year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. Conclusion: HBsAg‐negative, anti‐HBc–positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft‐versus‐host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451‐1461).
The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in ...predicting off-treatment durability has not been well investigated.
Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥ 2 years with undetectable HBV DNA levels on ≥ 3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000IU/mL).
184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37-1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (± 0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=-0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p>0.05).
Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.
Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving ...rituximab-containing chemotherapy have not been well described.
HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered.
Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients.
A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.
Gastric cancer （GC） is one of the leading causes ofcancer related death in the world, particularly in EastAsia. According to the Correa＇s cancer cascade, noncardiaGC is usually developed through a ...series of mucosal changes from non-atrophic gastritis to atrophicgastritis （AG）, intestinal metaplasia （IM）, dysplasiaand adenocarcinoma. Atrophic gastritis and IM aretherefore generally considered to be pre-neoplasticgastric lesions. Helicobacter pylori （H. pylori ） infectionis an important initiating and promoting step of thisgastric carcinogenesis cascade. Emerging long-termdata showed that eradication of H. pylori reduced therisk of subsequent cancer development. It howeverremains confusing whether eradication of the bacteriumin individuals with pre-neoplastic gastric lesions couldregress these changes as well as in preventing cancer.Whilst H. pylori eradication could likely regress AG,the presence of IM may be a point of no return inthis cascade. Hence, surveillance by endoscopy maybe indicated in those with extensive IM or those withincomplete IM, particularly in populations with highGC risk. The optimal interval and the best tool ofsurveillance endoscopy remains to be determined infuture studies.
Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term ...HBsAg seroclearance after entecavir cessation.
This study followed-up Chinese patients with chronic hepatitis B from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They were monitored closely for 48 weeks with regular HBV DNA, quantitative HBsAg (qHBsAg) and alanine aminotransferase (ALT) measurements. Entecavir was resumed at HBV DNA >2,000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every 6 months, regardless of entecavir resumption, to monitor for HBsAg seroclearance.
A total of 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited; 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1,000 IU/ml, respectively; 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p < 0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (hazard ratios ranging from 1.003-1.028, all p < 0.01) with excellent diagnostic performance (area under the receiver-operating characteristic curve 0.799-0.933, negative predictive value >90% at different time points), regardless of whether entecavir was resumed.
The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption.
Current predictors of HBsAg seroclearance after finite nucleos(t)ide analogue (NA) therapy have suboptimal predictive value. We demonstrated that the ALT/qHBsAg ratio may be able to reflect the balance between host control and virological activity. The ALT/qHBsAg ratio at different time points from end-of-treatment till week 48 independently and accurately predicted HBsAg seroclearance in patients who have stopped entecavir. The ALT/qHBsAg ratio may be utilized by clinicians for patient selection and retreatment decisions in finite NA therapy.
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•Predictors of HBsAg seroclearance following finite nucleos(t)ide analogue (NA) therapy have important clinical implications.•The ALT/qHBsAg ratio may reflect the balance between host control and virological activity after NA withdrawal.•The ALT/qHBsAg ratio from end-of-treatment up to week 48 predicted HBsAg seroclearance after stopping entecavir.•The ALT/qHBsAg ratio had excellent diagnostic performance for predicting HBsAg seroclearance.•The predictive performance of the ALT/qHBsAg ratio remained consistent, regardless of whether entecavir was resumed.
Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface ...antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined.
HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml
, developed.
One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively).
Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.
Blue-light imaging (BLI) is a new image-enhanced endoscopy with a wavelength filter similar to narrow-band imaging (NBI). We compared the 2 with white-light imaging (WLI) on proximal colonic lesion ...detection and miss rates.
In this 3-arm prospective randomized study with tandem examination of the proximal colon, we enrolled patients aged ≥40 years. Eligible patients were randomized in 1:1:1 ratio to receive BLI, NBI, or WLI during the first withdrawal from the proximal colon. The second withdrawal was performed using WLI in all patients. Primary outcomes were proximal polyp (pPDRs) and adenoma (pADRs) detection rates. Secondary outcomes were miss rates of proximal lesions found on tandem examination.
Of 901 patients included (mean age, 64.7 years; 52.9% men), 48.1% underwent colonoscopy for screening or surveillance. The corresponding pPDRs of the BLI, NBI, and WLI groups were 45.8%, 41.6, and 36.6%, whereas the corresponding pADRs were 36.6%, 33.8%, and 28.3%. There was a significant difference in pPDR and pADR between BLI and WLI groups (difference, 9.2% 95% confidence interval {CI}, 3.3-16.9 and 8.3% 95% CI, 2.7-15.9) and between NBI and WLI groups (difference, 5.0% 95% CI, 1.4-12.9 and 5.6% 95% CI, 2.1-13.3). Proximal adenoma miss rates were significantly lower with BLI (19.4%) than with WLI (27.4%; difference, –8.0%; 95% CI, –15.8 to –.1) but not between NBI (27.2%) and WLI.
Both BLI and NBI were superior to WLI on detecting proximal colonic lesions, but only BLI had lower proximal adenoma miss rates than WLI. (Clinical trial registration number: NCT03696992.)
Computer-aided detection (CADe) of colorectal polyps has been shown to increase adenoma detection rates, which would potentially shorten subsequent surveillance intervals.
The purpose of this study ...is to simulate the potential changes in subsequent colonoscopy surveillance intervals after the application of CADe in a large cohort of patients.
We simulated the projected increase in polyp and adenoma detection by universal CADe application in our patients who had undergone colonoscopy with complete endoscopic and histological findings between 2016 and 2020. The simulation was based on bootstrapping the published performance of CADe. The corresponding changes in surveillance intervals for each patient, as recommended by the US Multi-Society Task Force on Colorectal Cancer (USMSTF) or the European Society of Gastrointestinal Endoscopy (ESGE), were determined after the CADe was determined.
A total of 3735 patients who had undergone colonoscopy were included. Based on the simulated CADe effect, the application of CADe would result in 19.1% (n=714) and 1.9% (n=71) of patients having shorter surveillance intervals, according to the USMSTF and ESGE guidelines, respectively. In particular, all (or 2.7% (n=101) of the total) patients who were originally scheduled to have 3-5 years of surveillance would have their surveillance intervals shortened to 3 years, following the USMSTF guidelines. The changes in this group of patients were largely attributed to an increase in the number of adenomas (n=75, 74%) rather than serrated lesions being detected.
Widespread adoption of CADe would inevitably increase the demand for surveillance colonoscopies with the shortening of original surveillance intervals, particularly following the current USMSTF guideline.
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•Film formation in waterborne two-component polyurethane coatings was investigated.•Partially PEGylated polyisocyanate (PIC) enhances molecular mixing with polyol.•Increased ...unmodified PIC content in the formulation promotes stratification.•We developed a method for real-time monitoring of water permeation in coatings.•Stratification enhances the rate and extent of water uptake by the coating.
The coatings industry continually seeks advancements in waterborne two-component polyurethane (2 K WBPU) systems, given their potential for environmentally friendly applications and superior film properties. This study explores the mechanistic aspects of film formation in 2 K WBPU coatings formulated with an acrylic polyol and a polyisocyanate (PIC) derived from a trimer of hexamethylene diisocyanate (HDI-trimer). To enhance water dispersibility—a key parameter in industrial applications—the HDI-trimer is modified with a short polyethylene glycol, producing a hydrophilically modified PIC (hmPIC). While prior studies identified hmPIC as an effective reactive plasticizer for the polyol, the common practice of adding unmodified HDI-trimer (uPIC) to hmPIC for moisture sensitivity reduction necessitates a deeper understanding of film properties. Using fluorescence resonance energy transfer (FRET) and confocal fluorescence microscopy, we investigated the effects of blending uPIC with hmPIC on coalescence, phase separation, and film stratification in 2 K WBPU systems. Notably, environmental factors like relative humidity were found to influence film stratification significantly. This finding has critical implications for coating performance, such as durability and water resistance. A novel method was also introduced to monitor water permeation within stratified films, offering a valuable tool for optimizing film properties in real-world applications. This study underscores the importance of strategic component interactions in polymer coatings, suggesting that controlled film stratification can significantly enhance film performance in industrial settings.
Background
Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for nucleoside analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and ...durability of HBsAg seroclearance in NA-treated patients have not been well described.
Methods
We compared the HBsAg kinetics and long-term serologic outcomes of 51 chronic hepatitis B patients achieving HBsAg seroclearance during NA therapy with those of 51 HBsAg-positive controls, matched for age, sex, hepatitis B e antigen status, NA type, and treatment duration. Viral profiles before and after HBsAg seroclearance during and after NA treatment cessation were determined.
Results
The median time to HBsAg seroclearance and the median follow-up duration after HBsAg seroclearance were 61.2 and 51.6 months respectively. Patients achieving HBsAg seroclearance maintained high median rates of HBsAg reduction throughout therapy (first 6 months, 0.40 IU/mL/year; after year 1, 0.39 IU/mL/year;
p
= 0.809). For controls, the median rate of HBsAg reduction was significantly slower with time (first 6 months and after year 1, 0.19 and 0.05 IU/mL/year;
p
= 0.006). The difference in the median HBsAg reduction rates after year 1 between the two groups was significant (
p
< 0.001). The cumulative rates of antibody to HBsAg development and HBsAg seroreversion 72 months after HBsAg seroclearance were 68.9 and 8.3 % (one patient receiving immunosuppressive therapy; one patient with pre-S/S variant), respectively. Among 22 patients who discontinued therapy after HBsAg seroclearance, 21 remained HBsAg negative with undetectable hepatitis B virus DNA and one patient with reactivation had the pre-S/S variant.
Conclusion
NA-treated patients achieving HBsAg seroclearance uniquely maintained high rates of HBsAg reduction throughout treatment, with HBsAg seroclearance durable in most of the patients after treatment cessation.
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