Nucleic Acid Testing for the Detection of HBV DNA

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Association between antibiotic consumption and colon and rectal cancer development in older individuals: A territory‐wide study

Background: Antibiotics may alter colorectal cancer (CRC) risk due to gut dysbiosis. We aimed to study the specific and temporal effects of various antibiotics on CRC development in older individuals. Methods: This was a territory-wide retrospective cohort study. Subjects aged 60 years and older who did not have CRC diagnosed on screening/diagnostic colonoscopy diagnosed between 2005 and 2013 were recruited. Exclusion criteria were history of CRC, colectomy, inflammatory bowel disease, and CRC diagnosed within 6 months of index colonoscopy. Exposure was use of any antibiotics up to 5 years before colonoscopy. The primary outcomes were CRC diagnosed >6 m after colonoscopy. Covariates were patient demographics, history of colonic polyps/polypectomy, concomitant medication use (NSAIDs, COX-2 inhibitors, aspirin, and statins), and performance of endoscopy centers (colonoscopy volume and polypectomy rate). Stratified analysis was conducted according to nature of antibiotics and location of cancer. Results: Ninety seven thousand one hundred and sixty-two eligible subjects (with 1026 [1.0%] cases of CRC) were identified, 58,704 (60.4%) of whom were exposed to antibiotics before index colonoscopy. Use of antibiotics was associated with a lower risk of cancer in rectum (adjusted hazard ratio [aHR]: 0.64, 95% CI: 0.54–0.76), but a higher risk of cancer in proximal colon (aHR: 1.63, 95%CI: 1.15–2.32). These effects differed as regards the anti-anaerobic/anti-aerobic activity, narrow-/broad-spectrum, and administration route of antibiotics. Conclusions: Antibiotics had divergent effects on CRC development in older subjects, which varied according to the location of cancer, antibiotic class, and administration route

Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-neegative chronic hepatitis B: A multicentre cohort study

Entecavir; HBV DNA; TenofovirEntecavir; ADN del VHB; TenofovirEntecavir; ADN del VHB; TenofovirBackground & Aims Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Methods Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. Results We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels 20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p <0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p <0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p <0.001). Conclusions Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. Impact and Implications A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring.The CREATE study was supported by Fujirebio. Materials for HBcrAg testing were provided free of charge to several participating centres. Fujirebio had no influence on CREATE study design, data collection, data analysis, writing of the current manuscript, or the decision to submit for publication

Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels

HBV genotype; Viral antigenGenotipo VHB; Antígeno viralGenotip del VHB; Antigen viralBackground & Aims Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. Methods We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders. Results We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p 100 IU/ml) and HBcrAg (100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490–4.174, p = 0.001). Conclusions The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal.The CREATE study was supported by Fujirebio. No additional funding was obtained for this follow-up analysis

Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B

Antiviral therapy; IncidenceTerapia antiviral; IncidenciaTeràpia antiviral; IncidènciaBackground & Aims Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. Methods The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Results Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively). Conclusions This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Impact and implications Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. Clinical trial numbers NCT01940341; NCT02836249; NCT01940471; NCT02836236.This study was sponsored by Gilead Sciences. This article was based on the original studies GS-US-320-0108 and GS-US-320-0110 sponsored by Gilead Sciences. Support for third-party writing assistance for this article, provided by Julianna Catania, MPH, and Isabel Haber, BS, Costello Medical, US, was funded by Gilead in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)

Rates of metachronous adenoma after curative resection for left-sided or right-sided colon cancer

Background/Aims We determined the rates of metachronous colorectal neoplasm in colorectal cancer (CRC) patients after resection for right (R)-sided or left (L)-sided cancer. Methods Consecutive CRC patients who had undergone surgical resection for curative intent in our hospital between 2001 and 2004 were identified. R-sided colonic cancers refer to cancer proximal to splenic flexure whereas L-sided cancers include rectal cancers. Patients were included only if they had a clearing colonoscopy performed either before or within 6 months after the operation. Findings of surveillance colonoscopy performed up to 5 years after colonic resection were included in the analysis. Results Eight hundred and sixty-three CRC patients underwent curative surgical resection during the study period. Three hundred and twenty-seven patients (107 R-sided and 220 L-sided) fulfilled the inclusion criteria and had at least 1 postoperative surveillance colonoscopy performed. The proportion of patients who had polyp and adenoma on surveillance colonoscopy was significantly higher among patients with L-sided than R-sided cancers (polyps: 30.9% vs. 19.6%, P=0.03; adenomas: 25.5% vs. 13.1%, P=0.01). The mean number of adenoma per patient on surveillance colonoscopy was also higher for patients with L-sided than R-sided tumors (0.52; 95% confidence interval [CI], 0.37–0.68 vs. 0.22; 95% CI, 0.08–0.35; P<0.01). Multivariate analysis showed that L-sided cancers, age, male gender and longer follow-up were independent predictors of adenoma detection on surveillance colonoscopy. Conclusions Patients with Lsided cancer had a higher rate of metachronous polyps and adenoma than those with R-sided cancer on surveillance colonoscopy

Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication.

BACKGROUND: Although prior studies showed metformin could reduce gastric cancer (GC) risk in patients with diabetes mellitus, they failed to adjust for Helicobacter pylori infection and glycemic control. We aimed to investigate whether metformin reduced GC risk in H. pylori-eradicated diabetic patients and its association with glycemic control. METHODS: This was a territory-wide cohort study using hospital registry database, recruiting all diabetic patients who were prescribed clarithromycin-based triple therapy for H. pylori infection from 2003 to 2012. Subjects were observed from H. pylori therapy prescription until GC diagnosis, death, or end of study (December 2015). Exclusion criteria included GC diagnosed within first year of H. pylori therapy, prior history of GC or gastrectomy, and failure of H. pylori eradication. The hazard ratio (HR) of GC with metformin (defined as at least 180-day use) was estimated by Cox model with propensity score adjustment for covariates (age, sex, comorbidities, medications [including insulin], and time-weighted average hemoglobin A1c [HbA1c]). All statistical tests were two-sided. RESULTS: During a median follow-up of 7.1 years (IQR = 4.7-9.8), 37 (0.51%) of 7266 diabetic patients developed GC at a median age of 76.4 years (IQR = 64.8-81.5 years). Metformin use was associated with a reduced GC risk (adjusted HR = 0.49, 95% CI = 0.24 to 0.98). There was a trend towards a lower GC risk with increasing duration (Ptrend = .01) and dose of metformin (Ptrend = .02). HbA1c level was not an independent risk factor for GC. CONCLUSIONS: Metformin use was associated with a lower GC risk among H. pylori-eradicated diabetic patients in a duration- and dose-response manner, which was independent of HbA1c level

Statins Were Associated with a Reduced Gastric Cancer Risk in Patients with Eradicated Helicobacter Pylori Infection: A Territory-Wide Propensity Score Matched Study.

BACKGROUND: Individuals may still develop gastric cancer even after Helicobacter pylori eradication. We aimed to investigate statin effect on gastric cancer development in H. pylori-eradicated subjects. METHODS: All adult subjects who were prescribed clarithromycin-based triple therapy between 2003 and 2012 were identified in this retrospective cohort study utilizing a territory-wide electronic healthcare database. Patients were observed from index date of H. pylori therapy, and censored at gastric cancer diagnosis, death, or December 2015 (study end date). Statin use was defined as ≥180-day use after index date. Exclusion criteria included gastric cancer diagnosed within the first year after index date, previous gastric cancer or gastrectomy, and H. pylori treatment failure. Subdistribution hazard ratio (SHR) of gastric cancer with statins was calculated by competing risk regression with propensity score (PS) analysis matching 19 variables (age, sex, comorbidities, and other drug usage, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, aspirin, cyclooxygenase-2 inhibitors, and metformin). RESULTS: During a median follow-up of 7.6 years (interquartile range = 5.1-10.3), 169 (0.27%) of 63,605 patients developed gastric cancer at an incidence rate of 3.5 per 10,000 person-years. Among 22,870 PS-matched subjects, statins were associated with a lower gastric cancer risk (SHR = 0.34; 95% confidence interval, 0.19-0.61), in a duration- and dose-response manner (P trend < 0.05). CONCLUSIONS: Statins were associated with a lower gastric cancer risk in a duration- and dose-response manner among H. pylori-eradicated patients. IMPACT: This study provides evidence on the additional benefits of statins as chemopreventive agents against gastric cancer among H. pylori-eradicated patients