Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of ...embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding(GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran(150 mg b.i.d), rivaroxaban and high-dose edoxaban(60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.
Background & Aims
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key to viral persistence in chronic hepatitis B infection. Serum hepatitis B core‐related antigen (HBcrAg) is a ...novel marker for HBV disease. We aimed to determine whether HBcrAg could be a surrogate marker for intrahepatic cccDNA.
Methods
Three hundred and five liver biopsies and the corresponding sera collected from 138 nucleos(t)ide analogues‐treated patients were analysed. 124 patients had paired liver biopsies at baseline and 1‐year post‐treatment, and 43 patients had a third biopsy after 6‐12 years of treatment. Serum HBcrAg, HBV DNA and hepatitis B surface antigen (HBsAg), and intrahepatic HBV DNA and cccDNA were measured.
Results
HBcrAg strongly correlated with cccDNA (r=.70), intrahepatic total HBV DNA (r=.67) and serum HBV DNA (r=.69; all P<.0001). In the 130 samples with undetectable serum HBV DNA, HBcrAg was detectable in 101 (78%) samples, and HBcrAg levels still correlated positively with cccDNA (r=.42, P<.0001). At ≥6 years of therapy, the median logarithmic reduction in HBcrAg was 2.7 log kU/mL, which was comparable to the magnitude of reduction in cccDNA. Twenty‐one patients had undetectable cccDNA after ≥6 years of treatment, in whom 15 (71%) had detectable HBcrAg (range: 1.2‐537 kU/mL).
Conclusions
Serum HBcrAg is a reliable surrogate marker for intrahepatic cccDNA. HBcrAg could be a very sensitive marker to reflect the cccDNA content and persistence of disease even with the cccDNA levels below the detection limit of assays.
It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).
...This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases.
In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio SHR, 0.45; 95% confidence interval CI, 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77).
TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.
Concomitant non-alcoholic fatty liver disease is common in patients with chronic hepatitis B (CHB) infection, although its impact on liver-related outcomes remains controversial. We aimed to study ...the effect of hepatic steatosis on the risk of fibrosis progression and the likelihood of HBsAg seroclearance.
Treatment-naïve patients with CHB, normal alanine aminotransferase and low viraemia (serum HBV DNA <2,000 IU/ml) were prospectively recruited for baseline and 3-year transient elastography assessment. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1 stage increment of fibrosis. Hepatic steatosis and severe hepatic steatosis were defined as controlled attenuation parameter (CAP) ≥248 dB/m and ≥280 dB/m, respectively.
A total of 330 patients (median age 50.5 years, 41.2% male, median HBV DNA 189 IU/ml) were recruited. Twenty-two patients (6.7%) achieved HBsAg seroclearance during follow-up, and the presence of hepatic steatosis was associated with a significantly higher chance of HBsAg seroclearance (hazard ratio 3.246; 95% CI 1.278–8.243; p = 0.013). At baseline, 48.8% and 28.8% of patients had steatosis and severe steatosis, respectively, while 4.2% had F3/F4 fibrosis at baseline, increasing to 8.7% at 3 years. The rate of liver fibrosis progression in patients with persistent severe steatosis was higher than in those without steatosis (41.3% vs. 23%; p = 0.05). Persistent severe hepatic steatosis was independently associated with fibrosis progression (odds ratio 2.379; 95% CI 1.231–4.597; p = 0.01).
CAP measurements have predictive value in patients with virologically quiescent CHB. The presence of hepatic steatosis was associated with a higher risk of fibrosis progression but, paradoxically, a 3-fold increase in HBsAg seroclearance rate.
Co-existing fatty liver disease in patients with chronic viral hepatitis B infection leads to worsening liver fibrosis, but also increases the chance of cure from hepatitis B virus. Routine bedside assessment of liver fat content is important for risk assessment in treatment-naïve patients with chronic hepatitis B.
Display omitted
•Hepatic steatosis was associated with a 3-fold increase in likelihood of HBsAg seroclearance in quiescent CHB infection.•Cumulative probability of HBsAg seroclearance at 3 years was 18.4% in those with steatosis and low serum HBV DNA (<200 IU/ml).•Fibrosis progression was still observed in 25.2% patients despite virological quiescence.•Persistent severe hepatic steatosis was associated with a 2-fold increased risk of fibrosis progression at 36 months.•Routine CAP measurement in patients with apparently low-risk CHB has prognostic value.
The significance of hepatitis B e‐antigen (HBeAg) seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive ...scores for hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3‐ to 6‐monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC‐ESC) and HBsAg seroclearance (HBsAg‐ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow‐up of 36.0 and 18.3 years, respectively. Only 3.5% and 3.0% had persistently normal alanine aminotransferase (ALT) and HBV DNA <2logs IU/mL, respectively, after ESC. For patients with 100%, 100%‐90%, 90%‐50%, 50%‐10%, 10%‐0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC, respectively (P < 0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5%, respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The area under receiver operating characteristics for HCC‐ESC and HBsAg‐ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74, respectively. Conclusion: Male sex, older age at ESC, ALT, and higher level of HBV DNA were associated with higher rates of HCC after ESC. HCC‐ESC and HBsAg‐ESC predictive scores can determine the likelihood of developing HCC and achieving HBsAg seroclearance. (Hepatology 2018)
BackgroundTreatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining ...treatment cessation suitability has not been well-investigated.MethodsNucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.Results114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.ConclusionSerum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.Trial registration number NCT02738554
While governments around the world are embarking on the path to recovery from the COVID-19 crisis, sustainable tourism planning is crucial, in particular in the hospitality sector, which enhances the ...resilience of destinations. However, many destination management models overlook the role of urban zoning. Little is known about the impacts of land-use zoning on the hospitality and property industries, especially with the current disruption of short-term peer-to-peer accommodation like Airbnb. Euclidean zoning, also known as effects-based planning, has long been criticised in destination management for its exclusionary nature and lack of flexibility. With exclusionary zoning, property owners may only be able to use their land sub-optimally, and cities will be less efficient in responding to market changes in short-term and long-term accommodation demands, but planning intentions can be better controlled, and the property supply can be more stable. Taking Hong Kong as a noteworthy case, this study puts forward a conceptual framework that enables comparison of a novel zoning approach with the traditional zoning approach. This novel zoning approach encompasses both the short- and long-term rental sectors as a continuum of accommodation, ranging from hotels and serviced apartments to Airbnb and rental housing units under a unified regulatory and planning regime to enhance the switching options value. This novel zoning system can gear up the tourism sector with the rapid growth of the sharing economy and aligns with sustainable tourism to ensure long-term socioeconomic benefits to related stakeholders. We extract the data of Airbnb listings to construct the first Airbnb ADR Index (ADRI) by Repeat-sales method, and the results support our Switching Option Hypothesis.
Background
We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development.
Methods
This is a case–control study of 104 patients 52 HCC and 52 non-HCC (matched ...with age, gender, cirrhosis and treatment duration) on ≥ 3 years entecavir (ETV) with unquantifiable HBV DNA by Cobas Taqman assay v2.0 (Roche Diagnostics; lower limit of quantification LLOQ 20 IU/mL). Serial sera within 1, 1–2, and > 2 years prior to HCC diagnosis or last follow-up (LFU) were measured for HBV DNA and pre-genomic (pg) RNA using a highly sensitive semi-quantitative PCR assay with lower limit of detection of 10 IU/mL and LLOQ of 51.5 IU/mL, respectively.
Results
Among the 104 patients (80.8% male, median age 61.2 years old, 38.5% cirrhosis, median duration of ETV 45.5 months), 38.5% and 9.6% HCC patients had undetectable serum DNA and pgRNA, respectively, compared to 65.4% and 36.5% in non-HCC patients;
P
= 0.005 & 0.001, respectively, at the time of HCC diagnosis/LFU. Detectable HBV DNA and pgRNA were associated with a higher 2-year risk of HCC development (HR 2.79, 95% CI 1.424–5.468 & HR 4.544, 95% CI 1.07–19.289, respectively). No significant differences were observed for qHBsAg levels between HCC and non-HCC patients.
Conclusions
More than 50% CHB patients on ETV with HBV DNA < LLOQ by standard assay had persistent viraemia as determined by a more sensitive assay. Detectable HBV DNA or pgRNA by more sensitive assays was associated with HCC development. More potent viral suppression is required to further reduce the risk of HCC.
Background and aimsPostcolonoscopy colorectal cancer (PCCRC) accounts for up to 9% of all CRCs. Statins have been shown to be associated with a lower CRC risk. We aimed to investigate whether PCCRC ...risk was also lower among statin users.MethodsThis is a retrospective cohort study using a territory-wide electronic healthcare database in Hong Kong including patients aged 40 years or above who had undergone colonoscopies between 2005 and 2013. Exclusion criteria included prior colorectal cancer (CRC), inflammatory bowel disease, prior colectomy and CRC detected within 6 months of index colonoscopy. We defined statin use as at least 90-day use before index colonoscopy. Medication use was traced up to 5 years before index colonoscopy. PCCRC-3y was defined as cancer diagnosed between 6 and 36 months after index colonoscopy. Sites of CRC were categorised as proximal (proximal to splenic flexure) and distal cancer. The subdistribution HR (SHR) of PCCRC-3y with statin use was derived by propensity score matching based on covariates (including patient factors, concurrent medication use and endoscopy centre’s performance).ResultsOf 187 897 eligible subjects, 854 (0.45%) were diagnosed with PCCRC-3y. Statin use was associated with a lower PCCRC-3y risk (SHR: 0.72; 95% CI 0.55 to 0.95; p=0.018). Subgroup analysis shows that SHRs were 0.50 (95% CI 0.28 to 0.91; p=0.022) for proximal and 0.80 (95% CI 0.59 to 1.09; p=0.160) for distal cancer. Older (>60 years) patients, women and those without diabetes mellitus or polyps appeared to benefit more from statins.ConclusionsStatins were associated with a lower PCCRC risk, particularly for proximal cancer.