Search

Background The Coronavirus Disease 2019 (COVID-19) pandemic had a huge impact on healthcare systems globally. Decline in hospital admissions for common medical emergencies was observed. We investigated its collateral effect on hospitalizations and clinical outcomes in patients with gastrointestinal (GI) and liver diseases in Hong Kong. Methods We performed a territory-wide retrospective cohort study in Hong Kong from January 1, 2019, to May 31, 2020. Data were retrieved through Clinical Data Analysis and Reporting System. We included patients admitted to hospitals with top diagnoses of luminal GI cancers, pancreatico-hepatobiliary cancers, benign pancreaticobiliary disorders, liver diseases, non-infective enteritis and colitis, non-variceal and variceal upper gastrointestinal bleeding (UGIB). We excluded patient-based hospital admissions without emergency department attendance and length of stay equal to or shorter than one day. The primary endpoint was the total number of index hospital admissions related to these diagnoses at different time points. The secondary endpoints were in-hospital mortality, intensive care unit admission, elective or emergency operations and endoscopy. The COVID-19 period was defined as the time after the first local case in January 2020, week 4. Results We recorded a total of 195,867 hospital admissions related to GI diseases during the study period, and 125,049 of them were included in the final analysis. Comparing the same pre-COVID19 and COVID-19 periods, we observed a significant decline in the average number of hospitalizations for GI diseases (17.0% reduction, P Conclusions The number of hospitalizations related to GI diseases reduced drastically during the COVID-19 epidemic, yet no excessive in-hospital mortality was observed. More emergency endoscopies and operations were required, particularly for UGIB and benign pancreaticobiliary conditions.

Background & Aims: Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB). Methods: This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)–negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation. Results: Among 1552 patients with CHB, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7–16.8; P < .001) and among patients with HBsAg levels 30%). Incidence rate of hepatic decompensation and hepatocellular carcinoma was 0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with hepatocellular carcinoma. Conclusions: The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whites with

Background & Aims There have been conflicting results from studies comparing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with tenofovir disoproxil fumarate (TDF) vs those treated with entecavir. We compared the effects of TDF vs entecavir on HCC risk in a large cohort of patients with chronic HBV infection in China. Methods We performed a retrospective study of consecutive adults with chronic HBV infection who initially received treatment with entecavir or TDF, for at least 6 months, from January 2008 through June 2018. Patients who had cancers or liver transplantation before or within the first 6 months of treatment were excluded. Propensity score weighting and 1:5 matching were used to balance the clinical characteristics between the 2 groups. Fine-Gray model was used to adjust for competing risk of death and liver transplantation. Results We analyzed data from 29,350 patients (mean age, 52.9 ± 13.2 years; 18,685 men [63.7%]); 1309 were first treated with TDF (4.5%) and 28,041 were first treated with entecavir (95.5%). TDF-treated patients were younger (mean age, 43.2 years vs 53.4 years) and a lower proportion had cirrhosis (38 patients [2.9%] vs 3822 patients treated with entecavir [13.6%]). At a median follow-up time of 3.6 years after treatment began (interquartile range, 1.7–5.0 years), 8 TDF-treated patients (0.6%) and 1386 entecavir-treated patients (4.9%) developed HCC. Patients' clinical characteristics were comparable after propensity score weighting. TDF treatment was associated with a lower risk of HCC than entecavir treatment after propensity score weighting (weighted subdistribution hazard ratio, 0.36; 95% confidence interval 0.16–0.80; P = .013) and 1:5 matching (weighted subdistribution hazard ratio, 0.39; 95% confidence interval 0.18–0.84; P = .016). Conclusions In a retrospective analysis of 29,350 patients with chronic HBV infection in China, treatment with TDF was associated with a lower risk of HCC than treatment with entecavir, over a median follow-up time of 3.6 years.

Background & Aims The long-term prognosis of peptic ulcers associated with neither Helicobacter pylori nor nonsteroidal anti-inflammatory drugs (NSAIDs) is unknown. Methods This 7-year prospective cohort study recruited patients with bleeding ulcers from January to December 2000. H pylori –negative idiopathic bleeding ulcers were defined as having tested negative for H pylori , having no exposure to aspirin or analgesics within 4 weeks before endoscopy, and having no other identifiable causative factors. After ulcers healed, patients were divided into 2 groups: patients with prior H pylori –negative idiopathic bleeding ulcers ( H pylori –negative idiopathic ulcer cohort; n=120) and those with H pylori –positive, NSAID-negative bleeding ulcers who received eradication therapy ( H pylori ulcer cohort; n=213). Both groups were followed for ≤7 years without gastroprotective therapy. The primary endpoints were recurrent ulcer bleeding and mortality. Results The 7-year cumulative incidence of recurrent ulcer bleeding was 42.3% (95% CI, 36.5%–48.1%) in the H pylori –negative idiopathic ulcer cohort and 11.2% (95% CI, 8.8%–13.6%) in the H pylori ulcer cohort (a difference of 31.1%; 95% CI, 27.7%–34.5%; P H pylori –negative idiopathic ulcer cohort (87.6%; 95% CI, 83.0%–92.2%) than in the H pylori ulcer cohort (37.3%; 95% CI, 34.0%–40.6%) with a difference of 50.3% (95% CI, 49.0%–51.6%; P Conclusions Patients with history of H pylori –negative idiopathic bleeding ulcers have a high risk of recurrent ulcer bleeding and mortality.

It is not clear whether use of low-dose aspirin should be resumed after an episode of lower gastrointestinal (GI) bleeding. We assessed the long-term risks of recurrent lower GI bleeding and serious cardiovascular outcomes after aspirin-associated lower GI bleeding.We performed a retrospective study of patients diagnosed with lower GI bleeding (documented melena or hematochezia and absence of upper GI bleeding) from January 1, 2000 through December 31, 2007 at the Prince of Wales Hospital in Hong Kong. Using the hospital registry, we analyzed data from 295 patients on aspirin and determined their outcomes during a 5-year period. Outcomes included recurrent lower GI bleeding, serious cardiovascular events, and death from other causes, as determined by an independent, blinded adjudication committee. Outcomes were compared between patients assigned to the following groups based on cumulative duration of aspirin use:20% of the follow-up period (121 nonusers) vs ≥50% of the observation period (174 aspirin users).Within 5 years, lower GI bleeding recurred in 18.9% of aspirin users (95% confidence interval [CI], 13.3%-25.3%) vs 6.9% of nonusers (95% CI, 3.2%-12.5%; P = .007). However, serious cardiovascular events occurred in 22.8% of aspirin users (95% CI, 16.6%-29.6%) vs 36.5% of nonusers (95% CI, 27.4%-45.6%; P = .017), and 8.2% of aspirin users died from other causes (95% CI, 4.6%-13.2%) vs 26.7% of nonusers (95% CI, 18.7%-35.4%; P = .001). Multivariable analysis showed that aspirin use was an independent predictor of rebleeding, but protected against cardiovascular events and death.Among aspirin users with a history of lower GI bleeding, continuation of aspirin is associated with an increased risk of recurrent lower GI bleeding, but reduced risk of serious cardiovascular events and death.

Little is known about the validity of hepatocellular carcinoma (HCC) risk scores derived from treatment-naïve patients with chronic hepatitis B for patients treated with entecavir.We performed a retrospective-prospective cohort study of 1531 patients with chronic hepatitis B (age, 51 ± 12 years; 1099 male; 332 with clinical cirrhosis) who were treated with entecavir 0.5 mg daily for at least 12 months at Prince of Wales Hospital in Hong Kong from December 2005 to August 2012. The patients were assessed once every 3 to 6 months for symptoms, drug history, and adherence; blood samples were collected for biochemical analyses. We validated 3 HCC risk scores (CU-HCC, GAG-HCC, and REACH-B scores) based on data collected when patients began treatment with entecavir and 2 years later.After 42 ± 13 months of follow-up, 47 patients (2.9%) developed HCC. The 5-year cumulative incidence of HCC was 4.3% (95% confidence interval [CI], 3.6%-5.0%). Older age, presence of cirrhosis, and virologic remission after 24 months or more of therapy were independently associated with HCC in the entire cohort; advanced age and hypoalbuminemia were associated with HCC in patients without cirrhosis. The area under the receiver operating characteristic curves (AUCs) for baseline CU-HCC, GAG-HCC, and REACH-B scores for HCC were 0.80 (95% CI, 0.75-0.86), 0.76 (95% CI, 0.70-0.82), and 0.71 (95% CI, 0.62-0.81), respectively; the time-dependent AUCs 1 to 4 years after patients started treatment were comparable to those at baseline. The cutoff value of the baseline CU-HCC score identified patients who would develop HCC with 93.6% sensitivity and 47.8% specificity, the baseline GAG-HCC score with 55.3% sensitivity and 78.9% specificity, and the baseline REACH-B score with 95.2% sensitivity and 16.5% specificity. Compared with patients with CU-HCC scores5 at baseline, those with CU-HCC scores that either decreased from ≥5 to5 or remained ≥5 had a higher risk of HCC (5-year cumulative incidences, 0% vs 3.9% and 7.3%; P = .002 and P.001, respectively).The CU-HCC, GAG-HCC, and REACH-B HCC risk scores accurately predict which patients with chronic hepatitis B treated with entecavir will develop HCC.

G A A b st ra ct s the recurrence of LDA-related peptic ulcers has not been reported. We conducted a randomized, double-blind, double-dummy, active-controlled trial to assess the efficacy, doseresponse relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients in long-term LDA therapy. Methods: Patients were eligible for the trial if they had an endoscopically confirmed gastric or duodenal ulcer scars and were receiving long-term LDA (81 mg/day or 100 mg/day) therapy for cardiovascular and cerebrovascular protection. Patients on long-term LDA therapy were also eligible if they had a previous history of endoscopically confirmed active peptic ulcers, but did not present them at baseline endoscopy. Patients were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily or teprenone (mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of gastric and duodenal ulcers over 24 weeks. Secondary endpoints included an occurrence of bleeding ulcers with stigmata of recent hemorrhage or drop in hemoglobin level of more than 2 g/dl, changes from baseline in the modified Lanza score (endoscopic scoring system for gastroduodenal damage) or upper gastrointestinal symptom score, and newly-developed erosive esophagitis. Results: Among 472 randomized patients, 452 patients (rabeprazole 10 mg, n=151; rabeprazole 5 mg, n= 150; teprenone 150 mg, n=151) constituted the full analysis set. The cumulative recurrence rates of gastric and duodenal ulcers over 24 weeks in the 5and 10-mg rabeprazole groups were 2.8% and 1.4%, respectively, and both were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 6.1%, while bleeding ulcers were not observed in the 5or 10-mg rabeprazole groups. The rates of worsening in the modified Lanza and upper gastrointestinal symptom scores in the 5and 10-mg rabeprazole groups were significantly lower than those in the teprenone group. Significantly fewer patients developed erosive esophagitis in the 5 mg rabeprazole group (2%) and 10 mg rabeprazole group (0%), compared with the teprenone group (8.6%). Rabeprazole was well-tolerated at both doses. Conclusions: Rabeprazole prevents the recurrence of gastroduodenal ulcers with no evidence of a major dose response effect in patients taking LDA, and is well-tolerated.

BACKGROUND & AIMS: A limited number of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B respond to treatment with peginterferon alfa (PEG-IFN). We investigated whether IL28B genotypes are associated with response. METHODS: We studied 205 HBeAg-positive patients who were treated with PEG-IFN (some were also treated with lamivudine) at 11 European and Asian hospitals; genotype analysis was performed for IL28B rs12980275 and rs12979860. Response was defined as HBeAg loss with the appearance of antibodies to hepatitis B e antigen (anti-HBe) at the end of PEG-IFN therapy (HBeAg seroconversion), along with HBeAg seroconversion and hepatitis B surface antigen clearance during long-term follow-up. RESULTS: The patients were infected with hepatitis B virus (HBV) genotypes A (13%), B (20%), C (47%), and D (13%). The proportions of IL28B genotypes were 77%, 19%, and 5% for AA/AG/GG at rs12980275 and also for CC/CT/TT at rs12979860, respectively. IL28B genotype was significantly associated with HBeAg seroconversion at the end of treatment (P < .001); the adjusted odds ratio for seroconversion was 3.16 (95% confidence interval [CI], 1.26 - 8.52; P = .013) for AA versus AG/GG at rs12980275 after adjustment for HBV genotype, age, levels of HBV DNA and alanine aminotransferase, and combination therapy. IL28B genotype was independently associated with an increased probability of HBeAg seroconversion during long-term follow-up (adjusted hazard ratio [HR], 2.14; 95% CI, 1.14 - 4.31; P = .018 for AA vs AG/GG by Cox regression analysis). Similar results were obtained for rs12979860. IL28B genotype was also associated with hepatitis B surface antigen clearance (HR, 3.47 for AA vs AG/GG; 95% CI, 1.04 - 13.48; P = .042). CONCLUSIONS: Polymorphisms near IL28B are independently associated with serologic response to PEG-IFN in patients with HBeAg-positive chronic hepatitis B.