Clinical Gastroenterology and Hepatology最新文献

Background & aims: Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but the lack of comparative efficacy trials makes treatment choices a clinical challenge. This network-meta-analysis aimed to compare the relative efficacy of biologics and small molecules in achieving remission in patients with moderate to severe UC.

Methods: The literature was searched up to May 2024. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score [MES] ≤1). Secondary outcomes were the induction and maintenance of clinical remission, endoscopic (MES = 0) and histological remission. A sub-analysis was performed based on the RCT design and previous exposure to biologic therapy.

Results: We identified 36 studies that met our inclusion criteria, with 14,270 patients with UC. Upadacitinib ranked highest in inducing clinical remission (99.6%), and endoscopic improvement (99.2%), followed by risankizumab (91.4%) and (82.3%) respectively. In maintenance of endoscopic improvement, upadacitinib ranked first (98.6%) followed by filgotinib 200 mg (79.2%). Risankizumab ranked first in the induction of histological remission (89.4%). Followed by guselkumab (88.3%). Upadacitinib ranked first (93.1%) in maintaining histological remission followed by guselkumab (89.5%).

Conclusion: Upadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Furthermore, novel biologics such as risankizumab and guselkumab ranked high in achieving these outcomes. This study highlights the efficacy of small molecule drugs and novel selective IL-23s as alternatives to other biologics.

Background and aims: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain.

Methods: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log₁₀ IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable.

Results: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log₁₀ IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log₁₀ IU/mL, who exhibited the lowest HCC risk.

Conclusion: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

Background and aims: China is an endemic area for HEV infection. Estimating the prevalence and incidence of HEV infection in China plays a pivotal role in informing public health policies to prevent and control hepatitis E. This study aimed to investigate the prevalence of anti-HEV IgG and incidence of HEV seroconversion in China.

Methods: This study was based on the Meinian health check-up database in China. Participants who underwent testing for anti-HEV IgG at check-up centers in 24 provinces between 2017 and 2022 were included. In the cross-sectional analyses, overall prevalence and stratified prevalence in subpopulations with various characteristics were estimated and standardized according to the 2020 census of the Chinese population. In the longitudinal analyses, the occurrence of anti-HEV IgG positivity during the follow-up was defined as an incident HEV seroconversion. Overall and stratified incidence rates were estimated and expressed as per 100 person-years. Poisson regression was used to explore risk factors associated with HEV seroconversion.

Results: 85,238 and 11,154 participants were included in the cross-sectional and longitudinal analyses, respectively. The prevalence of anti-HEV IgG in the general population was 18.02%. During a median follow-up of 1.2 years, the incidence rate of HEV seroconversion was 1.79 per 100 person-years. Age ≥ 60 years, low socioeconomic status, living in coastal areas, living in areas with high drainage density, and living in areas with high anti-HEV IgG prevalence were independent risk factors for HEV seroconversion.

Conclusions: Our findings would help inform policy making for hepatitis E prevention and control in China, as well as in other endemic regions of the world.

Background & aims: We compared the effects of a 12-week intermittent calorie restriction (ICR) and standard of care (SOC) diet on liver fat content (LFC) in metabolic dysfunction-associated steatotic liver disease (MASLD) patients.

Methods: This randomized controlled trial included patients with MRI-proton density fat fraction (PDFF) ≥8%. Patients were randomly assigned to the ICR (5:2 diet) or SOC (80% of the recommended calorie intake) groups and stratified according to the body mass index (≥ or <25 kg/m²). The primary outcome was the proportion of patients who achieved a relative LFC reduction as measured by MRI-PDFF ≥30%.

Results: Seventy-two participants underwent randomization (36 patients with and 36 without obesity), and 63 (34 patients with and 29 without obesity) completed the trial. At week 12, a higher proportion of patients in the ICR arm achieved a relative LFC reduction of ≥30% compared to the SOC arm (72.2% vs. 44.4%; P=0.033), which was more prominent in the group with obesity (61.1% vs. 27.7%; P=0.033) than in the group without obesity (83.3% vs. 61.1%; P=0.352). The relative weight reduction was insignificant between the ICR and SOC arms (-5.3% vs. -4.2%; P=0.273); however, it was higher in the ICR arm compared to the SOC arm (-5.5% vs. -2.9%; P=0.039) in the group with obesity. Changes in fibrosis, muscle and fat mass, and liver enzyme levels were similar between the two groups (all P>0.05).

Conclusions: The ICR diet reduced LFC more effectively than SOC in patients with MASLD, particularly in patients with obesity. Additional studies are warranted in larger and more diverse cohorts.

Background and aim: Short-term mortality in alcohol-related hepatitis (AH) is high and no current therapy results in durable benefit. A role for IL-1ß has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1ß, in the treatment of patients with AH.

Methods: Participants with biopsy-confirmed AH and discriminant function ≥32 but MELD ≤27 were randomly allocated 1:1 to receive either CAN 3mg/kg or placebo (PBO). Liver biopsies were taken before, and 28 days after treatment. The primary endpoint was the overall histological improvement in inflammation analysed by modified Intention-To-Treat (mITT).

Results: Fifty-seven participants were randomised: 29 to CAN and 28 to PBO. Two participants had histology that did not corroborate the clinical diagnosis. Of the remaining 55 participants, paired histology data was evaluable from 48 participants. In CAN-treated participants, 14/24 (58%) demonstrated histological improvement compared to 10/24 (42%) in the PBO group (p=0.25). There was no improvement in prognostic scores of liver function. Four of the 55 participants (7%) died within 90 days; 2 in each group. The number of serious adverse events was similar between CAN vs PBO. In post-hoc exploratory analyses after adjustment for baseline prognostic factors, CAN therapy was associated with overall histological improvement (p=0.04).

Conclusion: CAN therapy in severe AH participants with MELD≤27 did not alter biochemical or clinical outcomes compared to PBO. Non-significant histological improvements did not translate into clinical benefit.

Background&aims: Globally, emergency departments (ED) are experiencing rising costs and crowding. Despite its importance, ED utilization and outcomes among patients with cirrhosis are understudied.

Methods: We analyzed Optum's de-identified Clinformatics® Data Mart Database, between 2008-2022, including adults with at least 180 days of enrollment. Liver transplant recipients were censored at the year of transplant. ED visits (stratified by liver vs non-liver related) were identified using validated billing code definitions. Linear regression was used to assess ED visits per year and logistic regression was used to assess 90-day mortality rates and discharge dispositions, with models adjusted for patient- and visit-level characteristics.

Results: Among 38,419,650 patients, 198,439 were with cirrhosis (median age 66[IQR 57-72]; 54% male; 62% white). In age-adjusted analysis, ED visits per person-year were 1.72[95CI 1.71-1.74] with cirrhosis vs 0.46[0.46-0.46] without cirrhosis, 1.66[1.66-1.66] for congestive heart failure (CHF), and 1.22[1.22-1.22] for chronic obstructive pulmonary disease (COPD). Age-adjusted 90-day mortality rates were 12.2%[95CI 12.1-12.4] with cirrhosis vs 4.8%[4.8-4.8] without cirrhosis, 6.9%[6.9-6.9] for CHF, and 6.3%[6.3-6.4] for COPD. Non-liver (vs liver-related) ED visits were more likely to lead to discharge home among patients with compensated (52.8%[52.2-53.5] vs 39.2% [38.5-39.8]) and decompensated (42.2%[41.5-42.8] vs 29.5%[29.0-30.1]) cirrhosis. In exploratory analysis, among patients who remained alive and were not readmitted for 30-days after ED discharge, those without any outpatient follow-up had higher 90-day mortality (22.0%[21.0-23.0]) than those with both primary care and gastroenterology/hepatology follow-up within 30-days (7.9%[7.3-8.5]).

Conclusions: Patients with cirrhosis have higher ED utilization and almost 2-fold higher post-ED visit mortality than CHF and COPD. These findings provide impetus for ED-based interventions to improve cirrhosis-related outcomes.

Background and aims: To investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore its association with progression to malignancy.

Methods: We enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy reexamination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during reexamination at the documented location (±2cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma (ESCC) identified over 6.78 years of follow-up and the secondary outcome was reexamination-detected severe dysplasia and above lesions (SDA). The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs.

Results: The proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted OR=6.16, 95%CI: 2.70 to 17.80), large LULs (adjusted OR=1.90, 95%CI: 1.18 to 3.15), and irregularly shaped LULs (adjusted OR=1.63, 95%CI: 1.03 to 2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage ESCC cases and 31 SDAs detected during reexamination were identified, all of which originated from patients with persistent LULs (P_{clinical-stageESCC} =0.136, P_{reexamination-detected SDA} =0.015).

Conclusion: The persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.

Background and aims: Hepatocellular carcinoma (HCC) risk prediction models established in patients with chronic hepatitis B (CHB) receiving nucleoside analogue (NA) rarely included viral factors because of mediocre predictability of traditional viral markers. Here, we investigate the role of serum hepatitis B virus (HBV) RNA, a novel biomarker, in predicting HCC risk in NA-treated patients.

Methods: A total of 1374 NA-treated patients were enrolled from two prospective CHB cohorts. Serum HBV RNA was detected at baseline, year 1, 2 and 3 of treatment. Cox proportional-hazard model was used to investigate the association of HBV RNA kinetics with HCC risk.

Results: After a median follow-up of 5.4 years, 76 patients developed HCC. HBV RNA declines at year 1 (adjusted hazard ratio (aHR) = 0.70, P = .009) and 2 (aHR = 0.71, P = .016) were independently associated with HCC risk. Patients with less HBV RNA decline at year 1 (=< 0.4 log₁₀ copies/mL) or 2 (=<0.6 log₁₀ copies/mL) had 2.22- and 2.09-folds higher HCC risk, respectively, than those with more declines. When incorporating these early on-treatment HBV RNA declines into existing HCC risk scores, including PAGE B, mPAGE B and aMAP score, they could enhance their predictive performance [i.e. C-index, 0.814 vs. 0.788 (Model _{(PAGE B + year-1 HBV RNA decline)}vs. PAGE B score based on baseline parameters)].

Conclusions: Serum HBV RNA declines at year 1 and 2 were significantly associated with on-treatment HCC risk. Incorporating early on-treatment HBV RNA declines into HCC risk prediction models can be useful tools to guide appropriate surveillance strategies in NA-treated patients.

Background: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time.

Methods: We utilized the N3C level 3 data set with uncensored dates to identify all chronic liver disease (CLD) patients with and without cirrhosis who had SARS-CoV-2 infection as of November 2023. We described the observed 30-day case fatality rate (CFR) by month of infection. We used adjusted survival analyses to calculate relative hazard of death by month of infection compared to infection at the onset of the COVID-19 pandemic.

Results: We identified 117,811 total CLD patients infected with SARS-CoV-2 between 3/2020-11/2023: 27,428 (23%) with cirrhosis and 90,383 (77%) without cirrhosis. The observed 30-day CFRs during the entire study period were 1.1% (1,016) for CLD patients without cirrhosis and 6.3% (1,732) with cirrhosis. Observed 30-day CFRs by month of infection varied throughout the pandemic and showed a sustained downward trend since 2022. Compared to infection in Quarter 2 of 2020 (at the beginning of the pandemic), the adjusted hazards of death at 30 days for infection in Quarter 3 of 2023 were 0.20 (95%CI 0.08-0.50) for CLD patients without cirrhosis and 0.35 (95%CI 0.18-0.69) for CLD patients with cirrhosis.

Conclusions: In this N3C study, we found that the observed 30-day CFR decreased progressively for both CLD patients with and without cirrhosis, consistent with broader trends seen in the general population.

Background and aims: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD.

Methods: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 U.S. sites from 2019-2022. Parents/guardians reported race, ethnicity, time between symptom onset and diagnosis, and other social determinants of health. Through bivariate and multivariable analyses using generalized estimating equations we evaluated associations between these factors and diagnosis time defined as ≤60 days, 61-180 days, 181-365 days and >365 days.

Results: We enrolled 869 participants (mean age at diagnosis 13.1 years, 52% male, 57% Crohn's disease (CD), 34% ulcerative colitis (UC), 8% Hispanic, 30% non-White). Overall, the mean time to diagnosis was 265.9 days. After adjustment, factors associated with longer diagnosis time included CD vs. UC (OR 2.6, 95% CI 1.9-3.5), 2 or more other health conditions (OR 1.7, 95% CI 1.1-2.7), and longer travel time to clinic [(> 1 hour (OR 1.7, 95% CI 1.2-2.4), > 2 hours (OR 1.8, 95% CI 1.2-2.9) each vs<30 minute]. There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust.

Conclusions: Consistent with prior literature, diagnostic delay is longer for CD than UC. Reassuringly, time to diagnosis is equitable across racioethnic groups. New models of diagnostic care are needed for communities affected by longer travel times.