Background
Functional dyspepsia (FD) susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, macrophage migration inhibitory factor MIF), motor (GNB3), and sensory ...dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747, and TRPV1 rs755622 gene polymorphisms with FD (Rome III criteria) in the Greek population.
Methods
We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% Helicobacter pylori positive) and 181 controls using polymerase chain reaction‐based methods and we measured disease symptoms’ burden with a modified Gastrointestinal Symptoms Related Scale.
Key Results
Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR 95% CI) with FD (2.65 1.42–4.94 and 1.67 1.23–2.26, respectively). The CT, TT genotypes, and T allele frequencies of GNB3 showed also significant association with FD (2.18 1.35–3.54, 3.46 1.30–9.23, and 2.18 1.48–3.19). While heterozygous GC MIF genotype was more common in dyspeptics (1.67 1.07–2.60), homozygous CC genotype and the C allele of TRPV1 gene were more prevalent in controls (0.47 0.25–0.87 and 0.69 0.51–0.92, respectively). None of the gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<.04) while belching score was lower (p=.027) in MIF CG dyspeptics.
Conclusion & Inferences
Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms, while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Crohn's disease (CD) presents heterogeneity in clinical phenotypes. Progression of disease and response to therapy have been associated, among other factors, with the extent and ...behavior of the disease. Real-world data on long term effectiveness of ustekinumab (UST) in CD based on disease characteristics are limited and conflicting1,2. The aim of this study is to describe real-world UST persistence according to disease distribution and perianal involvement in patients with CD.
Methods
This was a retrospective multicenter study involving adult patients with CD who received, at least, one dose of UST until August 2023, at 5 major hospitals in Athens, Greece. UST effectiveness based on treatment persistence was evaluated using Kaplan Meier curves for survival free of treatment discontinuation among patients with different disease extent and behavior. Log-rank test was used for statistical significance.
Results
A total of 147 adult CD patients who received biological treatment with UST for a median of 34 months (IQR 17-48) were included in the study. Patient baseline characteristics are shown in Table 1. UST treatment persistence rates were 93% (95% CI: 89-98) at 12 months and 87% (95% CI: 81-94) at 36 months. The persistence rate of UST differed significantly between patients with or without perianal disease (p=0.036) (Figure 1), while there was no significant difference based on disease extent (p=0.59) or behavior (p=0.31).
Conclusion
Our study showed that UST treatment persistence is similar in adult patients with CD, regardless of disease localization or behavior. Nonetheless, perianal disease involvement is associated with reduced treatment persistence.
References
1. Liefferinckx C, Verstockt B, Gils A, et al. Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn's Disease Who Failed Biologic Therapies: A National Cohort Study. J Crohns Colitis. 2019;13(11):1401-1409. doi:10.1093/ecco-jcc/jjz080
2. Iborra M, Beltrán B, Fernández-Clotet A, et al. Real-world long-term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry. Aliment Pharmacol Ther. 2020;52(6):1017-1030. doi:10.1111/apt.15958
Abstract
Background
Functional dyspepsia (
FD
) susceptibility might be influenced by polymorphisms of genes related to inflammation (
CD
14
,
macrophage migration inhibitory factor
MIF
), motor (
...GNB
3
), and sensory dysfunction (
GNB
3,
TRPV
1
). We examined the association between
CD
14
rs2569190,
GNB
3
rs5443,
MIF
rs222747, and
TRPV
1
rs755622 gene polymorphisms with
FD
(Rome III criteria) in the Greek population.
Methods
We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41%
Helicobacter pylori
positive) and 181 controls using polymerase chain reaction‐based methods and we measured disease symptoms’ burden with a modified Gastrointestinal Symptoms Related Scale.
Key Results
Homozygous for the
TT
genotype and the T allele of the
CD
14
gene were significantly associated (
OR
95%
CI
) with
FD
(2.65 1.42–4.94 and 1.67 1.23–2.26, respectively). The
CT
,
TT
genotypes, and T allele frequencies of
GNB
3
showed also significant association with
FD
(2.18 1.35–3.54, 3.46 1.30–9.23, and 2.18 1.48–3.19). While heterozygous
GC
MIF
genotype was more common in dyspeptics (1.67 1.07–2.60), homozygous
CC
genotype and the C allele of
TRPV
1
gene were more prevalent in controls (0.47 0.25–0.87 and 0.69 0.51–0.92, respectively). None of the gene polymorphism was related either to dyspepsia clinical syndrome type or to the
H. pylori
infection. Among dyspeptics,
CD
14
TT
genotype was related to lower epigastric pain burden score (
p
<.011);
CD
14
CT
genotype was related to higher epigastric burning and nausea burden scores (
p
<.04) while belching score was lower (
p
=.027) in
MIF
CG
dyspeptics.
Conclusion & Inferences
Functional dyspepsia susceptibility is related to
CD
14
,
GNB
3
,
MIF
, and
TRPV
1
gene polymorphisms, while
CD
14
and
MIF
gene variants are also associated with dyspepsia symptoms burden.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking (GSALT), anti-α4b7 integrin antibody, is an approved and effective treatment for patients with Ulcerative Colitis ...(UC) and Crohn’s Disease (CD). Biologic-naïve patients appear to respond better to treatment with VDZ, than anti-TNF exposed patients. Our study aimed to assess the long-term clinical effectiveness and benefit on health-related quality of life (HRQoL) of first line biologic treatment with VDZ in Greek patients with Inflammatory Bowel Disease.
Methods
Biologic-naïve patients with moderate to severe UC or CD, received VDZ and were prospectively followed as part of the multicenter observational study TROVE. Interim data were collected between November 2018 and May 2021. The primary endpoint was drug persistence at week 54. Secondary endpoints included clinical response at week 14 UC&CD, >50% decrease in patient reported outcomes (PRO2) and clinical remission UC, partial Mayo score (PMS)<3, PRO2-rectal bleeding=0 and stool frequency=0; CD, PRO2-abdominal pain≤1 and stool frequency≤3) at weeks 14 and 54. HRQoL was assessed using SIBDQ and EQ5D questionnaires.
Results
One-hundred and twenty patients from 19 centers were included Female: 55%, Age (mean): 47.8 years, UC/CD: 56%/44%, Disease duration (median): 2.6 years, Smokers: 25%. Baseline characteristics are shown in Table 1. At week 54, 72.1% (49/68) of UC patients and 84.6% (44/52) of CD patients continued treatment with VDZ. Among UC patients, clinical remission rates were 60.3% (n=41/68) and 50% (n=34/68) at weeks 14 and 54, respectively. Clinical remission rates for CD were 86.5% (n=45/52) (week 14) and 76.9% (n=40/52) (week 54). At week 14, among UC and CD patients with clinically active disease at baseline, 73.7% (n=42/57) and 83.8% (n=31/37) responded to VDZ treatment, respectively. Among patients who had endoscopy (n=14 UC; n=10 CD), rates of mucosal healing at week 54 were 35.7% for UC (MES 0) and 50% for CD (absence of ulceration) respectively. Non-response at week 14 was associated with higher probability of drug discontinuation at week 54 (OR 3.63; CI 1.19-11.1). Disease duration (<2years vs >5years) did not influence drug persistence at week 54 (P=0.25). Treatment was intensified in 12.2% of UC and 11.4% of CD patients. The mean increase in SIBDQ and EQ5D between weeks 0 and 54 were 14.6 and 14.4 respectively (for both P<0.001).
Conclusion
The majority of UC or CD biologic naive patients remain on VDZ one year after treatment commencement, with high clinical remission rates and improved HRQoL. Clinical response at week 14 predicts long-term drug persistence. Our results support the use VDZ as a first line biologic therapy in IBD patients.
The clinical study received funding from Takeda Hellas.
Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long‐term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore ...assessed the HCC incidence beyond year 5 of entecavir/tenofovir (ETV/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10‐center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/TDF for ≥1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5‐10 (median, 6.8) years. HCCs have been diagnosed in 101/1,951 (5.2%) patients within the first 5 years and 17/1,205 (1.4%) patients within 5‐10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness ≥12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender‐Hepatitis B score at baseline or year 5 developed HCC. Conclusion: The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially ≥50 years), lower platelets, and liver stiffness ≥12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444–1453).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) ...than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort.
We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset.
The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) total, with or without cirrhosis). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038).
In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF.
In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis.
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•Caucasians with chronic hepatitis B treated with entecavir vs. tenofovir had:•Similar rates of hepatocellular carcinoma up to 12 years•Similar rates of biochemical/virological response, HBsAg loss and mortality•Less frequent elastographic reversion of cirrhosis at year 5
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and ...the need for HCC surveillance in this setting.
Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5.
In years 5–12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809–0.814, 0.805–0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups.
In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy.
In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.
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•Study conducted in Caucasians with chronic hepatitis B, with or without cirrhosis, after 5 years of entecavir/tenofovir.•Age >50 years, baseline cirrhosis and liver stiffness ≥12 kPa at year 5 were independently associated with increased risk of HCC.•CAGE-B score based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 reliably predicted HCC risk >5 years.•SAGE-B score based only on age and LSM at year 5 was also a reliable predictor of HCC incidence >5 years.
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Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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