Introduction

Helicobacter pylori (H. pylori) infection has a high prevalence (44.8%) in China and is an important risk factor of gastrointestinal diseases including gastric cancer. Bismuth quadruple therapy (BQT; bismuth + acid suppressant + 2 antibiotics [ABs]) is the currently recommended first-line regimen for H. pylori in China. Increasing AB resistance poses a vital challenge and remarkably reduces the eradication rate (ER) from 95% to 80% globally and 89% to 78% in China. Real-world ER analysis assessed only quadruple therapy in a few single centers and did not focus on different antibiotic combinations and other different regimens.

Aims & Methods

This study was designed to evaluate the diagnosis and treatment pattern of H. pylori infection and the effectiveness of eradication therapy in real-world settings in China. In this retrospective, multicenter study (NCT05073367), de-identified patient data were extracted from the electronic medical records database of 3 hospitals between January 1, 2019, and March 31, 2021. Patients aged ≥18 years with a record of H. pylori infection diagnosis were included. Here we presented the eradication rate of different treatment regimens and the eradication rate of different years with different treatment regimens.

Results

A total of 1426 patients received ET with efficacy evaluation duration＞4 weeks after the eradication therapy and the total eradication rate was 72.09% (n=1028). Most patients (80.36%; n=1146) received standard BQT with an ER of 76.70% (n=879). 158 patients (11.08%) received dual therapy (ER=56.96%; n=90) and 122 patients (8.56%) received triple therapy (ER=48.36%; n=59). Compared with triple and dual therapies, BQT was the predominant regimen in all the years with an ER of 77.86%, 67.64%, and 82.78% in 2019, 2020, and 2021, respectively. The ER of dual therapy was 50% in 2020 and 61.22% in 2021. The triple therapy ER showed a decreasing trend with 78.57% (n=11), 46.25% (n=37), 39.29% (n=11) from 2019 to 2021. Among the BQT regimens, amoxicillin plus furazolidone based regimens showed a higher ER (87.44%; n=181), while the ER of amoxicillin plus levofloxacin, amoxicillin plus clarithromycin based BQT was 77.94% (n=159) and 76.07% (n=391), respectively. Amoxicillin plus furazolidone based BQT showed a higher ER of 87.30%, 83.02%, and 90.11% in 2019, 2020, and 2021 respectively (Table 1).
Table 1. Eradication rate of H. pylori positive patients based on the type of eradication therapy

Total (N=1426) → /Treatment regimens ↓	ER-success n (%)b	Year 2019 Success n (%)b	Year 2020 Success n (%) b	Year 2021 Success n (%)b
Total	1028 (72.09)	454 (77.87)	253 (60.96)	321 (75.00)
Bismuth Quadruple Therapy Amoxicillin and Clarithromycin Amoxicillin and Furazolidone Amoxicillin and Levofloxacin Amoxicillin and Metronidazole Other Bismuth Quadruple Therapy	879 (76.70) 391 (76.07) 181 (87.44) 159 (77.94) 2 (50.00) 146 (67.28)	443 (77.86) 169 (78.24) 55 (87.30) 126 (79.25) 2 (50.00) 91 (71.65)	186 (67.64) 106 (67.95) 44 (83.02) 10 (55.56) 0 (0.00) 26 (54.17)	250 (82.78) 116 (81.69) 82 (90.11) 23 (85.19) 0 (0.00) 29 (69.05)
Triple therapyc Dual therapyc	59 (48.36) 90 (56.96)	11 (78.57) 0 (0.00)	37 (46.25) 30 (50.00)	11 (39.29) 60 (61.22)

Abbreviations: N, total number; n, number in respective category.
^a% = The total usage count of BQT/Triple therapy/Dual therapy eradication therapy/the total usage count of all standard eradication therapies taken by eligible participants. Of BQT, the total usage count of different BQT/the total usage count of all BQT.
^b% = The number of participants with a negative efficacy evaluation result/the number of participants receiving certain eradication therapy.
^cConsidering the table size, outcomes of different treatment regimens under dual and triple therapy were not included in the table.

Conclusion

BQT-based regimens were predominantly prescribed for H. pylori management and the current H. pylori treatment regimens have a suboptimal eradication rate in the real-world settings.

Disclosure

The study was funded by Takeda China. Wensheng Pan, Yan Zhao, and Hongwei Xu have no conflicts of interest. Pengfei Li, Fang Zhou, and Li Xie are employees of Takeda, and they hold Takeda stock options. Medical writing for the development of this abstract was provided by Swathirajan CR, PhD, and Kusuma Kumari G, PhD, of Indegene Private Limited, and funded by Takeda China. Authors retained full control of the abstract content.

Introduction

Helicobacter pylori (HP) is regarded as a class I carcinogenic factor and eradication therapy can reduce the risk of gastric cancer. Patients with HP infections are administered with bismuth quadruple therapy (BQT), triple and dual therapies based on their eradication effectiveness. BQT (bismuth + acid suppressants + 2 antibiotics) and dual therapy are both recommended in China now. Comprehensive understanding on the distribution of current eradication therapies is required to identify gaps observed in real-world practice.

Aims & Methods

This multicenter, retrospective, real-world study (NCT05073367) extracted preexisting electronic data including adult patients (aged ≥18 years) with HP infection between January 1, 2019 and March 31, 2021 from 3 hospitals to assess the diagnosis and treatment pattern of HP infection and effectiveness of eradication therapy in China. In this abstract, we reported the distribution of eradication therapies, difference in initiation year for treatment, and treatment duration.

Results

Of the 22,971 eligible patients with HP infection, 13,233 (57.61%) were prescribed eradication regimens. Mean ± SD age of patients with eradication treatment was 43.7 ± 14.0 years; 65.94% of patients had medical insurance; and 54.50% of patients were women.
In patients who received eradication therapy, the BQT therapy was predominantly prescribed (85.39%; n=11301), followed by triple therapy (7.55%; n=999) and dual therapy (7.06%; n=934). Among those receiving BQT, use of amoxicillin + clarithromycin based regimens (38.72%; n=4376) were the most prevalent, followed by amoxicillin +furazolidone (18.35%; n=2074) and amoxicillin + levofloxacin (17.76%; n=2007) based combination regimens. Proportion of patients receiving BQT decreased over years: 97.24% patients in 2019, 79.98% in 2020, and 78.71% in 2021. The proportion of patients receiving dual and triple therapy increased over the years in 2019, 2020, and 2021 were shown in Table 1. A total of 10,903 patients were analyzed according to various treatment durations with the usage of various eradication therapies. Treatment duration is defined as the number of days that prescribed drugs can cover. Out of the three types of treatments, BQT had the highest proportion of 14-day treatment duration at 90.16%, followed by triple therapy at 76.78%, while dual therapy had the least proportion at 14.42%. For treatment duration >14 days, BQT, dual and triple therapy had a proportion of 4.38%, 82.35%, and 17.27% respectively.
Table 1. Distribution of eradication therapy based upon the type and year of treatment initiation

Treatment	Type of Eradication therapy (N=13, 234) n (%)a	Year of treatment initially prescribed , 2019 (N=4492) n (%)a	Year of treatment initially prescribed, 2020 (N=4125) n (%)a	Year of treatment initially prescribed, 2021 (N=4616) n (%)a
Total Bismuth quadruple therapy Amoxicillin and Clarithromycin Amoxicillin and Furazolidone Amoxicillin and Levofloxacin Amoxicillin and Metronidazole Amoxicillin and Tetracycline Furazolidone and Tetracycline Other Bismuth quadruple Triple therapyc Dual therapyc	13,234b (-) 11,301 (85.39) 4376 (38.72) 2074 (18.35) 2007 (17.76) 76 (0.67) 9 (0.08) 12 (0.11) 2747 (24.31) 999 (7.55) 934 (7.06)	4492 (-) 4368 (97.24) 1800 (41.21) 689 (15.77) 1021 (23.37) 27 (0.62) 5 (0.11) 1 (0.02) 825 (18.89) 105 (2.34) 19 (0.42)	4125 (-) 3299 (79.98) 1324 (40.13) 480 (14.55) 516 (15.64) 10 (0.30) 1 (0.03) 0 (0.00) 968 (29.34) 551 (13.36) 275 (6.67)	4617 (-) 3634 (78.71) 1252 (34.45) 905 (24.90) 470 (12.93) 39 (1.07)) 3 (0.08) 11 (0.30) 954 (26.25) 343 (7.43) 640 (13.86)

Abbreviations: N, total number; n, number in respective category.
^a% = The total usage count of BQT or Triple or Dual eradication therapy/the total usage count of all standard eradication therapies received by eligible participants. Of BQT, the total usage count of different BQT/the total usage count of all BQT.
^bThere is a recurrent patient who changed the treatment pattern from triple therapy (ilaprazole, clarithromycin, levofloxacin) to dual therapy (ilaprazole, ornidazole) after the recurrence.
^cConsidering the table size, outcomes of different treatment regimens under dual and triple therapy were not included in the table.

Conclusion

BQT-based regimen for 14 days was the predominant eradication regimens in all therapies, amoxicillin + clarithromycin based BQT was the most prevalent. Use of dual therapy gradually increased with years for HP eradication in the Chinese real-world clinical practice.

Disclosure

The study was funded by Takeda China. Wensheng Pan, Yan Zhao, and Hongwei Xu have no conflicts of interest. Pengfei Li, Fang Zhou, Li Xie are the employees of Takeda, and they hold Takeda stock options. Medical writing for the development of this abstract was provided by Kusuma Kumari G, PhD, of Indegene Private Limited, and funded by Takeda China. Authors retained full control of the abstract content.

Introduction

Hepatocellular carcinoma (HCC) is a global problem being fourth in terms of cancer-related deaths¹. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm focal liver lesions suspected as HCC at prior diagnostic tests such as ultrasound or alpha-foetoprotein, or both^2,3. According to guidelines^4,5,6, a single contrast-enhanced imaging techniques, with either computed tomography (CT) or magnetic resonance imaging (MRI) showing the typical hallmarks is sufficient to diagnose HCC in cirrhotic patients. However, a significant number of HCC show atypical imaging features, and therefore, are missed at imaging.
The advantages of CEUS over CT and MRI is the use of contrast agents not containing iodine and that are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines.

Aims & Methods

The aim was to assess the diagnostic accuracy of CEUS for the diagnosis of HCC of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting and to assess the diagnostic accuracy of CEUS for the diagnosis of resectable HCC in people with chronic liver disease and identify potential sources of heterogeneity in the results.
We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of HCC in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up.
Standard Cochrane methods ⁷ were used to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist⁸. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE^9,10. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs).

Results

We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the participant characteristics.
CEUS for HCC of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence).
CEUS for resectable HCC: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence).
The observed heterogeneity in the results remains unexplained.

Conclusion

Using CEUS, as an add-on test following abdominal ultrasound, to diagnose HCC of any size and stage, 22% of people with the tumor would be missed, and 6% of people without would unnecessarily undergo further testing or inappropriate treatment. As to resectable HCC, we found that 23% of people with resectable tumor would incorrectly be unresected, while 8% of people without HCC would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.

References

1) Forner A et al. Hepatocellular carcinoma. Lancet 2018;391(10127):1301-14.
2) Niu Y, et al. Contrast-enhanced ultrasonography for the diagnosis of small hepatocellular carcinoma: a metaanalysis and meta-regression analysis. Tumour Biology
2013;34(6):3667-74.
3) VogelA, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology2019;30(5):871-3.
4) Galle PR, et al. EASL clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology 2018;69(1):182-236.
5) Omata M, et al.Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatology International 2017;11:317-70
6) HeimbachJK,, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-80.
7) Macaskill P, et al. Chapter 10: Understanding meta-analysis Draft version (13 May 2022) for inclusion in: Deeks JJ, Bossuyt PM, Leeflang MM, TakwoingiY, editor(s). Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 2. London: Cochrane.
8) Whiting PF, Ret al. QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of Internal Medicine 2011;155(8):529-36.
9) McMaster University (developed by Evidence Prime) GRADEpro GDT. Version accessed 26 January 2022. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at gradepro.org.





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Disclosure

nothing to disclose

Introduction

GLIMMER (NCT02966834) was a Phase 2b study of the ileal bile acid transport (IBAT) inhibitor, linerixibat, for treatment of cholestatic pruritus in primary biliary cholangitis (PBC). The study included 147 patients: the largest trial in this population to date. GLIMMER had few restrictions on concomitant medications with the exceptions of other IBAT inhibitors, bile acid sequestrants and obeticholic acid; stable doses of other treatments were permitted.

Aims & Methods

In this analysis we explore the pruritus treatment history of patients entering GLIMMER. Investigators recorded details of prior and concomitant use of itch medications on the electronic case report form. For categorisation of prior and/or concomitant itch medication: prior only included patients who had tried and stopped at ≥1 pruritus medication before first study treatment and were not using anything else during treatment with linerixibat/placebo; concomitant only included patients who had used ≥1 pruritus medication in the past, which they continued to use during treatment; prior and concomitant included patients who had tried and stopped ≥1 pruritus medication prior to the study and, continued to use ≥1 pruritus medication during treatment with linerixibat/placebo. This post hoc analysis included all treatments prescribed for itch; guideline treatments were defined as bile acid sequestrants, naloxone, naltrexone, nalmefene, nalfurafine, sertraline, rifampicin or gabapentin. Pruritus severity was defined using worst itch numeric rating scale (NRS).

Results

At baseline, 24% of patients had mild (NRS <4), 52% moderate (NRS ≥4–<7) and 25% severe (NRS ≥7–10) pruritus. Mean age at baseline was 55.8 years but varied by itch severity, with mild patients being older (60.1 years) than those with moderate and severe pruritus (56.8 and 49.6 years, respectively). Median duration of pruritus at baseline was 6.3 years and those with mild pruritus tended to have a longer history than those with moderate or severe itch. Overall, a large proportion of patients were never previously treated: 37% (n = 55) had no prior/concomitant itch medications. Similar proportions of patients, 24% (n = 36) and 26% (n = 38), had received only prior itch medications or received prior and concomitant treatment for pruritus, respectively; 12% (n = 18) of patients were using only concomitant itch medications. Only 25% of patients were treated with cholestyramine, despite it being the guideline-recommended first-line therapy. Treatment history differed by baseline itch severity: 43% of mild patients had no prior or concomitant treatment versus 28% of severe patients. However, differences were less marked for concomitant pruritus therapy use: 43%, 36% and 39% of mild, moderate and severe patients, respectively, continued concomitant itch medicines in GLIMMER. The majority of concomitant itch treatments were non-guideline recommended, with only 39% receiving guideline treatments.

Conclusion

Consistent with the literature, increased itch severity is associated with younger age. Many patients do not receive treatment despite lengthy history of pruritus, while prior use of cholestyramine is limited despite its position in treatment guidelines.
Funding: GSK (201000).
Encore statement: This abstract was originally presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting on November 7, 2022, this encore is presented on behalf of the original authors with their permission.

Disclosure

HTS, AC, MMM, AJW and AR are employees of, and hold shares in GSK. SD is an employee of GSK.

Introduction

The best risk-stratification strategy to predict liver-related outcomes (LROs) in the population remains unclear. The Chronic Liver Disease (CLivD) risk score was recently developed and validated to predict LROs in the population. It could thus identify the at-risk population that warrants liver fibrosis screening with non-invasive tests such as FIB-4. The ClivD score is based on age, sex, waist-hip ratio, alcohol use, smoking, diabetes, and gamma-glutamyltransferase measurement.

Aims & Methods

We investigated the combined/sequential use of the ClivD score and FIB-4 for stratifying the risk for LROs in the UK Biobank population.
From the UK Biobank data, we identified 362,330 individuals with no baseline liver disease and data available to calculate the CLivD score and FIB-4. LROs were ascertained through linkage with electronic healthcare registries for hospitalizations, cancers, and deaths related to compensated or decompensated liver cirrhosis or hepatocellular carcinoma. Discrimination performance was assessed by 10-year competing-risk area-under-the-curve (AUC) values and absolute cumulative risks by the cumulative incidence functions considering death without liver disease as a competing-risk event.

Results

Mean age was 56.6 years (SD 8.1), 48% were men, mean BMI 27.2 kg/m2 (SD 4.6), 5% had diabetes, mean alcohol intake was 16.7 g/week (SD 16.6), and 10% were current smokers.
During a median follow-up of 12.6 years (IQR 12.0-13.4), there were 1285 incident LROs. Both the CLivD score and FIB-4 were significantly associated with LROs (P<0.001). The 10-year AUC-value of the CLivD score was 0.80 (95% CI 0.80-0.80) and of FIB-4, 0.75 (95% CI 0.75-0.75) for the prediction of LROs. The predictive performance of FIB-4 improved as a function of increasing CLivD scores: 10-year AUC values of FIB-4 were 0.61 in the minimal-risk CLivD subgroup as compared to 0.81 in the high-risk CLivD subgroup (Table). This effect modification of CLivD for FIB-4’s discrimination performance was also evident for absolute risks. Namely, within the minimal-risk CLivD subgroup, 10-year cumulative incidences of LROs ranged from 0.05% to 0.3% between low and high FIB-4 strata (Table). In contrast, within the high-risk CLivD subgroup, 10-year cumulative incidences of LROs ranged from 1.7% to 21.6% between low and high FIB-4 strata.

	Events / subjects	10-yr AUC (95% CI) of FIB-4 for LROs	10-yr risk for LROs
CLivD subgroup			Low FIB-4	Intermediate FIB-4	High FIB-4
Minimal risk	126 / 119,844	0.61 (0.61-0.62)	0.05%	0.1%	0.3%
Low risk	638 / 227,289	0.67 (0.67-0.67)	0.1%	0.2%	1.6%
Intermediate risk	179 / 10,936	0.74 (0.69-0.79)	0.5%	1.5%	7.3%
High risk	342 / 5,546	0.81 (0.79-0.84)	1.7%	3.9%	21.6%

Conclusion

Defining the at-risk population by the CLivD score markedly improves the predictive performance of FIB-4. Thus, sequential use of the CLivD score and FIB-4 emerges as a simple way to stratify the population regarding the risk for LRO.

Introduction

Liver fibrosis is the main prognostic driver and an independent risk factor for both hepatic and extrahepatic events and global mortality in patients with non-alcoholic fatty liver disease (NAFLD). Thus, many serum markers and scores for the assessment of fibrosis severity have been drawn up. Recently, researchers developed the easy Liver Fibrosis Test (eLIFT) and the BMI, AST/ALT ratio and Diabetes (BARD) score.

Aims & Methods

This study aimed to compare the eLIFT and the BARD scores with Transient Elastography for the assessment of liver fibrosis in obese patients with NAFLD.
We conducted a transversal study including obese patients recruited from the Department of Nutrition referred to our center for screening for liver steatosis and a non-invasive evaluation of liver fibrosis. We excluded patients who had pre-existing chronic liver disease, chronic alcohol consumers, or those with ongoing medication other than those for metabolic syndrome.
Demographic and clinical features of the participants were recorded. All participants underwent Transient Elastography (TE) and had their AST, ALT, gamma-glutamyl transferase (GGT), platelet count, and prothrombin time measured in a random blood sample, taken the same day of the TE. We calculated for each patient the eLIFT and BARD scores using standard formulas.
Liver stiffness measurements (LSM) used to define the risk for advanced fibrosis as low, indeterminate, and high, based on EASL guidelines 2021, were respectively: <8 kPa, ≥8 and < 12 kPa, and ≥12 kPa.
An eLIFT <8 indicated a low risk of advanced fibrosis, whereas a result ≥8 identified patients at risk of advanced fibrosis. The BARD score ranges from 0 to 4, considered low from 0 to 1 with a high negative predictive value (NPV) for advanced fibrosis, and considered high from 2 to 4 with a high risk of advanced fibrosis.

Results

A total of 213 obese patients with NAFLD were included, with a mean age of 49.04 ± 11.76 years, 88% were female. The mean body mass index (BMI) was 40.67 ± 10.16 kg/m² and the mean waist circumference (WC) was 115.07 ± 17.49 cm.
TE results revealed that 191 patients had a low risk of advanced fibrosis (89.7%), 13 had an indeterminate risk of advanced fibrosis (6.1%), and nine patients had a high risk of advanced fibrosis (4.2%). Using eLIFT, 195 patients were classified in the low-risk of advanced fibrosis group of which 187 had also a low risk based on TE and only 8 had a high risk of advanced fibrosis, which corresponds to a rate of sensitivity at 92.6%; specificity at 27.3%; NPV at 95.9%; and positive predictive value (PPV) at 16.7%.
The BARD score was low in 21 patients (9.9%) and high in 192 (90.1%). Among the 21 patients with a low BARD score, 19 had a low risk of advanced fibrosis based on LSM and two had a high risk of advanced fibrosis. In the group of patients with a high score, only nine had advanced fibrosis. Sensitivity was 8.5%; specificity was 90%; NPV was 94.4%; and PPV was 4.7%. Both scores had high NPV for a high risk of advanced fibrosis, but the BARD score had a lower sensibility than eLIFT, with better specificity.
AUROC were 0.515 (95% CI, 0.11-0.92) and 0.743 (95% CI, 0.49-0.99) for eLIFT and BARD scores, respectively.

Conclusion

Both eLIFT and BARD scores were useful for ruling out advanced fibrosis (NPV > 90%) in an obese population with NAFLD. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs.